High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia

A Pediatric Oncology Group study

Yoddanapudi Ravindranath, C. Philip Steuber, Jeffrey Krischer, Curt I. Civin, Jonathan M Ducore, Roger Vega, Paul Pitel, Susumu Inoue, Ernst Bleher, Charles Sexauer, John Hutter, Teresa Vietti

Research output: Contribution to journalArticle

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Abstract

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4 followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%]v34%[SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/μL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children ≥ 2 years and those with WBCs ≥ 100,000/μL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.

Original languageEnglish (US)
Pages (from-to)572-580
Number of pages9
JournalJournal of Clinical Oncology
Volume9
Issue number4
StatePublished - 1991

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Cytarabine
Secondary Prevention
Acute Myeloid Leukemia
Pediatrics
Remission Induction
Disease-Free Survival
Viral Structural Proteins
Thioguanine
Azacitidine
Asparaginase
6-Mercaptopurine
Daunorubicin
Vincristine
Etoposide
Prednisone
Methotrexate
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ravindranath, Y., Philip Steuber, C., Krischer, J., Civin, C. I., Ducore, J. M., Vega, R., ... Vietti, T. (1991). High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: A Pediatric Oncology Group study. Journal of Clinical Oncology, 9(4), 572-580.

High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia : A Pediatric Oncology Group study. / Ravindranath, Yoddanapudi; Philip Steuber, C.; Krischer, Jeffrey; Civin, Curt I.; Ducore, Jonathan M; Vega, Roger; Pitel, Paul; Inoue, Susumu; Bleher, Ernst; Sexauer, Charles; Hutter, John; Vietti, Teresa.

In: Journal of Clinical Oncology, Vol. 9, No. 4, 1991, p. 572-580.

Research output: Contribution to journalArticle

Ravindranath, Y, Philip Steuber, C, Krischer, J, Civin, CI, Ducore, JM, Vega, R, Pitel, P, Inoue, S, Bleher, E, Sexauer, C, Hutter, J & Vietti, T 1991, 'High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: A Pediatric Oncology Group study', Journal of Clinical Oncology, vol. 9, no. 4, pp. 572-580.
Ravindranath, Yoddanapudi ; Philip Steuber, C. ; Krischer, Jeffrey ; Civin, Curt I. ; Ducore, Jonathan M ; Vega, Roger ; Pitel, Paul ; Inoue, Susumu ; Bleher, Ernst ; Sexauer, Charles ; Hutter, John ; Vietti, Teresa. / High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia : A Pediatric Oncology Group study. In: Journal of Clinical Oncology. 1991 ; Vol. 9, No. 4. pp. 572-580.
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abstract = "In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4 followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85{\%} [SE = 2{\%}] in each group), induction deaths (6.5{\%} v 7.0{\%}), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34{\%} [SE = 11{\%}] v 29{\%} [SE = 4{\%}]), and disease-free survival (DFS at 3 years, 42{\%} [SE = 14{\%}]v34{\%}[SE = 4{\%}]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/μL had significantly better outcome (EFS of 55{\%} [SE = 10{\%}] and 36{\%} [SE = 5{\%}] at 3 years, respectively) than children ≥ 2 years and those with WBCs ≥ 100,000/μL (EFS of 27{\%} [SE = 5{\%}] and 20{\%} [SE = 9{\%}] at 3 years, respectively.",
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T1 - High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia

T2 - A Pediatric Oncology Group study

AU - Ravindranath, Yoddanapudi

AU - Philip Steuber, C.

AU - Krischer, Jeffrey

AU - Civin, Curt I.

AU - Ducore, Jonathan M

AU - Vega, Roger

AU - Pitel, Paul

AU - Inoue, Susumu

AU - Bleher, Ernst

AU - Sexauer, Charles

AU - Hutter, John

AU - Vietti, Teresa

PY - 1991

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N2 - In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4 followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%]v34%[SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/μL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children ≥ 2 years and those with WBCs ≥ 100,000/μL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.

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