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Tandem Orthotopic Living Donor Liver Transplantation Followed by Same Donor Haploidentical Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency

Freeman, Alexandra F. MD1; Yazigi, Nada2; Shah, Nirali N. MD3; Kleiner, David E.4; Parta, Mark5; Atkinson, Prescott6; Heller, Theo7; Holland, Steven M.1; Kaufman, Stuart S.2; Khan, Khalid M.2; Hickstein, Dennis D. MD8

doi: 10.1097/TP.0000000000002649
Original Clinical Science–Liver

Background. An 11-year-old girl with dedicator of cytokinesis 8 (DOCK8) deficiency was proposed for potentially curative hematopoietic stem cell transplantation (HSCT), the donor being her haploidentical mother. However, end-stage liver disease caused by chronic Cryptosporidium infection required liver transplantation before HSCT.

Methods. Consequently, a staged approach of a sequential liver transplant followed by a HSCT was planned with her mother as the donor for both liver and HSCT.

Results. The patient successfully underwent a left-lobe orthotopic liver transplant; however, she developed a biliary leak delaying the HSCT. Notably, the recipient demonstrated 3% donor lymphocyte chimerism in her peripheral blood immediately before HSCT. Haploidentical-related donor HSCT performed 2 months after liver transplantation was complicated by the development of acyclovir-resistant herpes simplex virus viremia, primary graft failure, and sinusoidal obstruction syndrome. The patient died from sinusoidal obstruction syndrome–associated multiorgan failure with Candida sepsis on day +40 following HSCT.

Conclusions. We discuss the many considerations inherent to planning for HSCT preceded by liver transplant in patients with primary immunodeficiencies, including the role of prolonged immunosuppression and the risk of infection before immune reconstitution. We also discuss the implications of potential recipient sensitization against donor stem cells precipitated by exposure of the recipient to the donor lymphocytes from the transplanted organ.

1 Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

2 Pediatric Liver Transplantation, Department of Pediatrics, MedStar Georgetown University Hospital, Washington, DC.

3 Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

4 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.

5 Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD.

6 Division of Pediatric Allergy, Asthma and Immunology, University of Alabama at Birmingham, Birmingham, AL.

7 Liver Diseases Branch, National Institute of Digestive, Diabetes, and Kidney Disease Institute, National Institutes of Health, Bethesda, MD.

8 Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Received 9 November 2018. Revision received 1 January 2019.

Accepted 18 January 2019.

This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E.

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

This trial is registered at (NCT01176006).

The authors declare no conflicts of interest.

A.F.F., N.Y., N.N.S., M.P., P.A., T.H., S.M.H., S.S.K., K.M.K., and D.D.H. contributed to coordination and care of the patient reported in this article. A.F.F., N.Y., N.N.S., and D.D.H. contributed to the first version of this article. A.F.F., N.N.S., and D.D.H. led the clinical transplant trial that this patient was enrolled on for hematopoietic stem cell transplantation with M.P. and S.M.H. also serving as investigators on the trial. D.E.K. provided pathological expertise in the evaluation of this patient. All authors reviewed the article and provided intellectual input and made critical revisions leading to the final submission of this article.

Correspondence: Nirali N. Shah, MD, National Institutes of Health, Building 10/CRC, Room 1-5750, 10 Center Dr, Bethesda, MD 20892. (

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