Treatment of relapsed or refractory acute promyelocytic leukemia.
Current treatment for acute promyelocytic leukemia (APL) usually includes an induction phase with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy, followed by a consolidation phase of anthracycline-based chemotherapy and maintenance therapy with ATRA with or without low-dose chemotherapy for 1-2 years. This treatment strategy results in a high complete remission (CR) rate of about 90% and an overall survival rate of 80%. About 5%-30% of patients relapse, mainly patients with high-risk APL. Relapse at extramedullary sites, which occurs in approximately 3%-5% of patients, is emerging as a new issue. Treatment of relapsed/advanced APL includes the use of arsenic trioxide (ATO), gemtuzumab ozogamicin, and hematopoietic stem cell transplantation. ATO is currently the most effective therapeutic agent in relapsed APL. Hematopoietic stem cell transplantation is becoming a common strategy after achieving remission with ATO. Autologous transplant appears to have a more favorable outcome than allogeneic transplant in this setting, particularly when carried out during second remission, primarily because of significantly higher treatment-related mortality with allogeneic transplants. Allogeneic transplant, however, should be strongly considered for patients who remain molecularly positive. Future directions for APL therapy should include developing agents that can prevent relapse, particularly for high-risk patients. Other future treatment strategies may include use of ATO administered concomitantly or sequentially with chemotherapy, gemtuzumab or FLT-3 inhibitors that may obviate the need for autologous transplantation, and posttransplant maintenance perhaps with FLT-3 inhibitors.
Tallman
Martin S
MS
Northwestern University Feinberg School of Medicine, Division of Hematology-Oncology, Robert H. Lurie Comprehensive Cancer Center, 676 N St. Clair Street, Suite 850, Chicago, IL 60611, USA. m-tallman@northwestern.edu
D000617:Aminoglycosides / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000079982:Gemtuzumab; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010087:Oxides / Q000627:therapeutic use; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000079982:Gemtuzumab; D051941:fms-Like Tyrosine Kinase 3; D000077237:Arsenic Trioxide