Curative strategies in acute promyelocytic leukemia.
Acute promyelocytic leukemia (APL) was initially described as a distinct clinical entity in 1957, one year before the first meeting of the American Society of Hematology. With routine administration of all-trans retinoic acid (ATRA) combined with chemotherapy in the early 1990s and arsenic trioxide (ATO) in the late 1990s, cure can now be expected in the majority of both newly diagnosed and relapsed patients. ATRA with anthracycline-based chemotherapy for induction and consolidation followed by ATRA plus low-dose chemotherapy maintenance is currently the standard of care for newly diagnosed patients. Early institution of ATRA before the diagnosis is confirmed by genetics and aggressive blood product support are important to reduce induction mortality, which remains approximately 10% among patients entered on clinical trials, but is certainly higher when all patients are considered. The relapse rate among high-risk patients is approximately 20%, and new strategies include administration of intensified anthracyclines, intermediate- or high-dose ara-C in either induction or consolidation, or ATO as early consolidation. Central nervous system (CNS) prophylaxis for such patients and those with relapsed disease may be important to prevent the development of extramedullary disease. New therapeutic strategies have focused on minimizing chemotherapy and administering ATRA plus ATO as initial therapy. Recent studies suggest that patients who are molecularly negative after intensive consolidation may not benefit from maintenance therapy. Most exciting is the combination of ATRA and ATO, given with minimal chemotherapy only for leukocytosis, which is a very effective new strategy for patients who are unable to tolerate anthracyclines or older adults and soon may replace conventional therapy for many patients. Patients with relapsed disease do well with ATO followed by autologous hematopoietic stem cell transplantation.
Tallman
Martin S
MS
Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611-2927, USA. m-tallman@northwestern.edu
Altman
Jessica K
JK
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D018572:Disease-Free Survival; D006131:Growth Inhibitors / Q000627:therapeutic use; D049673:History, 20th Century; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000266:history; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D010087:Oxides / Q000627:therapeutic use; D014212:Tretinoin / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001152:Arsenicals; D006131:Growth Inhibitors; D010087:Oxides; D003561:Cytarabine; D014212:Tretinoin; D000077237:Arsenic Trioxide; D003630:Daunorubicin