Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia

G. K. Rivera, W. E. Evans, D. K. Kalwinsky, J. Mirro, J. Ochs, L. W. Dow, M. Abromowitch, C. H. Pui, G. V. Dahl, A. T. Look

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combination of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distension, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.

Original languageEnglish (US)
Pages (from-to)201-206
Number of pages6
JournalJournal of Clinical Oncology
Volume3
Issue number2
DOIs
StatePublished - Jan 1 1985

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Teniposide
Therapeutics
Asparaginase
Leucovorin
Cytarabine
Vincristine
Prednisone
Pharmaceutical Preparations
Abdominal Pain
Disease-Free Survival
Weight Loss
Diarrhea
Leukemia
Clinical Trials
Hemorrhage
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rivera, G. K., Evans, W. E., Kalwinsky, D. K., Mirro, J., Ochs, J., Dow, L. W., ... Look, A. T. (1985). Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia. Journal of Clinical Oncology, 3(2), 201-206. https://doi.org/10.1200/JCO.1985.3.2.201

Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia. / Rivera, G. K.; Evans, W. E.; Kalwinsky, D. K.; Mirro, J.; Ochs, J.; Dow, L. W.; Abromowitch, M.; Pui, C. H.; Dahl, G. V.; Look, A. T.

In: Journal of Clinical Oncology, Vol. 3, No. 2, 01.01.1985, p. 201-206.

Research output: Contribution to journalArticle

Rivera, GK, Evans, WE, Kalwinsky, DK, Mirro, J, Ochs, J, Dow, LW, Abromowitch, M, Pui, CH, Dahl, GV & Look, AT 1985, 'Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia', Journal of Clinical Oncology, vol. 3, no. 2, pp. 201-206. https://doi.org/10.1200/JCO.1985.3.2.201
Rivera, G. K. ; Evans, W. E. ; Kalwinsky, D. K. ; Mirro, J. ; Ochs, J. ; Dow, L. W. ; Abromowitch, M. ; Pui, C. H. ; Dahl, G. V. ; Look, A. T. / Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia. In: Journal of Clinical Oncology. 1985 ; Vol. 3, No. 2. pp. 201-206.
@article{4170ebd761f04792ae1c5c61b085e71a,
title = "Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia",
abstract = "In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combination of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distension, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.",
author = "Rivera, {G. K.} and Evans, {W. E.} and Kalwinsky, {D. K.} and J. Mirro and J. Ochs and Dow, {L. W.} and M. Abromowitch and Pui, {C. H.} and Dahl, {G. V.} and Look, {A. T.}",
year = "1985",
month = "1",
day = "1",
doi = "10.1200/JCO.1985.3.2.201",
language = "English (US)",
volume = "3",
pages = "201--206",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "2",

}

TY - JOUR

T1 - Unexpectedly severe toxicity from intensive early treatment of childhood lymphoblastic leukemia

AU - Rivera, G. K.

AU - Evans, W. E.

AU - Kalwinsky, D. K.

AU - Mirro, J.

AU - Ochs, J.

AU - Dow, L. W.

AU - Abromowitch, M.

AU - Pui, C. H.

AU - Dahl, G. V.

AU - Look, A. T.

PY - 1985/1/1

Y1 - 1985/1/1

N2 - In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combination of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distension, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.

AB - In early 1984, we treated 13 consecutive patients with acute lymphoblastic leukemia (ALL) using an induction regimen of rapidly rotated combination of prednisone, vincristine, asparaginase, teniposide (VM-26), cytosine arabinoside, and high-dose methotrexate (MTX) followed by leucovorin rescue. The intent of this clinical trial, designated Total Therapy Study XI, is to test the hypothesis that greater initial leukemia cell kill will decrease opportunities for the development of drug-resistant mutants, with resultant improvement in the length of disease-free survival. Five patients experienced life-threatening gastrointestinal toxicity within three weeks of the start of treatment. One died. Three other patients had severe abdominal pain, abdominal distension, diarrhea, and weight loss, but not gastrointestinal bleeding. In the remaining five patients, toxicity was rapidly reversible, and each child was able to complete the planned course of chemotherapy. The study was then amended to switch high-dose MTX from the induction phase to the consolidation phase, allowing at least one week for mucosal recovery. Among the next 28 patients who were treated, none showed evidence of severe gastrointestinal toxicity. Patients now receive high-dose MTX alone as consolidation therapy and are tolerating it adequately. Drug timing should be examined critically when intensified multiple-agent regimens are being devised for initial treatment of ALL.

UR - http://www.scopus.com/inward/record.url?scp=0021989040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021989040&partnerID=8YFLogxK

U2 - 10.1200/JCO.1985.3.2.201

DO - 10.1200/JCO.1985.3.2.201

M3 - Article

C2 - 3918144

AN - SCOPUS:0021989040

VL - 3

SP - 201

EP - 206

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 2

ER -