Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Abstract

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.

• Authors: Aleksandar Radujkovic, Cesare Guglielmi, Stefania Bergantini, Simona Iacobelli, Anja van Biezen, Dragana Milojkovic, Alois Gratwohl, Antonius V M B Schattenberg, Leo F Verdonck, Dietger W Niederwieser, Theo de Witte, Nicolaus Kröger, Eduardo Olavarria, Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 21 Issue 7 Pg. 1230-6 (Jul 2015) ISSN: 1523-6536 [Electronic] United States
• PMID: 25797175 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunosuppressive Agents
• Myeloablative Agonists

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Chromosome Aberrations
• Chronic Disease
• Female
• Graft vs Host Disease (etiology, immunology, mortality, prevention & control)
• Graft vs Leukemia Effect
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (immunology, mortality, pathology, therapy)
• Lymphocyte Transfusion
• Male
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Prognosis
• Recurrence
• Retrospective Studies
• Sex Factors
• Siblings
• Survival Analysis
• Transplantation Conditioning
• Transplantation, Homologous
• Unrelated Donors