Published Ahead of Print on October 31, 2018, as doi:10.3324/haematol.2018.200121. Copyright 2018 Ferrata Storti Foundation.
Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at 1-year compared to unrelated donors by Michael A. Pulsipher, Brent R. Logan, Deidre M. Kiefer, Pintip Chitphakdithai, Marcie L. Riches, J. Douglas Rizzo, Paolo Anderlini, Susan F. Leitman, Hati Kobusingye, RaeAnne M. Besser, John P. Miller, Rebecca J. Drexler, Aly Abdel-Mageed, Ibrahim A. Ahmed, Luke P. Akard, Andrew S. Artz, Edward D. Ball, Ruthee-Lu Bayer, Carolyn Bigelow, Brian J. Bolwell, E. Randolph Broun, David C. Delgado, Katharine Duckworth, Christopher C. Dvorak, Theresa E. Hahn, Ann E. Haight, Parameswaran N. Hari, Brandon M. Hayes-Lattin, David A. Jacobsohn, Ann A. Jakubowski, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Michael Linenberger, Mark R. Litzow, Walter Longo, Margarida Magalhaes-Silverman, John M. McCarty, Joseph P. McGuirk, Shahram Mori, Vinod Parameswaran, Vinod K. Prasad, Scott D. Rowley, Witold B. Rybka, Indira Sahdev, Jeffrey R. Schriber, George B. Selby, Paul J. Shaughnessy, Shalini Shenoy, Thomas Spitzer, William T. Tse, Joseph P. Uberti, Madhuri Vusirikala, Edmund K. Waller, Daniel J. Weisdorf, Gregory A. Yanik, Willis H. Navarro, Mary M. Horowitz, Galen E. Switzer, Dennis L. Confer, and Bronwen E. Shaw Haematologica 2018 [Epub ahead of print] Citation: Michael A. Pulsipher, Brent R. Logan, Deidre M. Kiefer, Pintip Chitphakdithai, Marcie L. Riches, J. Douglas Rizzo, Paolo Anderlini, Susan F. Leitman, Hati Kobusingye, RaeAnne M. Besser, John P. Miller, Rebecca J. Drexler, Aly Abdel-Mageed, Ibrahim A. Ahmed, Luke P. Akard, Andrew S. Artz, Edward D. Ball, Ruthee-Lu Bayer, Carolyn Bigelow, Brian J. Bolwell, E. Randolph Broun, David C. Delgado, Katharine Duckworth, Christopher C. Dvorak, Theresa E. Hahn, Ann E. Haight, Parameswaran N. Hari, Brandon M. Hayes-Lattin, David A. Jacobsohn, Ann A. Jakubowski, Kimberly A. Kasow,Hillard M. Lazarus, Jane L. Liesveld, Michael Linenberger, Mark R. Litzow, Walter Longo, Margarida Magalhaes-Silverman, John M. McCarty, Joseph P. McGuirk, Shahram Mori, Vinod Parameswaran, Vinod K. Prasad, Scott D. Rowley, Witold B. Rybka, Indira Sahdev, Jeffrey R. Schriber, George B. Selby, Paul J. Shaughnessy, Shalini Shenoy, Thomas Spitzer, William T. Tse, Joseph P. Uberti, Madhuri Vusirikala, Edmund K. Waller, Daniel J. Weisdorf, Gregory A. Yanik, Willis H. Navarro, Mary M. Horowitz, Galen E. Switzer, Dennis L. Confer, and Bronwen E. Shaw. Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at 1-year compared to unrelated donors. Haematologica. 2018; 103:xxx doi:10.3324/haematol.2018.200121 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.
Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at 1-year compared to unrelated donors Michael A. Pulsipher1, Brent R. Logan2, Deidre M. Kiefer3, Pintip Chitphakdithai3, Marcie L. Riches4, J. Douglas Rizzo,2, Paolo Anderlini5, Susan F. Leitman6, Hati Kobusingye3, RaeAnne M. Besser3, John P. Miller7, Rebecca J. Drexler3, Aly Abdel-Mageed8, Ibrahim A. Ahmed9, Luke P. Akard10, Andrew S. Artz11, Edward D. Ball12, Ruthee-Lu Bayer13, Carolyn Bigelow14, Brian J. Bolwell15, E. Randolph Broun16, David C. Delgado17, Katharine Duckworth18, Christopher C. Dvorak19, Theresa E. Hahn20, Ann E. Haight21, Parameswaran N. Hari22, Brandon M. HayesLattin23, David A. Jacobsohn24, Ann A. Jakubowski25, Kimberly A. Kasow26, Hillard M. Lazarus27, Jane L. Liesveld28, Michael Linenberger29, Mark R. Litzow30, Walter Longo31, Margarida Magalhaes-Silverman32, John M. McCarty33, Joseph P. McGuirk34, Shahram Mori35, Vinod Parameswaran, 36, Vinod K. Prasad37, Scott D. Rowley38, Witold B. Rybka39, Indira Sahdev40, Jeffrey R. Schriber41, George B. Selby42, Paul J. Shaughnessy43, Shalini Shenoy44, Thomas Spitzer45, William T. Tse46, Joseph P. Uberti, 47, Madhuri Vusirikala48, Edmund K. Waller49, Daniel J. Weisdorf50, Gregory A. Yanik51, Willis H. Navarro3, Mary M. Horowitz2, Galen E. Switzer52, Dennis L. Confer3,7, Bronwen E. Shaw2 1
Children's Hospital Los Angeles, Los Angeles, CA; 2Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI; 3Center for International Blood and Marrow Transplant Research, Minneapolis, MN; 4University of North Carolina Hospitals, Chapel Hill, NC; 5M.D. Anderson Cancer Center, Houston, TX; 6Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD; 7National Marrow Donor Program/Be The Match, Minneapolis, MN; 8Helen DeVos Children's Hospital, Grand Rapids, MI; 9Children's Mercy Hospitals and Clinics, Kansas City, MO; 10Indiana Blood and Marrow Transplantation, Indianapolis, IN; 11University of Chicago Hospitals, Chicago, IL; 12 University of California, San Diego Medical Center, La Jolla, CA; 13North Shore University Hospital, Manhasset, NY; 14University of Mississippi Medical Center, Jackson, MS; 15Cleveland Clinic Foundation, Cleveland, OH; 16Jewish Hospital, Cincinnati, OH; 17Indiana University Hospital/Riley Hospital for Children, Indianapolis, IN; 18Wake Forest University Baptist Medical Center, Winston-Salem, NC; 19University of California San Francisco Benioff Children’s Hospital, San Francisco, CA; 20Roswell Park Cancer Institute, Buffalo, NY; 21Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA; 22Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; 23Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR; 24 Children's National Medical Center, Washington, DC; 25Memorial Sloan Kettering Cancer Center – Adult, New York, NY; 26University of North Carolina Healthcare, Chapel Hill, NC; 27 Seidman Cancer Center-University Hospitals Cleveland Medical Center, Cleveland, OH; 28 Strong Memorial Hospital - University of Rochester Medical Center, Rochester, NY; 29Fred Hutchinson Cancer Research Center, Seattle, WA; 30Mayo Clinic Rochester, Rochester, MN; 31 University of Wisconsin Hospital and Clinics, Madison, WI; 32University of Iowa Hospitals & Clinics, Iowa City, IA; 33Virginia Commonwealth University Massey Cancer Center Bone Marrow Transplant Program, Richmond, VA; 34University of Kansas, Westwood, KS; 35Florida Hospital Cancer Institute, Florida Center for Cellular Therapy, Orlando, FL; 36Avera McKennan Transplant Institute, Sioux Falls, SD; 37Duke University Medical Center, Durham, NC; 38 Hackensack University Medical Center, Washington, DC; 39Penn State Health Milton S.
1
Hershey Medical Center, Hershey, PA; 40Cohen Children’s Medical Center of New York, New Hyde Park, NY; 41Cancer Transplant Institute Honor Health, Scottsdale, AZ; 42HCA Health Services of Oklahoma, Inc., University of Oklahoma, Oklahoma City, OK; 43Texas Transplant Institute, San Antonio, TX; 44St. Louis Children's Hospital, St. Louis, MO; 45Massachusetts General Hospital, Boston, MA; 46Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; 47Karmanos Cancer Institute, Detroit, MI; 48University of Texas Southwestern Medical Center, Dallas, TX; 49Emory University Hospital, Atlanta, GA; 50University of Minnesota Medical Center, Fairview, Minneapolis, MN; 51The University of Michigan, Ann Arbor, MI; 52University of Pittsburgh, Pittsburgh, PA Authorship contributions: MAP, PA, DLC, RJD, MMH, SFL, BRL, JPM, JDR, GES, MLR designed the trial. MAP, WN, BES, HK, RMB, RJD oversaw and conducted the study. MAP, BES, BRL, DMK, PC analyzed and interpreted the data and wrote the manuscript. MAP, MLR, AAM, IAA, LPA, ASA, EDB, RLB, CB, BJB, ERB, DD, KD, CCD, TEH, AEH, PNH, BHL, DJ, AAJ, KAK, HL, JLL, ML, MRL, WL, JMM, JM, SM, VP, VKP, SDR, WBR, IS, JS, GBS, PJS, SS, MLR, MMS, TS, WT, JPU, MV, EKW, DJW, GAY enrolled related donors. The final manuscript was reviewed and approved by all authors. Running title: Toxicity in related versus unrelated HSC donors Corresponding author: Michael A. Pulsipher, MD Children's Hospital Los Angeles 4650 Sunset Blvd., Mailstop #62 Los Angeles, CA 90027 Email:
[email protected] Phone: (323) 361-2546 Sources of Support: The study was funded by R01 HL085707 through the NHLBI. Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/NCI) and the Johnny Crisstopher Children’s Charitable Foundation St. Baldrick’s Consortium Grant. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; a contract HHSH250201700006C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-17-1-2388, N00014-17-1-2850 and N00014-18-1-2045 from the Office of Naval Research; and grants from Adaptive Biotechnologies; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the
2
Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members Conflict-of-Interest disclosures: None of the authors has any conflict of interest to declare. Abstract word count: 282 Manuscript word count: 3178 Tables: 4 Figures: 2 Supplemental tables: 4 Supplemental figures: 4 ClinicalTrials.gov ID: NCT00948636
3
ABSTRACT Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation related toxicities we conducted a prospective observational trial of 11,942 related and
unrelated age 18-60. Bone marrow was collected at 37 transplant and 78 National Marrow Donor Program centers and peripheral blood stem cells were collected at 42 transplant and 87
unrelated donor centers in North America. Ascertainment of medical comorbidities occurred prior to donation and standardized pain and toxicity measures were assessed pre-donation, peridonation, and one year following. Multivariate analyses showed similar experiences for marrow collection in related and unrelated donors, however, related stem cell donors had increased risk of moderate (OR 1.42, p
