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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-03-0772.
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From The Ohio State University, Columbus; CALGB
Statistical Center, Durham, NC; University of Alabama at Birmingham;
National Cancer Institute, Bethesda, MD; Wake Forest University Medical
Center, Winston Salem, NC; University of Iowa, Iowa City; University of
North Carolina at Chapel Hill; Washington University, St Louis, MO;
North Shore University Hospital, Manhasset, NY; Duke University Medical
Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; Weill
Medical College of Cornell University, New York, NY; SUNY Upstate
Medical University, Syracuse, NY; Karmanos Cancer Institute, Wayne
State University School of Medicine, Detroit, MI; and University of
Chicago, IL.
We analyzed prospectively 1213 adults with de novo acute myeloid
leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All
patients received similar induction therapy. Median follow-up for
surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a
significantly better prognosis than normal karyotype. Prognostic impact
of many abnormalities could not be determined independently because of their association with complex karyotype. Neither complex karyotype nor
secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex
karyotypes had significantly worse outcomes than cytogenetically normal
patients. Based on outcome for specific cytogenetic abnormalities and
karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group,
the probability of achieving CR was 4.0 and 11.9 times lower, the
probability of relapse 3.0 and 4.4 times higher, and the risk of death
2.1 and 4.3 times higher than those for the intermediate and favorable
groups, respectively. We conclude that although the prognostic impact
of many recurring abnormalities has not been ascertained independently
of complex karyotype, cytogenetics is among the most useful factors
predicting attainment of CR, CIR, and long-term survival in adult AML.
(Blood. 2002;100:4325-4336) Acute myeloid leukemia (AML), once recognized as a
single disease, is a heterogeneous disorder with regard to morphology
and chromosome aberrations detected in the leukemic cells. The concept of classifying AML according to pretreatment karyotype has recently become acceptable to most leukemia investigators. This is based on the
ability of karyotype to predict response to induction therapy, relapse
risk, and overall survival (OS).1-15 Treatment of certain cytogenetic subsets, such as patients with t(15;17)(q22;q21) using all-trans retinoic acid (ATRA)16-19 and patients
with t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) using
repetitive doses of high-dose cytarabine, has resulted in markedly
improved outcome.10,12 In contrast, patients with other
aberrations, such as However, despite publication of large AML cytogenetic
series,11,13,15 questions still remain regarding the
prognostic significance of some recurrent aberrations, for example, +8,
del(9q), or translocations involving band 11q23 and specific partner
chromosomes. Similarly, the importance of secondary abnormalities in
patients with t(8;21), inv(16)/t(16;16), and t(9;11)(p22;q23) as their primary chromosome aberrations is debatable, and it is still unclear which definition of a complex karyotype To identify patients at highest risk for induction failure, relapse,
and shortened OS who might be candidates for novel treatment approaches, we analyzed data from a prospective cytogenetic study performed by Cancer and Leukemia Group B (CALGB). We describe the
outcome of 1213 adults with de novo AML categorized into cytogenetic groups comprising at least 5 cases. We also propose a stratification system that categorizes AML patients into favorable, intermediate, and
adverse risk groups with regard to probability of achieving CR,
remaining in remission, and long-term OS according to pretreatment cytogenetic findings.
Patients
Cytogenetic studies
Patients with adequate cytogenetics were grouped according to the presence of a recurrent abnormality noted in at least 5 patients, and clinical features and outcome were examined for each group. Hence, patients with 2 or more abnormalities may appear in more than one group. We observed in a number of patients that loss of material from the chromosome arms 5q, 7q, 17p, and 20q was due not only to deletions or the loss of the whole chromosome (monosomy) but also to various structural aberrations, for example, unbalanced translocations with a known partner chromosome, the presence of additional material of unknown origin (add), isochromosomes, and others. Because it is at present unknown whether clinical characteristics of patients with such aberrations are comparable to or different from those of patients with deletions of these chromosome arms, we categorized the patients with the aforementioned unbalanced aberrations other than del(5q), del(7q), and del(20q) separately and designated these groups as "loss of" material from the respective arm (eg, "loss of 5q"). To be included in a given karyotypic category, it was sufficient for the patient to have the aberration in only 1 of 2 or more clones identified in their karyotype. A complex karyotype was defined in our final risk stratification system as the presence of 3 or more chromosome abnormalities. Each reciprocal translocation was regarded as 1 abnormality. We also analyzed outcome data for patients with 3 or 4 abnormalities and for those with 5 or more abnormalities. Outcome of patients in each cytogenetic group was compared with the outcome of patients with a normal karyotype to identify groups that do better than, similar to, and worse than this well-recognized prognostic group. Treatment The therapies administered to patients in this study have been previously described and are summarized in Table 1.26-30 Induction therapy was identical in each of the 4 trials for patients under the age of 60 years. Postremission therapy differed among the trials, although high-dose cytarabine was administered in a similar fashion in each of the trials. Following sequential cycles of cytarabine consolidation therapy, all patients enrolled on CALGB 8221 and 8525 were assigned to receive 4 cycles of standard-dose cytarabine and daunorubicin as previously described.26,27 During treatment, patients underwent a BM aspiration following completion of cytarabine consolidation and maintenance therapy. Thereafter, patients were followed with BM testing every 3 months for 1 year, every 6 months for 2 years, and then every year for 2 additional years. Patients were followed yearly after 5 years of remission, with BM examinations being performed only if the blood counts suggested relapse of AML.Criteria for response and definition of relapse A CR was defined as the presence of morphologically normal BM and at least 1.5 × 109/L granulocytes and 100 × 109/L platelets in the blood. Relapse was defined as at least 5% leukemic blasts in a BM aspirate or new extramedullary leukemia in patients with a previously documented CR as defined previously.32 Failure to attain CR was divided into categories of early death (death within 30 days, more likely representative of regimen-related toxicity) and late death (more than 30 days, more likely to be associated with resistant disease).Statistical analyses The major objectives of this study were to examine the relationship between pretreatment cytogenetics and clinical end points in a prospectively studied group of AML patients with prolonged follow-up. The main end points analyzed were CR rate, cumulative incidence of relapse (CIR), and OS. We also analyzed the outcome of patients with 3 or 4 cytogenetic abnormalities, with complex karyotype with at least 3 and at least 5 abnormalities, and those with and without secondary abnormalities accompanying t(8;21), inv(16)/t(16;16), and t(9;11). Exploratory analyses were performed on cytogenetic subgroups with at least 5 patients by comparing them with patients with a normal karyotype with respect to the main end points.Patients were categorized into favorable, intermediate, and adverse
risk groups with respect to CR rate, CIR, and OS. Patients with a
normal karyotype were classified as intermediate risk. The
classification process was then carried out by first identifying cytogenetic subgroups that were significantly associated with favorable
outcome. Then, after removing those patients, the adverse risk group of
patients with a complex karyotype with 3 or more abnormalities
was identified, and these patients also were removed. Thereafter, the
CR rates, CIR, and OS of remaining patients with other abnormalities
were re-evaluated and compared with those of patients with a normal
karyotype. The favorable risk group included patients with
abnormalities conferring a significantly better CR rate, CIR, or OS
(P < .05), and patients in the intermediate risk group
had a similar (P Comparison of the proportions of complete responders between each cytogenetic group and normal-karyotype patients was based on the Fisher 2-tailed exact test.33 Comparisons of median age and leukocyte count between different cytogenetic groups and normal-karyotype patients were based on the Wilcoxon rank sum test.33 The CIR analysis included only patients that achieved a CR with time calculated from date of CR until relapse. Patients alive without relapse were censored, whereas those who died without relapse were counted as a competing cause of failure. The CIR and its standard error (SE) was estimated by the method of Gray, and differences between groups were analyzed using a test developed by Gray.34 The estimation of OS distributions was performed using the Kaplan-Meier method,35 and the differences between groups were analyzed using the log-rank statistic.36 Ninety-five percent confidence intervals (CIs) for OS probabilities were calculated according to the method of Simon and Lee.37 For OS, an event was death from any cause with patients alive at last follow-up censored. The outcome data were current as of January 2002. The relationship between clinical and laboratory factors and the
probability of attaining CR was analyzed with the logistic regression
model.38 The relationship between clinical and laboratory factors and CIR and OS was analyzed with the Cox regression
model.39 The factors examined included treatment protocol,
age (< 60,
Patients and treatment protocol outcome Of a total of 1795 patients registered on CALGB 8461 and the concurrent treatment studies, 1385 (77%) had adequate cytogenetic results. However, 74 of these patients were ineligible due to not having AML (n = 58), for other reasons (n = 8), or were not treated on the respective treatment trial (n = 8). Additionally, patients with t(15;17) (n = 88) and t(9;22) (n = 10) were excluded as described in "Patients and methods," leaving 1213 patients who are included in this report. The clinical features at presentation of these patients are shown in Table 2. This analysis includes patients treated over a decade, which introduces a possible confounding variable of different supportive care issues potentially altering the outcome results. Because treatment-related deaths due to infection and other acute leukemia complications are most common during induction, we compared the CR rates among the different trials. The CR proportions by treatment study for patients less than 60 years of age were similar (P = .83) as follows: CALGB 8221, 72%; CALGB 8525, 74%; CALGB 9022, 78%; and CALGB 9222, 75%. Similarly, the CR proportions by treatment study for patients aged at least 60 years were not significantly different (P = .05) as follows: CALGB 8221, 56%; CALGB 8525, 43%; and CALGB 8923, 54%. Figure 1 shows the OS for all patients included in this analysis. Finally, performance of stem cell transplantation (SCT) off-protocol in first CR or as part of salvage therapy could potentially confound analysis of OS. A total of 131 patients underwent SCT in first CR (n = 29) or following relapse (n = 102). Outcome for OS for the entire group of patients was similar irrespective of the inclusion or exclusion of patients who underwent SCT.
Frequency of karyotypic abnormalities in adults with de novo AML Table 3 summarizes the absolute frequency of recurrent chromosome abnormalities among the 1213 patients studied. Of these patients, 582 (48%) had a normal karyotype, whereas 631 (52%) had 1 or more clonal abnormalities. The nonprioritized classification demonstrates that +8, inv(16)/t(16;16), t(8;21), Y,
7, and del(5q) constitute the only recurring abnormalities with a
frequency above 3%. In Table 3, we also provide the percentages of
patients in whom each abnormality occurred as a sole chromosome change
and of those in whom each abnormality was part of a complex
karyotype with at least 3 or at least 5 abnormalities. These
proportions vary greatly among cytogenetic groups. In general, specific
reciprocal translocations that is, t(6;9)(p23;q34), t(6;11)(q27;q23),
t(8;21), t(9;11), t(11;19)(q23;p13.1), and inv(16)/t(16;16)were seen
less frequently as part of a complex karyotype, and most such
rearrangements, except t(8;21) and t(9;11), occurred as the sole
aberration in most patients carrying them. In contrast, unbalanced
structural and numeric aberrations (except +11) were detected
predominantly in conjunction with other aberrations, and several of
them, including +4, 5/5q, del(7q), loss of 7q, abn(12p), del(13q),
+14, 17/17p, 18, 20, and loss of 20q, were seen as part of a
complex karyotype with 3 or more abnormalities in at least two
thirds of patients in the respective groups. These data suggest that
assessment of outcome measures (CR, CIR, and OS) of recurring
abnormalities will have to consider the impact of complex
karyotype.
Treatment outcome by nonprioritized cytogenetic group Table 4 demonstrates that CR rates for patients with nonprioritized cytogenetic abnormalities varied considerably, from 94% to 17% depending on the kind of pretreatment abnormality. Compared with the normal karyotype group, whose CR rate was 68%, patients with t(8;21), inv(16)/t(16;16), and del(9q) had significantly higher CR rates. In contrast, patients with inv(3)/t(3;3),5/5q, 7, loss of 7q, +8, abn(12p), 17/17p,
18, 20, and loss of 20q had a significantly lower frequency of
attaining CR than patients with a normal karyotype. In most of these
cytogenetic subgroups, there was a higher frequency of resistant
disease as opposed to early death (Table 4). The CR rates of patients
with other chromosome abnormalities listed in Table 4 did not differ
significantly from that of karyotypically normal patients.
The analysis of OS and CIR demonstrates that patients with t(8;21) and
inv(16)/t(16;16) had a significantly improved probability of 5-year
survival and remaining relapse free, and patients with del(9q)
had an improved chance of 5-year survival compared with patients with a
normal karyotype (Table 5). Patients with
Secondary aberrations and a complex karyotype do not adversely
affect outcome of patients with common balanced rearrangements
 25 patients) balanced rearrangementsthat is, t(8;21),
inv(16)/t(16;16), and t(9;11). There were too few patients with at
least 5 abnormalities to examine whether a complex karyotype
with 5 or more abnormalities alters outcome of these patients. Table
6 demonstrates that for each of the
aforementioned balanced rearrangements, neither the presence of
secondary abnormalities nor a complex karyotype with 3 or more
abnormalities adversely affect outcome. This includes t(8;21)-positive
patients with del(9q), loss of a sex chromosome, +8, and those with
other secondary aberrations, for all of whom CR rates, CIR, and OS were
not significantly different from those of patients with an isolated
t(8;21). Likewise, for each group outlined in Table 6, CR rates, CIR,
and OS of patients who had at least 3 abnormalities were not
significantly different from those of patients who had only 1 or 2 aberrations. These findings provide support for treating AML patients
with t(8;21), inv(16)/t(16;16), and t(9;11) only by their primary
abnormality irrespective of the presence or absence of secondary
aberrations or a complex karyotype with 3 or more
abnormalities.
Complex karyotype: clinical features and outcome Different cytogenetic classifications have defined complex karyotype by the presence of at least 5 clonal aberrations11,15 or at least 3 abnormalities in the absence of t(8;21), inv(16)/t(16;16), and t(15;17).13,40 The classification of this category as at least 3 or at least 5 abnormalities is empiric, with little previous attempt to test if incremental increase in the number of chromosomal aberrations correlates with poorer outcome. To examine this clinically relevant issue, we analyzed the prognostic impact of the presence of 3 or 4 (n = 36) versus 5 or more (n = 99) abnormalities in patients who did not harbor t(8;21), inv(16)/t(16;16), or t(9;11). The influence of a complex karyotype with 3 or more abnormalities in patients with the aforementioned abnormalities was analyzed separately (Table 6). As shown in Table 7, patients with 3 or 4 abnormalities were younger and had significantly better CIR and 5-year OS than those with 5 or more abnormalities. However, both the CR rate and OS of patients with 3 or 4 abnormalities were significantly lower than those of the cytogenetically normal group (P = .02 and P = .002, respectively), whereas the CIR was significantly higher (P = .002). Only 1 of the patients with 3 or 4 abnormalities remains in remission at 5 years. Therefore, despite the difference in outcome between the patients with 3 or 4 aberrations and those with 5 or more aberrations, the low CR rate, 5-year OS, and the high CIR for patients in the former group justify combining patients with 3 or 4 abnormalities with patients with 5 or more abnormalities into 1 complex karyotype category defined by the presence of 3 or more abnormalities. The survival results are depicted in Figure 2.
Outcome of patients with trisomy 8 is poor in the absence of t(8;21), inv(16)/t(16;16), and t(9;11) Trisomy 8 is the most common trisomy in de novo AML (Table 3). However, the +8 group is heterogeneous, because +8 can be the sole abnormality detected, can be part of a complex karyotype, or can be the only secondary aberration accompanying primary rearrangements, including t(8;21), inv(16)/t(16;16), or t(9;11). Previous studies have shown that prognosis of AML patients with +8 depends on whether +8 is an isolated abnormality or is accompanied by aberrations bestowing favorable or adverse prognosis.11,41 We therefore examined the outcome of different subsets of patients with +8 in our series (Table 8). Patients with sole +8 and +8 with 1 additional abnormality other than t(8;21), inv(16)/t(16;16), and t(9;11) had significantly inferior OS, but not CR or CIR rates, while patients with +8 and a complex karyotype with 3 or more abnormalities had a significantly inferior CR rate, CIR, and OS compared with those with a normal karyotype. These data show that the impact of trisomy 8 is best predicted by the presence and nature of abnormalities that accompany it (Figure 3).
Prioritization schema that facilitates risk assessment for untreated de novo AML We developed a prioritization schema for the assignment of risk based on pretreatment karyotype according to the probability of achievement of CR, CIR, and OS for patients with AML. Patients with a normal karyotype were classified as intermediate risk. We classified all patients with t(8;21) and inv(16)/t(16;16) in the favorable and those with t(9;11) in the intermediate risk categories based on outcome data presented in Tables 4 and 5 and the absence of impact on outcome of complex karyotype with 3 or more abnormalities in these groups (Table 6). All other patients with a complex karyotype with 3 or more abnormalities were classified as having adverse risk. After excluding the patients thus classified, we analyzed the impact of specific aberrations on outcome for the remaining patients in cytogenetic groups that still comprised at least 5 patients (Table 9).
Patients with a significantly superior or inferior
(P < .05) CR rate, CIR, or OS relative to karyotypically
normal AML patients were classified in the favorable or adverse risk
group, respectively. Patients with a similar (P
When we categorized the patients according to this risk classification
system for success of induction treatment, the favorable risk group
comprised 177 (16%) patients, the intermediate risk group 800 (71%)
patients, and the adverse risk group 147 (13%) patients. Their CR
rates were 88%, 67%, and 32%, respectively. For 5-year CIR, the
favorable risk group comprised 156 (22%) patients, the intermediate
risk group 498 (70%) patients, and the adverse group 62 (9%)
patients. The estimated CIRs (with SE) at 5 years were 0.51 (0.04),
0.67 (0.02), and 0.92 (0.04), respectively. The CIR curves are shown in
Figure 4. For 5-year OS, the favorable risk group comprised 190 (17%) patients, the intermediate risk group
686 (61%) patients, and the adverse risk group 248 (22%) patients.
The estimated probabilities (with 95% CI) of 5-year OS were 55%
(47%-62%), 24% (21%-27%), and 5% (3%-8%), respectively. The
differences in OS are depicted in Figure
5.
We next analyzed factors related to the probability of attaining CR using the logistic regression model. Univariate analysis identified the following factors to have prognostic significance: cytogenetic risk (P < .001), treatment protocol (P < .001), age (P < .001), leukocyte count (P < .001), splenomegaly (P = .001), infection at study entry (P = .002), and hepatomegaly (P = .004). A forward stepwise multivariate analysis of 1118 cases with complete data on these variables selected cytogenetic risk (P < .001), age (P < .001), leukocyte count (P < .001), splenomegaly (P = .002), and infection at study entry (P = .02) to the model as joint predictors of attaining CR, where the P value for each variable is adjusted for variables preceding it in the list. When all variables in the model were considered, patients in the adverse cytogenetic group were 4.0 (95% CI, 2.7-5.9) times less likely to achieve CR than those in the intermediate group and 11.9 (95% CI, 4.9-28.9) times less likely than patients in the favorable group. Patients in the intermediate group were 3.0 (95% CI, 1.8-4.9) times less likely to achieve CR than those in the favorable group. The analysis of factors related to CIR was carried out using the Gray method for comparing the cumulative incidence of a competing risk. Univariate analysis identified the following factors to have prognostic significance: cytogenetic risk (P < .001), age (P < .001), leukocyte count (P < .001), treatment protocol (P = .002), and number of induction courses (P = .007). A forward stepwise multivariate Cox regression analysis of 711 cases with complete data on these variables selected cytogenetic risk (P < .001), age (P < .001), leukocyte count (P < .001), and number of induction courses (P = .01) to the model as joint predictors of CIR, where the P value for each variable is adjusted for variables preceding it in the list. When all variables in the model were considered, patients in the adverse cytogenetic group were 3.0 (95% CI, 2.2-4.0) times more likely to relapse than those in the intermediate group and 4.4 (95% CI, 2.6-7.8) times more likely to relapse than patients in the favorable group. Patients in the intermediate group were 1.5 (95% CI, 1.1-1.9) times more likely to relapse than those in the favorable group. The analysis of factors related to OS was carried out using the Cox regression model. Univariate analysis identified the following factors to have prognostic significance: cytogenetic risk (P < .001), treatment protocol (P < .001), age (P < .001), leukocyte count (P < .001), infection at study entry (P < .001), number of induction courses (P = .009), and percent marrow blasts (P = .04). A forward stepwise multivariate analysis of 1099 cases with complete data on these variables selected age (P < .001), cytogenetic risk (P < .001), leukocyte count (P < .001), and infection at study entry (P = .001) to the model as joint predictors of OS, where the P value for each variable is adjusted for variables preceding it in the list. When all variables in the model were considered, patients in the adverse cytogenetic group were 2.1 (95% CI, 1.8-2.5) times more likely to die than those in the intermediate group and 4.3 (95% CI, 2.9-6.3) times more likely to die than patients in the favorable group. Patients in the intermediate group were 2.0 (95% CI, 1.6-2.5) times more likely to die than those in the favorable group.
Our data, derived from a large group of adults with de novo AML with prolonged follow-up, show that specific cytogenetic findings at diagnosis are predictive of treatment outcome. This study is one of only a few large prospective series examining prognostic impact of cytogenetics in AML11,13,15 and includes a relatively homogeneous group of de novo AML patients who received similar induction chemotherapy, with most receiving modern intensification treatment. It is important to recognize that both our study and 3 other recent studies11,13,15 validate observations made originally by the International Workshops on Chromosomes in Leukemia in the 1980s1,2 and, it is hoped, will result in reaching a consensus with respect to the prognostic importance of specific pretreatment cytogenetic findings in AML. What does our large series add to the literature on cytogenetics in AML? Our initial goal was to identify the clinical significance of recurring chromosome abnormalities in previously untreated adults with de novo AML. Early into the analysis, we noted that although the most common balanced rearrangements, t(8;21), inv(16)/t(16;16), and t(9;11), were infrequently associated with a complex karyotype (Table 3), considerable proportions of patients with these rearrangements harbored secondary abnormalities. Therefore, we analyzed the impact of secondary abnormalities and karyotype complexity and found that neither the presence of a single secondary abnormality nor a complex karyotype influenced the outcome of AML patients with t(8;21), inv(16)/t(16;16), and t(9;11) who received contemporary treatment regimens. Our data, similar to one study11 but in contrast to another,42 do not show that secondary del(9q) confers a poor prognosis in patients with t(8;21). However, it is still possible that other specific secondary chromosome aberrations, occurring with a frequency too low to be currently tested for outcome, might affect prognosis of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Furthermore, secondary aberrations may become important when therapies targeting specific molecular rearrangements generated by primary abnormalities are used. This possibility is suggested by a recent study43 reporting that t(15;17)-positive acute promyelocytic leukemia (APL) patients with secondary aberrations were significantly less likely to benefit from treatment with ATRA than patients with t(15;17) alone. Other studies examining the impact of secondary abnormalities in APL have not confirmed this observation.44,45 We next sought to dissect the prognostic impact of the presence of 3 or 4 versus 5 or more abnormalities in patients who did not harbor t(8;21), inv(16)/t(16;16), or t(9;11). Patients with at least 5 abnormalities were older and had an inferior survival than patients with 3 or 4 abnormalities. Nonetheless, each of these patient subsets had a significantly lower probability of long-term OS than patients with a normal karyotype. Our data are in agreement with another series40 and provide justification for using at least 3 abnormalities as a definition of complex karyotype for risk stratification. Unlike other large studies,11,13,15 we analyzed the
outcome of patients with structural aberrations leading to loss of 5q,
7q, and 20q separately from outcome of patients with, respectively, The current study confirms and extends previous CALGB results indicating that outcome of patients with balanced 11q23 translocations depends on which partner chromosome is involved.9 While the CR rate, CIR, and OS of patients with t(9;11) were not statistically different from those of patients with a normal karyotype, the OS of patients with t(6;11) or t(11;19)(q23;p13.1) was significantly shorter, with no survivors at 5 years, despite CR rates comparable to the normal group. Thus, both our results and others3,11 support classifying patients with t(9;11) into the intermediate prognostic category, separately from patients with t(6;11) and t(11;19)(q23;p13.1) who have poor outcome. Although patients with other translocations involving 11q23 also appear to have poor outcome, the definitive assignment of risk category for patients with each of the individual 11q23 translocations will be possible only when a larger number of patients are analyzed in prospective studies. Many other aberrations associated with poor outcome in our nonprioritized analysis either never (eg, +14, loss of 17p) or rarely (eg, +4, del(7q)) occurred as a sole abnormality and were detected mainly as part of a complex karyotype. However, other recurrent abnormalities occurred in sufficient numbers in the absence of a complex karyotype to justify risk stratification, for example, t(6;9). Our data corroborate the results of others48,49 in that AML patients with t(6;9) are younger and have a dismal prognosis, with a 38% CR rate and no patient surviving 5 years. This poor outcome is not due to secondary abnormalities, because 6 of the 8 patients had t(6;9) as their sole aberration, and the karyotype of the 2 remaining patients was not complex. These data differ from the MRC studies that included patients with t(6;9) in the intermediate prognosis group.11,15 We emphasize, however, that some of the cytogenetic groups in Tables 9 and 10, including t(6;9), comprised relatively small numbers of patients. Consequently, further large prospective studies are necessary to confirm our risk group assignment of such smaller cytogenetic categories. Our cytogenetic risk system (Table 10) shares many common features with the MRC11 and Southwest Oncology Group/Eastern Cooperative Oncology Group13 (SWOG/ECOG) classifications but also differs in some aspects from them. For the favorable risk category, our system is like the MRC (and the German AML Study Group40) but differs from SWOG/ECOG in that we included all patients with t(8;21) in the favorable group, whereas SWOG/ECOG classified patients with t(8;21) and del(9q) or a complex karyotype in the unfavorable risk category. We also did not include patients with del(16q) in the favorable risk group, because del(16q) often differs from inv(16)/t(16;16) at the molecular level and has not been associated with a favorable outcome comparable to that of inv(16)/t(16;16).50-52 The intermediate subset in our series contrasts for several chromosome aberrations with both the MRC and SWOG/ECOG systems.11,13 This subset requires close scrutiny because therapeutic recommendations will be made relative to the appropriateness of SCT or other alternative therapy in first CR. Patients with isolated +8 or +8 with 1 abnormality other than t(8;21), inv(16)/t(16;16), or t(9;11) have been assigned to the intermediate risk group for CIR and the adverse risk group for OS. Patients with +21 have been classified as having intermediate risk for OS but adverse for CIR, whereas patients with +11 and +13 have been classified as having intermediate risk for both CIR and OS. However, each of these categories comprised all patients with a given trisomy, both those with an isolated trisomy and patients with a trisomy accompanied by other aberrations. A recent analysis from CALGB that also comprised patients enrolled on CALGB 9621, which includes SCT as postremission therapy,53 has shown that when only patients with isolated +8, +11, +13, and +21 were examined their OS was significantly worse than that of patients with a normal karyotype.54 Finally, because we desired to make definitive recommendations as to the outcome of specific karyotypes, we did not include in our risk classification system cytogenetic groups with too few patients to be analyzed. These include patients with del(7q) and +22 that were assigned intermediate risk status in the MRC classification.11 To assess the predictive value of our cytogenetic risk assessment model relative to other pretreatment prognostic factors, we performed multivariate analyses with respect to the main end points. These analyses demonstrated that cytogenetic risk, age, and presenting leukocyte count were most significantly associated with predicting attainment of CR. For CIR, cytogenetic risk, age, leukocyte count, and number of induction courses were predictive. In contrast, for survival, age entered the model before cytogenetic risk group and presenting leukocyte count, suggesting that other factors associated with elderly AML, independent of cytogenetics, contribute to outcome of patients with AML. These analyses confirm the importance of cytogenetics as a prognostic tool for predicting attainment of CR, CIR, and OS. The CALGB is currently using pretreatment cytogenetics to stratify patients for different types of postremission therapy.53 Ongoing and future studies will likely further modify prognostic categorization of AML patients by subdividing cytogenetic risk groups according to the results of molecular genetic investigations detecting such prognostically relevant mutations as an internal tandem duplication of the FLT3 gene,55,56 partial tandem duplication of the MLL gene,57,58 and other, as yet undiscovered, genetic alterations in AML.
This paper is dedicated to the memory of Richard K. Dodge.
Submitted March 13, 2002; accepted July 17, 2002.
Prepublished online as Blood First Edition Paper, August 1, 2002; DOI 10.1182/blood-2002-03-0772.
Supported by National Cancer Institute grants CA31946, 16058, and 77658, Kimmel Cancer Research Foundation, Leukemia and Lymphoma Society of America, D. Warren Brown Foundation, and the Coleman Leukemia Research Fund.
J.C.B. and K.M. contributed equally to this work.
A complete list of the Cancer and Leukemia Group B institutions, principal investigators, and cytogeneticists who participated in this study and contributed at least 5 patients, and additional grant support for participating institutions appear in "Appendix."
Richard K. Dodge died on August 24, 2002.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Presented in part at the 43rd annual meeting of the American Society of Hematology, Orlando, FL, December 10, 2001, and published in abstract form.59 Reprints: John C. Byrd, Division of Hematology and Oncology and the Comprehensive Cancer Center, The Ohio State University, B302A Starling Loving Hall, 320 West 10th Ave, Columbus, OH 43210-1240; e-mail: byrd-3{at}medctr.osu.edu.
1. Bloomfield CD, Goldman A, Hossfeld D, de la Chapelle A. Fourth International Workshop on Chromosomes in Leukemia 1982: clinical significance of chromosomal abnormalities in acute nonlymphoblastic leukemia. Cancer Genet Cytogenet. 1984;11:332-350[Medline] [Order article via Infotrieve]. 2. Arthur DC, Berger R, Golomb HM, et al. The clinical significance of karyotype in acute myelogenous leukemia. Cancer Genet Cytogenet. 1989;40:203-216[CrossRef][Medline] [Order article via Infotrieve]. 3. Fenaux P, Preudhomme C, Laï JL, Morel P, Beuscart R, Bauters F. Cytogenetics and their prognostic value in de novo acute myeloid leukaemia: a report on 283 cases. Br J Haematol. 1989;73:61-67[Medline] [Order article via Infotrieve].
4.
Schiffer CA, Lee EJ, Tomiyasu T, Wiernik PH, Testa JR.
Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia.
Blood.
1989;73:263-270 5. Stasi R, Del Poeta G, Masi M, et al. Incidence of chromosome abnormalities and clinical significance of karyotype in de novo acute myeloid leukemia. Cancer Genet Cytogenet. 1993;67:28-34[CrossRef][Medline] [Order article via Infotrieve]. 6. Dastugue N, Payen C, Lafage-Pochitaloff M, et al. Prognostic significance of karyotype in de novo adult acute myeloid leukemia. Leukemia. 1995;9:1491-1498[Medline] [Order article via Infotrieve]. 7. Ferrant A, Doyen C, Delannoy A, et al. Karyotype in acute myeloblastic leukemia: prognostic significance in a prospective study assessing bone marrow transplantation in first remission. Bone Marrow Transplant. 1995;15:685-690[Medline] [Order article via Infotrieve]. 8. Keating S, Suciu S, de Witte T, et al. Prognostic factors of patients with acute myeloid leukemia (AML) allografted in first complete remission: an analysis of the EORTC-GIMEMA AML 8A trial. Bone Marrow Transplant. 1996;17:993-1001[Medline] [Order article via Infotrieve].
9.
Mrózek K, Heinonen K, Lawrence D, et al.
Adult patients with de novo acute myeloid leukemia and t(9;11)(p22;q23) have a superior outcome to patients with other translocations involving band 11q23: a Cancer and Leukemia Group B study.
Blood.
1997;90:4532-4538
10.
Bloomfield CD, Lawrence D, Byrd JC, et al.
Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.
Cancer Res.
1998;58:4173-4179
11.
Grimwade D, Walker H, Oliver F, et al.
The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial.
Blood.
1998;92:2322-2333
12.
Byrd JC, Dodge RK, Carroll A, et al.
Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered.
J Clin Oncol.
1999;17:3767-3775
13.
Slovak ML, Kopecky KJ, Cassileth PA, et al.
Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study.
Blood.
2000;96:4075-4083 14. Mrózek K, Heinonen K, Bloomfield CD. Clinical importance of cytogenetics in acute myeloid leukaemia. Best Pract Res Clin Haematol. 2001;14:19-47[Medline] [Order article via Infotrieve].
15.
Grimwade D, Walker H, Harrison G, et al.
The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial.
Blood.
2001;98:1312-1320
16.
Fenaux P, Chastang C, Chevret S, et al.
A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia.
Blood.
1999;94:1192-1200
17.
Tallman MS, Andersen JW, Schiffer CA, et al.
All-trans-retinoic acid in acute promyelocytic leukemia.
N Engl J Med.
1997;337:1021-1028
18.
Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH.
Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the Randomized MRC Trial.
Blood.
1999;93:4131-4143 19. Asou N, Adachi K, Tamura U, et al. Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG). Cancer Chemother Pharmacol. 2001;48(suppl 1):S65-S71.
20.
Harris NL, Jaffe ES, Diebold J, et al.
World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.
J Clin Oncol.
1999;17:3835-3849 21. Jaffe ES,Harris NL,Stein H,Vardiman JW, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.
22.
Döhner H, Arthur DC, Ball ED, et al.
Trisomy 13: a new recurring chromosome abnormality in acute leukemia.
Blood.
1990;76:1614-1621 23. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33:451-458[Medline] [Order article via Infotrieve].
24.
Bennett JM, Catovsky D, Daniel MT, et al.
Proposed revised criteria for the classification of acute myeloid leukemia: a report of the French-American-British Cooperative Group.
Ann Intern Med.
1985;103:620-625 25. Bennett JM, Catovsky D, Daniel MT, et al. Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-M0). Br J Haematol. 1991;78:325-329[Medline] [Order article via Infotrieve]. 26. Mayer RJ, Schiffer CA, Peterson BA, et al. Intensive postremission therapy in adults with acute nonlymphocytic leukemia using various dose schedules of ara-C: a progress report from the CALGB. Semin Oncol. 1987;14(suppl 1):25-31[Medline] [Order article via Infotrieve].
27.
Mayer RJ, Davis RB, Schiffer CA, et al.
Intensive postremission chemotherapy in adults with acute myeloid leukemia.
N Engl J Med.
1994;331:896-903
28.
Stone RM, Berg DT, George SL, et al.
Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia.
N Engl J Med.
1995;332:1671-1677
29.
Moore JO, Dodge RK, Amrein PC, et al.
Granulocyte-colony stimulating factor (filgrastim) accelerates granulocyte recovery after intensive postremission chemotherapy for acute myeloid leukemia with aziridinyl benzoquinone and mitoxantrone: Cancer and Leukemia Group B Study 9022.
Blood.
1997;89:780-788 30. Moore JO, Powell B, Velez-Garcia E, et al. A comparison of sequential non-cross-resistant therapy or Ara-C consolidation following complete remission in adult patients <60 years with acute myeloid leukemia: CALGB 9222 [abstract]. Proc Annu Meet Am Soc Clin Oncol. 1997;16:14a. 31. Mitelman F, ed. ISCN 1995: An International System for Human Cytogenetic Nomenclature 1995. Basel, Switzerland: S Karger; 1995. 32. Cheson BD, Cassileth PA, Head DR, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990;8:813-819[Abstract]. 33. Armitage P. Statistical Methods in Medical Research. London United Kingdom: Blackwell Scientific Publications; 1971. 34. Gray RJ. A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16:1141-1154[CrossRef]. 35. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481[CrossRef]. 36. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer. 1977;35:1-39[Medline] [Order article via Infotrieve]. 37. Simon R, Lee YJ. Nonparametric confidence limits for survival probabilities and median survival time. Cancer Treat Rep. 1982;66:37-42[Medline] [Order article via Infotrieve]. 38. Hosmer DW, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley and Sons; 1989. 39. Cox DR. Regression models and life tables. J R Stat Soc B. 1972;34:187-202. 40. Schoch C, Haferlach T, Haase D, et al. Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients. Br J Haematol. 2001;112:118-126[CrossRef][Medline] [Order article via Infotrieve]. 41. Schoch C, Haase D, Fonatsch C, et al. The significance of trisomy 8 in de novo acute myeloid leukaemia: the accompanying chromosome aberrations determine the prognosis. Br J Haematol. 1997;99:605-611[CrossRef][Medline] [Order article via Infotrieve]. 42. Schoch C, Haase D, Haferlach T, et al. Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor. Leukemia. 1996;10:1288-1295[Medline] [Order article via Infotrieve]. 43. Wiernik PH, Kim H, Gundacker H, et al. Prognostic implication of additional cytogenetic aberrations in de novo acute myeloid leukemia (AML) with t(15;17), t(8;21) or inv(16)/t(16;16) [abstract]. Blood. 2001;98:457a. 44. De Botton S, Chevret S, Sanz M, et al. Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial. Br J Haematol. 2000;111:801-806[CrossRef][Medline] [Order article via Infotrieve]. 45. Hernández JM, Martín G, Gutiérrez NC, et al. Additional cytogenetic changes do not influence the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with an ATRA plus anthracyclin based protocol: a report of the Spanish group PETHEMA. Haematologica. 2001;86:807-813[Medline] [Order article via Infotrieve]. 46. Odero MD, Carlson KM, Calasanz MJ, Rowley JD. Further characterization of complex chromosomal rearrangements in myeloid malignancies: spectral karyotyping adds precision in defining abnormalities associated with poor prognosis [letter]. Leukemia. 2001;15:1133-1136[CrossRef][Medline] [Order article via Infotrieve]. 47. Mrózek K, Heinonen K, Theil KS, Bloomfield CD. Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q and 22q. Genes Chromosomes Cancer. 2002;34:137-153[CrossRef][Medline] [Order article via Infotrieve]. 48. Hollings PE, Cochrane J, Bowen JA, Rosman I, Fitzgerald PH. Growth characteristics in vitro of myeloid leukaemic cells with t(6;9). Leuk Lymphoma. 1995;17:281-288[Medline] [Order article via Infotrieve]. 49. Alsabeh R, Brynes RK, Slovak ML, Arber DA. Acute myeloid leukemia with t(6;9)(p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype. Am J Clin Pathol. 1997;107:430-437[Medline] [Order article via Infotrieve].
50.
Larson RA, Williams SF, Le Beau MM, Bitter MA, Vardiman JW, Rowley JD.
Acute myelomonocytic leukemia with abnormal eosinophils and inv(16) or t(16;16) has a favorable prognosis.
Blood.
1986;68:1242-1249 51. Marlton P, Keating M, Kantarjian H, et al. Cytogenetic and clinical correlates in AML patients with abnormalities of chromosome 16. Leukemia. 1995;9:965-971[Medline] [Order article via Infotrieve].
52.
Mrózek K, Prior TW, Edwards C, et al.
Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B study.
J Clin Oncol.
2001;19:2482-2492 53. Kolitz JE, George SL, Dodge RK, et al. Consolidation therapy by cytogenetic risk in adults with acute myeloid leukemia (AML) < 60 years in first complete remission (CR): results of CALGB 9621 [abstract]. Blood. 2001;98:688a. 54. Farag SS, Archer KJ, Mrózek K, et al. Isolated trisomy of chromosomes 8, 11, 13 and 21 is an adverse prognostic factor in adults with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Int J Oncol. 2002;21:1041-1051[Medline] [Order article via Infotrieve].
55.
Kottaridis PD, Gale RE, Frew ME, et al.
The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials.
Blood.
2001;98:1752-1759
56.
Whitman SP, Archer KJ, Feng L, et al.
Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a Cancer and Leukemia Group B study.
Cancer Res.
2001;61:7233-7239
57.
Caligiuri MA, Strout MP, Lawrence D, et al.
Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics.
Cancer Res.
1998;58:55-59 58. Schnittger S, Kinkelin U, Schoch C, et al. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia. 2000;14:796-804[CrossRef][Medline] [Order article via Infotrieve]. 59. Byrd JC, Mrózek K, Dodge R, et al. Pre-treatment cytogenetics predict initial induction success and overall survival in adult patients with de novo acute myeloid leukemia: results from CALGB 8461 [abstract]. Blood 2001;98:457a.
The following Cancer and Leukemia Group B institutions, principal investigators, and cytogeneticists participated in this study and contributed at least 5 patients: Wake Forest University School of Medicine, Winston-Salem, NC: David D. Hurd, Harold O. Goodman, and Mark J. Pettenati (grant no. CA03927); University of Maryland Cancer Center, Baltimore: David A. Van Echo, Stuart Schwartz, Joseph R. Testa, and Judith Stamberg (grant no. CA31983); Dana-Farber Cancer Institute, Boston, MA: George P. Canellos and Ramana Tantravahi (grant no. CA32291); North Shore University Hospital, Manhasset, NY: Daniel R. Budman and Prasad R. K. Koduru (grant no. CA35279); Weill Medical College of Cornell University, New York, NY: Scott Wadler and Ram S. Verma (grant no. CA07968); Duke University Medical Center, Durham, NC: Jeffrey Crawford and Sandra H. Bigner (grant no. CA47577); University of Alabama at Birmingham: Robert Diasio and Andrew J. Carroll (grant no. CA47545); University of Iowa Hospitals, Iowa City: Gerald H. Clamon and Shivanand R. Patil (grant no. CA47642); Dartmouth Medical School, Lebanon, NH: Marc S. Ernstoff and Doris H. Wurster-Hill (grant no. CA04326); University of Minnesota, Minneapolis: Bruce A. Peterson and Diane C. Arthur (grant no. CA16450); University of North Carolina, Chapel Hill: Thomas Shea and Kathleen W. Rao (grant no. CA47559); Long Island Jewish Medical Center, Lake Success, NY: Marc Citron, Alan L. Shanske, and Prasad R. K. Koduru (grant no. CA11028); University of Missouri/Ellis Fischel Cancer Center, Columbia: Michael C. Perry, Judith H. Miles, Jeffrey R. Sawyer, and Tim Huang (grant no. CA12046); SUNY Upstate Medical University, Syracuse, NY: Stephen L. Graziano and Constance K. Stein (grant no. CA21060); University of Tennessee Cancer Center, Memphis: Harvey B. Niell and Sugandhi A. Tharapel (grant no. CA47555); Walter Reed Army Medical Center, Washington, DC: Joseph J. Drabick and Rawatmal B. Surana (grant no. CA26806); Roswell Park Cancer Institute, Buffalo, NY: Ellis G. Levine and AnneMarie W. Block (grant no. CA02599); University of California, San Diego: Stephen L. Seagren and Renée Bernstein (grant no. CA11789); University of Chicago Medical Center, IL: Gini Fleming, Michelle M. LeBeau, and Diane Roulston (grant no. CA41287); Finsen Institute, Copenhagen, Denmark: Preben Philip; University of Massachusetts Medical Center, Worcester: Mary Ellen Taplin and Philip L. Townes (grant no. CA37135); Washington University School of Medicine, St Louis, MO: Nancy L. Bartlett and Michael S. Watson (grant no. CA77440); Massachusetts General Hospital, Boston: Michael L. Grossbard and Leonard L. Atkins (grant no. CA 12449); Mount Sinai School of Medicine, New York, NY: Lewis R. Silverman and Vesna Najfeld (grant no. CA04457); Medical University of South Carolina, Charleston: Mark R. Green and Eduardo S. Cantú (grant no. CA03927); McGill Department of Oncology, Montreal, QC: Brian Leyland-Jones and Jacqueline Emond (grant no. CA31809).
© 2002 by The American Society of Hematology.
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 |
|
  M. Heuser, L. M. Sly, B. Argiropoulos, F. Kuchenbauer, C. Lai, A. Weng, M. Leung, G. Lin, C. Brookes, S. Fung, et al. Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal Blood, November 5, 2009; 114(19): 3983 - 3993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Tiu, L. P. Gondek, C. L. O'Keefe, J. Huh, M. A. Sekeres, P. Elson, M. A. McDevitt, X. F. Wang, M. J. Levis, J. E. Karp, et al. New Lesions Detected by Single Nucleotide Polymorphism Array-Based Chromosomal Analysis Have Important Clinical Impact in Acute Myeloid Leukemia J. Clin. Oncol., November 1, 2009; 27(31): 5219 - 5226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhou, C. Bucher, M. E. Munger, S. L. Highfill, J. Tolar, D. H. Munn, B. L. Levine, M. Riddle, C. H. June, D. A. Vallera, et al. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia Blood, October 29, 2009; 114(18): 3793 - 3802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Haferlach, C. Mecucci, S. Schnittger, A. Kohlmann, M. Mancini, A. Cuneo, N. Testoni, G. Rege-Cambrin, A. Santucci, M. Vignetti, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features Blood, October 1, 2009; 114(14): 3024 - 3032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tang, P. Hirsch, F. Fava, S. Lapusan, C. Marzac, I. Teyssandier, J. Pardo, J.-P. Marie, and O. Legrand High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia Blood, October 1, 2009; 114(14): 2993 - 3000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Mardis, L. Ding, D. J. Dooling, D. E. Larson, M. D. McLellan, K. Chen, D. C. Koboldt, R. S. Fulton, K. D. Delehaunty, S. D. McGrath, et al. Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome N. Engl. J. Med., September 10, 2009; 361(11): 1058 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Borrello, H. I. Levitsky, W. Stock, D. Sher, L. Qin, D. J. DeAngelo, E. P. Alyea, R. M. Stone, L. E. Damon, C. A. Linker, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML) Blood, August 27, 2009; 114(9): 1736 - 1745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.-C. Gorin, M. Labopin, D. Blaise, J. Reiffers, G. Meloni, M. Michallet, T. de Witte, M. Attal, B. Rio, F. Witz, et al. Higher Incidence of Relapse With Peripheral Blood Rather Than Marrow As a Source of Stem Cells in Adults With Acute Myelocytic Leukemia Autografted During the First Remission J. Clin. Oncol., August 20, 2009; 27(24): 3987 - 3993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Walter, J. E. Payton, R. E. Ries, W. D. Shannon, H. Deshmukh, Y. Zhao, J. Baty, S. Heath, P. Westervelt, M. A. Watson, et al. Acquired copy number alterations in adult acute myeloid leukemia genomes PNAS, August 4, 2009; 106(31): 12950 - 12955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Langer, G. Marcucci, K. B. Holland, M. D. Radmacher, K. Maharry, P. Paschka, S. P. Whitman, K. Mrozek, C. D. Baldus, R. Vij, et al. Prognostic Importance of MN1 Transcript Levels, and Biologic Insights From MN1-Associated Gene and MicroRNA Expression Signatures in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., July 1, 2009; 27(19): 3198 - 3204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Krauter, K. Wagner, I. Schafer, R. Marschalek, C. Meyer, G. Heil, M. Schaich, G. Ehninger, D. Niederwieser, R. Krahl, et al. Prognostic Factors in Adult Patients up to 60 Years Old With Acute Myeloid Leukemia and Translocations of Chromosome Band 11q23: Individual Patient Data-Based Meta-Analysis of the German Acute Myeloid Leukemia Intergroup J. Clin. Oncol., June 20, 2009; 27(18): 3000 - 3006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Faderl, A. Pal, W. Bornmann, M. Albitar, D. Maxwell, Q. Van, Z. Peng, D. Harris, Z. Liu, I. Hazan-Halevy, et al. Kit Inhibitor APcK110 Induces Apoptosis and Inhibits Proliferation of Acute Myeloid Leukemia Cells Cancer Res., May 1, 2009; 69(9): 3910 - 3917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zuber, I. Radtke, T. S. Pardee, Z. Zhao, A. R. Rappaport, W. Luo, M. E. McCurrach, M.-M. Yang, M. E. Dolan, S. C. Kogan, et al. Mouse models of human AML accurately predict chemotherapy response Genes & Dev., April 1, 2009; 23(7): 877 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Hartford, S. Duan, S. M. Delaney, S. Mi, E. O. Kistner, J. K. Lamba, R. S. Huang, and M. E. Dolan Population-specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity Blood, March 5, 2009; 113(10): 2145 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kuwatsuka, K. Miyamura, R. Suzuki, M. Kasai, A. Maruta, H. Ogawa, R. Tanosaki, S. Takahashi, K. Koda, K. Yago, et al. Hematopoietic stem cell transplantation for core binding factor acute myeloid leukemia: t(8;21) and inv(16) represent different clinical outcomes Blood, February 26, 2009; 113(9): 2096 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Heuser, D. B. Yap, M. Leung, T. R. de Algara, A. Tafech, S. McKinney, J. Dixon, R. Thresher, B. Colledge, M. Carlton, et al. Loss of Mll5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation Blood, February 12, 2009; 113(7): 1432 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Akagi, S. Ogawa, M. Dugas, N. Kawamata, G. Yamamoto, Y. Nannya, M. Sanada, C. W. Miller, A. Yung, S. Schnittger, et al. Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype Haematologica, February 1, 2009; 94(2): 213 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Fehniger, J. C. Byrd, G. Marcucci, C. N. Abboud, C. Kefauver, J. E. Payton, R. Vij, and W. Blum Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13 Blood, January 29, 2009; 113(5): 1002 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Morra, G. Barosi, A. Bosi, F. Ferrara, F. Locatelli, M. Marchetti, G. Martinelli, C. Mecucci, M. Vignetti, and S. Tura Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation Haematologica, January 1, 2009; 94(1): 102 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Shah and J. E. Lancet Frontline Treatment of Acute Myeloid Leukemia: Are We Making Progress? ASCO Educational Book, January 1, 2009; 2009(1): 372 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Sekeres, P. Elson, M. E. Kalaycio, A. S. Advani, E. A. Copelan, S. Faderl, H. M. Kantarjian, and E. Estey Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients Blood, January 1, 2009; 113(1): 28 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Sekeres Treatment of older adults with acute myeloid leukemia: state of the art and current perspectives Haematologica, December 1, 2008; 93(12): 1769 - 1772. [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Larson, A. M. Thomas, N. Goyal, J. M. Shammo, J. J. Maciejewski, S. A. Gregory, and P. Venugopal Efficacy of a Two Day Induction Regimen for De Novo and Secondary AML with Intermediate and Adverse Cytogenetic Profiles Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 4027 - 4027. [Abstract]
|
|
|
|
|
|
G. Marcucci, K. Maharry, M. D. Radmacher, K. Mrozek, T. Vukosavljevic, P. Paschka, S. P. Whitman, C. Langer, C. D. Baldus, C.-G. Liu, et al. Prognostic Significance of, and Gene and MicroRNA Expression Signatures Associated With, CEBPA Mutations in Cytogenetically Normal Acute Myeloid Leukemia With High-Risk Molecular Features: A Cancer and Leukemia Group B Study J. Clin. Oncol., November 1, 2008; 26(31): 5078 - 5087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Breems, W. L.J. Van Putten, G. E. De Greef, S. L. Van Zelderen-Bhola, K. B.J. Gerssen-Schoorl, C. H.M. Mellink, A. Nieuwint, M. Jotterand, A. Hagemeijer, H. B. Beverloo, et al. Monosomal Karyotype in Acute Myeloid Leukemia: A Better Indicator of Poor Prognosis Than a Complex Karyotype J. Clin. Oncol., October 10, 2008; 26(29): 4791 - 4797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Li, J. Lu, M. Sun, S. Mi, H. Zhang, R. T. Luo, P. Chen, Y. Wang, M. Yan, Z. Qian, et al. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations PNAS, October 7, 2008; 105(40): 15535 - 15540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Paschka, G. Marcucci, A. S. Ruppert, S. P. Whitman, K. Mrozek, K. Maharry, C. Langer, C. D. Baldus, W. Zhao, B. L. Powell, et al. Wilms' Tumor 1 Gene Mutations Independently Predict Poor Outcome in Adults With Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., October 1, 2008; 26(28): 4595 - 4602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Radich Molecular Classification of Acute Myeloid Leukemia: Are We There Yet? J. Clin. Oncol., October 1, 2008; 26(28): 4539 - 4541. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Laubach and A. V. Rao Current and Emerging Strategies for the Management of Acute Myeloid Leukemia in the Elderly Oncologist, October 1, 2008; 13(10): 1097 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kujawski, P. Ouillette, H. Erba, C. Saddler, A. Jakubowiak, M. Kaminski, K. Shedden, and S. N. Malek Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia Blood, September 1, 2008; 112(5): 1993 - 2003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Whitman, B. Hackanson, S. Liyanarachchi, S. Liu, L. J. Rush, K. Maharry, D. Margeson, R. Davuluri, J. Wen, T. Witte, et al. DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication Blood, September 1, 2008; 112(5): 2013 - 2016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Maciejewski and G. J. Mufti Whole genome scanning as a cytogenetic tool in hematologic malignancies Blood, August 15, 2008; 112(4): 965 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.-C. Gorin, M. Labopin, F. Frassoni, N. Milpied, M. Attal, D. Blaise, G. Meloni, A. P. Iori, M. Michallet, R. Willemze, et al. Identical Outcome After Autologous or Allogeneic Genoidentical Hematopoietic Stem-Cell Transplantation in First Remission of Acute Myelocytic Leukemia Carrying Inversion 16 or t(8;21): A Retrospective Study From the European Cooperative Group for Blood and Marrow Transplantation J. Clin. Oncol., July 1, 2008; 26(19): 3183 - 3188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pulsoni, S. Iacobelli, M. Bernardi, M. Borgia, A. Camera, N. Cantore, F. Di Raimondo, P. Fazi, F. Ferrara, F. Leoni, et al. M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience Haematologica, July 1, 2008; 93(7): 1025 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lo-Coco, A. Cuneo, F. Pane, D. Cilloni, D. Diverio, M. Mancini, N. Testoni, A. Bardi, B. Izzo, N. Bolli, et al. Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia Haematologica, July 1, 2008; 93(7): 1017 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mrozek and C. D. Bloomfield Clinical Significance of the Most Common Chromosome Translocations in Adult Acute Myeloid Leukemia J Natl Cancer Inst Monographs, July 1, 2008; 2008(39): 52 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Klisovic, W. Blum, X. Wei, S. Liu, Z. Liu, Z. Xie, T. Vukosavljevic, C. Kefauver, L. Huynh, J. Pang, et al. Phase I Study of GTI-2040, an Antisense to Ribonucleotide Reductase, in Combination with High-Dose Cytarabine in Patients with Acute Myeloid Leukemia Clin. Cancer Res., June 15, 2008; 14(12): 3889 - 3895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Blum Post-remission therapy in acute myeloid leukemia: what should I do now? Haematologica, June 1, 2008; 93(6): 801 - 805. [Full Text] [PDF]
|
|
|
|
|
|
C. Langer, M. D. Radmacher, A. S. Ruppert, S. P. Whitman, P. Paschka, K. Mrozek, C. D. Baldus, T. Vukosavljevic, C.-G. Liu, M. E. Ross, et al. High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study Blood, June 1, 2008; 111(11): 5371 - 5379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. Lowenberg MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia Blood, May 15, 2008; 111(10): 5078 - 5085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Schlenk, K. Dohner, J. Krauter, S. Frohling, A. Corbacioglu, L. Bullinger, M. Habdank, D. Spath, M. Morgan, A. Benner, et al. Mutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1909 - 1918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Marcucci, M. D. Radmacher, K. Maharry, K. Mrozek, A. S. Ruppert, P. Paschka, T. Vukosavljevic, S. P. Whitman, C. D. Baldus, C. Langer, et al. MicroRNA Expression in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1919 - 1928. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wertheim and A. Bagg Nucleophosmin (NPM1) Mutations in Acute Myeloid Leukemia: An Ongoing (Cytoplasmic) Tale of Dueling Mutations and Duality of Molecular Genetic Testing Methodologies J. Mol. Diagn., May 1, 2008; 10(3): 198 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Garzon, S. Volinia, C.-G. Liu, C. Fernandez-Cymering, T. Palumbo, F. Pichiorri, M. Fabbri, K. Coombes, H. Alder, T. Nakamura, et al. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia Blood, March 15, 2008; 111(6): 3183 - 3189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wandt, U. Schakel, F. Kroschinsky, G. Prange-Krex, B. Mohr, C. Thiede, U. Pascheberg, S. Soucek, M. Schaich, and G. Ehninger MLD according to the WHO classification in AML has no correlation with age and no independent prognostic relevance as analyzed in 1766 patients Blood, February 15, 2008; 111(4): 1855 - 1861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. Tsimberidou, H. M. Kantarjian, S. Wen, S. O'Brien, J. Cortes, W. G. Wierda, C. Koller, S. Pierce, M. Brandt, E. J. Freireich, et al. The Prognostic Significance of Serum {beta}2 Microglobulin Levels in Acute Myeloid Leukemia and Prognostic Scores Predicting Survival: Analysis of 1,180 Patients Clin. Cancer Res., February 1, 2008; 14(3): 721 - 730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J.M. de Jonge, A. C. Weidenaar, A. ter Elst, H. M. Boezen, F. J.G. Scherpen, J. C.A. Bouma-ter Steege, G. J.L. Kaspers, B. F. Goemans, U. Creutzig, M. Zimmermann, et al. Endogenous Vascular Endothelial Growth Factor-C Expression Is Associated with Decreased Drug Responsiveness in Childhood Acute Myeloid Leukemia Clin. Cancer Res., February 1, 2008; 14(3): 924 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Whitman, A. S. Ruppert, M. D. Radmacher, K. Mrozek, P. Paschka, C. Langer, C. D. Baldus, J. Wen, F. Racke, B. L. Powell, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications Blood, February 1, 2008; 111(3): 1552 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Saddler, P. Ouillette, L. Kujawski, S. Shangary, M. Talpaz, M. Kaminski, H. Erba, K. Shedden, S. Wang, and S. N. Malek Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia Blood, February 1, 2008; 111(3): 1584 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lowenberg Acute Myeloid Leukemia: The Challenge of Capturing Disease Variety Hematology, January 1, 2008; 2008(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Majhail Old and New Cancers after Hematopoietic-Cell Transplantation Hematology, January 1, 2008; 2008(1): 142 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Jakubowski, T. N. Small, J. W. Young, N. A. Kernan, H. Castro-Malaspina, K. C. Hsu, M.-A. Perales, N. Collins, C. Cisek, M. Chiu, et al. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin Blood, December 15, 2007; 110(13): 4552 - 4559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. King and J. M. Rowe Recent Developments in Acute Myelogenous Leukemia Therapy Oncologist, October 1, 2007; 12(suppl_2): 14 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Karp, R. M. Ricklis, K. Balakrishnan, J. Briel, J. Greer, S. D. Gore, B. D. Smith, M. A. McDevitt, H. Carraway, M. J. Levis, et al. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias Blood, September 15, 2007; 110(6): 1762 - 1769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Dicker, C. Haferlach, W. Kern, T. Haferlach, and S. Schnittger Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia Blood, August 15, 2007; 110(4): 1308 - 1316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bullinger, F. G. Rucker, S. Kurz, J. Du, C. Scholl, S. Sander, A. Corbacioglu, C. Lottaz, J. Krauter, S. Frohling, et al. Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia Blood, August 15, 2007; 110(4): 1291 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Marcucci, K. Maharry, S. P. Whitman, T. Vukosavljevic, P. Paschka, C. Langer, K. Mrozek, C. D. Baldus, A. J. Carroll, B. L. Powell, et al. High Expression Levels of the ETS-Related Gene, ERG, Predict Adverse Outcome and Improve Molecular Risk-Based Classification of Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., August 1, 2007; 25(22): 3337 - 3343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Tallman, G. W. Dewald, S. Gandham, B. R. Logan, A. Keating, H. M. Lazarus, M. R. Litzow, J. Mehta, T. Pedersen, W. S. Perez, et al. Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission Blood, July 1, 2007; 110(1): 409 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schaich, R. F. Schlenk, H. K. Al-Ali, H. Dohner, A. Ganser, G. Heil, T. Illmer, R. Krahl, J. Krauter, C. Sauerland, et al. Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup Haematologica, June 1, 2007; 92(6): 763 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Weiss, M. R. Baer, C. B. Ambrosone, J. G. Blanco, A. Hutson, L. A. Ford, and K. B. Moysich Concordance of Pharmacogenetic Polymorphisms in Tumor and Germ Line DNA in Adult Patients with Acute Myeloid Leukemia Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 1038 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y-B Yu, J-P Gau, J-Y You, H-H Chern, W-K Chau, C-H Tzeng, C-H Ho, and H-C Hsu Cost-effectiveness of postremission intensive therapy in patients with acute leukemia Ann. Onc., March 1, 2007; 18(3): 529 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Meshinchi and R. J. Arceci Prognostic Factors and Risk-Based Therapy in Pediatric Acute Myeloid Leukemia Oncologist, March 1, 2007; 12(3): 341 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Lancet, I. Gojo, J. Gotlib, E. J. Feldman, J. Greer, J. L. Liesveld, L. M. Bruzek, L. Morris, Y. Park, A. A. Adjei, et al. A phase 2 study of the farnesyltransferase inhibitor tipifarnib in poor-risk and elderly patients with previously untreated acute myelogenous leukemia Blood, February 15, 2007; 109(4): 1387 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Kim, J. I. Eom, J.-W. Cheong, A. J. Choi, J. K. Lee, W. I. Yang, and Y. H. Min Protein Kinase CK2{alpha} as an Unfavorable Prognostic Marker and Novel Therapeutic Target in Acute Myeloid Leukemia Clin. Cancer Res., February 1, 2007; 13(3): 1019 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Spoo, M. Lubbert, W. G. Wierda, and J. A. Burger CXCR4 is a prognostic marker in acute myelogenous leukemia Blood, January 15, 2007; 109(2): 786 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mrozek, G. Marcucci, P. Paschka, S. P. Whitman, and C. D. Bloomfield Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood, January 15, 2007; 109(2): 431 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pedersen-Bjergaard, M. T. Andersen, and M. K. Andersen Genetic Pathways in the Pathogenesis of Therapy-Related Myelodysplasia and Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 392 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Marzac, I. Teyssandier, O. Calendini, J.-Y. Perrot, A.-M. Faussat, R. Tang, N. Casadevall, J.-P. Marie, and O. Legrand Flt3 Internal Tandem Duplication and P-Glycoprotein Functionality in 171 Patients with Acute Myeloid Leukemia Clin. Cancer Res., December 1, 2006; 12(23): 7018 - 7024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kalaycio, L. Rybicki, B. Pohlman, R. Dean, J. W. Sweetenham, S. Andresen, R. Sobecks, M. A. Sekeres, A. Advani, R. Davis, et al. Lactate Dehydrogenase (LDH) Level Predicts the Outcome of Patients with Acute Myelogenous Leukemia (AML) Following HLA-Matched Sibling Bone Marrow Transplant (BMT). Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 3013 - 3013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Frohling, R. F. Schlenk, S. Kayser, M. Morhardt, A. Benner, K. Dohner, H. Dohner, and for the German-Austrian AML Study Group Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B Blood, November 15, 2006; 108(10): 3280 - 3288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Radmacher, G. Marcucci, A. S. Ruppert, K. Mrozek, S. P. Whitman, J. W. Vardiman, P. Paschka, T. Vukosavljevic, C. D. Baldus, J. E. Kolitz, et al. Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study Blood, September 1, 2006; 108(5): 1677 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Paschka, G. Marcucci, A. S. Ruppert, K. Mrozek, H. Chen, R. A. Kittles, T. Vukosavljevic, D. Perrotti, J. W. Vardiman, A. J. Carroll, et al. Adverse Prognostic Significance of KIT Mutations in Adult Acute Myeloid Leukemia With inv(16) and t(8;21): A Cancer and Leukemia Group B Study J. Clin. Oncol., August 20, 2006; 24(24): 3904 - 3911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Rucker, L. Bullinger, C. Schwaenen, D. B. Lipka, S. Wessendorf, S. Frohling, M. Bentz, S. Miller, C. Scholl, R. F. Schlenk, et al. Disclosure of Candidate Genes in Acute Myeloid Leukemia With Complex Karyotypes Using Microarray-Based Molecular Characterization J. Clin. Oncol., August 20, 2006; 24(24): 3887 - 3894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Camos, J. Esteve, P. Jares, D. Colomer, M. Rozman, N. Villamor, D. Costa, A. Carrio, J. Nomdedeu, E. Montserrat, et al. Gene Expression Profiling of Acute Myeloid Leukemia with Translocation t(8;16)(p11;p13) and MYST3-CREBBP Rearrangement Reveals a Distinctive Signature with a Specific Pattern of HOX Gene Expression. Cancer Res., July 15, 2006; 66(14): 6947 - 6954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Faderl, S. Verstovsek, J. Cortes, F. Ravandi, M. Beran, G. Garcia-Manero, A. Ferrajoli, Z. Estrov, S. O'Brien, C. Koller, et al. Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older Blood, July 1, 2006; 108(1): 45 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Farag, K. J. Archer, K. Mrozek, A. S. Ruppert, A. J. Carroll, J. W. Vardiman, M. J. Pettenati, M. R. Baer, M. B. Qumsiyeh, P. R. Koduru, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461 Blood, July 1, 2006; 108(1): 63 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dong and G. C. Blobe Role of transforming growth factor-beta in hematologic malignancies Blood, June 15, 2006; 107(12): 4589 - 4596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Monzo, S. Brunet, A. Urbano-Ispizua, A. Navarro, G. Perea, J. Esteve, R. Artells, M. Granell, J. Berlanga, J. M. Ribera, et al. Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia Blood, June 15, 2006; 107(12): 4871 - 4879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Bloomfield, K. Mrozek, and M. A. Caligiuri Cancer and Leukemia Group B Leukemia Correlative Science Committee: Major Accomplishments and Future Directions. Clin. Cancer Res., June 1, 2006; 12(11): 3564s - 3571s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Cairoli, A. Beghini, G. Grillo, G. Nadali, F. Elice, C. B. Ripamonti, P. Colapietro, M. Nichelatti, L. Pezzetti, M. Lunghi, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study Blood, May 1, 2006; 107(9): 3463 - 3468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Baldus, C. Thiede, S. Soucek, C. D. Bloomfield, E. Thiel, and G. Ehninger BAALC Expression and FLT3 Internal Tandem Duplication Mutations in Acute Myeloid Leukemia Patients With Normal Cytogenetics: Prognostic Implications J. Clin. Oncol., February 10, 2006; 24(5): 790 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Oki, H. M. Kantarjian, X. Zhou, J. Cortes, S. Faderl, S. Verstovsek, S. O'Brien, C. Koller, M. Beran, B. N. Bekele, et al. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center Blood, February 1, 2006; 107(3): 880 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mrozek and C. D. Bloomfield Chromosome Aberrations, Gene Mutations and Expression Changes, and Prognosis in Adult Acute Myeloid Leukemia Hematology, January 1, 2006; 2006(1): 169 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Marcucci, C. D. Baldus, A. S. Ruppert, M. D. Radmacher, K. Mrozek, S. P. Whitman, J. E. Kolitz, C. G. Edwards, J. W. Vardiman, B. L. Powell, et al. Overexpression of the ETS-Related Gene, ERG, Predicts a Worse Outcome in Acute Myeloid Leukemia With Normal Karyotype: A Cancer and Leukemia Group B Study J. Clin. Oncol., December 20, 2005; 23(36): 9234 - 9242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Dohner, R. F. Schlenk, M. Habdank, C. Scholl, F. G. Rucker, A. Corbacioglu, L. Bullinger, S. Frohling, H. Dohner, and for the AML Study Group (AMLSG) Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations Blood, December 1, 2005; 106(12): 3740 - 3746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. W. Verhaak, C. S. Goudswaard, W. van Putten, M. A. Bijl, M. A. Sanders, W. Hugens, A. G. Uitterlinden, C. A. J. Erpelinck, R. Delwel, B. Lowenberg, et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance Blood, December 1, 2005; 106(12): 3747 - 3754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Baer, N. W. Cuviello, J. S. Shoemaker, R. C. Barrier Jr., M. A. Caligiuri, J. E. Kolitz, B. L. Powell, R. A. Larson, and C. D. Bloomfield Treatment Failure Is Strongly Predicted by P-Glycoprotein (Pgp) Function but Not by Multidrug Resistance Protein (MRP-1), Breast Cancer Resistance Protein (BCRP) or Lung Resistance Protein (LRP) in Acute Myeloid Leukemia (AML) Patients 60 Years and Older Receiving Intensive Chemotherapy (CALGB 9720/9760). Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 2349 - 2349. [Abstract]
|
|
|
|
|
|
M. Kalaycio, M. Sekeres, R. Sobecks, L. Rybicki, B. Pohlman, A. Advani, E. Kuczkowski, and B. Bolwell Cytogenetic Classification Systems and Overall Survival Following Bone Marrow Transplant (BMT) for Acute Myelogenous Leukemia (AML). Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 4500 - 4500. [Abstract]
|
|
|
|
|
|
E. Jourdan, J.-M. Boiron, N. Dastugue, N. Vey, G. Marit, F. Rigal-Huguet, L. Molina, N. Fegueux, A. Pigneux, C. Recher, et al. Early Allogeneic Stem-Cell Transplantation for Young Adults With Acute Myeloblastic Leukemia in First Complete Remission: An Intent-to-Treat Long-Term Analysis of the BGMT Experience J. Clin. Oncol., October 20, 2005; 23(30): 7676 - 7684. [Abstract] [Full Text] [PDF]
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S. Frohling, C. Scholl, D. G. Gilliland, and R. L. Levine Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications J. Clin. Oncol., September 10, 2005; 23(26): 6285 - 6295. [Abstract] [Full Text] [PDF]
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L. Bullinger and P. J.M. Valk Gene Expression Profiling in Acute Myeloid Leukemia J. Clin. Oncol., September 10, 2005; 23(26): 6296 - 6305. [Abstract] [Full Text] [PDF]
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G. Marcucci, K. Mrozek, A. S. Ruppert, K. Maharry, J. E. Kolitz, J. O. Moore, R. J. Mayer, M. J. Pettenati, B. L. Powell, C. G. Edwards, et al. Prognostic Factors and Outcome of Core Binding Factor Acute Myeloid Leukemia Patients With t(8;21) Differ From Those of Patients With inv(16): A Cancer and Leukemia Group B Study J. Clin. Oncol., August 20, 2005; 23(24): 5705 - 5717. [Abstract] [Full Text] [PDF]
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M. S. Tallman, D. G. Gilliland, and J. M. Rowe Drug therapy for acute myeloid leukemia Blood, August 15, 2005; 106(4): 1154 - 1163. [Abstract] [Full Text] [PDF]
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T. Haferlach, A. Kohlmann, S. Schnittger, M. Dugas, W. Hiddemann, W. Kern, and C. Schoch Global approach to the diagnosis of leukemia using gene expression profiling Blood, August 15, 2005; 106(4): 1189 - 1198. [Abstract] [Full Text] [PDF]
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G. Marcucci, W. Stock, G. Dai, R. B. Klisovic, S. Liu, M. I. Klisovic, W. Blum, C. Kefauver, D. A. Sher, M. Green, et al. Phase I Study of Oblimersen Sodium, an Antisense to Bcl-2, in Untreated Older Patients With Acute Myeloid Leukemia: Pharmacokinetics, Pharmacodynamics, and Clinical Activity J. Clin. Oncol., May 20, 2005; 23(15): 3404 - 3411. [Abstract] [Full Text] [PDF]
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J. O. Moore, S. L. George, R. K. Dodge, P. C. Amrein, B. L. Powell, J. E. Kolitz, M. R. Baer, F. R. Davey, C. D. Bloomfield, R. A. Larson, et al. Sequential multiagent chemotherapy is not superior to high-dose cytarabine alone as postremission intensification therapy for acute myeloid leukemia in adults under 60 years of age: Cancer and Leukemia Group B Study 9222 Blood, May 1, 2005; 105(9): 3420 - 3427. [Abstract] [Full Text] [PDF]
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D. A. Breems, W. L.J. Van Putten, P. C. Huijgens, G. J. Ossenkoppele, G. E.G. Verhoef, L. F. Verdonck, E. Vellenga, G. E. De Greef, E. Jacky, J. Van der Lelie, et al. Prognostic Index for Adult Patients With Acute Myeloid Leukemia in First Relapse J. Clin. Oncol., March 20, 2005; 23(9): 1969 - 1978. [Abstract] [Full Text] [PDF]
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J. C. Byrd, G. Marcucci, M. R. Parthun, J. J. Xiao, R. B. Klisovic, M. Moran, T. S. Lin, S. Liu, A. R. Sklenar, M. E. Davis, et al. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia Blood, February 1, 2005; 105(3): 959 - 967. [Abstract] [Full Text] [PDF]
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Abstract
Introduction
