Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies

R. F. Olsson; B. R. Logan; S. Chaudhury; X. Zhu; G. Akpek; B. J. Bolwell; C. N. Bredeson; C. C. Dvorak; V. Gupta; V. T. Ho; H. M. Lazarus; D. I. Marks; O. T.H. Ringdén; M. C. Pasquini; J. R. Schriber; K. R. Cooke

doi:10.1038/leu.2015.75

Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies

R. F. Olsson^*, B. R. Logan, S. Chaudhury, X. Zhu, G. Akpek, B. J. Bolwell, C. N. Bredeson, C. C. Dvorak, V. Gupta, V. T. Ho, H. M. Lazarus, D. I. Marks, O. T.H. Ringdén, M. C. Pasquini, J. R. Schriber, K. R. Cooke

^*Corresponding author for this work

Pediatrics

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

106 Scopus citations

Abstract

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 10 8 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.

Original language	English (US)
Pages (from-to)	1754-1762
Number of pages	9
Journal	Leukemia
Volume	29
Issue number	8
DOIs	https://doi.org/10.1038/leu.2015.75
State	Published - Aug 7 2015

Funding

RFO thanks the Swedish Society for Medical Research (SSMF), the Swedish Medical Society, the Centre for Clinical Research Sörmland, the David and Astrid Hagelén’s Foundation and the Karolinska Institutet for their financial support. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 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 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/ DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children’s Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick’s Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; and Wellpoint, Inc.

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

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10.1038/leu.2015.75

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Olsson, R. F., Logan, B. R., Chaudhury, S., Zhu, X., Akpek, G., Bolwell, B. J., Bredeson, C. N., Dvorak, C. C., Gupta, V., Ho, V. T., Lazarus, H. M., Marks, D. I., Ringdén, O. T. H., Pasquini, M. C., Schriber, J. R., & Cooke, K. R. (2015). Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia, 29(8), 1754-1762. https://doi.org/10.1038/leu.2015.75

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title = "Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies",

abstract = "Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 10 8 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.",

author = "Olsson, {R. F.} and Logan, {B. R.} and S. Chaudhury and X. Zhu and G. Akpek and Bolwell, {B. J.} and Bredeson, {C. N.} and Dvorak, {C. C.} and V. Gupta and Ho, {V. T.} and Lazarus, {H. M.} and Marks, {D. I.} and Ringd{\'e}n, {O. T.H.} and Pasquini, {M. C.} and Schriber, {J. R.} and Cooke, {K. R.}",

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Olsson, RF, Logan, BR, Chaudhury, S, Zhu, X, Akpek, G, Bolwell, BJ, Bredeson, CN, Dvorak, CC, Gupta, V, Ho, VT, Lazarus, HM, Marks, DI, Ringdén, OTH, Pasquini, MC, Schriber, JR & Cooke, KR 2015, 'Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies', Leukemia, vol. 29, no. 8, pp. 1754-1762. https://doi.org/10.1038/leu.2015.75

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AU - Olsson, R. F.

AU - Logan, B. R.

AU - Chaudhury, S.

AU - Zhu, X.

AU - Akpek, G.

AU - Bolwell, B. J.

AU - Bredeson, C. N.

AU - Dvorak, C. C.

AU - Gupta, V.

AU - Ho, V. T.

AU - Lazarus, H. M.

AU - Marks, D. I.

AU - Ringdén, O. T.H.

AU - Pasquini, M. C.

AU - Schriber, J. R.

AU - Cooke, K. R.

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AB - Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23 272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 10 8 per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.

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Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies

Abstract

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UN SDGs

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