Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: A PIDTC report

Lauri M. Burroughs, Aleksandra Petrovic, Ruta Brazauskas, Xuerong Liu, Linda M. Griffith, Hans D. Ochs, Jack J. Bleesing, Stephanie Edwards, Christopher C. Dvorak, Sonali Chaudhury, Susan E. Prockop, Ralph Quinones, Frederick D. Goldman, Troy C. Quigg, Shanmuganathan Chandrakasan, Angela R. Smith, Suhag Parikh, Blachy J. Dávila Saldaña, Monica S. Thakar, Rachel PhelanShalini Shenoy, Lisa R. Forbes, Caridad Martinez, Deepak Chellapandian, Evan Shereck, Holly K. Miller, Neena Kapoor, Jessie L. Barnum, Hey Chong, David C. Shyr, Karin Chen, Rolla Abu-Arja, Ami J. Shah, Katja G. Weinacht, Theodore B. Moore, Avni Joshi, Kenneth B. DeSantes, Alfred P. Gillio, Geoffrey D.E. Cuvelier, Michael D. Keller, Jacob Rozmus, Troy Torgerson, Michael A. Pulsipher, Elie Haddad, Kathleen E. Sullivan, Brent R. Logan, Donald B. Kohn, Jennifer M. Puck, Luigi D. Notarangelo, Sung Yun Pai, David J. Rawlings, Morton J. Cowan

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. We report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers from 2005 through 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs ‡5 years of age at the time of HCT (94% vs 66%; overall P 5.0008). OS was excellent regardless of donor type, even in cord blood recipients (90%). Conditioning intensity did not affect OS, but was associated with donor T-cell and myeloid engraftment after HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism <50% early after HCT. In addition, higher platelet counts were observed among recipients who achieved full (>95%) vs low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005, compared with prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution after either myeloablative or busulfan-containing reduced intensity conditioning.

Original languageEnglish (US)
Pages (from-to)2094-2105
Number of pages12
JournalBlood
Volume135
Issue number23
DOIs
StatePublished - Jun 4 2020

Bibliographical note

Funding Information:
The authors thank Catherine Chang, Tara Bani, and Elizabeth Dunn for project management and assistance; all of the study coordinators for collection of clinical data from PIDTC sites and the clinical care teams who provided care for patients; Sumathi Iyengar, Executive Director of the Wiskott-Aldrich Foundation, and all of the patients and families who have made this work possible; and Helen Crawford for her assistance with manuscript and figure preparation. This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH); Public Health Service, NIH, NIAID grant U54AI082973 (principal investigator [PI], M.J.C.; PIs from September 2019 forward, J.M.P. and D.B.K.); NIH, National Institute of Neurological Disorders and Stroke grant U54NS064808 and National Center for Advancing Translational Sciences grant U01TR001263 (PI, J. P. Krischer); NIH, NIAID grant R13AI094943 (PIs, M.J.C. and March 2018 forward, J.M.P.). The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS. The collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) is supported by the U54 grants listed here, along with support of the PBMTC Operations Center by the St. Baldrick's Foundation and NIH, National Heart, Lung and Blood Institute (NHLBI) grant/cooperative agreement U10HL069254 (PI, M.A.P.). Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by NIH, National Cancer Institute grant/cooperative agreement U24CA076518 (PI, M. M. Horowitz), and NHLBI, and NIAID; and NIH, NHLBI grant/cooperative agreement U01HL069294; by contracts HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration (HRSA/DHHS); and by grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research. In addition, the Dejoria Wiskott-Aldrich Research Fund and the Jeffrey Modell Foundation helped fund the mutation analyses and WASP expression studies for many of the patients included in this cohort. L.D.N. is supported by the Division of Intramural Research, NIH, NIAID grant 1 ZIA AI001222-02 (PI, L.D.N.). S.S. is supported by the Children's Discovery Institute, St. Louis Children's Hospital.

Funding Information:
This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH); Public Health Service, NIH, NIAID grant U54AI082973 (principal investigator [PI], M.J.C.; PIs from September 2019 forward, J.M.P. and D.B.K.); NIH, National Institute of Neurological Disorders and Stroke grant U54NS064808 and National Center for Advancing Translational Sciences grant U01TR001263 (PI, J. P. Krischer); NIH, NIAID grant R13AI094943 (PIs, M.J.C. and March 2018 forward, J.M.P.). The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS. The collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) is supported by the U54 grants listed here, along with support of the PBMTC Operations Center by the St. Baldrick’s Foundation and NIH, National Heart, Lung and Blood Institute (NHLBI) grant/cooperative agreement U10HL069254 (PI, M.A.P.). Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research (CIBMTR) is supported by NIH, National

Funding Information:
Cancer Institute grant/cooperative agreement U24CA076518 (PI, M. M. Horowitz), and NHLBI, and NIAID; and NIH, NHLBI grant/cooperative agreement U01HL069294; by contracts HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration (HRSA/DHHS); and by grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research. In addition, the Dejoria Wiskott-Aldrich Research Fund and the Jeffrey Modell Foundation helped fund the mutation analyses and WASP expression studies for many of the patients included in this cohort. L.D.N. is supported by the Division of Intramural Research, NIH, NIAID grant 1 ZIA AI001222-02 (PI, L.D.N.). S.S. is supported by the Children’s Discovery Institute, St. Louis Children’s Hospital.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • 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.

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