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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01176006.

Conflict of interest statement

Disclosure: The authors declare no conflicts of interest.

Figures

FIGURE 1.

Timeline illustrating absolute lymphocyte and neutrophil counts, along with hepatic transaminases and bilirubin through the duration of the patient’s clinical course. Relevant chimerism studies are also shown, along with the post-liver transplant immunosuppression and pre-HSCT conditioning regimen. Day 21 white blood cell count was too low to perform chimerism studies.

FIGURE 2.

Pre-HSCT Chest and Abdominal CT scan and liver pathology. A. Chest CT prior to liver transplant showing bronchiectasis of the right middle lobe. B. Abdominal CT prior to liver transplant showing hepatosplenomegaly, nodular liver contour, and evidence of portal hypertension with patent umbilical vein (arrow) and peri-gastric collaterals. Post-Mortem Liver Pathology Findings: C. Extensive hepatic hemorrhage and necrosis with dissociation of individual hepatocytes. D. Nearly complete occlusion of central vein by loose, pale staining matrix and red blood cells, E. Same vessel on a reticulin stain, showing the original collagen wall stained black with a looser basket weave collagen fiber deposition within the lumen.