In this issue of Blood, Saussele and colleagues from the German CML study group present data obtained from an interim safety analysis of a prospective multiarm trial in which allogeneic stem cell transplantation was used up front in selected low-risk CML patients, up front in patients presenting with advanced disease, or as planned second-line therapy after imatinib failure.1 

Strict criteria for whom transplantation would be offered were developed, with most patients receiving pretransplantation imatinib. In this setting, excellent outcomes were achieved with a 3-year projected overall survival of 91% after allogeneic transplantation in chronic phase. In advanced disease, the projected overall survival was 59%. Remarkably, 88% achieved complete molecular remission and, when a matched-pair analysis was performed of transplanted CML patients in first chronic phase versus matched nontransplantation patients derived from the imatinib-responsive group, 3-year survivals were equivalent. The authors' conclusions are that allogeneic transplantation could become the preferred second-line option after imatinib failure for suitable patients with appropriate matched donors.

Despite this well-designed prospective study, the reality remains that second-generation tyrosine kinase inhibitors (TKI) have become standard therapy in the CML world. These agents may replace imatinib as first-line therapy,2  as recent data presented at the American Society of Hematology meetings demonstrated superiority of nilotinib over imatinib in newly diagnosed patients. An updated set of management recommendations from the European LeukemiaNet for patients with chronic-phase CML defined a more standard and acceptable treatment pathway that would allow patients who fail imatinib to proceed to second-generation TKI for treatment purposes. Transplantation was third line. Allogeneic stem cell transplantation is reserved for patients who do not respond to second-generation TKI, develop the T315I-resistant mutation, or experience progression to accelerated or blast phase of their malignancy.3  It was still recommended that patients with primary presentation of accelerated phase or blast crisis proceed to early transplantation, after appropriate disease reduction with TKI therapy. This approach is consistent with many current institutional algorithms trying to balance the potential of the drug therapy with the proven efficacy and mortality risk of allogeneic transplantation.4 

What is most exciting about the data presented is that the treatment-related mortality had fallen to less than 10%, compared with previous results of 26% obtained in prospective transplantation trials performed by the same study group.5  This same observation of a reduction in treatment-related mortality has also been reported in the Center for International Blood and Marrow Transplant Research analysis of the impact of pretransplantation imatinib mesylate on the outcome of stem cell transplantation for CML. In patients with chronic-phase CML, there was a 30% reduction in treatment-related mortality for patients exposed to imatinib compared with a historical control group of CML patients who underwent stem cell transplantation, prior to the availability of imatinib.6  If the risk of treatment-related mortality can be successfully reduced for patients with CML undergoing transplantation with low tumor burden after TKI exposure and prior to further disease progression, then we again will find strong collaborations between the cell therapists and the drug therapists in defining optimal management pathways for all CML patients.

Conflict-of-interest disclosure: The author declares no competing financial interests. ■

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