Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Matthew J Wieduwilt¹, Leland Metheny², Mei-Jie Zhang^{3

4}, Hai-Lin Wang³, Noel Estrada-Merly³, David I Marks⁵, A Samer Al-Homsi⁶, Lori Muffly⁷, Nelson Chao⁸, David Rizzieri⁹, Robert Peter Gale¹⁰, Shahinaz M Gadalla¹¹, Mitchell Cairo¹², Alberto Mussetti^{13

14}, Steven Gore¹⁵, Vijaya Raj Bhatt¹⁶, Sagar S Patel¹⁷, Fotios V Michelis¹⁸, Yoshihiro Inamoto¹⁹, Sherif M Badawy^{20

21}, Edward Copelan²², Neil Palmisiano²³, Mohamed A Kharfan-Dabaja²⁴, Hillard M Lazarus²⁵, Siddhartha Ganguly²⁶, Christopher Bredeson²⁷, Miguel Angel Diaz Perez²⁸, Ryan Cassaday²⁹, Bipin N Savani³⁰, Karen Ballen³¹, Rodrigo Martino³², Baldeep Wirk³³, Ulrike Bacher³⁴, Mahmoud Aljurf³⁵, Asad Bashey³⁶, Hemant S Murthy²⁴, Jean A Yared³⁷, Ibrahim Aldoss³⁸, Nosha Farhadfar³⁹, Hongtao Liu⁴⁰, Hisham Abdel-Azim⁴¹, Edmund K Waller⁴², Melhem Solh⁴³, Matthew D Seftel⁴⁴, Marjolein van der Poel⁴⁵, Michael R Grunwald²², Jane L Liesveld⁴⁶, Rammurti T Kamble⁴⁷, Joseph McGuirk²⁶, Reinhold Munker⁴⁸, Jean-Yves Cahn⁴⁹, Jong Wook Lee⁵⁰, César O Freytes⁵¹, Maxwell M Krem⁴⁸, Lena E Winestone⁵², Usama Gergis⁵³, Sunita Nathan⁵⁴, Richard F Olsson^{55

56}, Leo F Verdonck⁵⁷, Akshay Sharma⁵⁸, Olle Ringdén⁵⁹, Brian D Friend⁶⁰, Jan Cerny⁶¹, Hannah Choe⁶², Saurabh Chhabra^{3

63}, Taiga Nishihori⁶⁴, Sachiko Seo⁶⁵, Biju George⁶⁶, Lee Ann Baxter-Lowe⁶⁷, Gerhard C Hildebrandt⁴⁸, Marcos de Lima⁶⁸, Mark Litzow⁶⁹, Partow Kebriaei⁷⁰, Christopher S Hourigan⁷¹, Muhammad Bilal Abid⁷², Daniel J Weisdorf⁷³, Wael Saber³

Affiliations

¹ University of Oklahoma, Stephenson Cancer Center, Oklahoma City, OK.
² University Hospitals Seidman Cancer Center, Cleveland, OH.
³ Center for International Blood and Marrow Transplant Research, Department of Medicine, and.
⁴ Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI.
⁵ Adult Bone Marrow Transplant, University Hospitals Bristol National Health Service Trust, Bristol, UK.
⁶ New York University Langone Health, New York, NY.
⁷ Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA.
⁸ Division of Cell Therapy and Hematology, Department of Medicine, Duke University Medical Center, Durham, NC.
⁹ Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC.
¹⁰ Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
¹¹ Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, MD.
¹² Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY.
¹³ Hematology Department, Institut Catalá d'Oncologia-Hospitalet, Barcelona, Spain.
¹⁴ Institut d'Investigació Biomédica de Bellvitge-Institut Català d'Oncologia, l'Hospitalet de Llobregat, El Prat de Llobregat, Spain.
¹⁵ Yale New Haven Hospital, New Haven, CT.
¹⁶ The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.
¹⁷ Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
¹⁸ Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, Toronto, Canada.
¹⁹ Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
²⁰ Division of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
²¹ Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL.
²² Deparment of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC.
²³ Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
²⁴ Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL.
²⁵ University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH.
²⁶ Division of Hematological Malignancies and Cellular Therapeutics, University of Kansas Health System, Kansas City, KS.
²⁷ The Ottawa Hospital Transplant and Cellular Therapy Program, Ottawa, ON, Canada.
²⁸ Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesus, Madrid, Spain.
²⁹ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
³⁰ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
³¹ Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, VA.
³² Division of Clinical Hematology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
³³ Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, PA.
³⁴ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³⁵ Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.
³⁶ Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA.
³⁷ Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD.
³⁸ City of Hope Medical Center, Duarte, CA.
³⁹ Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL.
⁴⁰ Section of Hematology/Oncology, University of Chicago Medicine, Chicago, IL.
⁴¹ Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA.
⁴² Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.
⁴³ The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA.
⁴⁴ Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁴⁵ Maastricht University Medical Center, Maastricht, The Netherlands.
⁴⁶ Department of Medicine, University of Rochester Medical Center, Rochester, NY.
⁴⁷ Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
⁴⁸ Markey Cancer Center, University of Kentucky, Lexington, KY.
⁴⁹ Department of Hematology, Centre Hospitalier Universitaire Grenoble Alpes, Université Grenoble Alpes, Grenoble, France.
⁵⁰ Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
⁵¹ University of Texas Health Science Center at San Antonio, San Antonio, TX.
⁵² Division of Allergy, Immunology, and Blood and Marrow Transplant, University of California San Francisco Benioff Children's Hospitals, San Francisco, CA.
⁵³ Department of Medical Oncology, Division of Hematological Malignancies, Thomas Jefferson University, Philadelphia, PA.
⁵⁴ Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL.
⁵⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵⁶ Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.
⁵⁷ Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands.
⁵⁸ Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.
⁵⁹ Translational Cell Therapy Group, Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
⁶⁰ Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
⁶¹ Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA.
⁶² The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH.
⁶³ Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
⁶⁴ Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
⁶⁵ Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
⁶⁶ Christian Medical College, Vellore, India.
⁶⁷ Children's Hospital Los Angeles, Los Angeles, CA.
⁶⁸ Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH.
⁶⁹ Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN.
⁷⁰ Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
⁷¹ Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
⁷² Divisions of Hematology/Oncology and Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; and.
⁷³ Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN.

PMID: 34547770
PMCID: PMC8753217
DOI: 10.1182/bloodadvances.2021004916

Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Matthew J Wieduwilt et al. Blood Adv. 2022.

. 2022 Jan 11;6(1):339-357.

doi: 10.1182/bloodadvances.2021004916.

Authors

Affiliations

¹ University of Oklahoma, Stephenson Cancer Center, Oklahoma City, OK.
² University Hospitals Seidman Cancer Center, Cleveland, OH.
³ Center for International Blood and Marrow Transplant Research, Department of Medicine, and.
⁴ Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI.
⁵ Adult Bone Marrow Transplant, University Hospitals Bristol National Health Service Trust, Bristol, UK.
⁶ New York University Langone Health, New York, NY.
⁷ Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA.
⁸ Division of Cell Therapy and Hematology, Department of Medicine, Duke University Medical Center, Durham, NC.
⁹ Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC.
¹⁰ Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.
¹¹ Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, MD.
¹² Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY.
¹³ Hematology Department, Institut Catalá d'Oncologia-Hospitalet, Barcelona, Spain.
¹⁴ Institut d'Investigació Biomédica de Bellvitge-Institut Català d'Oncologia, l'Hospitalet de Llobregat, El Prat de Llobregat, Spain.
¹⁵ Yale New Haven Hospital, New Haven, CT.
¹⁶ The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.
¹⁷ Blood and Marrow Transplant Program, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
¹⁸ Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, Toronto, Canada.
¹⁹ Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
²⁰ Division of Hematology, Oncology and Stem Cell Transplant, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
²¹ Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL.
²² Deparment of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC.
²³ Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
²⁴ Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL.
²⁵ University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH.
²⁶ Division of Hematological Malignancies and Cellular Therapeutics, University of Kansas Health System, Kansas City, KS.
²⁷ The Ottawa Hospital Transplant and Cellular Therapy Program, Ottawa, ON, Canada.
²⁸ Department of Hematology/Oncology, Hospital Infantil Universitario Niño Jesus, Madrid, Spain.
²⁹ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA.
³⁰ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
³¹ Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, VA.
³² Division of Clinical Hematology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
³³ Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, PA.
³⁴ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³⁵ Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia.
³⁶ Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA.
³⁷ Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD.
³⁸ City of Hope Medical Center, Duarte, CA.
³⁹ Division of Hematology/Oncology, University of Florida College of Medicine, Gainesville, FL.
⁴⁰ Section of Hematology/Oncology, University of Chicago Medicine, Chicago, IL.
⁴¹ Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA.
⁴² Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.
⁴³ The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA.
⁴⁴ Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁴⁵ Maastricht University Medical Center, Maastricht, The Netherlands.
⁴⁶ Department of Medicine, University of Rochester Medical Center, Rochester, NY.
⁴⁷ Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
⁴⁸ Markey Cancer Center, University of Kentucky, Lexington, KY.
⁴⁹ Department of Hematology, Centre Hospitalier Universitaire Grenoble Alpes, Université Grenoble Alpes, Grenoble, France.
⁵⁰ Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
⁵¹ University of Texas Health Science Center at San Antonio, San Antonio, TX.
⁵² Division of Allergy, Immunology, and Blood and Marrow Transplant, University of California San Francisco Benioff Children's Hospitals, San Francisco, CA.
⁵³ Department of Medical Oncology, Division of Hematological Malignancies, Thomas Jefferson University, Philadelphia, PA.
⁵⁴ Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL.
⁵⁵ Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
⁵⁶ Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden.
⁵⁷ Department of Hematology/Oncology, Isala Clinic, Zwolle, The Netherlands.
⁵⁸ Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN.
⁵⁹ Translational Cell Therapy Group, Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
⁶⁰ Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX.
⁶¹ Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA.
⁶² The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH.
⁶³ Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
⁶⁴ Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
⁶⁵ Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan.
⁶⁶ Christian Medical College, Vellore, India.
⁶⁷ Children's Hospital Los Angeles, Los Angeles, CA.
⁶⁸ Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH.
⁶⁹ Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN.
⁷⁰ Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
⁷¹ Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
⁷² Divisions of Hematology/Oncology and Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; and.
⁷³ Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN.

PMID: 34547770
PMCID: PMC8753217
DOI: 10.1182/bloodadvances.2021004916

Abstract

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

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Figures

**Figure 1.**
OS, LFS, CI of relapse, and CI of NRM comparing haploidentical HCT with posttransplant cyclophosphamide to matched sibling, 8/8 HLA-MUD, 7/8 HLA-MUD, or UCB HCT.

See this image and copyright information in PMC

References

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Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

Affiliations

Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

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