Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study

Michael A. Pulsipher; Brent R. Logan; Pintip Chitphakdithai; Deidre M. Kiefer; Marcie L. Riches; J. Douglas Rizzo; Paolo Anderlini; Susan F. Leitman; James W. Varni; Hati Kobusingye; Rae Anne 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; Nancy J. Bunin; 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 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; Bronwen E. Shaw; Dennis L. Confer

doi:10.1016/j.bbmt.2018.11.004

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study

Michael A. Pulsipher, Brent R. Logan, Pintip Chitphakdithai, Deidre M. Kiefer, Marcie L. Riches, J. Douglas Rizzo, Paolo Anderlini, Susan F. Leitman, James W. Varni, Hati Kobusingye, Rae Anne 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 BigelowBrian J. Bolwell, E. Randolph Broun, Nancy J. Bunin, 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 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, Bronwen E. Shaw, Dennis L. Confer

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34 ⁺ level before apheresis compared with younger RDs (age > 60, 59 × 10 ⁶ /L; age 41 to 60, 81 × 10 ⁶ /L; age 18 to 40, 121 × 10 ⁶ /L; P <.001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P <.001) and higher collection volumes (52% versus 32% > 24 L, P <.001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 10 ⁹ /L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P =.01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P <.001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P =.004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.

Original language	English (US)
Pages (from-to)	699-711
Number of pages	13
Journal	Biology of Blood and Marrow Transplantation
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.bbmt.2018.11.004
State	Published - Apr 2019

Bibliographical note

Funding Information:
Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI). Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/National Cancer Institute [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 NCI, the NHLBI, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 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 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. Asterisk indicates Corporate Members. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: M.A.P. P.A. D.L.C. R.J.D. M.M.H. S.F.L. B.R.L. J.P.M. J.D.R. G.E.S. M.L.R. and J.W.V. designed the trial. M.A.P. W.N. B.E.S. H.K. R.M.B. and R.J.D. oversaw and conducted the study. M.A.P. B.E.S. B.R.L. P.C. and D.M.K. analyzedand interpreted the data and wrote the manuscript. M.A.P. M.L.R. A.A.M. I.A.A. L.P.A. A.S.A. E.D.B. R.L.B. C.B. B.J.B. E.R.B. N.J.B. D.D. K.D. C.C.D. T.E.H. A.E.H. P.N.H. B.H.L. D.J. A.A.J. K.A.K. H.L. J.L.L. M.L. M.R.L. W.L. M.M.S. J.M.M. J.M. S.M. V.P. V.K.P. M.L.R. S.D.R. W.B.R. I.S. J.S. G.B.S. P.J.S. S.S. T.S. W.T. J.P.U. M.V. E.K.W. D.J.W. and G.A.Y. enrolled related donors. The final manuscript was reviewed and approved by all authors.

Funding Information:
Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI). Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/National Cancer Institute [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 NCI, the NHLBI, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 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 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. Asterisk indicates Corporate Members.

Funding Information:
Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI) . Additional funding for MAP was provided by 2UG1HL069254 ( NHLBI/National Cancer Institute [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 NCI , the NHLBI, and the National Institute of Allergy and Infectious Diseases ; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI ; contract HHSH250201700006C with Health Resources and Services Administration ; 3 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 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. Asterisk indicates Corporate Members.

Publisher Copyright:
© 2018 American Society for Blood and Marrow Transplantation

Keywords

BM collection toxicities
Donor safety
PBSC collection toxicities
Stem cell transplantation

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Journal Article
Research Support, N.I.H., Extramural

Publisher link

10.1016/j.bbmt.2018.11.004

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Cite this

Pulsipher, M. A., Logan, B. R., Chitphakdithai, P., Kiefer, D. M., Riches, M. L., Rizzo, J. D., Anderlini, P., Leitman, S. F., Varni, J. W., Kobusingye, H., Besser, R. A. M., Miller, J. P., Drexler, R. J., Abdel-Mageed, A., Ahmed, I. A., Akard, L. P., Artz, A. S., Ball, E. D., Bayer, R. L., ... Confer, D. L. (2019). Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study. Biology of Blood and Marrow Transplantation, 25(4), 699-711. https://doi.org/10.1016/j.bbmt.2018.11.004

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study. / Pulsipher, Michael A.; Logan, Brent R.; Chitphakdithai, Pintip et al.
In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 4, 04.2019, p. 699-711.

Research output: Contribution to journal › Article › peer-review

Pulsipher, MA, Logan, BR, Chitphakdithai, P, Kiefer, DM, Riches, ML, Rizzo, JD, Anderlini, P, Leitman, SF, Varni, JW, Kobusingye, H, Besser, RAM, Miller, JP, Drexler, RJ, Abdel-Mageed, A, Ahmed, IA, Akard, LP, Artz, AS, Ball, ED, Bayer, RL, Bigelow, C, Bolwell, BJ, Broun, ER, Bunin, NJ, Delgado, DC, Duckworth, K, Dvorak, CC, Hahn, TE, Haight, AE, Hari, PN, Hayes-Lattin, BM, Jacobsohn, DA, Jakubowski, AA, Kasow, KA, Lazarus, HM, Liesveld, JL, Linenberger, M, Litzow, MR, Longo, W, Magalhaes-Silverman, M, McCarty, JM, McGuirk, JP, Mori, S, Prasad, VK, Rowley, SD, Rybka, WB, Sahdev, I, Schriber, JR, Selby, GB, Shaughnessy, PJ, Shenoy, S, Spitzer, T, Tse, WT, Uberti, JP, Vusirikala, M, Waller, EK, Weisdorf, DJ, Yanik, GA, Navarro, WH, Horowitz, MM, Switzer, GE, Shaw, BE & Confer, DL 2019, 'Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study', Biology of Blood and Marrow Transplantation, vol. 25, no. 4, pp. 699-711. https://doi.org/10.1016/j.bbmt.2018.11.004

@article{63a0379c3dca4df2971fa218e91ce5c0,

title = "Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study",

abstract = " The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34 + level before apheresis compared with younger RDs (age > 60, 59 × 10 6 /L; age 41 to 60, 81 × 10 6 /L; age 18 to 40, 121 × 10 6 /L; P <.001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P <.001) and higher collection volumes (52% versus 32% > 24 L, P <.001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 10 9 /L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P =.01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P <.001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P =.004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.",

keywords = "BM collection toxicities, Donor safety, PBSC collection toxicities, Stem cell transplantation",

author = "Pulsipher, {Michael A.} and Logan, {Brent R.} and Pintip Chitphakdithai and Kiefer, {Deidre M.} and Riches, {Marcie L.} and Rizzo, {J. Douglas} and Paolo Anderlini and Leitman, {Susan F.} and Varni, {James W.} and Hati Kobusingye and Besser, {Rae Anne M.} and Miller, {John P.} and Drexler, {Rebecca J.} and Aly Abdel-Mageed and Ahmed, {Ibrahim A.} and Akard, {Luke P.} and Artz, {Andrew S.} and Ball, {Edward D.} and Bayer, {Ruthee Lu} and Carolyn Bigelow and Bolwell, {Brian J.} and Broun, {E. Randolph} and Bunin, {Nancy J.} and Delgado, {David C.} and Katharine Duckworth and Dvorak, {Christopher C.} and Hahn, {Theresa E.} and Haight, {Ann E.} and Hari, {Parameswaran N.} and Hayes-Lattin, {Brandon M.} and Jacobsohn, {David A.} and Jakubowski, {Ann A.} and Kasow, {Kimberly A.} and Lazarus, {Hillard M.} and Liesveld, {Jane L.} and Michael Linenberger and Litzow, {Mark R.} and Walter Longo and Margarida Magalhaes-Silverman and McCarty, {John M.} and McGuirk, {Joseph P.} and Shahram Mori and Prasad, {Vinod K.} and Rowley, {Scott D.} and Rybka, {Witold B.} and Indira Sahdev and Schriber, {Jeffrey R.} and Selby, {George B.} and Shaughnessy, {Paul J.} and Shalini Shenoy and Thomas Spitzer and Tse, {William T.} and Uberti, {Joseph P.} and Madhuri Vusirikala and Waller, {Edmund K.} and Weisdorf, {Daniel J.} and Yanik, {Gregory A.} and Navarro, {Willis H.} and Horowitz, {Mary M.} and Switzer, {Galen E.} and Shaw, {Bronwen E.} and Confer, {Dennis L.}",

note = "Funding Information: Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI). Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/National Cancer Institute [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 NCI, the NHLBI, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 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 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. Asterisk indicates Corporate Members. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: M.A.P. P.A. D.L.C. R.J.D. M.M.H. S.F.L. B.R.L. J.P.M. J.D.R. G.E.S. M.L.R. and J.W.V. designed the trial. M.A.P. W.N. B.E.S. H.K. R.M.B. and R.J.D. oversaw and conducted the study. M.A.P. B.E.S. B.R.L. P.C. and D.M.K. analyzedand interpreted the data and wrote the manuscript. M.A.P. M.L.R. A.A.M. I.A.A. L.P.A. A.S.A. E.D.B. R.L.B. C.B. B.J.B. E.R.B. N.J.B. D.D. K.D. C.C.D. T.E.H. A.E.H. P.N.H. B.H.L. D.J. A.A.J. K.A.K. H.L. J.L.L. M.L. M.R.L. W.L. M.M.S. J.M.M. J.M. S.M. V.P. V.K.P. M.L.R. S.D.R. W.B.R. I.S. J.S. G.B.S. P.J.S. S.S. T.S. W.T. J.P.U. M.V. E.K.W. D.J.W. and G.A.Y. enrolled related donors. The final manuscript was reviewed and approved by all authors. Funding Information: Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI). Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/National Cancer Institute [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 NCI, the NHLBI, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 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 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. Asterisk indicates Corporate Members. Funding Information: Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI) . Additional funding for MAP was provided by 2UG1HL069254 ( NHLBI/National Cancer Institute [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 NCI , the NHLBI, and the National Institute of Allergy and Infectious Diseases ; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI ; contract HHSH250201700006C with Health Resources and Services Administration ; 3 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 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. Asterisk indicates Corporate Members. Publisher Copyright: {\textcopyright} 2018 American Society for Blood and Marrow Transplantation",

year = "2019",

month = apr,

doi = "10.1016/j.bbmt.2018.11.004",

language = "English (US)",

volume = "25",

pages = "699--711",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier Inc.",

number = "4",

}

TY - JOUR

T1 - Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience

T2 - Report from the Related Donor Safety Study

AU - Pulsipher, Michael A.

AU - Logan, Brent R.

AU - Chitphakdithai, Pintip

AU - Kiefer, Deidre M.

AU - Riches, Marcie L.

AU - Rizzo, J. Douglas

AU - Anderlini, Paolo

AU - Leitman, Susan F.

AU - Varni, James W.

AU - Kobusingye, Hati

AU - Besser, Rae Anne M.

AU - Miller, John P.

AU - Drexler, Rebecca J.

AU - Abdel-Mageed, Aly

AU - Ahmed, Ibrahim A.

AU - Akard, Luke P.

AU - Artz, Andrew S.

AU - Ball, Edward D.

AU - Bayer, Ruthee Lu

AU - Bigelow, Carolyn

AU - Bolwell, Brian J.

AU - Broun, E. Randolph

AU - Bunin, Nancy J.

AU - Delgado, David C.

AU - Duckworth, Katharine

AU - Dvorak, Christopher C.

AU - Hahn, Theresa E.

AU - Haight, Ann E.

AU - Hari, Parameswaran N.

AU - Hayes-Lattin, Brandon M.

AU - Jacobsohn, David A.

AU - Jakubowski, Ann A.

AU - Kasow, Kimberly A.

AU - Lazarus, Hillard M.

AU - Liesveld, Jane L.

AU - Linenberger, Michael

AU - Litzow, Mark R.

AU - Longo, Walter

AU - Magalhaes-Silverman, Margarida

AU - McCarty, John M.

AU - McGuirk, Joseph P.

AU - Mori, Shahram

AU - Prasad, Vinod K.

AU - Rowley, Scott D.

AU - Rybka, Witold B.

AU - Sahdev, Indira

AU - Schriber, Jeffrey R.

AU - Selby, George B.

AU - Shaughnessy, Paul J.

AU - Shenoy, Shalini

AU - Spitzer, Thomas

AU - Tse, William T.

AU - Uberti, Joseph P.

AU - Vusirikala, Madhuri

AU - Waller, Edmund K.

AU - Weisdorf, Daniel J.

AU - Yanik, Gregory A.

AU - Navarro, Willis H.

AU - Horowitz, Mary M.

AU - Switzer, Galen E.

AU - Shaw, Bronwen E.

AU - Confer, Dennis L.

N1 - Funding Information: Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI). Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/National Cancer Institute [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 NCI, the NHLBI, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 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 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. Asterisk indicates Corporate Members. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: M.A.P. P.A. D.L.C. R.J.D. M.M.H. S.F.L. B.R.L. J.P.M. J.D.R. G.E.S. M.L.R. and J.W.V. designed the trial. M.A.P. W.N. B.E.S. H.K. R.M.B. and R.J.D. oversaw and conducted the study. M.A.P. B.E.S. B.R.L. P.C. and D.M.K. analyzedand interpreted the data and wrote the manuscript. M.A.P. M.L.R. A.A.M. I.A.A. L.P.A. A.S.A. E.D.B. R.L.B. C.B. B.J.B. E.R.B. N.J.B. D.D. K.D. C.C.D. T.E.H. A.E.H. P.N.H. B.H.L. D.J. A.A.J. K.A.K. H.L. J.L.L. M.L. M.R.L. W.L. M.M.S. J.M.M. J.M. S.M. V.P. V.K.P. M.L.R. S.D.R. W.B.R. I.S. J.S. G.B.S. P.J.S. S.S. T.S. W.T. J.P.U. M.V. E.K.W. D.J.W. and G.A.Y. enrolled related donors. The final manuscript was reviewed and approved by all authors. Funding Information: Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI). Additional funding for MAP was provided by 2UG1HL069254 (NHLBI/National Cancer Institute [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 NCI, the NHLBI, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 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 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. Asterisk indicates Corporate Members. Funding Information: Financial disclosure: This study was funded by R01 HL085707 through the National Heart, Lung and Blood Institute (NHLBI) . Additional funding for MAP was provided by 2UG1HL069254 ( NHLBI/National Cancer Institute [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 NCI , the NHLBI, and the National Institute of Allergy and Infectious Diseases ; Grant/Cooperative Agreement 1U24HL138660 from the NHLBI and NCI ; contract HHSH250201700006C with Health Resources and Services Administration ; 3 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 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. Asterisk indicates Corporate Members. Publisher Copyright: © 2018 American Society for Blood and Marrow Transplantation

PY - 2019/4

Y1 - 2019/4

N2 - The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34 + level before apheresis compared with younger RDs (age > 60, 59 × 10 6 /L; age 41 to 60, 81 × 10 6 /L; age 18 to 40, 121 × 10 6 /L; P <.001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P <.001) and higher collection volumes (52% versus 32% > 24 L, P <.001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 10 9 /L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P =.01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P <.001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P =.004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.

AB - The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34 + level before apheresis compared with younger RDs (age > 60, 59 × 10 6 /L; age 41 to 60, 81 × 10 6 /L; age 18 to 40, 121 × 10 6 /L; P <.001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P <.001) and higher collection volumes (52% versus 32% > 24 L, P <.001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 10 9 /L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P =.01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P <.001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P =.004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.

KW - BM collection toxicities

KW - Donor safety

KW - PBSC collection toxicities

KW - Stem cell transplantation

UR - http://www.scopus.com/inward/record.url?scp=85058455309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058455309&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2018.11.004

DO - 10.1016/j.bbmt.2018.11.004

M3 - Article

C2 - 30423480

AN - SCOPUS:85058455309

SN - 1083-8791

VL - 25

SP - 699

EP - 711

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 4

ER -

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study

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