Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected].
OBJECTIVE
Treatment of childhood relapsed acute lymphoblastic leukemia (ALL) remains a significant challenge. The goal of the Children's Oncology Group (COG) AALL01P2 study was to develop a safe and active chemotherapy reinduction platform, which could be used to evaluate novel agents in future trials.


METHODS
One hundred twenty-four patients with ALL and first marrow relapse received three, 35-day blocks of reinduction chemotherapy: 69 with early relapse (ER; < 36 months from initial diagnosis) and 55 with late relapse (LR). Minimal residual disease (MRD) was measured by flow cytometry after each treatment block.


RESULTS
Second complete remission (CR2) rates at the end of block 1 in 117 assessable patients were 68% +/- 6% for ER (n = 63) and 96% +/- 3% for LR (n = 54; P < .0001). Five of seven patients with T-cell ALL (T-ALL) failed to achieve CR2. Among patients in CR2, MRD greater than 0.01% was detected at the end of block 1 in 75% +/- 7% of ER (n = 36) versus 51% +/- 8% of LR (n = 43; P = .0375) and 12-month event-free survival was 80% +/- 7% versus 58% +/- 7% in MRD-negative versus positive patients (P < .0005). Blocks 2 and 3 of therapy resulted in reduction of MRD burden in 40 of 56 patients who were MRD positive after block 1. Toxicity was acceptable during all three blocks with five deaths (4%) from infections.


CONCLUSIONS
The AALL01P2 regimen is a tolerable and active reinduction platform, suitable for testing in combination with novel agents in B-precursor ALL. Alternative strategies are needed for T-ALL. Serial MRD measurements were feasible and prognostic of outcome.
Raetz
Elizabeth A
EA
New York University School of Medicine, Hassenfeld Children's Center for Cancer and Blood Disorders, 160 E 32nd St, New York, NY 10016, USA. elizabeth.raetz@nyumc.org
Borowitz
Michael J
MJ
Devidas
Meenakshi
M
Linda
Stephen B
SB
Hunger
Stephen P
SP
Winick
Naomi J
NJ
Camitta
Bruce M
BM
Gaynon
Paul S
PS
Carroll
William L
WL
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D019046:Bone Marrow Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D017254:Leukemic Infiltration; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction
D003561:Cytarabine; D003907:Dexamethasone; D004317:Doxorubicin; D011241:Prednisone; D015255:Idarubicin