|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
CLINICAL OBSERVATONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From the Department of Blood and Bone Marrow
Transplantation and Biomathematics, University of Texas MD Anderson
Cancer Center, Houston, TX.
A reduced-intensity preparative regimen consisting of
melphalan and a purine analog was evaluated for allogeneic
transplantation in 86 patients who had a variety of hematologic
malignancies and were considered poor candidates for conventional
myeloablative therapies because of age or comorbidity. Seventy-eight
patients received fludarabine 25 mg/m2 daily for 5 days in
combination with melphalan 180 mg/m2 (n = 66) or 140 mg/m2 (n = 12). Eight patients received
cladribine 12 mg/m2 continuous infusion for 5 days with
melphalan 180 mg/m2. The median age was 52 years (range,
22-70 years). Disease status at transplantation was either first
remission or first chronic phase in 7 patients, untreated first relapse
or subsequent remission in 16 patients, and refractory leukemia or
transformed chronic myelogenous leukemia in 63 patients. Nonrelapse
mortality rates on day 100 were 37.4% for the fludarabine/melphalan
combination and 87.5% for the cladribine/melphalan combination. The
median percentage of donor cells at 1 month in 75 patients was 100%
(range, 0%-100%). The probability of grade 2-4 and 3-4 acute
graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95%
CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57%
for patients in first remission or chronic phase and 49% for patients
with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival
was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with
associated comorbidities, and long-term disease control can be achieved
with reduced-intensity conditioning in this population.
(Blood. 2001;97:631-637) High-dose chemoradiotherapy with allogeneic bone
marrow transplantation (BMT) has been extensively used in young
patients with advanced hematologic malignancies. Approximately 30% of
patients can achieve long-term disease control, with
transplantation-related deaths accounting for 30% of treatment
failures and relapse rates of 50% to 60% commonly
reported.1-3 Allogeneic bone marrow transplantation has
been limited to young patients because of the increased risk for
regimen-related toxicities and graft-versus-host disease (GVHD) that
occurs with increasing age.4,5 Improvements in supportive care, GVHD prophylaxis, and cytomegalovirus (CMV) prophylaxis has now
enabled many centers to increase the age limit for BMT, but few are
performing allogenic stem cell transplantation on patients older than
55 years. Older patients, however, constitute a large group of patients
with extremely poor prognosis if conventional induction therapy is
used. Consequently, novel therapeutic options must be
explored.6,7
The use of nonablative regimens to obtain donor cell engraftment
followed by donor lymphocytes to exploit a graft-versus-leukemia effect
has demonstrated that it is possible to achieve mixed and full
chimerism after nonmyeloablative therapy. However, in patients with
refractory disease remissions are usually short-lived, and there is
little time to exploit a potentially beneficial graft-versus-leukemia effect.8,9
High-dose melphalan has been successful in effecting durable remissions
in patients with acute leukemia and other hematologic malignancies with
little extramedullary toxicity.10,11 Similarly, purine
analogs have been shown to inhibit the mechanisms of DNA repair after
alkylator-induced damage.12 Therefore, reduced-intensity conditioning with melphalan/purine analog combinations could
potentially achieve disease remission and engraftment of allogeneic
cells with acceptable toxicity. Herein we report the results of our initial trials using purine analog/melphalan reduced-intensity combinations in patients with a variety of hematologic malignancies who
underwent allogeneic progenitor cell transplantation at MD Anderson
Cancer Center and were considered poor candidates for conventional
myeloablative therapy because of age or concurrent medical conditions.
Patient eligibility
Treatment plan
Supportive care GVHD prophylaxis consisted of tacrolimus (FK506; Prograf, Fujisawa, Japan) dosed to maintain blood levels between 5 and 10 ng/dL and methotrexate 5 mg/m2 on days 1, 3, 6, and 11 in 81 patients. During the pilot trial 3 patients received cyclosporine/steroids as GVHD prophylaxis because of the unavailability of assays to monitor tacrolimus levels, and 2 patients received tacrolimus/steroids. GVHD was continued for a minimum of 3 months for patients with high-risk disease and a minimum of 6 months for patients with low-risk disease or for recipients of unrelated or mismatched donor bone marrow. Donor lymphocyte infusions were not routinely administered to patients unless cytogenetic or morphologic relapse was documented.Antibacterial, antifungal, and antiviral prophylaxes were performed according to institutional protocols. These included trimethrophim/sulfamethoxazole for Pneumocystis carinii prophylaxis, acyclovir for herpes simplex virus prophylaxis, fluconazole for fungal prophylaxis, and penicillin and norfloxacillin or ciprofloxacillin for bacterial prophylaxis. CMV prophylaxis consisted of biweekly surveillance blood and urine cultures for CMV using shell-vial and rapid-antigen techniques. Recipients of unrelated or mismatched related donor transplants or patients on high-dose steroid therapy received prophylactic ganciclovir 5 mg/kg intravenously 5 times weekly until day 100. Patients who became antigenemic or had positive shell-vial cultures were treated with ganciclovir 5 mg/kg intravenously twice daily for 14 days then daily for 8 weeks. All patients received filgrastim 5 µg/kg subcutaneously daily from day 7 until an absolute neutrophil count of more than 1.5 × 109/L was achieved for 3 days in a row according to our current institutional guidelines. Packed red blood cells were transfused to maintain hemoglobin levels of 8 gm/dL or more, and platelets were transfused to keep the platelet count at 20 × 109/L or greater. All blood products were filtered and irradiated to 1500 cGy. Patients with neutropenic fever were treated with broad-spectrum antibiotics according to institutional protocols. Patients with grade 2 or greater acute GVHD received at least 0.5 mg/kg methylprednisolone every 6 hours and could be enrolled on any existing protocol for the treatment of GVHD. Bone marrow aspiration was performed routinely 3 to 4 weeks after infusion and then 3 and 12 months later; aspirates were sent for morphologic evaluation, fluorescence in situ hybridization, cytogenetics, and chimerism evaluation. Clinical endpoints Major endpoints included survival and disease-free survival as of June 1, 1999 using Kaplan-Meier estimates.13 Neutrophil recovery was defined as an absolute neutrophil count of more than 0.5 × 109/L for 3 consecutive days. Platelet recovery was defined as a platelet count of more than 20.0 × 109/L independent of platelet transfusions for at least 7 days. Complete remission was determined by standard disease-specific criteria as defined by the International Bone Marrow Transplant Registry (IBMTR). Acute and chronic GVHD were scored according to published guidelines.14,15 Chimerism was determined on bone marrow samples by cytogenetics or restriction fragment-length polymorphisms using established techniques.16,17 Toxicity was graded according to Bearman criteria.18 For chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes (MDS), and acute myelogenous leukemia (AML), relapse was defined by standard morphologic criteria, conventional cytogenetic analysis, or both. Cytogenetic relapse was documented by the presence and persistence in more than 2 consecutive tests of the cytogenetic abnormality that defined the disease (Philadelphia chromosome for CML and patient-specific cytogenetic abnormalities for AML, MDS, and ALL). Patients with cytogenetic relapse were scored as treatment failures for the purpose of disease-free survival (DFS) analysis, regardless of their subsequent response to salvage therapy. The presence of minimal residual disease using polymerase chain reaction-based technology was not used to guide therapy or to define relapse after transplantation.Statistical methods Associations between pairs of covariates were assessed graphically for pairs of numerical variables by examining scatterplots, by Wilcoxon-Mann-Whitney and Kruskal-Wallis19 tests for categorical and continuous variables, and by the Fisher exact test20 and its generalizations21 for pairs of categorical variables. Unadjusted probabilities of survival, DFS, regimen-related death (nonrelapse mortality), and times to grade 2 or greater or grade 4 or greater GVHD were estimated using the Kaplan-Meier method.13 Unadjusted between-group comparisons of survival and DFS were made using the log rank test.22 The Cox proportional hazards model23 and its generalizations24 were used to assess the ability of treatments and patient characteristics to predict survival and DFS, with goodness-of-fit assessed by the Grambsch-Therneau test,25 Schoenfeld residual plots, martingale residual plots, and likelihood ratio statistics. All scatterplots were smoothed using the lowess method of Cleveland,26 with variables transformed as appropriate based on these plots. Confidence intervals for probabilities were computed using the hrinkage method of Ghosh.27 Each multivariate Cox model was obtained by first performing a backward elimination with P cutoff of .05, then allowing either treatment-covariate interactions or any variable previously deleted to enter the final model if P < .05. For these model fits, covariates exhibiting high collinearity were segregated so that no 2 collinear variables were allowed in the same model. All computations were carried out on a DEC Alpha 2100 5/250 system computer (Digital Electronics Corporation, Nashua, NH) in Splus28 and StatXact (Cytel Software, Cambridge, MA) using both the standard Splus functions and the Splus survival analysis package of Therneau.28-30
Patient and disease characteristics From February 1996 to December 1998, 86 patients received preparative regimens with melphalan and purine analogs. Patient and disease characteristics are summarized in Table 1. In brief, the median age was 52 years (range, 22-70 years); 52 patients were men and 34 were women. Thirty-four patients had AML, 9 had MDS, and 27 had CML, whereas 13 patients had lymphoma, and 3 had ALL. Median time to transplantation was 547 days (range, 27-6626 days). The median number of prior therapies was 3 (range, 0-8), with 24 patients having undergone earlier transplantations with a different source of stem cells (except one patient). Seven patients were treated in either first remission or first chronic phase (good-risk category), and 16 patients were in an untreated first relapse or a subsequent remission (intermediate risk). Forty-two patients had either refractory disease or were beyond first salvage, and 21 patients had transformed CML according to the criteria used by the IBMTR (bad risk).
Patients were considered poor candidates for conventional myeloablative
therapy either because of age (56% of the patients were older than 50)
or concurrent medical condition, as shown in Table
2. Nine patients had no obvious comorbid
condition but were considered poor candidates for conventional
myeloablative therapy because of previous medical complications such as
congestive heart failure, fungal infection, pericarditis with chronic
steroid therapy, or history of serious organ dysfunction and
chemotherapy.
Toxicities Regimen-related toxicities are summarized in Tables 3 and 4. Fludarabine/melphalan combinations were associated with 10 instances of grade 3-4 Bearman toxicities and 3 toxic deaths among the 29 nonrelapse deaths occurring before day 100. The main factors contributing to these deaths were bad risk category, active infection, and extensive prior therapy. The combination of cladribine/melphalan at the dose and schedule used was associated with 5 cases of grade 3-4 renal toxicity and 7 deaths before day 100. Three of these patients had undergone more than 2 prior regimens and had refractory disease. However, the occurrence of severe toxicities in 3 of 4 patients with untreated first relapse receiving this therapy led us to close this treatment arm to further patient accrual. The nonrelapse mortality rate at 100 days was 37.4% for patients receiving fludarabine/melphalan combinations and 87.5% for patients receiving cladribine/melphalan. For all patients, the nonrelapse mortality rate at 2 years was 44.7%. Patients in a bad risk category, recipients of unrelated donor cells, recipients of cladribine/melphalan, or patients with 3 or more prior therapies were at higher risk for nonrelapse death.
Engraftment and chimerism All 76 patients surviving more than 21 days achieved a neutrophil recovery of more than 0.5 × 109/L in a median of 14 days (range, 9-35 days). Fifty-five patients achieved platelet transfusion independence at a median of 21 days (range, 9-118 days), and the other 21 patients had relapses or died before achieving this endpoint. Seventy-five patients had chimerism studies using cytogenetics or molecular techniques, and the median percentage of donor cells at the time of first post-transplant bone marrow examination (approximately 30 days after stem cell transplantation) was 100% (range, 0%-100%). Five patients had less than 50% donor cells. Of these 5 patients, 2 failed to clear bone marrow blasts, one had full autologous reconstitution, another became fully chimeric after immunosuppression withdrawal, and one had secondary graft failure and died of infectious complications. At 3 months, 40 of 42 patients in remission had more than 90% donor cells using the same techniques. At 1 year all 17 patients in remission had 100% donor cell engraftment by the same techniques.Acute and chronic GVHD Thirty-four patients had grade 2-4 acute GVHD for a probability of 0.49 (95% CI, 0.38-0.60); of these, 19 patients had grade 3-4 acute GVHD for a probability of 0.29 (95% CI, 0.18-0.41). Sixteen of the 41 deaths before day 100 were related to acute GVHD. Patients receiving unrelated donor transplants had a trend toward a higher risk for acute GVHD (grade 2-4, 62% vs 41% [P = .05]; grade 3-4, 39% vs 19% [P = .10]). Deaths from acute GVHD were more common in recipients of unrelated donor transplants than in other donor types (11 of 40 vs 4 of 46; P = .026). Chronic GVHD developed in 21 of 46 evaluable patients, for an actuarial risk of 68% ± 9%.Responses Twenty-six of 43 patients with AML/MDS achieved complete remission. Of the 17 patients who did not, one did not clear bone marrow blasts, 10 died before day 30, 5 died before platelet transfusion independence from transplantation complications, and one died of progressive disease. Nineteen of the 27 patients with CML achieved complete remission. Of the 8 patients who did not, one patient had autologous reconstitution and 7 died of transplantation complications before platelet transfusion independence.Among the 16 remaining patients, 1 of 3 patients with ALL, 1 of 4 patients with Hodgkin disease, and 2 of 9 patients with non-Hodgkin lymphoma achieved complete remission. All other patients died of transplantation-related complications. Overall survival and disease-free survival The overall 2-year survival probability was 0.28 (95% CI, 0.20-0.39) for all patients. On univariate analysis significant prognostic factors for survival included risk category, number of prior therapies, donor sex, and preparative regimen (fludarabine vs cladribine/melphalan). The probability of disease-free survival at 2 years was 0.23 (95% CI, 0.15-0.34) for all patients. Significant factors associated with improved disease-free survival on univariate analysis included better risk category, fewer prior therapies, better performance status, and male sex of donor (Table 5). Survival and disease-free survival according to diagnosis and risk group are demonstrated in Figure 1.
Twenty-three patients had relapses at a median of 120 days (range, 0-369 days). Nineteen were on immunosuppressive therapy at the time of relapse, and this therapy was withdrawn. Only one patient with CML responded to immunosuppression withdrawal and achieved complete remission, but this patient subsequently died of complications of chronic GVHD. Five patients received chemotherapy followed by donor lymphocyte infusion; 3 achieved complete remission. One has remained in complete remission for more than 1 year, and 2 had relapses within 3 months. Two patients received donor lymphocyte infusions in conjunction with immunosuppression withdrawal and failed to respond. Cox regression model analyses Multivariate Cox regression models for survival and nonrelapse mortality were obtained using the variable selection algorithm described in the "Statistical methods" section. Each of the following was associated with decreased relative risk for death: good or intermediate prognosis risk group, therapy with fludarabine/melphalan 180, and shorter time to transplantation (up to 4 years) (Table 6). Although receiving a transplant from a matched, unrelated donor was moderately associated with increased mortality (RR [relative risk] = 1.85; P = .054) compared to receiving a transplant from a sibling donor (6 of 6 or 5 of 6) based on a univariate Cox model analysis, this association was insignificant after accounting for the covariates in Table 6. Patients whose donors were female had more prior therapies (62% with 3 or more prior treatments vs 39% for those with male donors; P = .0516), waited longer for transplantation (median, 21.5 months vs 15.5 months; P = .38), and had a higher probability of a bad risk score (83% vs 64%; P = .0052). Because the 3 variables donor sex, 3 or more
prior therapies, and risk categorywere highly associated, at most one of these variables was allowed in each fitted multivariate Cox model.
Starting with the model summarized in Table 6, if poor risk
group is replaced by female donor, then RR = 1.72 for
this new variable (P = .056), with the effects of
treatment and time to transplantation essentially unchanged. Similarly,
if poor risk group is replaced by 3 or more prior
therapies, RR = 2.13 for the new variable
(P = .007).
For nonrelapse mortality, the multivariate Cox model covariates were use of cladribine/melphalan (RR = 8.06, P < .001), 3 or more prior therapies (RR = 2.46, P = .011), and time to transplantation up to 4 years (RR = 1.04/mo, P = .004). Because only 8 of the 86 patients received cladribine/melphalan, separate Cox model fits were obtained for the subset of 78 patients who were treated with fludarabine/melphalan. In this subgroup, the multivariate Cox model included the 2 covariates time to transplantation up to 4 years (RR = 1.03/mo, P = .009) and 3 or more prior therapies (RR = 2.58, P = .002). In this model, if 3 or more prior treatments is replaced by poor risk group, RR = 2.29 is the new variable (P = .026). A similar analysis of the 78 fludarabine/melphalan patients for nonrelapse mortality yielded a Cox model having the same covariates as for overall survival, with RR = 1.04/mo (P = .007) for time to transplantation and RR = 2.19 for 3 or more prior therapies (P = .032).
Based on our initial experience with fludarabine-based nonmyeloablative conditioning regimens, we hypothesized that a reduced-intensity conditioning with melphalan/purine analog combinations could be well tolerated in patients considered poor candidates for conventional myeloablative therapies. This combination should also be adequately immunosuppressive to allow engraftment of allogeneic progenitor cells, including those procured from unrelated or mismatched donors. The rationale for this hypothesis was based on the broad-spectrum activity of melphalan in a variety of hematologic malignancies, the tolerability of high-dose melphalan in debilitated patients with myeloma, and the possibility that purine analogs could inhibit the mechanisms of DNA repair from alkylator-induced DNA damage, thus providing for a potential synergistic effect of purine analogs and melphalan.10-12,31 Melphalan is a bifunctional alkylating agent with broad-spectrum activity in a variety of hematologic malignancies.10 It has been used as a single agent for conditioning in allogeneic bone marrow transplantation. Singhal et al11 reported on 28 patients who underwent allogeneic BMT for acute leukemia or lymphoblastic lymphoma conditioned with melphalan 240 mg/m2 followed by bone marrow from an HLA-identical sibling. Twenty-two patients had sustained engraftment. The 3-year probabilities of transplantation-related mortality and relapse rates were 35% and 62% with a 10-year disease-free survival rate of 25%.11 The myeloablative dose of melphalan has not been determined. Moreau et al31 treated 102 patients with 140 mg/m2 melphalan. The duration of neutropenia was 23.5 days for patients receiving granulocyte-macrophage colony-stimulating factor and 29 days for patients not receiving growth factors. However, 10 of 102 patients experienced fatal complications with this therapy, suggesting that doses above 140 mg/m2 should not be explored without stem cell support. The 100-day nonrelapse mortality rate for the fludarabine/melphalan combination was 37%. Fatal toxicities directly related to the preparative regimens occurred in 3 of 29 patients who died of nonrelapse causes before day 100. In contrast, the combination of cladribine and melphalan was significantly more toxic. Fatal regimen-related toxicities developed in 4 of 8 patients, leading to the early closure of this treatment arm. The toxicity of cladribine/melphalan was unexpected because, as a single agent, cladribine has been administered in doses up to 21 mg/m2 with neurotoxicity in 4 of 8 patients being the dose-limiting toxicity.32,33 The combination of cladribine and cytarabine has been explored with and without stem cell support. Kornblau et al34 reported their results with cladribine and cytarabine combinations during a phase I/II trial. In the phase I portion of the trial, 6 of 25 patients had serum creatinine levels higher than 2 mg/dL, and 2 patients required dialysis at dose levels of 9 and 13 mg/m2 daily for 7 days. In phase II of their study, the same dose of cladribine was used as in this report (12 mg/m2 daily for 5 days). At this dose level, 6 of 17 patients had serum creatinine increases greater than 1.5 mg/dL, but none required dialysis.34 Similarly, no patients with renal failure requiring dialysis were observed when cladribine/cytarabine combinations were used with stem cell support.8 The reason for this increased renal toxicity is unknown, but it could have been caused by synergistic toxic effects on the kidneys by melphalan and cladribine. The main causes of death before day 100 in patients receiving the fludarabine/melphalan combinations were infection and GVHD. The risk for grade III-IV GVHD in this patient population, whose median age was greater than 50, was 19% for transplants from related donors and 39% for transplants from unrelated donors (which were serologically matched for class I antigens and molecular matches for DRB1). Although this incidence is similar to what Petersdorf et al35 reported for younger patients receiving myeloablative therapies, it is still high, and efforts to reduce the risk for GVHD are being explored (ie, pretransplantation ATG and molecular matching for DRB2 and DQ, if possible). Kottaridis et al36 have reported on the preliminary results with CAMPATH-1H used before reduced conditioning with 140 mg/m2 fludarabine/melphalan and have shown that this agent can significantly reduce the risk for GVHD after related and unrelated marrow transplantation and possibly enhance engraftment. Further exploration of this and other approaches to reduce GVHD after nonablative stem cell transplantation are warranted because the risk for GVHD will remain substantial in these patients, and their tolerance to treatment with high-dose steroids may be reduced. Our initial experience with patients who have refractory AML and undergo nonmyeloablative stem cell transplantation with either fludarabine, idarubicin and cytarabine, or cladribine and cytarabine demonstrated that this strategy was feasible and resulted in the engraftment of donor cells. However, patients with refractory disease had rapid recurrence, and the combination did not seem to be immunosuppressive enough to allow for the engraftment of unrelated donor cells, at least in patients with CML.8,37 Other groups have explored different combinations of agents to develop reduced-intensity or nonmyeloablative regimens with the same goal of achieving engraftment with minimal toxicity. The Seattle group has described the use of low-dose (200 cGy), single-fraction total body irradiation as a preparative regimen for nonablative stem cell transplantation; the true nonablative characteristics of this regimen are confirmed by the low incidence of myelosuppression.38 The regimen was immunosuppressive enough to allow engraftment in 24 of the first 29 patients treated, toxicity was minimal, and 7 patients attained or maintained complete remission at the time of the report.38,39 Slavin et al9 pioneered the use of fludarabine in combination with 8 mg/kg busulfan. The initial report of this combination consisted of 28 patients with a variety of malignant and nonmalignant disorders. The combination was well tolerated, and, as in our experience, GVHD was the most important cause of early death. The disease-free survival rate of 77% at 14 months is encouraging, but it cannot be directly compared to the current report because the median age in the Hadassah report was 36 years whereas in our report it was 52 years.9 Comparative studies between different reduced-intensity conditioning regimens are needed to determine whether any regimen is superior or better tolerated than another. This report demonstrates that melphalan/purine analog combinations allow for almost universal engraftment of allogeneic progenitor cells, including those procured from unrelated or mismatched related donors. Ninety-three percent of the patients showed between 80% and 100% donor cell engraftment by day 30, and all patients in continued remission at 6 months and 1 year showed primarily donor-derived hematopoiesis. Remissions in these patients were durable, particularly in patients without refractory or bulky disease. The disease-free survival rates of 57% at 1 year for the 7 patients in first remission or chronic phase and 49% for patients with untreated first relapse or in remission at the time of transplantation are comparable to results obtained in younger patients who have undergone myeloablative therapy. In summary, reduced-intensity conditioning with fludarabine/melphalan combinations is feasible in older patients with associated comorbidities; the treatment allows the engraftment of unrelated and mismatched progenitor cells with acceptable levels of toxicity. Disease recurrence and GVHD continue to be the most important causes of treatment failure. Our study, however, demonstrates that long-term disease control can be achieved by allogeneic transplantation in older patients who have hematologic malignancies and that further development of these preparative regimens, including the treatment of patients in chronic phase or first remission, is warranted. For patients with very poor performance status or refractory disease, alternative strategies must be explored.
Submitted February 2, 2000; accepted October 4, 2000.
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.
Reprints: Sergio Giralt, Department of Blood and Bone Marrow Transplantation, University of Texas MD Anderson Cancer Center, Box 65, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: sgiralt{at}notes.mdacc.tmc.edu.
1. Advisory Committee of the International Bone Marrow Transplant Registry. Report from the International Bone Marrow Transplant Registry. Bone Marrow Transplant. 1989;48:453-458.
2.
Bortin MM, Horowitz MM, Gale RP, et al.
Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s.
JAMA.
1992;268:607-612
3.
Armitage JO.
Bone marrow transplantation.
N Engl J Med.
1994;330:827-838
4.
Ringden O, Horowitz M, Gale R, et al.
Outcome after allogeneic bone marrow transplant for leukemia in older adults.
JAMA.
1993;270:57-60
5.
Klingemann H, Storb R, Fefer A, et al.
Bone marrow transplantation in patients aged 45 years and older.
Blood.
1986;67:770-776 6. Preisler H, Anderson K, Rai K, et al. The frequency of long-term remission in patients with acute myelogenous leukemia treated with conventional maintenance chemotherapy: a study of 760 patients with a minimal follow-up time of 6 years. Br J Hematol. 1989;71:189-194[Medline] [Order article via Infotrieve]. 7. Keating M, Kantarjian H, Smith T, et al. Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J Clin Oncol. 1989;7:1071-1080[Abstract].
8.
Giralt S, Estey E, Albitar M, et al.
Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy.
Blood.
1997;89:4531-4536
9.
Slavin S, Nagler A, Naparstak E, et al.
Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.
Blood.
1998;91:756-763
10.
Sarosy G, Leyland-Jones B, Soochan P, Cheson B.
The systemic administration of intravenous melphalan.
J Clin Oncol.
1988;6:1768-1782 11. Singhal S, Powles R, Treleaven J, Horton C, Swansbury GJ, Mehta J. Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility in women. Bone Marrow Transplant. 1996;18:1049-1055[Medline] [Order article via Infotrieve].
12.
Li L, Keating MJ, Plunkett W, Yang LY.
Fludarabine-mediated repair inhibition of cisplatin-induced DNA lesions in human chronic myelogenous leukemia-blast crisis K562 cells: induction of synergistic cytotoxicity independent of reversal of apoptosis resistance.
Mol Pharmacol.
1997;52:798-806 13. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457[CrossRef]. 14. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft versus host disease in human recipients of marrow from HLA matched sibling donors. Transplantation. 1974;18:295[Medline] [Order article via Infotrieve]. 15. Schulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host disease syndrome in man: a long term clinical pathologic study of 20 Seattle patients. Am J Med. 1980;69:204[CrossRef][Medline] [Order article via Infotrieve]. 16. Standing Committee on Human Cytogenetic Nomenclature. An international system for human cytogenetic nomenclature 20 (1978 ISCN). Cytogenet Cell Genet. 1978;21:309[Medline] [Order article via Infotrieve]. 17. Yam P, Petz L, Knowlton R, et al. Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation. Transplantation. 1987;43:399[Medline] [Order article via Infotrieve].
18.
Bearman SI, Appelbaum FR, Buckner CD, et al.
Regimen related toxicities in patients undergoing bone marrow transplantation.
J Clin Oncol.
1988;6:1562 19. Snedecor GW, Cochran WG. Statistical Methods. 7th ed. Ames, IA: Iowa State University Press; 1980. 20. Fisher RA. The condition under which ?2 measures the discrepancy between observation and hypothesis. J Royal Stat Soc. 1924;87:442. 21. Mehta CR. The exact analysis of contingency tables in medical research. Stat Meth Med Res. 1994;3:135[Medline] [Order article via Infotrieve]. 22. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;60:163. 23. Cox DR. Regression models and life tables (with discussion). J R Stat Soc B. 1972;34:187. 24. Fleming TR, Harrington DP. Counting Processes and Survival Analysis. New York, NY: Wiley; 1991.
25.
Grambsch PM, Therneau TM.
Proportional hazards tests and diagnostics based on weighted residuals.
Biometrika.
1994;81:515 26. Cleveland WS. Robust locally-weighted regression and smoothing scatterplots. J Am Stat Assoc. 1979;74:829[CrossRef]. 27. Ghosh BK. A comparison of some approximate confidence intervals for the binomial parameter. J Am Stat Assoc. 1979;74:894[CrossRef]. 28. Becker RA, Chambers JM, Wilks AR. The New S Language. Pacific Grove, CA: Wadsworth; 1988. 29. StatXact 3 for Windows. Cambridge, MA: Cytel Corporation; 1995. 30. Therneau TM. A package for survival analysis in S. Mayo Clinic Foundation; 1994.
31.
Moreau P, Fiere D, Bezwoda WR, et al.
Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma.
J Clin Oncol.
1997;15:660-666 32. Larson R, Mick R, Spielberger R, O'Brien S, Ratain M. Dose escalation trial of cladribine using five daily intravenous infusions in patients with advanced hematologic malignancies. J Clin Oncol. 1996;14:188-195[Abstract].
33.
Vahdat L, Wong E, Wile M, Rosenblum M, Foley K, Warrell R.
Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.
Blood.
1994;84:3429 34. Kornblau S, Gandhi V, Andreeff M, et al. Clinical and laboratory studies of 2-chlorodeoxyadenosine ± cytosine arabinoside for relapsed or refractory acute myelogenous leukemia in adults. Leukemia. 1996;10:1563-1569[Medline] [Order article via Infotrieve].
35.
Petersdorf E, Gooley T, Anasetti C, et al.
Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient.
Blood.
1998;92:3515-3520 36. Kottaridis D, Chakraverty R, Milligan D, et al. A nonmyeloablative regimen for allografting high-risk patients: low toxicity, stable engraftment without GVHD, disease control and potential for GVL with adoptive immunotherapy [abstract]. Blood. 1999;94(suppl 1):348a. 37. Giralt S, Gajewski J, Khouri I, et al. Induction of graft-vs-leukemia as primary treatment of chronic myelogenous leukemia [abstract]. Blood. 1997;90:418a. 38. McSweeney P, Wagner J, Maloney D, et al. Outpatient PBSC allografts using immunosuppression with low dose TBI before, and cyclosporine (CSP) and mycophenolate mofetil (MMF) after transplant. Blood. 1998;92(suppl 1):519a. 39. Molina A, Storb R. Hematopoietic stem cell transplantation in older adults. In: Rowe J,Lazarus H,Carella A, eds. Handbook of Bone Marrow Transplantation. London United Kingdom: Martin Dunitz; 2000:111-138.
© 2001 by The American Society of Hematology.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
 |
|
  N. Matsuno, A. Wake, N. Uchida, K. Ishiwata, H. Araoka, S. Takagi, M. Tsuji, H. Yamamoto, D. Kato, Y. Matsuhashi, et al. Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation Blood, August 20, 2009; 114(8): 1689 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Kohrt, B. B. Turnbull, K. Heydari, J. A. Shizuru, G. G. Laport, D. B. Miklos, L. J. Johnston, S. Arai, W.-K. Weng, R. T. Hoppe, et al. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors Blood, July 30, 2009; 114(5): 1099 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ayuk, J. A. Perez-Simon, A. Shimoni, A. Sureda, T. Zabelina, R. Schwerdtfeger, R. Martino, H. G. Sayer, A. Alegre, J.-J. Lahuerta, et al. Clinical impact of human Jurkat T-cell-line-derived antithymocyte globulin in multiple myeloma patients undergoing allogeneic stem cell transplantation Haematologica, September 1, 2008; 93(9): 1343 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Marks, K. Potthoff, J. Hahn, G. Ihorst, H. Bertz, A. Spyridonidis, E. Holler, and J. M. Finke Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies Blood, July 15, 2008; 112(2): 415 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Lazarus, G. L. Phillips, R. H. Herzig, D. D. Hurd, S. N. Wolff, and G. P. Herzig High-Dose Melphalan and the Development of Hematopoietic Stem-Cell Transplantation: 25 Years Later J. Clin. Oncol., May 10, 2008; 26(14): 2240 - 2243. [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]
|
|
|
|
|
|
P. Kebriaei, M. A. Detry, S. Giralt, A. Carrasco-Yalan, A. Anagnostopoulos, D. Couriel, I. F. Khouri, P. Anderlini, C. Hosing, A. Alousi, et al. Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia Blood, November 1, 2007; 110(9): 3456 - 3462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Brunstein, J. N. Barker, D. J. Weisdorf, T. E. DeFor, J. S. Miller, B. R. Blazar, P. B. McGlave, and J. E. Wagner Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease Blood, October 15, 2007; 110(8): 3064 - 3070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Devetten and J. Armitage Hematopoietic cell transplantation: progress and obstacles Ann. Onc., September 1, 2007; 18(9): 1450 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Martino, R. Parody, T. Fukuda, J. Maertens, K. Theunissen, A. Ho, G. J. Mufti, N. Kroger, A. R. Zander, D. Heim, et al. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation Blood, November 1, 2006; 108(9): 2928 - 2936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schmid, M. Schleuning, R. Schwerdtfeger, B. Hertenstein, E. Mischak-Weissinger, D. Bunjes, S. v. Harsdorf, C. Scheid, U. Holtick, H. Greinix, et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation Blood, August 1, 2006; 108(3): 1092 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Montserrat, C. Moreno, J. Esteve, A. Urbano-Ispizua, E. Gine, and F. Bosch How I treat refractory CLL Blood, February 15, 2006; 107(4): 1276 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Hegenbart, D. Niederwieser, B. M. Sandmaier, M. B. Maris, J. A. Shizuru, H. Greinix, C. Cordonnier, B. Rio, A. Gratwohl, T. Lange, et al. Treatment for Acute Myelogenous Leukemia by Low-Dose, Total-Body, Irradiation-Based Conditioning and Hematopoietic Cell Transplantation From Related and Unrelated Donors J. Clin. Oncol., January 20, 2006; 24(3): 444 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tauro, C. Craddock, K. Peggs, G. Begum, P. Mahendra, G. Cook, J. Marsh, D. Milligan, A. Goldstone, A. Hunter, et al. Allogeneic Stem-Cell Transplantation Using a Reduced-Intensity Conditioning Regimen Has the Capacity to Produce Durable Remissions and Long-Term Disease-Free Survival in Patients With High-Risk Acute Myeloid Leukemia and Myelodysplasia J. Clin. Oncol., December 20, 2005; 23(36): 9387 - 9393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lowsky, T. Takahashi, Y. P. Liu, S. Dejbakhsh-Jones, F. C. Grumet, J. A. Shizuru, G. G. Laport, K. E. Stockerl-Goldstein, L. J. Johnston, R. T. Hoppe, et al. Protective conditioning for acute graft-versus-host disease. N. Engl. J. Med., September 29, 2005; 353(13): 1321 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Molina, J. Zain, D. A. Arber, M. Angelopolou, M. O'Donnell, J. Murata-Collins, S. J. Forman, and A. Nademanee Durable Clinical, Cytogenetic, and Molecular Remissions After Allogeneic Hematopoietic Cell Transplantation for Refractory Sezary Syndrome and Mycosis Fungoides J. Clin. Oncol., September 1, 2005; 23(25): 6163 - 6171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schmid, M. Schleuning, G. Ledderose, J. Tischer, and H.-J. Kolb Sequential Regimen of Chemotherapy, Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation, and Prophylactic Donor Lymphocyte Transfusion in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome J. Clin. Oncol., August 20, 2005; 23(24): 5675 - 5687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. van Besien, A. Artz, S. Smith, D. Cao, S. Rich, L. Godley, D. Jones, P. Del Cerro, D. Bennett, B. Casey, et al. Fludarabine, Melphalan, and Alemtuzumab Conditioning in Adults With Standard-Risk Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome J. Clin. Oncol., August 20, 2005; 23(24): 5728 - 5738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Girgis, C. Hallemeier, W. Blum, R. Brown, H.-s. Lin, H. Khoury, L. T. Goodnough, R. Vij, S. Devine, M. Wehde, et al. Chimerism and clinical outcomes of 110 recipients of unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide Blood, April 15, 2005; 105(8): 3035 - 3041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Cao, J. A. Shizuru, R. M. Wong, K. Sheehan, G. G. Laport, K. E. Stockerl-Goldstein, L. J. Johnston, M. J. Stuart, F. C. Grumet, R. S. Negrin, et al. Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose Blood, March 15, 2005; 105(6): 2300 - 2306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Cornelissen and B. Lowenberg Role of Allogeneic Stem Cell Transplantation in Current Treatment of Acute Myeloid Leukemia Hematology, January 1, 2005; 2005(1): 151 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Rettig, J. K. Ritchey, J. L. Prior, J. S. Haug, D. Piwnica-Worms, and J. F. DiPersio Kinetics of In Vivo Elimination of Suicide Gene-Expressing T Cells Affects Engraftment, Graft-versus-Host Disease, and Graft-versus-Leukemia after Allogeneic Bone Marrow Transplantation J. Immunol., September 15, 2004; 173(6): 3620 - 3630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. L. Ho, A. Pagliuca, M. Kenyon, J. E. Parker, A. Mijovic, S. Devereux, and G. J. Mufti Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning Blood, September 15, 2004; 104(6): 1616 - 1623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Diaconescu, C. R. Flowers, B. Storer, M. L. Sorror, M. B. Maris, D. G. Maloney, B. M. Sandmaier, and R. Storb Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors Blood, September 1, 2004; 104(5): 1550 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Sorror, M. B. Maris, B. Storer, B. M. Sandmaier, R. Diaconescu, C. Flowers, D. G. Maloney, and R. Storb Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities Blood, August 15, 2004; 104(4): 961 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. de Lima, D. Couriel, P. F. Thall, X. Wang, T. Madden, R. Jones, E. J. Shpall, M. Shahjahan, B. Pierre, S. Giralt, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS Blood, August 1, 2004; 104(3): 857 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. de Lima, A. Anagnostopoulos, M. Munsell, M. Shahjahan, N. Ueno, C. Ippoliti, B. S. Andersson, J. Gajewski, D. Couriel, J. Cortes, et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation Blood, August 1, 2004; 104(3): 865 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Besien, S. Smith, J. Anastasi, R. Larson, M. Thirman, T. Odenike, and W. Stock Irreversible myelosuppression after fludarabine-melphalan conditioning: observations in patients with graft rejection Blood, June 1, 2004; 103(11): 4373 - 4374. [Full Text] [PDF]
|
|
|
|
|
|
C. Carvallo, N. Geller, R. Kurlander, R. Srinivasan, O. Mena, T. Igarashi, L. M. Griffith, W. M. Linehan, and R. W. Childs Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors Blood, February 15, 2004; 103(4): 1560 - 1563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Casper, W. Knauf, T. Kiefer, D. Wolff, B. Steiner, U. Hammer, R. Wegener, H.-D. Kleine, S. Wilhelm, A. Knopp, et al. Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation Blood, January 15, 2004; 103(2): 725 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Barlogie, J. Shaughnessy, G. Tricot, J. Jacobson, M. Zangari, E. Anaissie, R. Walker, and J. Crowley Treatment of multiple myeloma Blood, January 1, 2004; 103(1): 20 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Deeg, T. A. Gooley, M. E. D. Flowers, G. E. Sale, J. T. Slattery, C. Anasetti, T. R. Chauncey, K. Doney, G. E. Georges, H.-P. Kiem, et al. Allogeneic hematopoietic stem cell transplantation for myelofibrosis Blood, December 1, 2003; 102(12): 3912 - 3918. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. T. Ueno, Y. C. Cheng, G. Rondon, N. M. Tannir, J. L. Gajewski, D. R. Couriel, C. Hosing, M. J. de Lima, P. Anderlini, I. F. Khouri, et al. Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors Blood, November 15, 2003; 102(10): 3829 - 3836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wong, S. A. Giralt, T. Martin, D. R. Couriel, A. Anagnostopoulos, C. Hosing, B. S. Andersson, P. Cano, M. Shahjahan, C. Ippoliti, et al. Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years Blood, October 15, 2003; 102(8): 3052 - 3059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Goldman and J. V. Melo Chronic Myeloid Leukemia -- Advances in Biology and New Approaches to Treatment N. Engl. J. Med., October 9, 2003; 349(15): 1451 - 1464. [Full Text] [PDF]
|
|
|
|
|
|
E. Bachar-Lustig, S. Reich-Zeliger, and Y. Reisner Anti-third-party veto CTLs overcome rejection of hematopoietic allografts: synergism with rapamycin and BM cell dose Blood, September 15, 2003; 102(6): 1943 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Maris, D. Niederwieser, B. M. Sandmaier, B. Storer, M. Stuart, D. Maloney, E. Petersdorf, P. McSweeney, M. Pulsipher, A. Woolfrey, et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies Blood, September 15, 2003; 102(6): 2021 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Barker, D. J. Weisdorf, T. E. DeFor, B. R. Blazar, J. S. Miller, and J. E. Wagner Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning Blood, September 1, 2003; 102(5): 1915 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-E. Filmont, J. Czernin, C. Yap, D. H. S. Silverman, A. Quon, M. E. Phelps, and C. Emmanouilides Value of F-18 Fluorodeoxyglucose Positron Emission Tomography for Predicting the Clinical Outcome of Patients With Aggressive Lymphoma Prior to and After Autologous Stem-Cell Transplantation Chest, August 1, 2003; 124(2): 608 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bornhauser, B. Storer, J. T. Slattery, F. R. Appelbaum, H. J. Deeg, J. Hansen, P. J. Martin, G. B. McDonald, W. G. Nichols, J. Radich, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells Blood, August 1, 2003; 102(3): 820 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mohty, J.-O. Bay, C. Faucher, B. Choufi, K. Bilger, O. Tournilhac, N. Vey, A.-M. Stoppa, D. Coso, C. Chabannon, et al. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen Blood, July 15, 2003; 102(2): 470 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mielcarek, P. J. Martin, W. Leisenring, M. E. D. Flowers, D. G. Maloney, B. M. Sandmaier, M. B. Maris, and R. Storb Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation Blood, July 15, 2003; 102(2): 756 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Radich, T. Gooley, W. Bensinger, T. Chauncey, R. Clift, M. Flowers, P. Martin, J. Slattery, D. Sultan, and F. R. Appelbaum HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen Blood, July 1, 2003; 102(1): 31 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Morris, P. Rebello, K. J. Thomson, K. S. Peggs, C. Kyriakou, A. H. Goldstone, S. Mackinnon, and G. Hale Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications Blood, July 1, 2003; 102(1): 404 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Elliott, W. L. Nichols Jr, E. A. Plumhoff, S. M. Ansell, A. Dispenzieri, D. A. Gastineau, M. A. Gertz, D. J. Inwards, M. Q. Lacy, I. N. M. Micallef, et al. Posttransplantation Thrombotic Thrombocytopenic Purpura: A Single-Center Experience and a Contemporary Review Mayo Clin. Proc., April 1, 2003; 78(4): 421 - 430. [Abstract] [PDF]
|
|
|
|
|
|
G. G. Wulf, K.-L. Luo, M. A. Goodell, and M. K. Brenner Anti-CD45-mediated cytoreduction to facilitate allogeneic stem cell transplantation Blood, March 15, 2003; 101(6): 2434 - 2439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Niederwieser, M. Maris, J. A. Shizuru, E. Petersdorf, U. Hegenbart, B. M. Sandmaier, D. G. Maloney, B. Storer, T. Lange, T. Chauncey, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases Blood, February 15, 2003; 101(4): 1620 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. L. Ho, M. Kenyon, I. El-Hemaidi, S. Devereux, A. Pagliuca, and G. J. Mufti Reduced-intensity allogeneic hematopoietic stem cell transplantation with alemtuzumab conditioning regimens: survival does not plateau until after day 200 Blood, January 15, 2003; 101(2): 779 - 780. [Full Text] [PDF]
|
|
|
|
|
|
G. Mufti, A. F. List, S. D. Gore, and A. Y.L. Ho Myelodysplastic Syndrome Hematology, January 1, 2003; 2003(1): 176 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Barille-Nion, B. Barlogie, R. Bataille, P. L. Bergsagel, J. Epstein, R. G. Fenton, J. Jacobson, W. M. Kuehl, J. Shaughnessy, and G. Tricot Advances in Biology and Therapy of Multiple Myeloma Hematology, January 1, 2003; 2003(1): 248 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Robinson, A. H. Goldstone, S. Mackinnon, A. Carella, N. Russell, C. R. de Elvira, G. Taghipour, and N. Schmitz Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation Blood, December 15, 2002; 100(13): 4310 - 4316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kroger, H. G. Sayer, R. Schwerdtfeger, M. Kiehl, A. Nagler, H. Renges, T. Zabelina, B. Fehse, F. Ayuk, G. Wittkowsky, et al. Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality Blood, December 1, 2002; 100(12): 3919 - 3924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. I. Marks, R. Lush, J. Cavenagh, D. W. Milligan, S. Schey, A. Parker, F. J. Clark, L. Hunt, J. Yin, S. Fuller, et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation Blood, October 16, 2002; 100(9): 3108 - 3114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Perez-Simon, P. D. Kottaridis, R. Martino, C. Craddock, D. Caballero, R. Chopra, J. Garcia-Conde, D. W. Milligan, S. Schey, A. Urbano-Ispizua, et al. Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders Blood, October 16, 2002; 100(9): 3121 - 3127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Branson, R. Chopra, P. D. Kottaridis, G. McQuaker, A. Parker, S. Schey, R. K. Chakraverty, C. Craddock, D. W. Milligan, R. Pettengell, et al. Role of Nonmyeloablative Allogeneic Stem-Cell Transplantation After Failure of Autologous Transplantation in Patients With Lymphoproliferative Malignancies J. Clin. Oncol., October 1, 2002; 20(19): 4022 - 4031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Martino, M. D. Caballero, J. A. Perez Simon, C. Canals, C. Solano, A. Urbano-Ispizua, J. Bargay, A. Leon, J. Sarra, G. F. Sanz, et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes Blood, August 28, 2002; 100(6): 2243 - 2245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hunault-Berger, N. Ifrah, and P. Solal-Celigny Intensive therapies in follicular non-Hodgkin lymphomas Blood, July 30, 2002; 100(4): 1141 - 1152. [Full Text] [PDF]
|
|
|
|
|
|
M. E. H. M. Van Hoef ; and S. Mackinnon Nonmyeloablative transplantation challenged by experimentation Blood, July 30, 2002; 100(4): 1508 - 1509. [Full Text] [PDF]
|
|
|
|
|
|
S. Chakrabarti, S. Mackinnon, R. Chopra, P. D. Kottaridis, K. Peggs, P. O'Gorman, R. Chakraverty, T. Marshall, H. Osman, P. Mahendra, et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution Blood, May 29, 2002; 99(12): 4357 - 4363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Appelbaum and B. Sandmaier Sensitivity of Renal Cell Cancer to Nonmyeloablative Allogeneic Hematopoietic Cell Transplantations: Unusual or Unusually Important? J. Clin. Oncol., April 15, 2002; 20(8): 1965 - 1967. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Saito, Y. Kanda, M. Kami, K. Kato, N. Shoji, S. Kanai, T. Ohnishi, Y. Kawano, K. Nakai, T. Ogasawara, et al. Therapeutic Potential of a Reduced-Intensity Preparative Regimen for Allogeneic Transplantation with Cladribine, Busulfan, and Antithymocyte Globulin against Advanced/Refractory Acute Leukemia/Lymphoma Clin. Cancer Res., April 1, 2002; 8(4): 1014 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Devine, R. Hoffman, A. Verma, R. Shah, B. A. Bradlow, W. Stock, V. Maynard, E. Jessop, D. Peace, M. Huml, et al. Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia Blood, March 15, 2002; 99(6): 2255 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Chakraverty, K. Peggs, R. Chopra, D. W. Milligan, P. D. Kottaridis, S. Verfuerth, J. Geary, D. Thuraisundaram, K. Branson, S. Chakrabarti, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen Blood, February 1, 2002; 99(3): 1071 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Druker, S. G. O'Brien, J. Cortes, and J. Radich Chronic Myelogenous Leukemia Hematology, January 1, 2002; 2002(1): 111 - 135. [Abstract] [Full Text]
|
|
|
|
|
|
D. Hoelzer, N. Gokbuget, O. Ottmann, C.-H. Pui, M. V. Relling, F. R. Appelbaum, J. J.M. van Dongen, and T. Szczepanski Acute Lymphoblastic Leukemia Hematology, January 1, 2002; 2002(1): 162 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Maloney, B. M. Sandmaier, S. Mackinnon, and J. A. Shizuru Non-Myeloablative Transplantation Hematology, January 1, 2002; 2002(1): 392 - 421. [Abstract] [Full Text]
|
|
|
|
|
|
P. Corradini, C. Tarella, A. Olivieri, A. M. Gianni, C. Voena, F. Zallio, M. Ladetto, M. Falda, M. Lucesole, A. Dodero, et al. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies Blood, January 1, 2002; 99(1): 75 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Socie, R. A. Clift, D. Blaise, A. Devergie, O. Ringden, P. J. Martin, M. Remberger, H. J. Deeg, T. Ruutu, M. Michallet, et al. Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies Blood, December 15, 2001; 98(13): 3569 - 3574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Storb, R. Champlin, S. R. Riddell, M. Murata, S. Bryant, and E. H. Warren Non-Myeloablative Transplants for Malignant Disease Hematology, January 1, 2001; 2001(1): 375 - 391. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
Top
Abstract
Introduction