Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia

Abstract

Disease relapse is a major cause of treatment failure after reduced-intensity allografts and while donor lymphocyte infusions (DLIs) can be effective salvage therapy they are associated with severe graft-versus-host disease (GVHD) when administered early after transplantation. We have therefore examined whether imatinib mesylate can delay relapse and postpone the requirement for DLI in 22 patients with chronic myeloid leukemia (CML) allografted using a reduced-intensity regimen. Imatinib was commenced on day + 35 and continued until 1 year after transplantation. Posttransplantation imatinib was well tolerated and abolished the risk of relapse during this period. Twenty-one patients completed 11 months of imatinib therapy, 15 of whom subsequently relapsed and received DLI. Ten patients to date have achieved molecular remission after DLI. Adjunctive targeted therapy allows the kinetics of disease relapse after a reduced-intensity allograft to be manipulated and represents a novel strategy by which outcome may be improved in patients who undergo transplantation for CML and other leukemias.

Prophylactic impact of imatinib administration after allogeneic stem cell transplantation on the incidence and severity of chronic graft versus host disease in patients with Philadelphia chromosome-positive leukemia

“…This might be the reason why no cGVHD was observed in a post-SCT imatinib trial for prevention of disease progression. 8 Cumulative incidences Abbreviations: GVHD, graft-versus-host disease; SCT, stem cell transplantation. *P-value o0.05 was considered significant.…”

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

“…Also, the application of tyrosine kinase inhibitors (TKIs) of the first [29][30][31][32] or second generation [33] as preemptive strategy in the post-transplant period deserves further attention.…”

Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML

“…One such approach might be the adjunctive use of a drug such as azacitidine with activity against residual host leukaemic blasts to manipulate the kinetics of disease relapse and postpone or eliminate the requirement for DLI. 93 The future of RIC allogeneic SCT in AML The advent of reduced-intensity preparative regimens has transformed the landscape of allogeneic transplantation for AML in less than a decade. Therefore, there is now a case for a prospective comparison of outcome after RIC and myeloablative conditioning regimens in younger patients with AML-particularly those aged between 35 and 50 whose TRM we know to be unacceptably high.…”