The role of autologous transplantation for acute myeloid leukemia in first and second remission.
Since 1986, the University of California San Francisco has developed novel approaches to autologous transplantation for acute myeloid leukemia (AML). Strategies have included intensive preparative regimens using busulfan and etoposide, and evolving strategies for pre-transplant consolidation and stem cell collection. Treatment-related mortality has been low (<5%), and after problems with slow engraftment and extended mucosal and skin toxicity in initial studies using 4-hydroperoxycyclophosphamide (4-HC)-purged bone marrow, peripheral blood autologous stem cell transplantation (ASCT) has been well tolerated even in older patients. In particular, careful attention to avoiding neurotoxicity associated with the use of high-dose cytarabine has limited dropout rates. Long-term event-free survival (EFS) has been excellent in first remission (CR1) cytogenetically favorable groups, particularly with post-transplant treatment for acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA; EFS 88%). ASCT in advanced disease showed overall long-term EFS of 44%; patients with APL in second remission achieved long-term EFS of 64%. Even among those failing primary induction, after remission induction with an alternative regimen, EFS was 61%. ASCT appears to be a treatment of choice for those in APL CR2, and offers some curative potential for AML CR2. The role of ASCT for those in CR1 is less clear, in part because high dropout rates in large randomized studies complicates interpretation of those studies. New directions for ASCT in the treatment of AML should focus on improving therapy, including calibrated intensification of induction regimens using plasma-kinetics targeting of dosages and the development and incorporation of immunotherapies into consolidation regimens.
Linker
Charles
C
Department of Medicine, University of California, San Francisco Cancer Center, 400 Parnassus Avenue, Room A-502, San Francisco, CA 94143, USA. linkerc@medicine.ucsf.edu
D000208:Acute Disease; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000235:genetics / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000628:therapy*; D012074:Remission Induction; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous