Intensified induction chemotherapy in adult acute myeloid leukemia followed by high-dose chemotherapy and autologous peripheral blood stem cell transplantation: an Eastern Cooperative Oncology Group trial (E4995).
The feasibility of intensified therapy in adults < 61-years-old with de novo acute myeloid leukemia (AML) was evaluated by adding high-dose cytarabine (HDAC) to conventional induction therapy and in post-remission therapy prior to peripheral blood stem cell transplantation (PBSCT). Patients were treated with conventional induction therapy (daunorubicin days 1-3 and cytarabine days 1-7), followed by HDAC (2 gm/M2) every 12 h ( x 6) on days 8-10. Patients in complete remission (CR) with HLA-matched siblings were assigned to allogeneic PBSCT; the others received two courses of HDAC (3 gm/M2 every 12 h on days 1, 3, and 5) given 1 month apart. Peripheral blood stem cells were then harvested and infused after high-dose chemotherapy. Of 62 eligible, evaluable patients, 47 (76%) achieved CR. The mortality rate was 10% (6 patients); no deaths occurred during the two post-remission courses of HDAC. Fifteen patients were assigned to allogeneic PBSCT and 32 to autologous PBSCT. All surviving patients have been followed for more than 4 years. Including all patients scheduled to receive autoPBSCT in an intent-to-treat analysis, after a median 5-year follow-up the current, non-actuarial, four-year event-free and overall survival was 47% and 47%, respectively. Intensified induction therapy was associated with more toxicity than conventional induction therapy, and the CR rate did not improve. Nevertheless, intensive post-remission therapy was well tolerated, no treatment-related mortality occurred with autologous PBSCT, and disease-free survival and overall survival were lengthy.
Cassileth
Peter A
PA
University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA. pcassile@med.miami.edu
Lee
Sandra J
SJ
Litzow
Mark R
MR
Miller
Kenneth B
KB
Stadtmauer
Edward A
EA
Tallman
Martin S
MS
Lazarus
Hillard M
HM
Bennett
John M
JM
Paietta
Elisabeth
E
Dewald
Gordon W
GW
Rowe
Jacob M
JM
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D012074:Remission Induction; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D003561:Cytarabine; D003630:Daunorubicin