The Role of Donor Lymphocyte Infusion (DLI) and Imatinib Mesylate in the Treatment of Relapse after Allogenic Stem Cell Transplant for Chronic Myeloid Leukemia.

Abstract

During the period 1988 to 2004, 89 patients underwent allogeneic stem cell transplantation for chronic myeloid leukemia (CML). At the time of transplant 63 were in chronic phase (CP) 1, 3 in CP-2, 6 in accelerated phase and 11 in blast transformation. Eighty six patients who survived more than 2 weeks were evaluable for relapse of which 15 (17.4%) had a relapse. Of these 10 had a molecular relapse (defined by real-time quantitative reverse transcriptase-polymerase chain reaction [RQ-PCR]) while 5 had a hematological relapse. At the time of relapse, 9 patients (60%) were complete chimeras with no detectable recipient band on VNTR analysis, while 3 (20%) were mixed chimeras and 3 (20%) had no donor DNA. Two of this cohort of 15 patients was free of disease after reduction of immunosuppression. Escalating doses of DLI was given to 10 patients while 3 patients were primarily treated with Imatinib. Among the patients receiving DLI, 2 patients (20%) achieved molecular remission, 2 patients underwent a second BMT and one these two one is presently in molecular remission. Six patients did not respond to DLI and were started on Imatinib and 2 (33%) of these have achieved hematological and molecular remission and have only donor cells on VNTR analysis. Three patients were primarily treated with Imatinib and at a median duration of six months of treatment, 2 are in molecular remission while one patient has not shown a molecular response while continuing to remain in hematological remission. Imatinib was well tolerated in these patients at a dose of 400 mg/day with no significant side effects. The overall remission rates with DLI alone was 20% while the use of Imatinib either alone or after DLI failed, achieved remission in 4 out of 9 patients (44%) Two out of 3 patients with a mixed chimerism achieved complete donor chimerism after Imatinib therapy while 2 patients reverted from their mixed status to full donor chimerism after DLI. Some of the patients in relapse were still complete chimeras and remained so after achieving CR with Imatinib. This may be related to the fact that RQ-PCR is one log more sensitive than the Genescan used for chimerism analysis. Analysis of this small cohort of patients suggests that imatinib is superior to DLI for achieveing molecular remission in patients with CML who relapse after stem cell transplant. The role and sequence of treatment with imatinib mesylate or DLI in the management of relapse after allogeneic stem cell transplantation for CML needs to be defined with a randomized trial.Response to DLI/Imatinib following relapse post BMTTotal no. of Allogenic Transplants for CML89Evaluable for relapse86Total no. of Relapsed patients15Patients with DLI alone and in CR2/10(20%)Patients with imatinib alone with CR2/3 (66%)Patients with DLI failure and response with Imatinib2/6 (33%)Overall response with DLI/Imatinib6/15 (40%)