Molecular and cytogenetic response of chronic myelogenous leukemia treated with imatinib mesylate: one institutional experience in Japan

2008 ◽  
Vol 88 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Yasuhito Nannya ◽  
Hiromitsu Yokota ◽  
Yumiko Sato ◽  
Go Yamamoto ◽  
Takashi Asai ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Institutional Experience

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 ◽  
Vol 101 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Interferon Α ◽  
Combination Regimens ◽  
Philadelphia Chromosome Positive

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.

scholarly journals Hematopathologic and cytogenetic findings in imatinib mesylate treated chronic myelogenous leukemia patients: 2.5 years' experience

2010 ◽  
Vol 67 (10) ◽  
pp. 802-806 ◽  
Author(s):  
Irena Cojbasic ◽  
Lana Macukanovic-Golubovic
Keyword(s):  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
Median Time ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Specific Activity ◽  
Chronic Phase ◽  
Previous Treatment ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia

Background/Aim. Imatinib mesylate, a tyrosine kinase inhibitor with specific activity against the breakpoint cluster region - Abelson murine leukemia (BCR-ABL) tyrosine kinase has been developed for treatment of chronic myelogenous leukemia (CML). Its hematologic and cytogenetic effects have been evaluated in a series of clinical trials. The aim of this study was to report hematologic and cytogenetic response in CML patients during the treatment with imatinib mesylate. Methods. A total of 21 patients were treated and observed from July 2006 to December 2008. The median time from CML diagnosis was no more than 12 months, so all the patients received previous treatment with hydroxyurea for which the median time was 3 months. The patients received imatinib mesylate in an effective oral dose of 400 to 800 mg daily, which was followed with peripheral blood counts, bone marrow examination, and cytogenetic studies at 6, 12, 18 and 24 months. Results. Complete hematologic responses were reported for 19 (90.48%) of 21 patients studied. Among 19 patients who had a response, 16 (86%) did so within 3 months. The best cytogenetic response rate at any time during the study treatment with imatinib mesylate, among 14 patients in which cytogenetic response evaluated was: complete cytogenetic response in 7 (50%) patients, partial cytogenetic response in 6 (42.9%) patients and minor cytogenetic response in 1 (7.1%) patient. No patients had progressed to accelerated or blastic phase. The most frequent adverse effects that seemed to be related to treatment with imatinib mesylate were edema and musculosceletal pain; overall, most were mild. Only one patient discontinued treatment because of hematologic toxic effects. Conclusion. The results obtained in this study confirm that imatinib mesylate induces a complete hematological and cytogenetic response in a high percentage of patients with chronic-phase CML.

Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4298-4305 ◽  
Author(s):  
Martine Gardembas ◽  
Philippe Rousselot ◽  
Michel Tulliez ◽  
Magda Vigier ◽  
Agnès Buzyn ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Kinase Domain ◽  
Myelogenous Leukemia ◽  
Tyrosine Kinase Domain ◽  
Phase 2 ◽  
Phase 2 Trial

AbstractIn chronic myelogenous leukemia (CML) imatinib mesylate has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr-abl fusion protein. Using this agent alone high rates of cytogenetic responses were recorded. However, several mechanisms of resistance have been described. In vitro studies examining the effects of imatinib mesylate plus cytarabine have shown synergistic antiproliferative effects of this combination. Thus, the CML French Group decided to perform a phase 2 trial testing a combination of imatinib mesylate and low-dose cytarabine in 30 previously untreated patients in chronic phase. Treatment was administered on 28-day cycles. Patients were treated continuously with imatinib mesylate orally at a dose of 400 mg daily. Cytarabine was given on days 15 to 28 of each cycle at an initial dose of 20 mg/m2/d via subcutaneous injection. Adverse events were frequently observed with grade 3 or 4 hematologic toxicities and nonhematologic toxicities in 53% (n = 16) and 23% (n = 7) of patients, respectively. The cumulative incidence of complete cytogenetic response (CCR) at 12 months was 83% and at 6 months 100% of the patients achieved complete hematologic response (CHR). We concluded that the combination was safe and promising given the rates of response. (Blood. 2003;102:4298-4305)

Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 473-475 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Standard Dose ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Poor Response ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Minor Response ◽  
Ph Reduction

We investigated whether increasing the dose of imatinib mesylate might overcome drug resistance in patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) whose disease manifests relapse or refractoriness to therapy. Fifty-four patients with Ph+ CML in chronic phase and with hematologic or cytogenetic resistance or relapse on imatinib mesylate therapy at 400 mg orally daily were treated with a higher dose of 400 mg orally twice daily (800 mg daily, 47 patients; or 600 mg daily increased from 300 mg daily, 7 patients). Among 20 patients treated for hematologic resistance or relapse, 13 (65%) achieved a complete (n = 9) or partial (n = 4) hematologic response, but only 1 had a cytogenetic partial response (Ph reduction from 100% to 10%) and 1 had a minor response (Ph reduction from 100% to 50%). Among 34 patients treated for cytogenetic resistance or relapse, 19 (56%) achieved a complete (n = 6) or partial (n = 7) cytogenetic response. We conclude that higher doses of imatinib mesylate may overcome disease-poor response to conventional doses and that this approach deserves further evaluation as frontline therapy for newly diagnosed CML.

Survival benefit with imatinib mesylate versus interferon-α–based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia

Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 1835-1840 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Daniel Jones ◽  
Francis Giles ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Survival Benefit ◽  
Survival Rates ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Interferon Α ◽  
Newly Diagnosed ◽  
The Impact

Abstract A survival benefit for imatinib mesylate versus interferon-α therapy could not be demonstrated in the randomized study in newly diagnosed Philadelphia chromosome (Ph)–positive chronic-phase chronic myelogenous leukemia (CML) due to the high rate of crossover (90%) from interferon-α to imatinib mesylate within a year of study entry. We compared survival in 279 patients with newly diagnosed CML treated with imatinib mesylate at our institution (2000-2004) to 650 patients treated with interferon-α (1982-1997). The complete cytogenetic response rates were 87% with imatinib mesylate and 28% with interferon-α (P < .001). The estimated 3-year survival rates were 96% with imatinib mesylate and 81% with interferon-α (P < .01). Survival rates with imatinib mesylate were significantly better than with interferon-α within each of the CML prognostic risks groups. By multivariate analysis, imatinib mesylate therapy was identified as an independent favorable prognostic factor, after accounting for the impact of pretreatment factors (hazard ratio, 0.44; P < .01). By landmark analysis at 12 months, survival within each cytogenetic response category was similar with imatinib mesylate or interferon-α, suggesting that the survival benefit of imatinib mesylate (versus interferon-α in newly diagnosed CML) is through improving cytogenetic response.

Hematopathologic and cytogenetic findings in imatinib mesylate–treated chronic myelogenous leukemia patients: 14 months' experience

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Rita M. Braziel ◽  
Teresa M. Launder ◽  
Brian J. Druker ◽  
Susan B. Olson ◽  
R. Ellen Magenis ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Treatment Interruption ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Cytogenetic Changes ◽  
Polymerase Chain

Abstract Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferon-alfa treatment, imatinib mesylate–treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription–polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate–treated CML patients.

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

2010 ◽  
Vol 138 (5-6) ◽  
pp. 305-308 ◽  
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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