Ten‐year experience of unrelated bone marrow donor transplants in children with malignant and non‐malignant conditions

Abstract

Children who require a marrow transplant may receive such hematopoietic cells from one of many sources. This study reviews the experience of one center with 58 children who received marrow from unrelated donors over a 10-year period. These children had a variety of malignant and non-malignant diseases. During that time period, only three of these children had failed to meet engraftment criteria. All donor marrow specimens were T-lymphocyte-depleted using an antibody/complement methodology. No difference was demonstrated in outcome between donors who were perfectly HLA-DR DNA matched versus those who were only partially matched. The increased size of various marrow donor registries has increased the number of potential donors available for these patients. The lack of a requirement for perfect matching means that there is an ever-increasing number of donors available. No graft-versus-host disease (GvHD) or grade III-IV GvHD was associated with a poorer outcome. Stable, long-term engraftment with minimal morbidity has been demonstrated in these children as evidenced by stability of survival curves by two years after marrow transplant.

Milestones in the development of pediatric hematopoietic stem cell transplantation—50 years of progress

“…Mismatched familial transplants are characterized by one or more major histocompatibility loci differences between donor and recipient, or complete haploidentical transplants, where there is a complete disparity at one of the two HLA A, B or DR loci, and these transplants took place in great numbers in the 1980s and early 1990s (13). Most, but not all, of these clinical protocols attempted to overcome the significant graft‐vs.‐host disease problems by removing more than two logs of T‐lymphocytes from the donor stem cell inoculum (29, 31). From these experiments, the investigators derived a great deal of knowledge and experience in the role of T‐lymphocytes when removing them from the transplant inoculum.…”

“…In addition, the removal of T‐lymphocytes increased the potential for opportunistic infections due to the subsequent delay in T‐lymphocyte recovery, and the delay in T‐lymphocyte recovery led to an increased relapse rate in those patients receiving such marrow grafts which were T‐lymphocyte depleted. However, the goal of using mismatched or haploidentical donors had achieved an important milestone which was now making it possible for every patient who had a disease that could be treated with hematopoietic stem cell transplant to be eligible for such treatment, without limitations as to whether a donor was available or not (31). The only children who failed to find a donor when considering the use of hematopoietic stem cells from mismatched or haploidentical family donors were those who had been adopted and whose families were not traceable, or alternatively children who had no siblings or parents due to some sort of environmental accident or early death.…”

“…With increasing recruitment efforts through the 1980s and into the 1990s, well over 4,000,000 donors have been registered world‐wide and listed in the NMDP registry, making it possible to find close if not perfect matches more than half the time for individuals without a matched familial donor. Several studies have documented that children will tolerate some histocompatibility difference between donor and recipient, making it possible to find unrelated donors for children with an ever increasing frequency (31). Again, another milestone had been achieved in the development of the pediatric hematopoietic stem cell field by continuing to increase the population of children eligible for transplant by defining new groups of donors, thereby circumventing the earlier problem whereby many patients could not avail themselves of marrow transplant therapy for lack of a matched related allogeneic donor.…”