Three decades of transplantation for chronic myeloid leukemia: what have we learned?

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 755-763 ◽  
Author(s):  
Jiří Pavlů ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Jane F. Apperley

Abstract Last year marked 30 years of hematopoietic stem cell transplantation as a curative treatment of chronic myeloid leukemia (CML). Initially studies used stem cells from identical twins but techniques rapidly developed to use cells first from HLA-identical siblings and later unrelated donors. During the 1990s CML became the most frequent indication for allogeneic transplantation worldwide. This, together with the relative biologic homogeneity of CML in chronic phase, its responsiveness to graft-versus-leukemia effect and the ability to monitor low level residual disease placed CML at the forefront of research into different strategies of stem cell transplantation. The introduction of BCR-ABL1 tyrosine kinase inhibitors during the last decade resulted in long-term disease control in the majority of patients with CML. In those who fail to respond and/or develop intolerance to these agents, transplantation remains an effective therapeutic solution. The combination of tyrosine kinase inhibitors with transplantation is an exciting new strategy and it provides inspiration for similar approaches in other malignancies.

Author(s):  
ELİFCAN ALADAĞ KARAKULAK ◽  
İBRAHİM CELALETTİN HAZNEDAROĞLU

Background: With an annual incidence of 1-2 in a million, Ph*(+) chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disease that makes myeloid neoplastic cells breed out of control. This BCR-ABL (+) myeloproliferative disease makes up about 15-20% of all leukemia cases in adults. CML is seen more in males than females, with a rate of three to two. However, it does not show difference in prevalence in terms of age. CML consists of three clinical phases. The first one is the chronic phase, defined by rising white blood cell levels and also by myeloid proliferation and bone marrow maturation. While this phase does not exhibit complications, in diagnosis, it composes most of the patients. The second phase is the accelerated phase, which the disease progresses onto if it is not treated or does not respond to treatment. This time usually takes about three years. The third phase is the blastic phase. The chronic phase can still progress onto the next two phases within the first 2 years, with a rate of 10%. In the following years, the possibility increases by a 15-20% each year. Tyrosine kinase inhibitors (TKI) are the revolutionary drugs for the management of disease course in CML. Methods: The aim of this review is to assess current approaches to CML patient’s follow-up and treatment with TKI. The CML and TKI literature search was made in PubMed, Web of Science, Scopus with particular focus on the randomized clinical trials, recommendations, guidelines and expert opinions. Results: In managing CML, various treatment methods have been utilized for many decades. Prior to the development of tyrosine kinase inhibitors (TKI), interferon alpha was the primary tool, which was then complemented by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was actually successful in slowing the disease down in the long term and curing up to a 50% of the patients. Then the coming of imatinib era opened up different treatment perspectives. For the patients resistant or intolerant to the imatinib, second and third generation TKIs are successfully used in distinct CML disease states. Conclusion: The survival benefits of TKI including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib for the CML patients are outstanding. TKI-related adverse events could impact on the clinical course especially in long-term drug administrations. Current aim for the CML disease management in TKI era is to provide age- and sex-matched normal life duration to the CML patients. Keywords: Chronic, myeloid, leukemia, tyrosine, kinase, inhibitors


Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3641-3647 ◽  
Author(s):  
Elias Jabbour ◽  
Jorge Cortes ◽  
Fabio P. S. Santos ◽  
Dan Jones ◽  
Susan O'Brien ◽  
...  

Abstract Hematopoietic stem cell transplantation (HSCT) is effective therapy for patients with chronic myelogenous leukemia (CML) but is now mostly indicated for patients who develop resistance to tyrosine kinase inhibitors (TKIs), which can be associated with point mutations in BCR-ABL1. We reviewed the outcomes of imatinib-resistant CML patients (chronic phase, n = 34; accelerated phase [AP], n = 9; and blast phase [BP], n = 4) who underwent HSCT and had BCR-ABL1 sequencing. Mutations were found in 19 patients (40%); 15 of 19 had advanced CML (AP + BP + second chronic phase). Patients with mutations were more likely to transform to AP/BP at time of imatinib failure (69% vs 35%, P = .03). Forty-two patients (89%) responded to HSCT: 32 (68%) had at least a major molecular response. The 2-year event-free survival was 36% and 58% (P = .05) for the mutant and nonmutant groups, respectively; and the 2-year overall survival was 44% and 76% (P = .02), respectively. HSCT is an important salvage option for TKI-resistant patients with or without BCR-ABL1 mutations. Patients with mutations were more likely to develop advanced disease and had worse outcomes after HSCT. HSCT should be considered early for patients deemed to have a low probability of responding to second-generation TKI.


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