Poor Outcome of Domino Hematopoietic Stem Cell Transplantation in Humans - an International Case Series

Background

Domino hematopoietic stem cell transplantation (HSCT) refers to a situation where an HSCT recipient serves as the donor for another (HLA-identical) recipient. Several successful cases have been reported, suggesting that acquired tolerance to HLA-antigens in the first recipient allows for engraftment in the second recipient, with low risk of graft-versus-host disease (GvHD). However, no systematic analyses on the outcome of domino HSCT have been performed.

Methods

A retrospective, questionnaire-based study was performed within the European Bone Marrow Transplant (EBMT) network and the Primary Immune Deficiency Treatment Consortium (PIDTC). Primary outcome measures were survival and re-transplantation; secondary outcome measures were incidence of GvHD and time to neutrophil and platelet engraftment.

Findings

We identified 11 domino-HSCTs performed in 9 different centers, between September, 1992 and March, 2016. Indications were immune deficiency (n=9), inborn errors of metabolism (n=1) and hereditary bone marrow failure (n=1). The outcome of domino recipients was poor and inferior to their donors and to published cases. Only five recipients (45%) survived with long-term donor engraftment, of whom one required repeated donor-lymphocyte infusions. Four recipients (36%) required re-transplantation and two (18%) engrafted but died from infectious complications. The time between domino-HSCT and re-transplantation ranged up to 190 months. No differences were found in CD34⁺ cell dose, total nucleated cell dose, nor in kinetics of engraftment between successful domino HSCTs and those resulting in re-transplantation. One domino recipient and six primary recipients developed GvHD.

Interpretation

This study demonstrates the disappointing outcome of domino-HSCT. Alternative donor sources, if available, should be considered. Replicative stress on the transplanted stem cells, loss of "stem-ness", and immune-mediated mechanisms may contribute to the limited engraftment upon serial transplantation. In addition, our results stress the importance of systematic evaluation of published and unpublished cases for unbiased clinical decision making.