Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia

J. Ochs, G. K. Rivera, B. H. Pollock, G. Buchanan, W. Crist, A. I. Freeman

Research output: Contribution to journalArticle

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Abstract

Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patiens with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term even-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial reduction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered.

Original languageEnglish (US)
Pages (from-to)1671-1677
Number of pages7
JournalCancer
Volume66
Issue number8
StatePublished - 1990

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Teniposide
Cytarabine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow
Pharmaceutical Preparations
Transplants
Controlled Hypotension
Complementary Therapies
Survivors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. / Ochs, J.; Rivera, G. K.; Pollock, B. H.; Buchanan, G.; Crist, W.; Freeman, A. I.

In: Cancer, Vol. 66, No. 8, 1990, p. 1671-1677.

Research output: Contribution to journalArticle

Ochs, J. ; Rivera, G. K. ; Pollock, B. H. ; Buchanan, G. ; Crist, W. ; Freeman, A. I. / Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. In: Cancer. 1990 ; Vol. 66, No. 8. pp. 1671-1677.
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abstract = "Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48{\%}) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patiens with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term even-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial reduction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered.",
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AU - Crist, W.

AU - Freeman, A. I.

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N2 - Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patiens with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term even-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial reduction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered.

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