A Retrospective Survey of Imatinib Mesylate Treatment for Chronic Myeloid Leukemia in a Northern France Region.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4800-4800
Author(s):  
Selim Corm ◽  
Ariane Leroyer ◽  
Mathieu Wemeau ◽  
Bruno Bregman ◽  
Abderrahim Oukessou ◽  
...  
Keyword(s):  
Survival Rate ◽  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Real Life ◽  
Chronic Phase ◽  
Disease Stage ◽  
Northern France ◽  
Advanced Phase

Abstract Objective: To describe the use and results of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) in the Nord-Pas de Calais Region in Northern France (~ 4 millions inhabitants). Methods: we identified all IM treated patients (pts) within the population of all confirmed diagnosis of CML occurred during the period 1985–2004. IM resistance (haematological and cytogenetic imatinib failure and suboptimal response) was evaluated according to the European LeukemiaNet consensus. Results: 302 pts (38.6% of the global cohort of diagnosis) were included in this retrospective study. If we consider new diagnosis occurred after Januar 1st 2001, 163 pts (90.6%) have been treated by IM. At the initiation of IM: 18 pts (6%) were in advanced phase (accelerated and blastic), 245 pts (81,1%) in chronic phase (CP) (with Ph+ metaphases > 35%), 35 (11,6%) had major cytogenetic response (MCyR) obtained with interferon (IFN) or bone marrow transplantation (BMT). Four pts (1,3%) had an unknown status. The percentage of alive pts at the last update (December 31th 2005) according to the disease stage at initiation of treatment is given in the table 1.In the sample of 245 CP pts, 139 (56.7%) had been previously treated by IFN, the median CML duration prior to IM was 4.7 months [0–174], the median IM treatment duration was 31.3 months [0.5–72.3] and the median follow-up after IM initiation was 36 month [5.2–72.3]. 214 pts (87.30%) were alive at the last update with 169 (79%) still on IM and 161 (75.2%) on IM as monotherapy. The median and mean IM daily doses of alive pts are 400 mg and 409.5 mg, respectively. Seventeen pts (6.9%) stopped IM for intolerance. The haematological and cytogenetic follow-up was informative for 206 CP pts (84.1%): MCyR 155 pts (75.2%) and CCyR 144 pts (69.9%). IM resistance occurred in 73 (35.4%) of these 206 evaluable pts, including 23 (11.1%) accelerations and blastic transformations. In the subgroup of IM resistant pts 47 (64.4%) have increased their IM posology. The mean of the maximum daily dose in the resistant subgroup was 607.5 mg (median 600 mg). BCR-ABL kinase domain mutations were found in 15 (20.5%) pts amoung IM resistant population. The estimated 5-years survival rate of the CP pts is 81.3%. Previous treatment by IFN doesn’t influence significantly the survival, nor the duration of the disease before IM initiation, even if we found a trend for a better survival when this period was inferior to 6 months (5 years survival rate 90.4% vs 77.5%, p=0.16). BMT was performed for 31 pts (10.3%) including 19 pts (6.3%) after the initiation of IM therapy. Conclusion: these real life observations show the large use of IM in the last years and its great impact on the management and the survival of CML pts. IM resistance occurs in 1/3 of pts but the disease duration prior to IM is heterogeneous. An increase of IM dose has been tried in most IM resistant pts. The response to the different therapy adaptations is under study and will be presented. The vast majority of pts are still on IM therapy at the last update. Table 1

scholarly journals Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy

Cancer ◽  
2012 ◽  
Vol 118 (12) ◽  
pp. 3116-3122 ◽  
Author(s):  
Hagop Kantarjian ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
Stefan Faderl ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Interferon Alpha ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Interferon Alpha Therapy ◽  
Long Term Follow Up ◽  
Alpha Therapy

Stem cell transplantation for chronic myeloid leukemia in children

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1224-1231 ◽  
Author(s):  
Kate Cwynarski ◽  
Irene A. G. Roberts ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Ronald Brand ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Advanced Phase

Abstract Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome–positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P = .05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P = .001; LFS HR, 1.8; 95% CI, 1.2-2.6; P = .003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P = .006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P = .003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors.

Progression of Chronic Myeloid Leukemia to Blast Crisis During Treatment With Imatinib Mesylate

2004 ◽  
Vol 128 (9) ◽  
pp. 980-985
Author(s):  
Yin Xu ◽  
Andrea E. Wahner ◽  
Phuong L. Nguyen
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Imatinib Therapy

Abstract Context.—Previous investigators have reported discrepancies between hematologic, marrow morphologic, and cytogenetic responses to imatinib mesylate among patients with chronic myeloid leukemia (CML). In addition to disease refractoriness, rare instances of disease progression from chronic phase to blast crisis during imatinib therapy have recently been anecdotally reported. Objectives.—To describe the clinicopathologic features of 3 patients with CML who rapidly progressed from chronic phase to blast crisis while taking imatinib and to perform a review of the literature. Design.—Morphologic, immunophenotypic, and cytogenetic analyses were performed on the 3 patients at the time of initial diagnosis, during imatinib therapy, and at blast crisis. Results.—The 3 patients were men, aged 39, 42, and 43 years. Two had been treated with hydroxyurea for 16 and 21 months before imatinib therapy, while 1 was started on a regimen of imatinib following diagnosis. Despite a hematologic response in all 3 patients, none of them achieved cytogenetic remission, and all progressed to blast crisis at 7 to 10 months of imatinib therapy. Blood findings during blast transformation were heterogeneous, including normal blood morphologic findings in 1 patient, leukocytosis with circulating blasts and basophilia in 1, and marked pancytopenia in 1. All 3 marrow specimens demonstrated moderate to marked diffuse reticulin fibrosis with more than 20% blasts. Clonal cytogenetic evolution was evident in 2 of the 3 patients and included an extra Philadelphia chromosome in both. All 3 patients underwent allogeneic bone marrow transplantation. One was alive with no evidence of disease at 14 month follow-up, while 2 had residual disease after bone marrow transplantation and died of complications at 4 and 5 months after transplantation. Conclusions.—Blood data did not always reflect marrow status. Therefore, bone marrow follow-up is critical for monitoring of response. Our findings suggest that significant progression of marrow reticulin fibrosis during imatinib therapy can be an indicator for a return or progression of CML and, in some patients with CML, imatinib may promote cytogenetic clonal evolution, resulting in a poor response to treatment.

Sustained Responses and Resistance to Imatinib Mesylate in the First 173 Chronic Myeloid Leukemia Patients Accrued by the SCREEN Multicenter Study: First Interim Report.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4276-4276
Author(s):  
Paolo Vigneri ◽  
Fabio Stagno ◽  
Stefania Stella ◽  
Alessandra Cupri ◽  
Michele Massimino ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Molecular Response ◽  
Primary Resistance ◽  
Secondary Resistance

Abstract Abstract 4276 Introduction Imatinib mesylate (IM) has shown unprecedented effectiveness in the treatment of Chronic Myeloid Leukemia (CML) patients (pts) in the chronic phase of the disease. As most of the data concerning the efficacy of the drug derive either from a single sponsored trial or from single institution reports, we decided to accrue all CML pts diagnosed in the Italian region of Sicily to the observational SCREEN (Siciliy CML Regional Enterprise) study, to evaluate the hematological, cytogenetic and molecular responses of this unselected population to IM. Patients and Methods Although the study is still ongoing, 173 consecutive CML pts have been enrolled between January 2005 and June 2009 (cutoff time for the first interim analysis) by one of the 12 institutions involved. Each center was responsible for the diagnosis, treatment (IM 400 mg qd) and follow-up of the pts accrued, while all molecular analyses were centralized in Catania. Median follow-up time was 31 months. Eleven pts (6.3%) are currently off study. Results Pts characteristics were as follows: 95 males (54.9%) and 78 females (45.1%) were enrolled with a median age of 53 years (range 24-90). Eighty-nine pts (51.4%) were low Sokal risk, 62 (35.8%) were intermediate risk and 22 (12.8%) were high risk. Nine pts (5.2%) displayed additional chromosomal abnormalities. Median leukocyte counts (1×109L) were 67.6 (range 3.4-718), median hemoglobin (g/L) was 122 (range 75-170) while median platelet counts (1×109L) were 317 (range 67-2620). Cumulative incidences of complete hematologic response (CHR) and complete cytogenetic response (CCyR) were 98.3% and 85% respectively, while 59.2% of pts obtained a major molecular response (MMR). At 54 months, estimated overall survival was 95.6%. Estimated progression free survival (accounting for all pts that failed IM according to the European Leukemia Net criteria) was 75.1%. Thirty pts (17.3%) presented resistance to IM, either because of failure to obtain a satisfactory response (primary resistance, 21 pts) or because of loss of previously obtained responses (secondary resistance, 9 pts). Thirty-three pts (19%) presented a suboptimal response, 8 because of failure to achieve a CCyR by 12 months of therapy and the remaining 25 because of lack of a MMR after 18 months of IM. Only 3 pts (1.7%) were intolerant to IM. Interestingly, the median amount of BCR-ABL transcript at diagnosis (measured according to the International standardized Scale) displayed by pts that failed IM or achieved a suboptimal response (106.5IS) was significantly higher than that of pts obtaining an optimal response (61.9 IS p=0.0031). Conclusions IM is a highly effective and well-tolerated treatment for most chronic phase CML pts, producing high rates of CHR and CCyR. Approximately 60% of cases will also achieve a MMR. 35-40% of pts will either fail IM or obtain only partially satisfying results (suboptimal response). High levels of BCR-ABL transcript at diagnosis might allow a rapid identification of this less responsive pt population. Disclosures: No relevant conflicts of interest to declare.

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