TY - JOUR
T1 - All-trans retinoic acid in acute promyelocytic leukemia
T2 - Long-term outcome and prognostic factor analysis from the North American Intergroup protocol
AU - Tallman, Martin S.
AU - Andersen, Janet W.
AU - Schiffer, Charles A.
AU - Appelbaum, Frederick R.
AU - Feusner, James H.
AU - Woods, William G.
AU - Ogden, Angela
AU - Weinstein, Howard
AU - Shepherd, Lois
AU - Willman, Cheryl
AU - Bloomfield, Clara D.
AU - Rowe, Jacob M.
AU - Wiernik, Peter H.
N1 - Publisher Copyright:
© 2002 by The American Society of Hematology.
PY - 2002/12/15
Y1 - 2002/12/15
N2 - We previously reported a benefit for alltrans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American IntergroupAPL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) orATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was considered. However, female sex, classical M3 morphology (vs the microgranular variant [M3v]), and treatment-white blood cell count (WBC) interaction (ATRA/WBC below 2 × 109/L [2000/μL] best, DA/WBC above 2 × 109/L worst) were each significantly associated with improved DFS (P < .05). Treatment with ATRA, WBC below 2 × 109/L, and absence of bleeding disorder were each significantly associated with improved OS. Age more than 15 years, female sex, and treatment-morphology interaction (DA/M3v worst,ATRAbest regardless of morphology) were each significantly associated with improved DFS based on maintenance randomization. The improvement in outcome with ATRA in APL was maintained with long-term follow-up.
AB - We previously reported a benefit for alltrans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American IntergroupAPL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) orATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was considered. However, female sex, classical M3 morphology (vs the microgranular variant [M3v]), and treatment-white blood cell count (WBC) interaction (ATRA/WBC below 2 × 109/L [2000/μL] best, DA/WBC above 2 × 109/L worst) were each significantly associated with improved DFS (P < .05). Treatment with ATRA, WBC below 2 × 109/L, and absence of bleeding disorder were each significantly associated with improved OS. Age more than 15 years, female sex, and treatment-morphology interaction (DA/M3v worst,ATRAbest regardless of morphology) were each significantly associated with improved DFS based on maintenance randomization. The improvement in outcome with ATRA in APL was maintained with long-term follow-up.
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U2 - 10.1182/blood-2002-02-0632
DO - 10.1182/blood-2002-02-0632
M3 - Article
C2 - 12393590
AN - SCOPUS:0037115195
SN - 0006-4971
VL - 100
SP - 4298
EP - 4302
JO - Blood
JF - Blood
IS - 13
ER -