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. .

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 &lt; 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 &lt; .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.

Imatinib as Front-Line Treatment in Chronic Myelogenous Leukemia: How Important is the Achievement of Complete Cytogenetic Response after 3 Months?

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4271-4271
Author(s):  
Roberto Latagliata ◽  
Massimo Breccia ◽  
Ida Carmosino ◽  
Federico Vozella ◽  
Paola Volpicelli ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Risk Score ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Imatinib Treatment ◽  
Front Line ◽  
Prognostic Role ◽  
Complete Cytogenetic Response ◽  
Pre Treatment

Abstract Abstract 4271 The achievement of Complete Cytogenetic Response (CCyR) (Ph+ cells 0%) with Imatinib treatment still remains the most important objective in Chronic Myelogenous Leukemia (CML) patients. According to The European Leukemia NET guidelines, CCyR should be achieved within the 12th month of treatment while at 3 months of treatment the goal should be complete haematological response. To address the prognostic role of the early achievement of CCyR, we revised 108 chronic phase CML patients [M/F 57/51, median age 54.9 years, interquartile range (IR) 40.8 – 68.1] treated with front-line Imatinib at our Institution from June 2002 to June 2008 who had evaluable karyotype after 3 months of treatment. At onset, median WBC and PLT counts were 78.4 × 109/l (IR 34.0 – 135.9) and 399 × 109/l (IR 282 – 585), respectively. Sokal risk score was low in 52 patients (48.1%), intermediate in 49 (45.4%) and high in 7 (6.5%); a short pre-treatment phase (< 3 months) with Hydroxyurea was administered to 94/108 patients (87%). After 3 months of Imatinib treatment, 84 patients (77.7%) achieved CCyR while 24 patients (22.3%) still presented Ph+ metaphases (median value 40%, IR 20 - 80) at cytogenetic analysis. At univariate analysis, factors with a negative prognostic impact on achievement of CCyR at 3 months were palpable spleen enlargement (p=0.002), WBC count at onset > 100.0 × 109/l (p=0.01) and pre-treatment with Hydroxyurea (p=0.032); on the contrary, sex, age, Sokal risk score and PLT value did not appear to affect early CCyR achievement. Among the 84 patients in CCyR after 3 months, there were 10 failures during follow-up (6 cytogenetic relapses, 2 molecular relapses and 2 evolution to blastic phase); among the 24 patients who did not achieve early CCyR, there were 12 failures during follow-up (9 primary resistances and 3 cytogenetic relapses). The difference in the incidence of failures during follow-up in the 2 groups was highly significant (p<0.001). In conclusion, the achievement of CCyR at 3 months seems unrelated to traditional prognostic factors (Sokal); furthermore, in our experience it appears to have an important prognostic role, as patients not achieving it showed a significantly higher rate of failures during the follow-up. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 2873-2878 ◽  
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] &lt; 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 &lt; 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)

Complete Cytogenetic Response After 3 Months Is a Very Early Indicator of Good Response to Imatinib As Front-Line Treatment in Chronic Myelogenous Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3783-3783 ◽  
Author(s):  
Roberto Latagliata ◽  
Massimo Breccia ◽  
Ida Carmosino ◽  
Federico Vozella ◽  
Paola Volpicelli ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Risk Score ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Front Line ◽  
Prognostic Role ◽  
Complete Cytogenetic Response ◽  
Pre Treatment

Abstract Abstract 3783 The achievement of Complete Cytogenetic Response (CCyR, Ph+ cells 0%) with Imatinib (IM) treatment still remains a crucial objective in Chronic Myelogenous Leukemia (CML) patients. According to The European Leukemia NET guidelines, CCyR should be achieved within the 12th month of treatment. To address the incidence and prognostic role of a very early achievement of CCyR, we revised 150 chronic phase CML patients [M/F 75/75, median age 56.6 years, interquartile range (IR) 41.8 – 68.4] treated with front-line IM at our Institution from June 2002 to December 2010 who had evaluable karyotype after 3 months of treatment. At onset, median WBC and PLT counts were 75.9 × 109/l (IR 35.3 – 125.5) and 402 × 109/l (IR 281 – 592), respectively. Sokal risk score was low in 72 patients (48.2%), intermediate in 68 (44.8%) and high in 10 (7.0%); a short pre-treatment phase (< 3 months) with Hydroxyurea (HU) was administered to 132/150 patients (88.0%). Starting daily dose of IM was 400 mg in 133 patients (88.6%), 800 mg in 12 (8.0%) and 300 mg in 5 (3.4%). After 3 months of IM treatment, 118 patients (78.6%) achieved CCyR while 32 patients (21.4%) still presented Ph+ metaphases (< 33% 14 patients and ≥ 33% 18 patients) at cytogenetic analysis. At univariate analysis, factors with a negative prognostic impact on achievement of CCyR at 3 months were palpable spleen enlargement (p<0.001) and WBC count > 100.0 × 109/l at onset (p<0.001); on the contrary, sex, age > 65 years, Sokal risk score, PLT count > 500 × 109/l at onset and pre-treatment with HU did not appear to affect early CCyR achievement. Among the 118 patients in CCyR after 3 months, there were 12 failures (10.1%) during subsequent follow-up (2 suboptimal responses for molecular resistance, 7 cytogenetic relapses, 2 molecular relapses and 1 evolution to blastic phase); among the 32 patients who did not achieve early CCyR, there were 18 failures (56.2%) during subsequent follow-up (12 primary cytogenetic resistances and 6 cytogenetic relapses). The difference in the incidence of failures during follow-up in the 2 groups was highly significant (p<0.001). 5-year overall survival was 96.4% in patients achieving CCyR at 3 months and 92.1% in patients not achieving CCyR at 3 months (p=0.42); 5-year event-free survival was 83.3% in patients achieving CCyR at 3 months and 35.2% in patients not achieving CCyR at 3 months (p<0.0001). In conclusion, the achievement of CCyR at 3 months is a frequent result with IM treatment and seems unrelated to traditional prognostic factors (Sokal); furthermore, in our experience it appears to have an important prognostic role, as patients not achieving it show a significantly higher rate of failures during subsequent follow-up. Thus, the achievement of CCyR at 3 months could be a very early and useful indicator of excellent response to IM beyond ELN guidelines, making possible an early and effective identification of patients in whom more potent (but also more expensive) 2nd generation TKI are not needed. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Significance of Increasing Levels of Minimal Residual Disease in Patients With Philadelphia Chromosome–Positive Chronic Myelogenous Leukemia in Complete Cytogenetic Response

2009 ◽  
Vol 27 (22) ◽  
pp. 3659-3663 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jianqin Shan ◽  
Daniel Jones ◽  
Susan O'Brien ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Therapeutic Interventions ◽  
Molecular Response ◽  
Complete Cytogenetic Response

Purpose The aim of this study was to evaluate the clinical relevance of increases in quantitative polymerase chain reaction (QPCR) levels in patients with chronic myelogenous leukemia (CML) who are in complete cytogenetic response (CGCR) on therapy. Patients with Philadelphia chromosome (Ph)–positive CML receiving tyrosine kinase inhibitors (TKIs) are frequently monitored for response by QPCR studies for minimal molecular disease. The clinical significance of increasing levels of QPCR in patients in CGCR is uncertain. Patients and Methods One hundred sixteen patients in durable CGCR, and on imatinib therapy for at least 18 months, had increases in QPCR levels (documented at least twice consecutively) as defined by literature reports. These were further analyzed by the achievement of major molecular response (MMR) defined as QPCR ≤ 0.05%, as well as by the degree of increase in QPCR. Results Only 11 (9.5%) of 116 patients with increases in QPCR had CML progression; 10 of them were among 44 patients (23%) who either lost a MMR or never had a MMR, and had more than 1 log increase of QPCR. Conclusion Most patients with increases in QPCR remain in CGCR. Patients who lose a MMR or never achieve a MMR, and have more than 1 log increase of QPCR, should be monitored more closely, and may be evaluated for mutations of BCR-ABL kinase domain and considered for investigational therapeutic interventions.

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