Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group

Author:

Matloub Yousif1,Bostrom Bruce C.2,Hunger Stephen P.3,Stork Linda C.4,Angiolillo Anne5,Sather Harland6,La Mei6,Gastier-Foster Julie M.7,Heerema Nyla A.8,Sailer Scott9,Buckley Patrick J.10,Thomson Blythe11,Cole Catherine12,Nachman James B.13,Reaman Gregory14,Winick Naomi15,Carroll William L.16,Devidas Meenakshi17,Gaynon Paul S.18

Affiliation:

1. Division of Hematology-Oncology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH;

2. Children's Hospitals and Clinics of Minnesota, Minneapolis, MN;

3. The University of Colorado School of Medicine and the Children's Hospital, Aurora, CO;

4. Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR;

5. Children's National Medical Center, Washington, DC;

6. Operation Center, Children's Oncology Group, Arcadia, CA;

7. Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH;

8. Department of Pathology, The Ohio State University, Columbus, OH;

9. University of North Carolina at Chapel Hill, Chapel Hill, NC;

10. Duke University Medical Center, Durham, NC;

11. Hematology-Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA;

12. Princess Margaret Hospital for Children, Perth, Australia;

13. The University of Chicago Comer Children's Hospital, Chicago, IL;

14. Chair's Office, Children's Oncology Group, Bethesda, MD;

15. University of Texas Southwestern Medical Center, Dallas, TX;

16. New York University Cancer Institute, New York, NY;

17. Children's Oncology Group Statistics and Data Center, Gainesville, and University of Florida, Gainesville, FL; and

18. Division of Hematology-Oncology, Children's Hospital Los Angeles, Los Angeles, CA

Abstract

Abstract Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference38 articles.

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4. Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment.;Mastrangelo;Med Pediatr Oncol,1986

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