HLA-Haploidentical Hematopoietic Cell Transplantation for Treatment of Nonmalignant Diseases Using Nonmyeloablative Conditioning and Post-Transplant Cyclophosphamide

Kanwaldeep K. Mallhi, Meera A. Srikanthan, Kelsey K. Baker, Haydar A. Frangoul, Troy R. Torgerson, Aleksandra Petrovic, Amy E. Geddis, Paul A. Carpenter, K. Scott Baker, Brenda M. Sandmaier, Monica S. Thakar, Suzanne Skoda-Smith, Hans Peter Kiem, Rainer Storb, Ann E. Woolfrey, Lauri M. Burroughs

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Allogeneic hematopoietic cell transplant (HCT) is often the only curative therapy for patients with nonmalignant diseases; however, many patients do not have an HLA-matched donor. Historically, poor survival has been seen after HLA-haploidentical HCT because of poor immune reconstitution, increased infections, graft-versus-host disease (GVHD), and graft failure. Encouraging results have been reported using a nonmyeloablative T cell–replete HLA-haploidentical transplant approach in patients with hematologic malignancies. Here we report the outcomes of 23 patients with various nonmalignant diseases using a similar approach. Patients received HLA-haploidentical bone marrow (n = 17) or granulocyte colony-stimulating factor–mobilized peripheral blood stem cell (n = 6) grafts after conditioning with cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, and 2 or 4 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, tacrolimus, ± sirolimus. Median patient age at HCT was 10.8 years. Day 100 transplant-related mortality (TRM) was 0%. Two patients died at later time points, 1 from intracranial hemorrhage/disseminated fungal infection in the setting of graft failure and 1 from infection/GVHD. The estimated probabilities of grades II to IV and III to IV acute GVHD at day 100 and 2-year National Institutes of Health consensus chronic GVHD were 78%, 26%, and 42%, respectively. With a median follow-up of 2.5 years, the 2-year overall and event-free rates of survival were 91% and 78%, respectively. These results are encouraging and demonstrate favorable disease-specific lineage engraftment with low TRM in patients with nonmalignant diseases using nonmyeloablative conditioning followed by T cell–replete HLA-haploidentical grafts. However, additional strategies are needed for GVHD prevention to make this a viable treatment approach for patients with nonmalignant diseases.

Original languageEnglish (US)
Pages (from-to)1332-1341
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Issue number7
StatePublished - Jul 2020
Externally publishedYes

Bibliographical note

Funding Information:
Financial disclosure: Supported by the National Cancer Institute of the National Institutes of Health under award number P01 HL122173 and P30CA015704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, which had no involvement in the study design; the collection, analysis, and interpretation of data; the writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy


  • Haploidentical transplantation
  • Nonmalignant diseases
  • Nonmyeloablative conditioning
  • Post-transplant cyclophosphamide


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