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 Tallman & 8 others Celalettin Ustun, Peter H. Wiernik, Richard Maziarz, Matt Kalaycio, Edwin Alyea, Uday Popat, Ronald Sobecks, Wael Saber

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hematopoietic Stem Cell Transplantation
B-Cell Chronic Lymphocytic Leukemia
Transplants
Leukemia
Transplantation
Tissue Donors
T-Lymphocytes
Unrelated Donors
Chromosome Deletion
Neoplasm Antigens
Hematologic Neoplasms
Therapeutics
Major Histocompatibility Complex
Disease-Free Survival
B-Lymphocytes
Bone Marrow
Alleles
Survival
Incidence
Research

Keywords

  • Allogeneic transplantation
  • CLL
  • HLA

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia. / Hill, Brian T.; Ahn, Kwang Woo; Hu, Zhen Huan; Aljurf, Mahmoud; Beitinjaneh, Amer; Cahn, Jean Yves; Cerny, Jan; Kharfan-Dabaja, Mohamed A.; Ganguly, Siddhartha; Ghosh, Nilanjan; Grunwald, Michael R.; Inamoto, Yoshihiro; Kindwall-Keller, Tamila; Nishihori, Taiga; Olsson, Richard F.; Saad, Ayman; Seftel, Matthew; Seo, Sachiko; Szer, Jeffrey; Tallman, Martin; Ustun, Celalettin; Wiernik, Peter H.; Maziarz, Richard; Kalaycio, Matt; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Saber, Wael.

In: Biology of Blood and Marrow Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Hill, BT, Ahn, KW, Hu, ZH, Aljurf, M, Beitinjaneh, A, Cahn, JY, Cerny, J, Kharfan-Dabaja, MA, Ganguly, S, Ghosh, N, Grunwald, MR, Inamoto, Y, Kindwall-Keller, T, Nishihori, T, Olsson, RF, Saad, A, Seftel, M, Seo, S, Szer, J, Tallman, M, Ustun, C, Wiernik, PH, Maziarz, R, Kalaycio, M, Alyea, E, Popat, U, Sobecks, R & 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. https://doi.org/10.1016/j.bbmt.2017.10.015
Hill, Brian T. ; Ahn, Kwang Woo ; Hu, Zhen Huan ; Aljurf, Mahmoud ; Beitinjaneh, Amer ; Cahn, Jean Yves ; Cerny, Jan ; Kharfan-Dabaja, Mohamed A. ; Ganguly, Siddhartha ; Ghosh, Nilanjan ; Grunwald, Michael R. ; Inamoto, Yoshihiro ; Kindwall-Keller, Tamila ; Nishihori, Taiga ; Olsson, Richard F. ; Saad, Ayman ; Seftel, Matthew ; Seo, Sachiko ; Szer, Jeffrey ; Tallman, Martin ; Ustun, Celalettin ; Wiernik, Peter H. ; Maziarz, Richard ; Kalaycio, Matt ; Alyea, Edwin ; Popat, Uday ; Sobecks, Ronald ; Saber, Wael. / Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia. In: Biology of Blood and Marrow Transplantation. 2018.
@article{dd36ebe141354a6fbbba74edd291a007,
title = "Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia",
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.",
keywords = "Allogeneic transplantation, CLL, HLA",
author = "Hill, {Brian T.} and Ahn, {Kwang Woo} and Hu, {Zhen Huan} and Mahmoud Aljurf and Amer Beitinjaneh and Cahn, {Jean Yves} and Jan Cerny and Kharfan-Dabaja, {Mohamed A.} and Siddhartha Ganguly and Nilanjan Ghosh and Grunwald, {Michael R.} and Yoshihiro Inamoto and Tamila Kindwall-Keller and Taiga Nishihori and Olsson, {Richard F.} and Ayman Saad and Matthew Seftel and Sachiko Seo and Jeffrey Szer and Martin Tallman and Celalettin Ustun and Wiernik, {Peter H.} and Richard Maziarz and Matt Kalaycio and Edwin Alyea and Uday Popat and Ronald Sobecks and Wael Saber",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2017.10.015",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

AU - Hill, Brian T.

AU - Ahn, Kwang Woo

AU - Hu, Zhen Huan

AU - Aljurf, Mahmoud

AU - Beitinjaneh, Amer

AU - Cahn, Jean Yves

AU - Cerny, Jan

AU - Kharfan-Dabaja, Mohamed A.

AU - Ganguly, Siddhartha

AU - Ghosh, Nilanjan

AU - Grunwald, Michael R.

AU - Inamoto, Yoshihiro

AU - Kindwall-Keller, Tamila

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Saad, Ayman

AU - Seftel, Matthew

AU - Seo, Sachiko

AU - Szer, Jeffrey

AU - Tallman, Martin

AU - Ustun, Celalettin

AU - Wiernik, Peter H.

AU - Maziarz, Richard

AU - Kalaycio, Matt

AU - Alyea, Edwin

AU - Popat, Uday

AU - Sobecks, Ronald

AU - Saber, Wael

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Allogeneic transplantation

KW - CLL

KW - HLA

UR - http://www.scopus.com/inward/record.url?scp=85041598291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041598291&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2017.10.015

DO - 10.1016/j.bbmt.2017.10.015

M3 - Article

JO - Biology of Blood and Marrow Transplantation

T2 - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

ER -