Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT.

Abstract

BACKGROUND:

Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population.

PATIENTS AND METHODS:

Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted.

RESULTS:

Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%).

CONCLUSION:

Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor.

• Authors: Michel van Gelder, Dimitris Ziagkos, Liesbeth de Wreede, Anja van Biezen, Peter Dreger, Martin Gramatzki, Matthias Stelljes, Niels Smedegaard Andersen, Nicolaas Schaap, Antonin Vitek, Dietrich Beelen, Vesa Lindström, Jürgen Finke, Jacob Passweg, Matthias Eder, Maciej Machaczka, Julio Delgado, William Krüger, Luděk Raida, Gerard Socié, Pavel Jindra, Boris Afanasyev, Eva Wagner, Yves Chalandon, Anja Henseler, Stefan Schoenland, Nicolaus Kröger, Johannes Schetelig, CLL Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 17 Issue 10 Pg. 667-675.e2 (10 2017) ISSN: 2152-2669 [Electronic] United States
• PMID: 28694085 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• HLA Antigens

Topics

• Adult
• Aged
• Chromosome Aberrations
• Female
• HLA Antigens
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Kaplan-Meier Estimate
• Leukemia, Lymphocytic, Chronic, B-Cell (diagnosis, genetics, mortality, therapy)
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• Risk Factors
• Tissue Donors
• Transplantation Conditioning (adverse effects, methods)
• Transplantation, Homologous
• Treatment Outcome