Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia

Comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: A childrens cancer group report

David G. Tubergen, Gerald S. Gilchrist, Richard T. O'Brien, Peter Felix Coccia, Borland N. Sather, Mary J. Waskerwitz, G. Denman Hammond

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Abstract

Purpose: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. Patients and Methods: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. Results: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71 % EPS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P =.04). Conclusion: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.

Original languageEnglish (US)
Pages (from-to)520-526
Number of pages7
JournalJournal of Clinical Oncology
Volume11
Issue number3
DOIs
StatePublished - Jan 1 1993

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Central Nervous System Diseases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Radiation
Recurrence
Neoplasms
Therapeutics
Survival Rate
Disease-Free Survival
Maintenance
Life Tables
Berlin
Bone Marrow

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia : Comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: A childrens cancer group report. / Tubergen, David G.; Gilchrist, Gerald S.; O'Brien, Richard T.; Coccia, Peter Felix; Sather, Borland N.; Waskerwitz, Mary J.; Hammond, G. Denman.

In: Journal of Clinical Oncology, Vol. 11, No. 3, 01.01.1993, p. 520-526.

Research output: Contribution to journalArticle

Tubergen, David G. ; Gilchrist, Gerald S. ; O'Brien, Richard T. ; Coccia, Peter Felix ; Sather, Borland N. ; Waskerwitz, Mary J. ; Hammond, G. Denman. / Prevention of CNS disease in intermediate-risk acute lymphoblastic leukemia : Comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: A childrens cancer group report. In: Journal of Clinical Oncology. 1993 ; Vol. 11, No. 3. pp. 520-526.
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abstract = "Purpose: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. Patients and Methods: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. Results: Life-table estimates at 7 years show a 93{\%} and 91{\%} CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68{\%} and 64{\%}. The differences are not significant. Patients who received more intensive systemic therapy had a 94{\%} CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90{\%} and 80{\%} rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72{\%} and 71 {\%} EPS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61{\%} v 53{\%}) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P =.04). Conclusion: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.",
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T2 - Comparison of cranial radiation and intrathecal methotrexate and the importance of systemic therapy: A childrens cancer group report

AU - Tubergen, David G.

AU - Gilchrist, Gerald S.

AU - O'Brien, Richard T.

AU - Coccia, Peter Felix

AU - Sather, Borland N.

AU - Waskerwitz, Mary J.

AU - Hammond, G. Denman

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N2 - Purpose: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. Patients and Methods: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. Results: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71 % EPS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P =.04). Conclusion: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.

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