Prediction of initial cytogenetic response for subsequent major and complete cytogenetic response to imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia

Abstract Fifty patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) in early chronic phase received imatinib mesylate, 400 mg orally daily. After a median follow-up of 9 months, 49 patients (98%) achieved a complete hematologic response and 45 patients (90%) achieved a major cytogenetic response, complete in 36 patients (72%). Compared with similar patients who received interferon-α with or without hydroxyurea or other interferon-α combination regimens, those receiving imatinib mesylate had higher incidences of complete and major (Ph < 35%) cytogenetic responses at 3 months (34% and 74% versus 1%-4% and 9%-24%, respectively), 6 months (52% and 80% versus 3%-7% and 11%-28%, respectively), and 9 months (60% and 77% versus 5%-11% and 14%-30%, respectively; P < .001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts × 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response.

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Prognostic factors associated with complete cytogenetic response in patients with chronic myelogenous leukemia on imatinib mesylate therapy

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1006305c ◽

2010 ◽

Vol 138 (5-6) ◽

pp. 305-308 ◽

Cited By ~ 2

Author(s):

Irena Cojbasic ◽

Lana Macukanovic-Golubovic

Keyword(s):

Bone Marrow ◽

Prognostic Factors ◽

Imatinib Mesylate ◽

Chronic Myelogenous Leukemia ◽

Philadelphia Chromosome ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

Base Line ◽

Complete Cytogenetic Response ◽

Pre Treatment

Introduction Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has proved to be most effective therapy of Philadelphia chromosome-positive chronic myelogenous leukemia. Imatinib induces complete haematological and cytogenetic response in high percentage of patients. Objective The aim of this study was to identify potential prognostic factors before beginning treatment with imatinib associated with complete cytogenetic response. Methods We analyzed 20 patients with newly diagnosed Philadelphia positive chronic myelogenous leukemia treated at our institution from June 2006 until May 2009. These patients were treated with imatinib mesylate in oral dose of 400 to 800 mg daily. Complete blood counts were performed every month, while serum chemistry evaluations and bone marrow evaluations including morphology and cytogenetics were performed every 6 months. Results Of the 20 patients analyzed in this study, 19 (95%) achieved complete haematologic response within three months. In all patients cytogenetic analyses were done and all have achieved absolute cytogenetic response. The best cytogenetic response rate at any time during study treatment among 20 patients was: complete cytogenetic response in 15, partial cytogenetic response in three and minor cytogenetic response in two patients. Among 11 observed base-line patients' characteristics five were independent predictors of a high rate of complete cytogenetic response; the absence of blasts and basophils in peripheral blood, the presence of less than 5 percent of bone marrow blasts, white blood cell count less than 10x109/L and the absence of splenomegaly (p<0.01). Conclusion Our results showed that some pre-treatment characteristics of patients might be the cause of differences in treatment outcome. On the basis of this analysis, we identified several pre-treatment patients' characteristics to be independent prognostic factors for achievement of complete cytogenetic response. .

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Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽

10.1182/blood.v99.10.3547 ◽

2002 ◽

Vol 99 (10) ◽

pp. 3547-3553 ◽

Cited By ~ 207

Author(s):

Hagop M. Kantarjian ◽

Jorge Cortes ◽

Susan O'Brien ◽

Francis J. Giles ◽

Maher Albitar ◽

...

Keyword(s):

Imatinib Mesylate ◽

Chronic Myelogenous Leukemia ◽

Response Rate ◽

Philadelphia Chromosome ◽

Response To Therapy ◽

Myelogenous Leukemia ◽

Control Group ◽

Blast Phase ◽

Molecular Abnormalities ◽

Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

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Outcome of patients with Philadelphia chromosome-positive chronic myelogenous leukemia post-imatinib mesylate failure

Cancer ◽

10.1002/cncr.22569 ◽

2007 ◽

Vol 109 (8) ◽

pp. 1556-1560 ◽

Cited By ~ 57

Author(s):

Hagop Kantarjian ◽

Susan O'Brien ◽

Moshe Talpaz ◽

Gautam Borthakur ◽

Farhad Ravandi ◽

...

Keyword(s):

Imatinib Mesylate ◽

Chronic Myelogenous Leukemia ◽

Philadelphia Chromosome ◽

Myelogenous Leukemia ◽

Philadelphia Chromosome Positive

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High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemia

Blood ◽

10.1182/blood-2003-11-3800 ◽

2004 ◽

Vol 103 (8) ◽

pp. 2873-2878 ◽

Cited By ~ 283

Author(s):

Hagop Kantarjian ◽

Moshe Talpaz ◽

Susan O'Brien ◽

Guillermo Garcia-Manero ◽

Srdan Verstovsek ◽

...

Keyword(s):

Imatinib Mesylate ◽

Quantitative Polymerase Chain Reaction ◽

Philadelphia Chromosome ◽

Chronic Phase ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

High Dose ◽

Molecular Response ◽

Newly Diagnosed ◽

Complete Cytogenetic Response

Abstract 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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