scholarly journals 40 Long term comparison of relapse and overall survival in patients with chronic myeloid leukemia (CML) and acute lymphocytic leukemia (all) treated with unrelated or related donor allogeneic marrow/stem cell transplantation

2003 ◽  
Vol 9 (2) ◽  
pp. 76-77
Author(s):  
S.A. Al-Sukbun ◽  
E. Abella ◽  
R.D. Baynes ◽  
C. Karanes ◽  
R.D. Dansey
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Related Donor ◽  
Allogeneic Marrow ◽  
Marrow Stem Cell

Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation–related imatinib failure

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1421-1423 ◽  
Author(s):  
Elias Jabbour ◽  
Jorge Cortes ◽  
Hagop M. Kantarjian ◽  
Sergio Giralt ◽  
Dan Jones ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Acute Lymphocytic Leukemia ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Abl Kinase

Abstract Resistance to imatinib mesylate is an emerging problem in the treatment of chronic myeloid leukemia (CML), often associated with point mutations in the Bcr-Abl kinase domain. Outcome of patients with such mutations after allogeneic stem cell transplantation (Allo-SCT) is unknown. Ten imatinib-resistant patients with Bcr-Abl kinase mutations received a transplant: 9 had CML (3 in chronic phase, 4 in accelerated phase, and 2 in blast phase) and 1 had Philadelphia-positive acute lymphocytic leukemia (ALL). Patients harbored 9 different protein kinase mutations (T315I mutation, n = 2). Preparative regimens were ablative (n = 7) and nonablative (n = 3). All patients engrafted; there were no treatment-related deaths. Disease response was complete molecular (CMR; n = 7), major molecular (n = 2), and no response (n = 1). Three patients (mutations Q252H, E255K, and T315I) died of relapse after Allo-SCT. Seven patients are alive (6 in CMR) for a median of 19 months. Allo-SCT remains an important salvage option for patients who develop resistance to imatinib through Bcr-Abl mutations.

scholarly journals Estimating leukemia-free survival after allografting for chronic myeloid leukemia: a new method that takes into account patients who relapse and are restored to complete remission

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Charles Craddock ◽  
Richard M. Szydlo ◽  
John P. Klein ◽  
Francesco Dazzi ◽  
Eduardo Olavarria ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
New Method ◽  
Free Survival ◽  
Number Of Patients ◽  
Unrelated Donors

Abstract A significant number of patients who relapse after allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) will achieve sustained remissions after treatment with interferon-, second transplants, or donor lymphocyte infusions (DLI) from the original stem cell donor. Because leukemia-free survival (LFS) is at present defined as survival without evidence of relapse at any time posttransplant, patients who relapse but are then restored to complete remission are treated as failures when estimating LFS. We have established a new category of LFS, termed current LFS (CLFS), which we define as survival without evidence of leukemia at the time of most recent assessment. To gauge the contribution of treatment for relapse to the efficacy of allogeneic SCT in the management of CML in chronic phase, we compared conventional LFS and CLFS in 189 consecutive patients who underwent SCT over a 7-year period with a minimum follow-up of 3 years. Patients with sibling donors (n = 111) received cyclosporine and methotrexate as prophylaxis for graft versus host disease; patients with unrelated donors (n = 78) also received Campath-1G or 1H as intravenous T-cell depletion. The 5-year LFS defined conventionally was 36% (CI: 29% to 43%) versus a 5-year CLFS of 49% (CI: 36% to 62%). This new method of defining LFS confirms the view that appropriate “salvage” therapy, principally DLI, makes a major contribution to the capacity of allogeneic SCT to produce long-term LFS in patients who receive SCT for CML and emphasizes the importance of redefining LFS to take account of successful treatment of relapse.

scholarly journals Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

2016 ◽  
Vol 34 (20) ◽  
pp. 2333-2340 ◽  
Author(s):  
Jorge E. Cortes ◽  
Giuseppe Saglio ◽  
Hagop M. Kantarjian ◽  
Michele Baccarani ◽  
Jiří Mayer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pleural Effusion ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Phase Iii ◽  
Blast Phase ◽  
Once Daily ◽  
Study Results ◽  
Treatment Naïve

Purpose We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients and Methods Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). Results At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. Conclusion These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP.

Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3456-3462 ◽  
Author(s):  
Partow Kebriaei ◽  
Michelle A. Detry ◽  
Sergio Giralt ◽  
Antonio Carrasco-Yalan ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n =30), 1 antigen-mismatched related (n =4), or matched unrelated (n =30). With median follow-up of 7 years, overall survival (OS) and progression-free survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronic-phase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time.

Randomized Comparison of Primary Allogeneic Stem Cell Transplantation and Best Available Drug Treatment in Chronic Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 427-427 ◽  
Author(s):  
Rudiger Hehlmann ◽  
Markus Pfirrmann ◽  
Andreas Hochhaus ◽  
Martin C. Müller ◽  
Jörg Hasford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Drug Treatment ◽  
Treatment Strategy ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Line Treatment ◽  
Survival Curves ◽  
Related Donor

Abstract Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients (pts) with chronic myeloid leukemia (CML). This concept has been challenged by persisting transplantation mortality and improved drug therapy. In order to verify retrospective and observational results and to counsel pts and doctors about survival prospects with each treatment strategy, a randomized controlled trial was designed to compare primary HSCT and best available drug treatment in a cohort of 621 newly diagnosed CML pts in chronic phase. Assignment to treatment strategy was by eligibility for HSCT and genetic randomization according to availability of a matched related donor. Evaluation followed the intention to treat principle. 354 pts (62% male; median age 40 years, range 11–59) were eligible and randomized. 135 pts (38 %) had a matched related donor of which 123 (91%) received a transplant within a median of 10 months (range 2–106) from diagnosis. 4 pts died before scheduled transplantation, 8 pts withdrew consent. 219 pts (62%) had no related donor and received best available drug treatment. Of these, 97 pts (44%) received a matched unrelated donor (MUD) transplant in 1st chronic phase and were censored at the time of transplantation. As 1st line treatment after randomization pts received interferon alpha based therapy. In the course of the study a total of 197 pts were switched to imatinib after failure of interferon alpha. Currently 31 (57%) of 54 living pts of the drug treatment group receive imatinib or 2nd generation tyrosine kinase inhibitors (dasatinib n=2, nilotinib n=1). With a median observation time of 8.9 years (range 4.2–11.2) median survival of all 621 pts was 8.1 years. During the first 8 years after diagnosis survival curves of drug treated patients were superior to those of transplanted patients reflecting transplant-related mortality. Beyond 8 years survival curves were no longer distinct. 5 (10) year survival was 62% (53%) for transplanted and 73% (52%) for drug treated pts, in the low risk group 68% (59%) for transplanted and 85% (62%) for drug treated pts, respectively. Survival was superior for drug treated pts up to the cutpoint of survival curves at year 8 (p=0.041) and during the study period up to 11 years from diagnosis (p=0.049), particularly so in low risk pts (p=0.027 to cutpoint, p=0.032 overall). Significantly higher proportions of complete cytogenetic remissions (91% vs 61%, p=0.002) and of major molecular responses (ratio BCR-ABL/ABL <0.1%; 81% vs 45%, p=0.001) were found in the transplant group indicating higher levels of residual disease in the group receiving drug treatment. In summary, the general recommendation of HSCT as 1st line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first and a risk adapted strategy according to the individual disease and transplantation risks thereafter. HSCT remains an important treatment option in a risk adapted strategy on the basis of higher cytogenetic and molecular long term remission rates.

scholarly journals Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5697-5700 ◽  
Author(s):  
Franck Emmanuel Nicolini ◽  
Grzegorz W. Basak ◽  
Simona Soverini ◽  
Giovanni Martinelli ◽  
Michael J. Mauro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Blast Phase

Abstract T315I+ Philadelphia chromosome–positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABLT315I mutations. Median follow-up was 52 months from mutation detection and 26 months from transplantation. At transplantation, 51.5% of patients with chronic myeloid leukemia were in the chronic phase and 4.5% were in advanced phases. Median overall survival after transplantation was 10.3 months (range 5.7 months to not reached [ie, still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome–positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABLT315I mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors.

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