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RESEARCH PRODUCT

Hematopoietic Stem Cell Transplantation in APL

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description

The indication for hematopoietic stem cell transplant (HSCT) in APL has evolved historically from a widespread use in frontline therapy during the pre-ATRA era to a virtual rejection of this indication when patients are treated with modern treatments containing all-trans retinoic acid (ATRA), either in combination with chemotherapy, arsenic trioxide (ATO), or both. This indication has gradually been abandoned and explicitly rejected by the European LeukemiaNet recommendations. The high cure rate obtained using ATRA plus chemotherapy or ATRA plus ATO indicates that there is no role for HSCT for patients who achieve molecular remission at the end of consolidation. The HSCT in first complete remission has been relegated only for the very small fraction of patients with persistent MRD at the end of consolidation or for those who relapse. In the pre-ATO era, relapsed patients were usually treated with readministration of ATRA and chemotherapy as salvage therapy, generally containing high-dose cytarabine and an anthracycline, followed by further post-remission chemotherapy and/or HSCT. ATO-based regimens are presently regarded as the first option for treatment of relapsed APL. The selection of the most appropriate post-remission treatment option for patients in second CR, as well as the modality of HSCT when it is indicated, depends on a variety of prognostic and logistic variables, such as pretransplant molecular status, duration of first remission, age, and donor availability. There are no strict guidelines as regards the choice of autologous or allogeneic HSCT for relapsed patients in second CR. Autologous HSCT is associated with a lower transplantation-related mortality and is a reasonable option in patients without detectable MRD and prolonged duration of first CR (more than 1 year). In contrast, allogeneic HSCT involves a greater risk of nonrelapse mortality, but offers a potentially greater antileukemic activity due to the graft-versus-leukemia effect. Allogeneic HSCT could be, therefore, recommended in patients failing to achieve a second molecular remission and for those with short first CR duration.