Meta-analysis and meta-regression analysis to compare the outcomes of chemotherapy for T- and B-lineage acute lymphoblastic leukemia (ALL): the use of dexamethasone, L-asparaginase, and/or methotrexate may improve the outcome of T-lineage ALL

Ann Hematol. 2016 Jan;95(1):87-92. doi: 10.1007/s00277-015-2510-0. Epub 2015 Sep 22.

Abstract

The effects of intensive regimens and the roles of drugs used might differ between T- and B-lineage acute lymphoblastic leukemia (ALL). We performed a literature search for clinical studies published from January 1998 to March 2013. Studies were eligible for inclusion in the analyses if they included more than 80 patients with adult ALL who were treated with a uniform regimen and compared T- and B-lineage ALL. Studies that included only adolescent or elderly patients were excluded. We identified 11 clinical studies, which included a total of 381 and 1366 patients with T- and B-lineage ALL, respectively, and performed meta-analyses using the selected studies. Nine studies included patients with Philadelphia chromosome-positive (Ph+) ALL. A meta-analysis using the random-effect model demonstrated superior survival in patients with T-lineage ALL compared to those with B-lineage ALL (hazard ratio 1.78, 95 % confidence interval 1.50-2.11), though the inclusion of patients with Ph+ ALL in B-lineage ALL must have influenced this result strongly. We performed meta-regression analyses, adjusted according to whether or not patients with Ph+ ALL were included in each study. Use of dexamethasone (Dex), higher dose of methotrexate (MTX), and higher dose of L-asparaginase (L-asp) were associated with a significant trend toward a better outcome in T-lineage ALL. A meta-regression analysis including Dex and the dose of L-asp or MTX together as covariates showed that these factors were independently significant. In conclusion, the use of Dex and high-dose L-asp or MTX may improve the outcome of T-lineage ALL. This hypothesis should be tested in a prospective study including only patients with Ph-negative ALL.

Keywords: Acute lymphoblastic leukemia; Dexamethasone; L-asparaginase; Meta-analysis; Methotrexate.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Asparaginase / administration & dosage
  • Clinical Trials as Topic / methods
  • Dexamethasone / administration & dosage
  • Humans
  • Methotrexate / administration & dosage
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prospective Studies
  • Regression Analysis
  • Treatment Outcome

Substances

  • Dexamethasone
  • Asparaginase
  • Methotrexate