Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group

• Published in: Blood Vol. 117; no. 11; pp. 3010 - 3015
• Main Authors: Freyer, David R., Devidas, Meenakshi, La, Mei, Carroll, William L., Gaynon, Paul S., Hunger, Stephen P., Seibel, Nita L.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 17.03.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cause of Death; Child; Child, Preschool; Clinical Trials and Observations; Cohort Studies; Hematologic and hematopoietic diseases; Humans; Infant; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - prevention & control; Recurrence; Survival Analysis; Treatment Outcome; Human; Cancerology; Treatment; Hematology; Lymphoproliferative syndrome; Intensity; Malignant hemopathy; Acute lymphocytic leukemia; Malignant tumor; Child; Survival; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-07-294678

While intensification of therapy has improved event-free survival (EFS) and survival in newly diagnosed children with acute lymphoblastic leukemia (ALL), postrelapse outcomes remain poor. It might be expected that patients relapsing after inferior initial therapy would have a higher retrieval rate than after superior therapy. In the Children's Oncology Group Study CCG-1961, significantly superior EFS and survival were achieved with an augmented (stronger) versus standard intensity regimen of postinduction intensification (PII) for children with newly diagnosed high-risk ALL and rapid day 7 marrow response (EFS/survival 81.2%/88.7% vs 71.7%/83.4%, respectively). This provided an opportunity to evaluate postrelapse survival (PRS) in 272 relapsed patients who had received randomly allocated initial treatment with augmented or standard intensity PII. As expected, PRS was worse for early versus late relapse, marrow versus extramedullary site, adolescent versus younger age and T versus B lineage. However, no difference in 3-year PRS was detected for having received augmented versus standard intensity PII (36.4% ± 5.7% vs 39.2% ± 4.1%; log rank P = .72). Similar findings were noted within subanalyses by timing and site of relapse, age, and immunophenotype. These findings provide insight into mechanisms of relapse in ALL, and are consistent with emergence of a resistant subclone that has acquired spontaneous mutations largely independent of initial therapy. This study is registered at www.clinicaltrials.gov as NCT00002812.