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

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 Lindstrom, Juergen Finke, Jacob Passweg, Matthias Eder, Maciej Machaczka, Julio Delgado, William Krueger, Ludek Raida, Gerard SociePavel Jindra, Boris Afanasyev, Eva Wagner, Yves Chalandon, Anja Henseler, Stefan Schoenland, Nicolaus Kroeger, Johannes Schetelig, CLL Subcomm Chronic Malignancies W, European Soc Blood Marrow Transpla

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

Patients with chronic lymphocytic leukemia with del(17p) or del(11q) have poor long-term prognosis with targeted therapies. Conversely, this retrospective European Society for Blood and Marrow Transplantation registry study shows that young high cytogenetic risk responsive patients with human leukocyte antigen-matched donors have a high 8-year progression-free survival and low 2-year non-relapse mortality after allogeneic stem cell transplantation. This treatment then may compare favorably with targeted therapies for younger high cytogenetic risk patients.

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. (C) 2017 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)667-675.e2
Number of pages11
JournalClinical Lymphoma Myeloma & Leukemia
Volume17
Issue number10
DOIs
Publication statusPublished - Oct 2017

Keywords

  • del(17p)
  • HLA-matched donor
  • Kinase- and BCL2 inhibitor refractory
  • Non-relapse mortality
  • Risk factor analysis
  • MATCHED UNRELATED DONOR
  • MARROW TRANSPLANTATION
  • EUROPEAN-SOCIETY
  • FOLLOW-UP
  • RELAPSED CLL
  • IBRUTINIB
  • SURVIVAL
  • BLOOD
  • MULTICENTER
  • THERAPY

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