Researchers from M.D. Anderson Cancer Center have reported that 6 of 10 patients with chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL) who were resistant to Gleevec (imatinib) were in complete molecular remission after an allogeneic stem cell transplant. The details of this study appeared in the August 15, 2006 issue of Blood.

Prior to the development of Gleevec, allogeneic stem cell transplantation was the treatment of choice for younger patients with newly diagnosed CML. However, since the advent of Gleevec very few patients receive a transplant prior to exposure to Gleevec. Gleevec is currently the treatment of choice for newly diagnosed patients with CML and is also routinely incorporated into combined therapy for Philadelphia chromosome positive ALL.

Some patients with CML and ALL become resistant to Gleevec, and resistance is usually associated with Bcr-Abl mutations. Several drugs have been developed which are effective for patients with Bcr-Able mutations. At the present time the only potentially curative approach to the treatment of Gleevec-resistant patients with CML and ALL is an allogeneic stem cell transplant. However, there is very little published data on the effectiveness of salvage transplants in Gleevec-resistant patients.

The current study evaluated the effectiveness of allogeneic stem cell transplantation in 9 patients with CML and one with Philadelphia chromosome positive ALL. Three of the CML patients were in chronic phase, 4 in accelerated phase and 2 in blastic phase. A myeloablative regimen of busulfan and cytoxan were used in 7 patients and 3 received reduced intensity fludarabine based regimens. Half the patients received stem cells from a related and half from an unrelated stem cell donor.

Complete molecular remission was achieved in 7 patients and 6 of these remain in remission. Three patients died of progressive disease: one was transplanted for ALL, one for accelerated phase of CML and one for blastic phase of CML. Two of the 3 patients transplanted with a reduced intensity regimen are alive and one has a complete molecular remission and one is still responding to therapy. Importantly, there were no treatment related deaths in this study.

Comments:  Although these are small numbers, these data suggest that allogeneic stem cell transplantation from a related or unrelated donor is effective salvage therapy for patients who fail Gleevec due to Bcr-Able mutations. There appeared to be success with both ablative and reduced intensity regimens, which means that older patients can be treated safely.

Reference: Jabbour E, Cortes Kantarjian HM, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia dn acute lymphocytic leukemia after Ccr-Abl kinase mutation-related failure. Blood. 2006;108:1421-1423.

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