Tandem Orthotopic Living Donor Liver Transplantation Followed by Same Donor Haploidentical Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency: Tandem Liver and Bone Marrow Transplant in DOCK8 Deficiency

Background: An 11-year old girl with 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 percent donor lymphocyte chimerism in her peripheral blood immediately prior to HSCT. Haploidentical related donor HSCT performed two months after liver transplantation was complicated by the development of acyclovir-resistant HSV viremia, primary graft failure, and sinusoidal obstruction syndrome (SOS). The patient died from SOS 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 prior to 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. Acknowledgments: 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 U.S. Government. This trial is registered at Clinicaltrials.gov NCT01176006 Disclosure: The authors declare no conflicts of interest. Corresponding author: Nirali N. Shah , National Institutes of Health, Building 10/CRC, Room 1-5750, 10 Center Drive, Bethesda, MD 20892, USA. Phone 240-760-6199 , Email: shahnn@mail.nih.gov Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2G9INS9