Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

Brian T. Hill, Kwang Woo Ahn, Zhen Huan Hu, Mahmoud Aljurf, Amer Beitinjaneh, Jean Yves Cahn, Jan Cerny, Mohamed A. Kharfan-Dabaja, Siddhartha Ganguly, Nilanjan Ghosh, Michael R. Grunwald, Yoshihiro Inamoto, Tamila Kindwall-Keller, Taiga Nishihori, Richard F. Olsson, Ayman Saad, Matthew Seftel, Sachiko Seo, Jeffrey Szer, Martin TallmanCelalettin Ustun, Peter H. Wiernik, Richard T. Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber

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Abstract

Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL.

Original languageEnglish (US)
Pages (from-to)581-586
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number3
DOIs
StatePublished - Mar 2018
Externally publishedYes

Keywords

  • Allogeneic transplantation
  • CLL
  • HLA

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    Hill, B. T., Ahn, K. W., Hu, Z. H., Aljurf, M., Beitinjaneh, A., Cahn, J. Y., Cerny, J., Kharfan-Dabaja, M. A., Ganguly, S., Ghosh, N., Grunwald, M. R., Inamoto, Y., Kindwall-Keller, T., Nishihori, T., Olsson, R. F., Saad, A., Seftel, M., Seo, S., Szer, J., ... Saber, W. (2018). Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia. Biology of Blood and Marrow Transplantation, 24(3), 581-586. https://doi.org/10.1016/j.bbmt.2017.10.015