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

Author:

Freeman, Alexandra F

Yazigi, Nada

Shah, Nirali N

Kleiner, David E

Parta, Mark

Atkinson, Prescott

Heller, Theo

Holland, Steven M

Kaufman, Stuart S

Khan, Khalid M

Hickstein, Dennis D
Author Address

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Pediatric Liver Transplantation, Department of Pediatrics, MedStar Georgetown University Hospital, Washington DC., Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD., Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute., Division of Pediatric Allergy, Asthma and Immunology, University of Alabama at Birmingham, Birmingham, AL., Liver Diseases Branch, National Institute of Digestive, Diabetes, and Kidney Disease Institute, National Institutes of Health, Bethesda, MD., Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.,

Abstract:

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. 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. 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. 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.

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