Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts

Abstract

Summary:During the reproductive period, mothers and offspring exchange hematopoietic cells and develop a form of immunological tolerance bidirectionally. To examine whether previous experience of such communication has any remote effect when maternal hematopoietic cells are later transplanted to the children, we retrospectively compared the outcomes of blood and marrow stem cell transplantation from maternal donors (n = 46) to those from paternal donors (n = 50) by using the database of the Japanese nationwide surveys for adult hematopoietic cell transplants between 1990 and 1998. At 5 years, recipients of maternal hematopoietic cells had a significantly higher overall survival than patients receiving paternal grafts (60% vs 32%, P = 0.006). Although no significant difference was observed in the occurrence of severe acute GVHD (grade уIII) and the relapse of malignant diseases between two groups, the probability of non-relapse treatment-related mortality was significantly lower after maternal donor transplants. Furthermore, multivariate analysis revealed that parental donor type was the only factor significantly associated with overall survival. In conclusion, our analysis indicates superior survival of maternally donated recipients in hematopoietic stem-cell transplantations from biological parents. This finding has important implications in the selection of alternative familial donors, and warrants further prospective analysis of parental donor transplantations. Allogeneic hematopoietic stem cell transplantation after myeloablative or nonmyeloablative chemoradiotherapy is a potentially curative treatment for various hematologic and hereditary diseases. 1,2 Since the availability of an HLAidentical sibling donor is often limited, most patients eligible for allogeneic stem cell transplants have to seek an alternative donor who is not fully histocompatible with themselves. 3-5 HLA-phenotypically matched or partiallymismatched parents represent an important stem-cell source for such patients, because both mother and father genetically share at least one HLA haplotype with their children.Maternal and paternal donations differ in the transplant situation because only the mother-child pair has had the opportunity to establish bidirectional immunological tolerance during pregnancy and maybe thereafter. For example, maternal peripheral blood lymphocytes were shown to be immunologically unresponsive to those of the infant for several months following delivery. 6 On the other hand, about half of the patients receiving multiple transfusions as adults did not form antibodies against the non-inherited maternal HLA antigens, 7 indicating the persistence of acquired B cell unresponsiveness to maternal antigens into adult life. More surprisingly, semi-allogeneic fetal hematopoietic cells were detectable from parous women not only during gestation but also many years after childbirth, [8][9][10][11] suggesting a long-lasting form of the maternal tolerance to fetal HLA antigens of paternal origin.To date, the role of such previo...

Indirect evidence that maternal microchimerism in cord blood mediates a graft-versus-leukemia effect in cord blood transplantation

“…Importantly, anti-IPA memory T cells persist in the mother for decades. This finding probably explains the recent findings of Stern et al (7) that HLA-haploidentical hematopoietic stem cell (HSC) transplants from mother to child have lower relapse rates and improved survival compared with paternal grafts, confirming and extending earlier studies (8).…”

Reduced-intensity non-T-cell depleted HLA-haploidentical stem cell transplantation for older patients based on the concept of feto-maternal tolerance

“…Despite the frequent detection of feto-maternal microchimerism, 10 the results in renal transplantation, 7 and the retrospective analysis of conventional SCT 8,9 all of which strongly support the concept of feto-maternal tolerance, immunological and clinical evidence has been limited. Furthermore, long-term problems, such as slow immune reconstitution in mismatched SCT 11 and lateonset GVHD in RIST 12 may influence outcome, especially in older patients.…”

“…7 With this in mind, retrospective analysis of Japanese nationwide surveys for adult conventional SCT demonstrated a higher overall survival in patients receiving maternal hematopoietic stem cell (HSC) compared with those receiving paternal HSC. 8 A retrospective analysis by the International Bone Marrow Transplantation Registry (IBMTR) revealed the effect of tolerance to NIMA on occurrence of GVHD in the setting of conventional transplantation. 9 Although the duration of follow-up is too short for reliable evaluation in the setting of an aggressive disease, favorable engraftment and control of GVHD were observed in our study.…”

A feasibility study on the prediction of acute graft-vs.-host disease before hematopoietic stem cell transplantation based on fetomaternal tolerance

“…5 Maternal grafts were found to be associated with better outcome than paternal grafts. 4,6 These clinical studies have been performed based on the presence of fetomaternal microchimerism as a result of fetomaternal immunological tolerance. Nevertheless, some cases developed severe acute graftvs.-host disease (GVHD) despite the existence of microchimeric cells.…”