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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2873-2878.
Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-11-3800.
 Previous Article | Table of Contents | Next Article 
PLENARY PAPERS
High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemia
Hagop Kantarjian,
Moshe Talpaz,
Susan O'Brien,
Guillermo Garcia-Manero,
Srdan Verstovsek,
Francis Giles,
Mary Beth Rios,
Jianqin Shan,
Laurie Letvak,
Deborah Thomas,
Stefan Faderl,
Alessandra Ferrajoli, and
Jorge Cortes
From the Departments of Leukemia and Bioimmunotherapy, The University of Texas, M. D. Anderson Cancer Center, Houston, TX; and Novartis Pharmaceuticals, East Hanover, NJ.
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Abstract
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Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P = .0005), major molecular response (QPRC < 0.05%; P = .00001), and complete molecular response (undetectable BCR-ABL; P = .001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML. (Blood. 2004; 103:2873-2878)
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Introduction
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Imatinib mesylate (STI571, Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) is a selective Bcr-Abl protein tyrosine kinase inhibitor against c-abl, bcr/abl, c-kit, and platelet-derived growth factor receptor (PDGF-R).1,2 Imatinib has demonstrated significant activity in all phases of Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML).3-12 The recommended dosage is 400 mg daily for chronic phase CML and 600 mg daily for CML in transformation. In patients with previously untreated early chronic phase CML, 400 mg imatinib orally daily has produced complete hematologic responses (CHRs) in more than 95% of patients, and complete cytogenetic responses in 60% to 75%.11,12 However, patients with undetectable levels of BCR-ABL assessed by polymerase chain reaction (PCR) studies (complete molecular response) represented only 5% to 15%. Achievement of a complete cytogenetic response with interferon alpha (IFN- ) has been associated with 10-year survival rates of 70% to 85%.13-17 Patients with undetectable BCR-ABL levels after IFN- have not relapsed after long-term follow-up.13,15 Thus, while achievement of a complete cytogenetic response is an important short-term goal in CML therapy, reaching undetectable levels of BCR-ABL may improve long-term event-free survival.
Several observations suggest that higher dosages of imatinib may be more effective. The initial phase 1 trial showed a clear dose-response relationship.3 Complete hematologic response rates were 98% with daily imatinib doses of 300 mg or higher, compared with 56% with 200 or 250 mg daily, and lower rates with dosages less than 200 mg. Cytogenetic responses were 54% with dosages 300 mg/day or higher, but were rare at lower dosages. In accelerated phase CML, patients treated with 600 mg imatinib daily had higher response rates, and longer response and survival durations.7 In chronic phase CML after IFN- failure, imatinib dosage escalation to 800 mg daily after CML relapse at 400 mg daily recaptured CHR in 60% of patients and improved cytogenetic response to a major one in 40%.18 Amplification of the BCR-ABL gene or overexpression of its protein product are known mechanisms of resistance. Several mutations within the Abl structure in Bcr-Abl result in relative rather than absolute resistance to imatinib. Some resistance mechanisms may be overcome with imatinib dosage escalation.19-22
We have recently treated 36 patients in late chronic CML after IFN- failure with 400 mg imatinib orally twice daily. The complete cytogenetic response rate was 89%, and 41% had undetectable levels of BCR-ABL.23 These results appear to be significantly better than with 400 mg imatinib daily in chronic phase CML after IFN- failure.5,6 In this study, we investigated the efficacy and toxicity of high-dose imatinib (800 mg daily) in newly diagnosed CML, and compared the results with standard-dose imatinib (400 mg daily) in a similar CML population.
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Patients and methods
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Study group
Patients with newly diagnosed Ph-positive CML in early chronic phase (diagnosis to therapy < 12 months) were eligible for our institutional investigational new drug (IND) study (ID-01_151). Patients were required to be 15 years or older and to have adequate performance status (Eastern Cooperative Oncology Group [ECOG], 0 to 2), serum creatinine less than 176.8 µM (2 mg/dL), total bilirubin less than 34.2 µM (2 mg/dL), and normal cardiac function (New York Heart Association class 3-4 cardiac disease excluded). Patients previously treated with imatinib were not eligible; prior therapy with hydroxyurea was allowed, but prior therapy with IFN- or cytarabine was allowed only for a month or less. Women of childbearing age were required to have a negative pregnancy test before starting imatinib, and all patients at risk were required to use contraception during therapy. Patients provided written informed consent before entry into the study; the study was reviewed and approved by the internal review board of our institution (M.D. Anderson Cancer Center) and performed in accordance with the Declaration of Helsinki.
Patients with accelerated or blastic phase CML were excluded.24,25 Patients with cytogenetic clonal evolution were eligible if there were no other criteria of accelerated phase CML.
Treatment and dose modifications
Imatinib was given orally at 400 mg twice daily. Hydroxyurea was allowed for debulking during the first 4 weeks of therapy. Anagrelide was permitted for up to 3 weeks.
Dose reductions of imatinib for nonhematologic or hematologic toxic effects were as follows. For persistent grade 2 nonhematologic toxic effects, therapy was interrupted until recovery to grade 1 or less and resumed at the original dosage level. If grade 2 toxicity recurred, treatment was interrupted again until recovery and resumed at a daily dosage of 600 mg. For grade 3 or 4 nonhematologic toxicity, therapy was interrupted until recovery to grade 1 or less and resumed at a daily dosage of 600 mg. For severe hematologic toxicity (granulocyte count of < 0.5 x 109/L or a platelet count of < 40 x 109/L), therapy was interrupted until the neutrophils recovered to 109/L or higher and/or platelets to 60 x 109/L or higher. If the toxicity resolved within 2 weeks, treatment was resumed at the original dosage. If toxicity resolved after more than 2 weeks, or if it recurred after resuming therapy, the dosage was reduced to 600 mg. Further dose reductions to 400 mg or 300 mg daily were allowed using the same guidelines for hematologic and nonhematologic toxicity. Patients developing anemia received packed red blood cell transfusions or blood products at the discretion of the investigator, or 40 000 units erythropoietin subcutaneously once a week until the hemoglobin level increased to 120 g/L (12 g/dL) or more.
Monitoring
Complete blood counts and serum chemistry were done weekly during the first 4 weeks, then every 6 to 8 weeks thereafter. Bone marrow studies, including morphologic and cytogenetic or fluorescent in situ hybridization (iFISH) analysis, and quantitative PCR studies, were performed every 3 months in the first year, then every 3 to 6 months. Patients were followed for survival at least every 3 months. Drug safety parameters were evaluated at each visit and graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC), version 2.0.
Statistical considerations
Response criteria were as previously described.26 A CHR was defined as a white blood cell count of less than 10 x 109/L, a platelet count of less than 450 x 109/L, no immature cells (blasts, promyelocytes, myelocytes) in the peripheral blood, and disappearance of all signs and symptoms related to leukemia (including palpable splenomegaly) lasting for at least 4 weeks. Response was further categorized by the best cytogenetic response: complete, 0% Ph-positive cells; partial, 1% to 34% Ph-positive cells; and minor, 35% to 90% Ph-positive cells. Major cytogenetic response included complete plus partial cytogenetic responses (Ph-positive cells 0%-34%). Cytogenetic response was judged by standard cytogenetic analysis of metaphase spreads. Patients were categorized by their best cytogenetic or molecular response. Differences among variables were compared by the chi-square test. Time to disease transformation was calculated from the time treatment began until appearance of accelerated or blastic phase disease. Survival was calculated from the time treatment began until death from any cause. Survival and time to event curves were estimated by the Kaplan-Meier method and compared by the log rank test.
Cytogenetic and PCR analysis
Cytogenetic analysis was performed by the G-banding technique. Marrow specimens were examined on direct or short-term (24-hour) cultures; at least 20 metaphases were analyzed. PCR was done by real-time reverse transcriptase–PCR, and negative results (ie, undetectable transcript) were confirmed by nested PCR as previously reported.27 The sensitivity of the test is 1:100 000. The quantitative PCR (QPCR) analysis measured the BCR-ABL/ABL percentage ratio. For the purpose of this analysis, a complete molecular response was defined as negative (undetectable) BCR-ABL levels. A major molecular response was defined as BCR-ABL/ABL values less than 0.05%. This was based on previous studies identifying BCR-ABL/ABL values of 0.045% to 0.1% to be prognostically important.28,29 A BCR-ABL/ABL ratio of 0.05% is roughly equivalent to a 3-log reduction in disease.30
Historical control group
For comparative purposes, 50 patients with newly diagnosed Ph-positive CML treated on an institutional IND study (ID01-015) with 400 mg imatinib orally daily were analyzed. All patients were entered in the study from April to May 2001.11 The study of the historical control group immediately preceded the current study (which entered patients from June 2001 until April 2003).
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Results
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Study group
From June 2001 until April 2003, 114 patients were enrolled on the institutional IND study (ID-01_151). Their median age was 48 years (range, 17-84 years). Risk group (Sokal) stratification for 99 patients with evaluable data was as follows: good, 41%; intermediate, 37%; and poor, 21%. Their characteristics are summarized in Table 1. There were 50 patients (44%) who had received other therapies (IFN-, 1; hydrea, 49). There were 6 patients (5%) who had cytogenetic clonal evolution (other than complex Ph translocations or loss of chromosome Y): 3 with double Ph, 3 with other abnormalities. The median follow-up of the study group was 15 months and of the historical control group 31 months.
Response
Of the patients, 112 (98%) achieved CHR (Table 2). A major cytogenetic response was noted in 109 patients (96%): complete in 103 (90%) and partial in 6 (5%). Complete cytogenetic response was achieved in 59 patients (52%) at 3 months of therapy, and in 94 (82%) at 6 months. Compared with standard-dose imatinib, high-dose imatinib was associated with achievement of significantly better complete cytogenetic responses (P = .0005; Figure 1). Patients with Sokal high risk had a lower complete cytogenetic response rate (76% versus 95%; P = .03). There were no other significant differences in the incidence of complete cytogenetic response by known prognostic factors (eg, older age, splenomegaly, thrombocytosis) within the small numbers involved. All 6 patients with clonal evolution achieved a complete cytogenetic response (and disappearance of cytogenetic clonal evolution).
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Figure 1.. Estimated cumulative incidence of complete cytogenetic response in the study and historical control groups. CR indicates complete response.
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Figure 2 shows the values of BCR-ABL/ABL percentage ratio during imatinib therapy. There was a consistent and significant decline of these ratios over time. The median BCR-ABL/ABL percentage ratio decreased from 0.90% (range, 0%-107%) after 3 months to 0.030% (range, 0%-51%) after 12 months of therapy. Of 112 patients evaluable for molecular response, 71 (63%) achieved ratios of less than 0.05%, including 31 patients (28%) who had undetectable transcripts (confirmed by nested PCR). There were 48 patients who had at least 2 consecutive PCR values less than 0.05%, and 10 patients had at least 2 consecutive analyses with undetectable transcripts. Compared with standard-dose imatinib, patients receiving high-dose imatinib achieved significantly better major (BCR-ABL/ABL ratio < 0.05%; Figure 3; P = .00001) and complete (BCR-ABL/ABL negative ratio; Figure 4; P = .001) molecular responses. The estimated cumulative 18-month incidence of complete molecular response was 28% with high-dose imatinib versus 7% with standard-dose imatinib.
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Figure 2.. BCR-ABL/ABL percentage ratio over the course of therapy. Results are expressed for each evaluable patient at each 3-month period. Number of evaluable patients is shown on top. The dotted line represents a percentage ratio of 0.05%. Percentages shown under this line represent the proportion of patients below this threshold at each time point.
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Figure 3.. Estimated cumulative incidence of major molecular response (BCR-ABL/ABL ratio < 0.05%) in the study and historical control groups.
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Figure 4.. Estimated cumulative incidence of complete molecular response (undetectable BCR-ABL levels, confirmed by nested QPCR) in the study and historical control groups.
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Time to progression and survival
Of the 114 patients treated, 96 (84%) remain alive in chronic phase on imatinib therapy. The other 18 patients stopped therapy because of noncompliance (n = 4), insurance issues (n = 3), toxicity (n = 7), cytogenetic refractoriness (n = 3), and death unrelated to imatinib (n = 1). After a median follow-up of 15 months (range, 3-27 months), 112 patients (98%) are alive in chronic phase. Among all patients, 2 died—one from complications of allogeneic stem cell transplantation done in chronic phase (100% Ph-positive at 6 months) and the second of unrelated causes. None of the 114 patients have transformed; transformation-free status was better with high-dose imatinib (Figure 5; P = .004). Only 3 of 167 patients on either study have died (Figure 6). No patient in the current study group has developed chromosomal abnormalities in the emerging Ph-negative cells (2 did so in the historical group).
Response duration
Of the 109 patients with a major cytogenetic response, 11 were taken off therapy for issues not related to response (noncompliance, 2; insurance, 2; toxicity, 6; death, 1). Of 98 patients with a major cytogenetic response continuing therapy, 95 continue to have a durable major response: 3 patients had disease relapse (defined as either reappearance of Ph-positive cells  10% after complete cytogenetic response, or an increase of Ph-positive cells by 30% or more, or an increase to 65% or more documented once) after 4, 6, and 18 months from the time the major cytogenetic response was achieved. After a median follow-up time of 10 months from complete cytogenetic response (range, 1-24 months), only 1 (1%) of 103 patients who achieved a complete cytogenetic response has lost his response (to 85% Ph-positive). Among the 10 patients alive and off imatinib for reasons other than response, 2 of 9 who were in complete cytogenetic response had an increase of Ph-positive cells to 10% and 30%, respectively. The patient who stopped therapy while in partial cytogenetic response continues with this response. The median follow-up time from achievement of BCR-ABL/ABL percentage ratio of less than 0.05% is 10 months (range, 1-21 months). None of the 71 patients who have achieved these ratios had a cytogenetic relapse; 11 of 71 patients have had an increased ratio to more than 0.05% intermittently.
Toxicity and dose intensity
Common adverse events are listed in Table 3. Fluid retention, skin rash, nausea, diarrhea, and muscle cramps were common, but similar in frequency with that seen with standard-dose imatinib. Grade 3 or higher nonhematologic adverse events were uncommon: skin rash (n = 7, 6%), cardiac (n = 4, 4%), liver toxicity (n = 8, 7%), bone pain (n = 3, 3%), nausea and vomiting, diarrhea, fluid retention, and fatigue (1 patient each, total 4). All toxicities were reversible with dose reductions or treatment interruptions. Hematologic toxicity is also shown in Table 3: grade 3 or higher neutropenia in 41 patients (36%), thrombocytopenia in 29 patients (25%), and anemia in 11 (10%).
After 3 months of therapy, 77 (68%) of 114 patients were receiving the planned dosage; 37 patients (32%) had dose reduction for toxicity to 600 mg daily (n = 27) or 300 to 400 mg daily (n = 10; Figure 7). The imatinib dosage of 800 mg daily was maintained in 70 (64%) of 109 evaluable patients at 6 months, and in 52 (66%) of 79 evaluable patients at 12 months. Dose reduction to 600 mg daily resolved the toxicity in most patients; 22 patients (19%) have required dose reductions to 400 mg daily or lower (300 mg is the lowest acceptable dose); 12 patients have required dose reductions after 4 months of therapy. The most common causes for dose reduction were myelosuppression in 18 patients (15%, thrombocytopenia in 11, neutropenia in 6, both in 1), skin rash (n = 13, 11%), fatigue (n = 4, 3%), bone pain (n = 7, 6%), fluid retention (n = 5, 4%), congestive heart failure (n = 3), fever or infection (n = 3), liver dysfunction (n = 2), and gastrointestinal (n = 2). Some patients required dose reduction for more than one of the toxicities listed. For significant anemia, 40 patients received erythropoietin (Procrit; Ortho Biotech, Bridgewater, NJ); no dose reductions were required for anemia.
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Discussion
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A body of evidence suggested that higher dosages of imatinib may be associated with better disease control and with overcoming relative CML resistance to imatinib.18-23 Initiation of high-dose imatinib early in the course of CML may also reduce the emergence of imatinib-resistant CML clones. In this study, we treated 114 patients with newly diagnosed Ph-positive CML in chronic phase with 400 mg imatinib orally twice daily. The overall complete cytogenetic response rate was 90%. Molecular responses were excellent: 63% of patients achieved a major molecular response, which was complete in 28%. The 12-month cumulative incidence of complete cytogenetic response was 95%, of a major molecular response 60%, and of a complete molecular response 26%. These complete cytogenetic and molecular response rates are unprecedented. With a median follow-up time of 15 months, the estimated 2-year survival rate is 94%. Compared with standard-dose imatinib, high-dose imatinib was associated with better complete cytogenetic and major/complete molecular responses (Figures 2, 3, 4). Progression-free survival was also better (Figure 5), although the number of events is very small.
In previous studies with IFN- regimens, the complete cytogenetic response rates were 5% to 25%.16,17,26,31-33 Patients who achieved a complete cytogenetic response had estimated 10-year survival rates of 70% to 80%,13-15 which made achievement of a complete cytogenetic response an early surrogate end point for long-term survival, and a major therapeutic objective. The complete cytogenetic response rate of 90% in this study is encouraging in relation to long-term prognosis, assuming the prognostic significance of a complete cytogenetic response achieved with imatinib is similar to that achieved with IFN- therapy. Except for Sokal risk group, no pretreatment characteristics have predicted for differences in the incidence of complete cytogenetic response. All 6 patients with cytogenetic clonal evolution achieved a complete cytogenetic response. No chromosomal abnormalities have so far been observed in the Ph-negative cells.34
Achievement of a major molecular response (reduction of BCR-ABL/ABL ratio by 3-log or more, or to < 0.05%) has become the focus of newer regimens. Hochhaus et al previously reported that patients who attained BCR-ABL/ABL ratios of 0.045% or less with IFN- therapy had an estimated 3-year relapse rate of 0% versus 80% for those having lesser degrees of molecular response.28 Molecular remissions have been reported infrequently with standard-dose imatinib. In a study by Hochhaus et al, all 55 patients with CML in complete cytogenetic remission after imatinib therapy remained PCR-positive with median follow-up of 1.3 years.35 In the International Randomized Study of Interferon versus STI571 (IRIS trial) in newly diagnosed CML, patients achieving 3-log or more reductions of BCR-ABL/ABL (about 38% of patients) currently have an estimated 2-year progression-free survival rate of 100%.30 In our analysis of patients in chronic phase CML who achieved a complete cytogenetic response with imatinib, 29% of patients achieved BCR-ABL/ABL ratios of 0.05% or less on imatinib, and 13% had undetectable transcripts. Patients who had major molecular responses had a progression rate of 3% versus 21% for those who had fewer degrees of disease reduction (P < .001).36 In the present study, the incidence of major molecular response (BCR-ABL/ABL ratio < 0.05%, roughly equivalent to 3-log reduction) was 63%, and of complete molecular response 28%. The 18-month cumulative incidence of major molecular response was 72% with high-dose imatinib versus 42% with standard-dose imatinib (Figure 3). The 18-month cumulative incidence of complete molecular response was 28% with high-dose imatinib versus 7% with standard-dose imatinib (Figure 4). Of note, the incidences of major molecular response (42%) and of undetectable BCR-ABL (7%) at 18 months in the historical group (standard-dose imatinib) were similar to those reported in the IRIS study.12,30 None of our patients who had a major molecular response have had a cytogenetic relapse. The methodology for molecular analysis varies in different studies, and some techniques reported in the literature may be more sensitive.37 However, using the identical molecular technique at our institution, we demonstrated better quality molecular response with high-dose versus standard-dose imatinib, as well as similar incidences of major molecular responses and undetectable BCR-ABL levels with standard-dose imatinib as was reported in the IRIS study.12,30
Several investigations now aim to increase the frequency of PCR negativity with CML therapy. Most are resorting to combining imatinib with IFN- or cytarabine (ara-C) as frontline therapy, in single-arm or randomized designs. These combinations may introduce early toxicity (often not palatable to patients) and synergistic myelosuppression (compromising imatinib dose delivery). An alternative would be to introduce additional therapy at the time of maximal stable response achieved with imatinib (short of a PCR-negative status). In our study, the cumulative incidence of PCR negativity continues to increase with therapy (Figure 4). This should be considered in strategies that implement additional therapeutic strategies (such as vaccines, interferon, decitabine, homoharringtonine, or others) to evaluate their effect on increasing the rate of PCR-negative response.
High-dose imatinib was associated with more hematologic toxicity. In a phase 1 study of imatinib in chronic phase CML, patients were treated with escalating dosages of 25 mg to 1000 mg daily. A maximum tolerated dosage was not defined, and further dose escalations were not pursued because of evidence of biologic and clinical activity. In patients with accelerated phase CML, there was no difference in the incidence of severe hematologic or nonhematologic toxicity among patients treated with 400 mg or 600 mg daily. In our previous study of high-dose imatinib in chronic phase CML after IFN- failure, fluid retention was more likely to require therapy (ie, grade 2 according to the NCI CTC), but grade 3 edema was rare.23 Severe skin rashes were more common. This was partly confirmed in the current study, which showed a similar incidence of severe extramedullary side effects with 400 mg versus 800 mg of imatinib daily. Myelosuppression was more frequent with 800 mg, although manageable with dose reductions or with growth factor support (erythropoietin, filgrastim). After 12 months of therapy, 66% of patients continued to receive 800 mg imatinib daily, and 16% were receiving 600 mg daily. Thus, higher imatinib dosages could be delivered to most patients in early chronic phase CML.
In summary, high-dose imatinib 800 mg daily resulted in unprecedented high rates of complete cytogenetic and molecular responses. If such responses have similar long-term significance as seen in previous studies, they may translate into major improvement in the prognosis of CML.
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Footnotes
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Submitted November 12, 2003;
accepted December 13, 2003.
Prepublished online as Blood First Edition Paper, December 24, 2003; DOI 10.1182/blood-2003-11-3800.
Supported in part by the Betty Foster Leukemia Research Fund and the CML PO1 CA49639. J.C. is a Clinical Research Scholar of the Leukemia and Lymphoma Society.
L.L. is employed by Novartis Pharmaceuticals, whose potential product was studied in the present work.
An Inside Blood analysis of this article appears in the front of this issue.
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: Hagop Kantarjian, Department of Leukemia, M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 428, Houston, TX 77030; e-mail: hkantarj{at}mdanderson.org.
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References
|
|---|
- Druker BJ, Tamuira S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2: 561-566.[CrossRef][Medline]
[Order article via Infotrieve]
- Beran M, Cao X, Estrov Z, et al. Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization. Blood. 1994;83: 1922-1928.[Abstract/Free Full Text]
- Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344: 1031-1037.[Abstract/Free Full Text]
- Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest. 2000;105: 3-7.[Medline]
[Order article via Infotrieve]
- Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346: 645-652.[Abstract/Free Full Text]
- Kantarjian HM, Talpaz M, O'Brien S, et al. Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results. Clin Cancer Res. 2002;8: 2177-2187.[Abstract/Free Full Text]
- Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99: 1928-1937.[Abstract/Free Full Text]
- Kantarjian HM, O'Brien S, Cortes JE, et al. Treatment of Philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res. 2002;8: 2167-2176.[Abstract/Free Full Text]
- Sawyers CL, Hochhaus A, Feldman E, et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood. 2002;99: 3530-3539.[Abstract/Free Full Text]
- Kantarjian HM, Cortes J, O'Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood. 2002;99: 3547-3553.[Abstract/Free Full Text]
- Kantarjian HM, Cortes JE, O'Brien S, et al. Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. Blood. 2003;101: 97-100.[Abstract/Free Full Text]
- O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348: 994-1004.[Abstract/Free Full Text]
- Mahon F, Delbrel X, Cony-Makhoul P, et al. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia-like syndrome in mice with v-abl and BCR/ABL. J Clin Oncol. 2003;20: 214-220.
- Bonifazi F, de Vivo A, Gianantonio R, et al. Chronic myeloid leukemia and interferon-a: a study of complete cytogenetic responders. Blood. 2001;98: 3074-3081.[Abstract/Free Full Text]
- Kantarjian H, O'Brien S, Cortes J, et al. Complete cytogenetic and molecular responses to interferon-a based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer. 2003;97: 1033-1041.[CrossRef][Medline]
[Order article via Infotrieve]
- Garcia-Manero G, Faderl S, O'Brien S, Cortes J, Talpaz M, Kantarjian H. Chronic myelogenous leukemia: a review and update of therapeutic strategies. Cancer. 2003;98: 437-457.[CrossRef][Medline]
[Order article via Infotrieve]
- Faderl S, Talpaz M, Estrov Z, Kantarjian HM. Chronic myelogenous leukemia: biology and therapy. Ann Intern Med. 1999;131: 207-219.[Abstract/Free Full Text]
- Kantarjian HM, Talpaz M, O'Brien S, et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003;101: 473-475.[Abstract/Free Full Text]
- Weisberg E, Griffin JD. Mechanism of resistance to the ABL tyrosine kinase inhibitor STI571 in BCR/ABL-transformed hematopoietic cell lines. Blood. 2000;95: 3498-3505.[Abstract/Free Full Text]
- Mahon FX, Deininger MW, Schultheis B, et al. Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance. Blood. 2000;96: 1070-1079.[Abstract/Free Full Text]
- le Coutre P, Tassi E, Varella-Garcia M, et al. Induction of resistance to the Abelson inhibitor STI571 in human leukemic cells through gene amplification. Blood. 2000;95: 1758-1766.[Abstract/Free Full Text]
- Hochhaus A. Cytogenetic and molecular mechanisms of resistance to imatinib. Semin Hematol. 2003;40: 69-79.[Medline]
[Order article via Infotrieve]
- Cortes J, Giles F, O'Brien S, et al. Result of high-dose imatinib mesylate in patients with Philadelphia chromosome-positive chronic myeloid leukemia after failure of interferon-a. Blood. 2003;102: 83-86.[Abstract/Free Full Text]
- Kantarjian H, Dixon D, Keating MJ, et al. Characteristics of accelerated disease in chronic myelogenous leukemia. Cancer. 1988;61: 1441-1446.[CrossRef][Medline]
[Order article via Infotrieve]
- Kantarjian HM, Keating MJ, Talpaz M, et al. Chronic myelogenous leukemia in blast crisis: analysis of 242 patients. Am J Med. 1987;83: 445-454.[CrossRef][Medline]
[Order article via Infotrieve]
- Kantarjian HM, Smith T, O'Brien S, Beran M, Pierce S, Talpaz M, The Leukemia Service. Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. Ann Intern Med. 1995;122: 254-261.[Abstract/Free Full Text]
- Kantarjian HM, Talpaz M, Cortes J, et al. Quantitative polymerase chain reaction monitoring of BCR-ABL during therapy with imatinib mesylate (STI571; Gleevec) in chronic-phase chronic myelogenous leukemia. Clin Cancer Res. 2003;9: 160-166.[Abstract/Free Full Text]
- Hochhaus A, Reiter A, Saussele S, et al. Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. Blood. 2000;95: 62-66.[Abstract/Free Full Text]
- Paschka P, Muller M, Merx K, et al. Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon-alpha: low levels of residual disease are associated with continuous remission. Leukemia. 2003;17: 1687-1694.[CrossRef][Medline]
[Order article via Infotrieve]
- Hughes T, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349: 1423-1432.[Abstract/Free Full Text]
- Kantarjian HM, O'Brien S, Smith TL, et al. Treatment of Philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low-dose cytarabine. J Clin Oncol. 1999;17: 284-292.[Abstract/Free Full Text]
- Guilhot F, Chastang C, Michallet M, et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med. 1997;337: 223-229.[Abstract/Free Full Text]
- Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. N Engl J Med. 1994;330: 820-825.[Abstract/Free Full Text]
- Medina J, Kantarjian H, Talpaz, et al. Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. Cancer. 2003;98: 1905-1911.[CrossRef][Medline]
[Order article via Infotrieve]
- Hochhaus A, Lahaye T, Kreil S, et al. Interim analysis of imatinib treatment in 300 patients with chronic myelogenous leukemia (CML): evaluation of response and resistance [abstract]. Proceedings ASCO. 2002;21: 262a.
- Cortes J, O'Brien S, Talpaz M, et al. Clinical significance of molecular response in chronic myeloid leukemia (CML) after imatinib mesylate (Gleevec) therapy: low levels of residual disease predict for response duration [abstract]. Blood. 2003;102: 416a.
- Merx K, Muller MC, Kreil S, et al. Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha. Leukemia. 2002;16: 1579-1583.[CrossRef][Medline]
[Order article via Infotrieve]
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|
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|
|
|
|
|
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113(10):
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|
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[PDF]
|
|
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|
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112(10):
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|
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|
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|
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|
|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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[Full Text]
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|
|
|
|
|
|
|
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93(2):
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[Full Text]
[PDF]
|
|
|
|
|
|
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111(3):
1039 - 1043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Jin, Y. Tabe, S. Konoplev, Y. Xu, C. E. Leysath, H. Lu, S. Kimura, A. Ohsaka, M.-B. Rios, L. Calvert, et al.
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January 1, 2008;
7(1):
48 - 58.
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[PDF]
|
|
|
|
|
|
|
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January 1, 2008;
2008(1):
307 - 312.
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[Full Text]
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|
|
|
|
|
|
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November 15, 2007;
110(10):
3540 - 3546.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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13(20):
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|
|
|
|
|
|
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|
|
|
|
|
|
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110(8):
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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J. Clin. Oncol.,
October 1, 2007;
25(28):
4445 - 4451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Schiffer
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N. Engl. J. Med.,
July 19, 2007;
357(3):
258 - 265.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kantarjian, R. Pasquini, N. Hamerschlak, P. Rousselot, J. Holowiecki, S. Jootar, T. Robak, N. Khoroshko, T. Masszi, A. Skotnicki, et al.
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Blood,
June 15, 2007;
109(12):
5143 - 5150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Picard, K. Titier, G. Etienne, E. Teilhet, D. Ducint, M.-A. Bernard, R. Lassalle, G. Marit, J. Reiffers, B. Begaud, et al.
Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia
Blood,
April 15, 2007;
109(8):
3496 - 3499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Sinai, R. E. Berg, J. M. Haynie, M. J. Egorin, R. L. Ilaria Jr, and J. Forman
Imatinib Mesylate Inhibits Antigen-Specific Memory CD8 T Cell Responses In Vivo
J. Immunol.,
February 15, 2007;
178(4):
2028 - 2037.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ma, R. Tseng, M. Gorre, I. Jilani, M. Keating, H. Kantarjian, J. Cortes, S. O'Brien, F. Giles, and M. Albitar
Plasma RNA as an alternative to cells for monitoring molecular response in patients with chronic myeloid leukemia
Haematologica,
February 1, 2007;
92(2):
170 - 175.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Branford
Chronic Myeloid Leukemia: Molecular Monitoring in Clinical Practice
Hematology,
January 1, 2007;
2007(1):
376 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Steensma and R. E. Richard
Myeloproliferative disorders
ASH Self-Assessment Program,
January 1, 2007;
2007(1):
172 - 227.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. R. Luo, Z. Yang, A. Camuso, R. Smykla, K. McGlinchey, K. Fager, C. Flefleh, S. Castaneda, I. Inigo, D. Kan, et al.
Dasatinib (BMS-354825) Pharmacokinetics and Pharmacodynamic Biomarkers in Animal Models Predict Optimal Clinical Exposure
Clin. Cancer Res.,
December 1, 2006;
12(23):
7180 - 7186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Baccarani, G. Saglio, J. Goldman, A. Hochhaus, B. Simonsson, F. Appelbaum, J. Apperley, F. Cervantes, J. Cortes, M. Deininger, et al.
Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet
Blood,
September 15, 2006;
108(6):
1809 - 1820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi, G. Barosi, R. A. Mesa, F. Cervantes, H. J. Deeg, J. T. Reilly, S. Verstovsek, B. Dupriez, R. T. Silver, O. Odenike, et al.
International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT)
Blood,
September 1, 2006;
108(5):
1497 - 1503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Quintas-Cardama and J. E. Cortes
Chronic Myeloid Leukemia: Diagnosis and Treatment
Mayo Clin. Proc.,
July 1, 2006;
81(7):
973 - 988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kantarjian, F. Giles, L. Wunderle, K. Bhalla, S. O'Brien, B. Wassmann, C. Tanaka, P. Manley, P. Rae, W. Mietlowski, et al.
Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL.
N. Engl. J. Med.,
June 15, 2006;
354(24):
2542 - 2551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. L. Wang, J. W. Lee, E. Cesarman, D. K. Jin, and B. Csernus
Molecular Monitoring of Chronic Myelogenous Leukemia: Identification of the Most Suitable Internal Control Gene for Real-Time Quantification of BCR-ABL Transcripts
J. Mol. Diagn.,
May 1, 2006;
8(2):
231 - 239.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Koyama, S. Koschmieder, S. Tyagi, I. Portero-Robles, J. Chromic, S. Myloch, H. Nurnberger, T. Rossmanith, W.-K. Hofmann, D. Hoelzer, et al.
Inhibition of phosphotyrosine phosphatase 1B causes resistance in BCR-ABL-positive leukemia cells to the ABL kinase inhibitor STI571.
Clin. Cancer Res.,
April 1, 2006;
12(7 Pt 1):
2025 - 2031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Ault, H. Kantarjian, S. O'Brien, S. Faderl, M. Beran, M. B. Rios, C. Koller, F. Giles, M. Keating, M. Talpaz, et al.
Pregnancy Among Patients With Chronic Myeloid Leukemia Treated With Imatinib
J. Clin. Oncol.,
March 1, 2006;
24(7):
1204 - 1208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Mauro and R. T. Maziarz
Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia: When Should It Be Used?
Mayo Clin. Proc.,
March 1, 2006;
81(3):
404 - 416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Hughes
ABL Kinase Inhibitor Therapy for CML: Baseline Assessments and Response Monitoring
Hematology,
January 1, 2006;
2006(1):
211 - 218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chiaretti, A. Guarini, M. S. De Propris, S. Tavolaro, S. Intoppa, A. Vitale, S. Iacobelli, L. Elia, C. Ariola, J. Ritz, et al.
ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications
Blood,
January 1, 2006;
107(1):
197 - 204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kimura, H. Naito, H. Segawa, J. Kuroda, T. Yuasa, K. Sato, A. Yokota, Y. Kamitsuji, E. Kawata, E. Ashihara, et al.
NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia
Blood,
December 1, 2005;
106(12):
3948 - 3954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Hess, D. Bunjes, W. Siegert, R. Schwerdtfeger, G. Ledderose, B. Wassmann, G. Kobbe, M. Bornhauser, A. Hochhaus, A. J. Ullmann, et al.
Sustained Complete Molecular Remissions After Treatment With Imatinib-Mesylate in Patients With Failure After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia: Results of a Prospective Phase II Open-Label Multicenter Study
J. Clin. Oncol.,
October 20, 2005;
23(30):
7583 - 7593.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Golemovic, S. Verstovsek, F. Giles, J. Cortes, T. Manshouri, P. W. Manley, J. Mestan, M. Dugan, L. Alland, J. D. Griffin, et al.
AMN107, a Novel Aminopyrimidine Inhibitor of Bcr-Abl, Has In vitro Activity against Imatinib-Resistant Chronic Myeloid Leukemia
Clin. Cancer Res.,
July 1, 2005;
11(13):
4941 - 4947.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. C. Wolff, D. R. Veach, W. P. Tong, W. G. Bornmann, B. Clarkson, and R. L. Ilaria Jr
PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia
Blood,
May 15, 2005;
105(10):
3995 - 4003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cortes, M. Talpaz, S. O'Brien, D. Jones, R. Luthra, J. Shan, F. Giles, S. Faderl, S. Verstovsek, G. Garcia-Manero, et al.
Molecular Responses in Patients with Chronic Myelogenous Leukemia in Chronic Phase Treated with Imatinib Mesylate
Clin. Cancer Res.,
May 1, 2005;
11(9):
3425 - 3432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Dewar, A. C. Cambareri, A. C. W. Zannettino, B. L. Miller, K. V. Doherty, T. P. Hughes, and A. B. Lyons
Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib
Blood,
April 15, 2005;
105(8):
3127 - 3132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Quintas-Cardama, H. Kantarjian, M. Talpaz, S. O'Brien, G. Garcia-Manero, S. Verstovsek, M. B. Rios, K. Hayes, A. Glassman, B. N. Bekele, et al.
Imatinib mesylate therapy may overcome the poor prognostic significance of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia
Blood,
March 15, 2005;
105(6):
2281 - 2286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi, G. W. Dewald, M. L. Litzow, J. Cortes, M. J. Mauro, M. Talpaz, and H. M. Kantarjian
Chronic Myeloid Leukemia: Current Application of Cytogenetics and Molecular Testing for Diagnosis and Treatment
Mayo Clin. Proc.,
March 1, 2005;
80(3):
390 - 402.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. L. Ilaria Jr.
Pathobiology of Lymphoid and Myeloid Blast Crisis and Management Issues
Hematology,
January 1, 2005;
2005(1):
188 - 194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Cortes, S. O'Brien, and H. Kantarjian
Discontinuation of imatinib therapy after achieving a molecular response
Blood,
October 1, 2004;
104(7):
2204 - 2205.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Pardanani and A. Tefferi
Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders
Blood,
October 1, 2004;
104(7):
1931 - 1939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Kantarjian, J. E. Cortes, S. O'Brien, R. Luthra, F. Giles, S. Verstovsek, S. Faderl, D. Thomas, G. Garcia-Manero, M. B. Rios, et al.
Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-{alpha}
Blood,
October 1, 2004;
104(7):
1979 - 1988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Stone
Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach
Oncologist,
June 1, 2004;
9(3):
259 - 270.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. O'Brien, A. Tefferi, and P. Valent
Chronic Myelogenous Leukemia and Myeloproliferative Disease
Hematology,
January 1, 2004;
2004(1):
146 - 162.
[Abstract]
[Full Text]
[PDF]
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|
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Top
Abstract
Introduction
