scholarly journals Persistent splenomegaly during imatinib therapy and the definition of complete hematological response in chronic myelogenous leukemia

2010 ◽  
pp. NA-NA
Author(s):  
Zdenek Racil ◽  
Hana Klamova ◽  
Jaroslava Voglova ◽  
Edgar Faber ◽  
Filip Razga ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Hematological Response ◽  
Definition Of ◽  
Complete Hematological Response

Chronic Myelogenous Leukemia Patients with Highly Nilotinib-Resistant BCR-ABL Mutations Demonstrate Similar Efficacy to Dasatinib, but Have a Higher Likelihood of Developing New Mutations in the Event of Clinical Resistance

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3755-3755
Author(s):  
Qian Jiang ◽  
Ya-Zhen Qin ◽  
Yue-Yun Lai ◽  
Bin Jiang ◽  
Hao Jiang ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Cytogenetic Response ◽  
Similar Efficacy ◽  
Myelogenous Leukemia ◽  
Mutation Status ◽  
Specific Mutation ◽  
Hematological Response ◽  
Clinical Resistance ◽  
Significant Difference ◽  
New Mutations

Abstract Abstract 3755 Objective: Assess the outcome of imatinib- and/or nilotinib-failure chronic myelogenous leukemia (CML) patients with pre-existing, highly nilotinib-resistant mutations (Y253H, E255K/V and F359V/C), during dasatinib therapy. Methods: Sixty-one CML patients who failed imatinib (n=44) or imatinib and nilotinib (n=17), including 20 in chronic phase (CP), 16 in accelerated phase (AP) and 25 in blast phase (BP), were switched to dasatinib, except for patients with highly dasatinib-resistant mutations (T315I/A, F317L/V/I/C and V299L). Patients were grouped into 3 cohorts: no mutation (n=22), no-specific mutation (any mutation except highly nilotinib-resistant mutations; n=15), or specific mutation (Y253H, E255K/V or F359V/C; n=24), according to baseline BCR-ABL mutation status. Cumulative incidence frequencies of hematological response (HR), complete hematological response (CHR), major cytogenetic response (MCR), complete cytogenetic response (CCR) and major molecular response (MMR) were compared. Probabilities of clinical resistance to dasatinib (according to European LeukemiaNet recommendations), progression-free survival (PFS) and overall survival (OS), and dynamics of BCR-ABL mutations during dasatinib therapy were also assessed. Results: Prior nilotinib was associated with a higher proportion of specific mutation versus no mutation (50.0% vs 13.6%, P=0.001) and non-specific mutation (50.0% vs 13.3%, P=0.02). Patients harboring specific mutation also had a higher frequency of advanced phase CML before dasatinib treatment than patients with no mutation (83.3% vs 50.0%, P=0.008), and a similar frequency to those with non-specific mutation (83.3% vs 66.7%, P=0.266). Response, PFS and OS rates, and follow-up duration were similar among the 3 cohorts by baseline mutation status, as shown in Table. Probability of clinical resistance to dasatinib in patients with specific mutation was not significantly different to those with no mutation (54.2% vs 77.3%, P=0.100) or non-specific mutation (54.2% vs 33.3%, P=0.204) despite that there was a significant difference between the cohort with no mutation and non-specific mutation (77.3% vs 33.3%, P=0.008). Among 32 patients who developed clinical resistance to dasatinib and were assessed for BCR-ABL mutation status, newly detectable mutations were identified in 14 patients and most frequently occurred in those already harboring specific mutation versus those with no mutation (76.9% vs 26.7%, P=0.008) and non-specific mutation (76.9% vs 0%, P=0.015) at baseline. T315I (9/14, 64.3%) was the most common newly acquired BCR-ABL mutation. Harboring specific mutation compared with other mutation states at baseline (76.9% vs 16.7%, P=0.001), and developing hematological resistance rather than cytogenetic resistance during dasatinib therapy (65.0% vs 8.1%, P=0.002), were identified as risk factors associated with the development of new mutations. Conclusions: Imatinib- and/or nilotinib-failure patients with highly nilotinib-resistant BCR-ABL mutations demonstrate similar efficacy to dasatinib as those with no or any other mutation. However, patients with highly nilotinib-resistant mutations had a higher likelihood of developing new mutations at the time of clinical resistance. More extensive studies are needed to assess the significance of various BCR-ABL mutations prior to and during tyrosine kinase inhibitor therapy for CML. Disclosures: No relevant conflicts of interest to declare.

Imatinib Mesylate Versus Allogeneic HSCT for Patients with Chronic Myelogenous Leukemia In Accelerated Phase: A Single Center Experience In China After a 9-Year Follow-up

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2347-2347
Author(s):  
Qian Jiang ◽  
Lan-Ping Xu ◽  
Dai-Hong Liu ◽  
Kaiyan Liu ◽  
Shan-Shan Chen ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Myelogenous Leukemia ◽  
Low Risk ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Intermediate Risk ◽  
Free Survival ◽  
Poor Risk ◽  
Risk Patients

Abstract Abstract 2347 The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the imatinib era in patients with chronic myelogenous leukemia (CML) in accelerated phase (AP) has not been evaluated due to few comparison study published. A prospective study was designed to compare the outcome of imatinib versus allo-HSCT for AP CML according to the World Health Organization (WHO) 2001 classification in our center (Registration Number: ChiCTR-TNC-10000955). In imatinib group, imatinib were given at an initial dose of 400 mg or 600 mg daily. In allo-HSCT group, the recommended treatment prior to transplantation was a short-term imatinib therapy less than 3 months. From April 2001 to September 2008, 132 patients were enrolled, 87 in imatinib group and 45 in allo-HSCT group, respectively, according to their intention. In allo-HSCT group, 19 patients performed transplant from a HLA-matched sibling donor, 23 from a HLA-mismatched sibling/haploidentical donor, and 3 from a HLA-mismatched unrelated donor. The end time of evaluation was April 2010. After a median follow-up of 45 months (range, 7–108 months) for 53 living patients on imatinib and 65 months (range, 18–108 months) for 38 living patients post allo-HSCT, imatinib was inferior to allo-HSCT in outcome, with the estimated 6-year event-free survival (EFS), overall survival (OS) and progression-free survival (PFS) rates of 39.2% vs 71.7% (P=0.035), 51.4% vs 83.3% (P=0.023), and 48.3% vs 95.2% (P=0.000), respectively. A multivariate analysis of the total population of 132 patients adding pretreatment characteristics and therapy (imatinib versus allo-HSCT) indicated that longer CML disease duration, pretreatment anemia and higher percentage of peripheral blasts were independent adverse prognostic factors for OS and PFS in common, imatinib therapy was only associated with shorter PFS. In order to analyze whether therapy play an important role in survival differences among patients with or without common pretreatment poor prognostic factors for OS and PFS, we categorized the entire cohort into low-risk (neither factor, n=40), intermediate-risk (either factor, n=59) or poor-risk (at least two factors, n=33). Therapy had no influence on the outcome in low-risk patients, with the estimated 6-year EFS, OS and PFS rates of 80.9% vs 80.7% (P=0.898), 100% vs 81.2% (P=0.114), and 85.2% vs 95.2% (P=0.365), in imatinib group vs allo-HSCT group, respectively. EFS and OS showed no difference by therapy in intermediate-risk patients, with the estimated 6-year EFS and OS rates of 47.1% vs 61.9% (P=0.788), and 61.3% vs 81.3% (P=0.773), in imatinib group vs allo-HSCT group, respectively. However more patients developed a relapse in advanced phase with imatinib compared to those with allo-HSCT, the estimated 6-year PFS rates were 55.7% vs 92.9% (P=0.047), respectively. The superiority of allo-HSCT was extremely significant in poor-risk patients, with the estimated 5-year EFS, OS and PFS rates of 9.3% vs 66.7% (P=0.034), 17.7% vs 100% (P=0.008) and 18.8% vs 100% (P=0.006), in imatinib group vs allo-HSCT group, respectively. We conclude that allo-HSCT is the first-line option for all patients with CML in AP; it is superior to imatinib with evident survival advantage for poor/intermediate-risk patients. However, the outcome of imatinib and allo-HSCT were equally good in low-risk patients with CML in AP. For such patients, it may also be advised that imatinib remains the primary option by carefully monitoring of MRD, and allo-HSCT may be considered if there is evidence of imatinib resistance. Disclosures: No relevant conflicts of interest to declare.

The Biology of Chronic Myelogenous Leukemia: Implications for Imatinib Therapy

2007 ◽  
Vol 44 ◽  
pp. 4-14 ◽  
Author(s):  
Ricardo H. Alvarez ◽  
Hagop Kantarjian ◽  
Jorge E. Cortes
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy

scholarly journals Long-term outcome following imatinib therapy for chronic myelogenous leukemia, with assessment of dosage and blood levels: the JALSG CML202 study

2012 ◽  
Vol 103 (6) ◽  
pp. 1071-1078 ◽  
Author(s):  
Kazunori Ohnishi ◽  
Chiaki Nakaseko ◽  
Jin Takeuchi ◽  
Shin Fujisawa ◽  
Tadashi Nagai ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Imatinib Therapy ◽  
Blood Levels ◽  
Term Outcome ◽  
Long Term Outcome
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