Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: A Pediatric Oncology Group report

J. H. Laver, Julio Barredo, M. Amylon, M. Schwenn, J. Kurtzberg, B. M. Camitta, J. Pullen, M. P. Link, M. Borowitz, Y. Ravindranath, S. B. Murphy, J. Shuster

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) post-induction. modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC > 50,000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186,000/mm3 and 200,000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs 7% (s.e. 3%) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.

Original languageEnglish
Pages (from-to)369-373
Number of pages5
JournalLeukemia
Volume14
Issue number3
StatePublished - Mar 22 2000
Externally publishedYes

Fingerprint

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Radiation Effects
Radiation
Pediatrics
Central Nervous System
Cytarabine
Disease-Free Survival
Cell Lineage
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Leukemia
Teniposide
Central Nervous System Agents
T-Lymphocytes
T-Cell Leukemia
Central Nervous System Diseases
Vincristine
Granulocyte Colony-Stimulating Factor
Drug Combinations
Therapeutics

Keywords

  • Childhood acute lymphoblastic leukemia
  • Cranial radiation
  • T cell leukemia

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Laver, J. H., Barredo, J., Amylon, M., Schwenn, M., Kurtzberg, J., Camitta, B. M., ... Shuster, J. (2000). Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: A Pediatric Oncology Group report. Leukemia, 14(3), 369-373.

Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia : A Pediatric Oncology Group report. / Laver, J. H.; Barredo, Julio; Amylon, M.; Schwenn, M.; Kurtzberg, J.; Camitta, B. M.; Pullen, J.; Link, M. P.; Borowitz, M.; Ravindranath, Y.; Murphy, S. B.; Shuster, J.

In: Leukemia, Vol. 14, No. 3, 22.03.2000, p. 369-373.

Research output: Contribution to journalArticle

Laver, JH, Barredo, J, Amylon, M, Schwenn, M, Kurtzberg, J, Camitta, BM, Pullen, J, Link, MP, Borowitz, M, Ravindranath, Y, Murphy, SB & Shuster, J 2000, 'Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: A Pediatric Oncology Group report', Leukemia, vol. 14, no. 3, pp. 369-373.
Laver, J. H. ; Barredo, Julio ; Amylon, M. ; Schwenn, M. ; Kurtzberg, J. ; Camitta, B. M. ; Pullen, J. ; Link, M. P. ; Borowitz, M. ; Ravindranath, Y. ; Murphy, S. B. ; Shuster, J. / Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia : A Pediatric Oncology Group report. In: Leukemia. 2000 ; Vol. 14, No. 3. pp. 369-373.
@article{c4b0bcfeba924530aae762827ef6743c,
title = "Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: A Pediatric Oncology Group report",
abstract = "Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) post-induction. modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC > 50,000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186,000/mm3 and 200,000/mm3, respectively. CNS involvement at diagnosis was seen in 16{\%} of the CRT+ and 23{\%} of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs non-irradiated groups (P = 0.46). The 3-year event-free survival was 65{\%} (s.e. 6{\%}) and 63{\%} (s.e. 4{\%}) for the non-irradiated vs the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18{\%} (s.e. 5{\%}) vs 7{\%} (s.e. 3{\%}) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.",
keywords = "Childhood acute lymphoblastic leukemia, Cranial radiation, T cell leukemia",
author = "Laver, {J. H.} and Julio Barredo and M. Amylon and M. Schwenn and J. Kurtzberg and Camitta, {B. M.} and J. Pullen and Link, {M. P.} and M. Borowitz and Y. Ravindranath and Murphy, {S. B.} and J. Shuster",
year = "2000",
month = "3",
day = "22",
language = "English",
volume = "14",
pages = "369--373",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia

T2 - A Pediatric Oncology Group report

AU - Laver, J. H.

AU - Barredo, Julio

AU - Amylon, M.

AU - Schwenn, M.

AU - Kurtzberg, J.

AU - Camitta, B. M.

AU - Pullen, J.

AU - Link, M. P.

AU - Borowitz, M.

AU - Ravindranath, Y.

AU - Murphy, S. B.

AU - Shuster, J.

PY - 2000/3/22

Y1 - 2000/3/22

N2 - Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) post-induction. modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC > 50,000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186,000/mm3 and 200,000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs 7% (s.e. 3%) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.

AB - Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) post-induction. modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC > 50,000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186,000/mm3 and 200,000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs 7% (s.e. 3%) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.

KW - Childhood acute lymphoblastic leukemia

KW - Cranial radiation

KW - T cell leukemia

UR - http://www.scopus.com/inward/record.url?scp=0034009371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034009371&partnerID=8YFLogxK

M3 - Article

C2 - 10720128

AN - SCOPUS:0034009371

VL - 14

SP - 369

EP - 373

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 3

ER -