High‐dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude total therapy study X

Minnie Abromowitch, Judith Ochs, Ching‐Hon ‐H Pui, David Kalwinsky, Gaston K. Rivera, Diane Fairclough, A. Thomas Look, H. Omar Hustu, Sharon B. Murphy, William E. Evans, Gary V. Dahl, W. Paul Bowman

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Abstract

High‐dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard‐risk ALL: a leukocyte count < 100 × 109/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone‐vin‐cristine‐asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow‐up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalMedical and Pediatric Oncology
Volume16
Issue number5
DOIs
StatePublished - 1988

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Cranial Irradiation
6-Mercaptopurine
Central Nervous System
Teniposide
Therapeutics
Remission Induction
Drug Therapy
B-Cell Antigen Receptors
Cytarabine
Leukocyte Count
Doxorubicin
Cyclophosphamide
Sheep
Erythrocytes
Recurrence

Keywords

  • chemotherapy
  • complete remission
  • cranial irradiation
  • survival

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Cancer Research

Cite this

High‐dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia : St. Jude total therapy study X. / Abromowitch, Minnie; Ochs, Judith; Pui, Ching‐Hon ‐H; Kalwinsky, David; Rivera, Gaston K.; Fairclough, Diane; Look, A. Thomas; Hustu, H. Omar; Murphy, Sharon B.; Evans, William E.; Dahl, Gary V.; Bowman, W. Paul.

In: Medical and Pediatric Oncology, Vol. 16, No. 5, 1988, p. 297-303.

Research output: Contribution to journalArticle

Abromowitch, M, Ochs, J, Pui, CHH, Kalwinsky, D, Rivera, GK, Fairclough, D, Look, AT, Hustu, HO, Murphy, SB, Evans, WE, Dahl, GV & Bowman, WP 1988, 'High‐dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude total therapy study X', Medical and Pediatric Oncology, vol. 16, no. 5, pp. 297-303. https://doi.org/10.1002/mpo.2950160502
Abromowitch, Minnie ; Ochs, Judith ; Pui, Ching‐Hon ‐H ; Kalwinsky, David ; Rivera, Gaston K. ; Fairclough, Diane ; Look, A. Thomas ; Hustu, H. Omar ; Murphy, Sharon B. ; Evans, William E. ; Dahl, Gary V. ; Bowman, W. Paul. / High‐dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia : St. Jude total therapy study X. In: Medical and Pediatric Oncology. 1988 ; Vol. 16, No. 5. pp. 297-303.
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abstract = "High‐dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard‐risk ALL: a leukocyte count < 100 × 109/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone‐vin‐cristine‐asparaginase induced complete remissions in 95{\%} of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow‐up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67{\%} of the patients receiving HDMTX and 56{\%} of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.",
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AU - Look, A. Thomas

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