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

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 t...

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Published inBlood 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
LanguageEnglish
Published Washington, DC Elsevier Inc 17.03.2011
Americain Society of Hematology
American Society of Hematology
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Abstract 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.
AbstractList 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.
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.
Author Seibel, Nita L.
Devidas, Meenakshi
La, Mei
Gaynon, Paul S.
Hunger, Stephen P.
Freyer, David R.
Carroll, William L.
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  organization: New York University Cancer Institute, New York, NY
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  givenname: Paul S.
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Issue 11
Keywords Human
Cancerology
Treatment
Hematology
Lymphoproliferative syndrome
Intensity
Malignant hemopathy
Acute lymphocytic leukemia
Malignant tumor
Child
Survival
Cancer
Language English
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Snippet While intensification of therapy has improved event-free survival (EFS) and survival in newly diagnosed children with acute lymphoblastic leukemia (ALL),...
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SubjectTerms 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
Title Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group
URI https://dx.doi.org/10.1182/blood-2010-07-294678
https://www.ncbi.nlm.nih.gov/pubmed/21193696
https://search.proquest.com/docview/857816414
https://pubmed.ncbi.nlm.nih.gov/PMC3062307
Volume 117
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