Birth Order and Transplantation Outcome in HLA-Identical Sibling Stem Cell Transplantation: An Analysis on Behalf of the Center for International Blood and Marrow Transplantation

Abstract

Background Allogeneic stem cell transplantation is the most effective treatment option for many hematological malignancies, but graft-versus-host-disease (GvHD) remains a major cause of treatment failure. Besides well established risk factors for the outcome of transplantation, recent single-center studies have identified a birth order effect in HLA-identical sibling stem cell transplantation with lower incidence of acute and chronic extensive graft-versus-host disease (aGvHD/cGvHD) and improved overall survival when a donor is younger than the recipient. One hypothesized mechanism is microchimerism due to fetomaternal and transmaternal sibling cell trafficking during pregnancy as the donor is exposed to recipient antigens in utero. Design and Methods The aim of this study was to validate single-center data in a multicenter cohort provided by the Center for International Blood and Marrow Transplantation (CIBMTR). All adult and pediatric patients (n=11,365) with a diagnosis of a hematologic malignancy receiving an allogeneic stem cell transplantation from an HLA-identical sibling donor from 1990 to 2007 were included. Results When donors were younger than recipients, there was a significantly lower aGvHD II-IV° and cGvHD rate for children as well as lower cGvHD rate for adolescents. However, the hypothesized overall positive effect of lower relapse and better survival when donors are younger than recipients was not observed in this large multicenter study. Conclusions Our data suggest that if otherwise equally matched, a graft from a sibling younger than the patient may be superior to an older one for child and adolescent stem cell transplant patients.

Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis

“…We were, however, able to validate previously reported single center and CIBMTR results on the effect of birth order in MSD HCT, where a donor younger than the recipient favorably impacted risk of acute and chronic GVHD. (22, 23) In our analysis, adolescents receiving grafts from younger siblings were at decreased risk for cGVHD.…”

Gender influences the birth order effect in HLA-identical stem cell transplantation

“…1,6 Additionally, we show that gender might be one of the causal factors. Interestingly, the birth order effect was significant in the adult female donor/female recipient SCT pairs.…”

EBMT−NIH−CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment

“…Three primary areas differ in the pediatric population with regards to GvHD assessment: (1) some criteria used in adults are difficult to apply in young children (e.g. PFTs and Schirmer’s test for children under the age of 6 [18]); (2) the incidence of cGvHD appears lower in children [42, 43]; and (3) approximately 50% of pediatric transplants are performed for nonmalignant disorders, where tissue repair defects that may impact development of GvHD are more common (e.g. increase of aGvHD in Fanconi Anemia patients [44]).…”