Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT

Abstract

This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versushost disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was

The changing scene of allogeneic stem cell transplantation for chronic myeloid leukemia—a report from the German Registry covering the period from 1998 to 2004

“…Further, in this analysis, SCT in CML was more frequently performed from unrelated than from related donors (55% vs. 45%), without any influence on survival in accordance to previous reports [13,14,24]. However, others suggested worsening of prognosis by unrelated SCT in subgroups of patients: An NMDP study described for those CML patients in chronic phase undergoing early transplantation in the first year from diagnosis a similar or only slightly inferior 5-year DFS after matched unrelated vs. matched sibling transplantation, while there was a substantially worse 5-year DFS after matched URD in case of delayed SCT.…”

“…Therefore, allo-SCT took a shift towards advanced disease or cases with imatinib resistance [11,12]. Reduced intensity conditioning (RIC) broadened transplantation strategies [13] and allowed the inclusion of patients with comorbidity, advanced disease, or higher age [14], who would have been excluded from SCT in former years.…”

The EBMT risk score

“…The score is valid independent of the pretreatment and holds even today with tyrosine kinase inhibitors as primary treatment. [13][14][15] Patients transplanted at an older age, in a more advanced disease stage, after a longer time interval from diagnosis with a donor other than an HLA identical sibling donor and with a female donor for a male recipient had uniformly a worse outcome compared with younger patients, transplanted still in first chronic phase within 1 year from diagnosis from an HLA identical sex-matched sibling donor.…”

Hematopoietic stem cell transplantation for childhood malignancies of myeloid origin

“…25 Several HSCT trials have attempted to lower toxicity in children by using approaches such as reduced-intensity conditioning (RIC), low-dose DLI, and so on. 26 The development of imatinib and subsequently other tyrosine kinase (TK) inhibitors that are successful at obtaining long-term cytogenetic response has changed therapeutic strategies for CML. However, TK inhibitors have not proven to be curative and HSCT still remains the only proven curative approach to children with CML.…”