Response of children with high-risk acute lymphoblastie leukemia treated with and without cranial irradiation: A report from the Children's Cancer Group

James Nachman, Harland N. Sather, Joel M. Cherlow, Martha G. Sensel, Paul S. Gaynon, John N. Lukens, Lawrence Wolff, Michael E. Trigg

Research output: Contribution to journalArticle

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Abstract

Purpose: Intensified intrathecal (IT) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either IT methotrexate (MTX) and CRT or intensified IT MTX alone. Patients and Methods: Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count ≤ 50,000/μL or age ≤ 10 years, excluding those with lymphomatous features) who achieved an RER (≤ 25% marrow blasts on day 7) to induction therapy and locked CNS disease at diagnosis were randomized to receive systemic therapy with either IT MTX and CRT (regimen A, n = 317) or intensified IT MTX alone (regimen B, n = 319). Results: Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1% ± 4.0% (SD)and 70.4% ± 4.2% for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1% ± 3.4% and 75.0% ± 2.7% for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B. Conclusion: For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either IT MTX plus CRT or intensified IT MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified IT MTX may protect against late bone marrow relapse.

Original languageEnglish (US)
Pages (from-to)920-930
Number of pages11
JournalJournal of Clinical Oncology
Volume16
Issue number3
StatePublished - Mar 1998
Externally publishedYes

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Cranial Irradiation
Methotrexate
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Radiotherapy
Neoplasms
Disease-Free Survival
Bone Marrow
Recurrence
Drug Therapy
Therapeutics
Induction Chemotherapy
Central Nervous System Diseases
Berlin
Regimen B
Pediatrics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nachman, J., Sather, H. N., Cherlow, J. M., Sensel, M. G., Gaynon, P. S., Lukens, J. N., ... Trigg, M. E. (1998). Response of children with high-risk acute lymphoblastie leukemia treated with and without cranial irradiation: A report from the Children's Cancer Group. Journal of Clinical Oncology, 16(3), 920-930.

Response of children with high-risk acute lymphoblastie leukemia treated with and without cranial irradiation : A report from the Children's Cancer Group. / Nachman, James; Sather, Harland N.; Cherlow, Joel M.; Sensel, Martha G.; Gaynon, Paul S.; Lukens, John N.; Wolff, Lawrence; Trigg, Michael E.

In: Journal of Clinical Oncology, Vol. 16, No. 3, 03.1998, p. 920-930.

Research output: Contribution to journalArticle

Nachman, J, Sather, HN, Cherlow, JM, Sensel, MG, Gaynon, PS, Lukens, JN, Wolff, L & Trigg, ME 1998, 'Response of children with high-risk acute lymphoblastie leukemia treated with and without cranial irradiation: A report from the Children's Cancer Group', Journal of Clinical Oncology, vol. 16, no. 3, pp. 920-930.
Nachman, James ; Sather, Harland N. ; Cherlow, Joel M. ; Sensel, Martha G. ; Gaynon, Paul S. ; Lukens, John N. ; Wolff, Lawrence ; Trigg, Michael E. / Response of children with high-risk acute lymphoblastie leukemia treated with and without cranial irradiation : A report from the Children's Cancer Group. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 3. pp. 920-930.
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abstract = "Purpose: Intensified intrathecal (IT) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either IT methotrexate (MTX) and CRT or intensified IT MTX alone. Patients and Methods: Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count ≤ 50,000/μL or age ≤ 10 years, excluding those with lymphomatous features) who achieved an RER (≤ 25{\%} marrow blasts on day 7) to induction therapy and locked CNS disease at diagnosis were randomized to receive systemic therapy with either IT MTX and CRT (regimen A, n = 317) or intensified IT MTX alone (regimen B, n = 319). Results: Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1{\%} ± 4.0{\%} (SD)and 70.4{\%} ± 4.2{\%} for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1{\%} ± 3.4{\%} and 75.0{\%} ± 2.7{\%} for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B. Conclusion: For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either IT MTX plus CRT or intensified IT MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified IT MTX may protect against late bone marrow relapse.",
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T1 - Response of children with high-risk acute lymphoblastie leukemia treated with and without cranial irradiation

T2 - A report from the Children's Cancer Group

AU - Nachman, James

AU - Sather, Harland N.

AU - Cherlow, Joel M.

AU - Sensel, Martha G.

AU - Gaynon, Paul S.

AU - Lukens, John N.

AU - Wolff, Lawrence

AU - Trigg, Michael E.

PY - 1998/3

Y1 - 1998/3

N2 - Purpose: Intensified intrathecal (IT) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either IT methotrexate (MTX) and CRT or intensified IT MTX alone. Patients and Methods: Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count ≤ 50,000/μL or age ≤ 10 years, excluding those with lymphomatous features) who achieved an RER (≤ 25% marrow blasts on day 7) to induction therapy and locked CNS disease at diagnosis were randomized to receive systemic therapy with either IT MTX and CRT (regimen A, n = 317) or intensified IT MTX alone (regimen B, n = 319). Results: Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1% ± 4.0% (SD)and 70.4% ± 4.2% for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1% ± 3.4% and 75.0% ± 2.7% for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B. Conclusion: For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either IT MTX plus CRT or intensified IT MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified IT MTX may protect against late bone marrow relapse.

AB - Purpose: Intensified intrathecal (IT) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either IT methotrexate (MTX) and CRT or intensified IT MTX alone. Patients and Methods: Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count ≤ 50,000/μL or age ≤ 10 years, excluding those with lymphomatous features) who achieved an RER (≤ 25% marrow blasts on day 7) to induction therapy and locked CNS disease at diagnosis were randomized to receive systemic therapy with either IT MTX and CRT (regimen A, n = 317) or intensified IT MTX alone (regimen B, n = 319). Results: Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1% ± 4.0% (SD)and 70.4% ± 4.2% for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1% ± 3.4% and 75.0% ± 2.7% for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B. Conclusion: For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either IT MTX plus CRT or intensified IT MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified IT MTX may protect against late bone marrow relapse.

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