Bone marrow (stem cell) transplantation has historically depended on the availability of a compatible (HLA-matched) brother or sister. Because of genetic inheritance, however, only a minority of children have a compatible sibling. To compensate for this, bone marrow donor registries and placental (cord) blood banks (another source of transplantable blood-forming stem cells) have been developed. While these sources of unrelated, i.e. from donors outside the family, stem cells have been quite useful for the cure of high-risk leukemia, their use for non-malignant conditions such as thalassemia major (TM) or sickle cell disease (SCD), have been limited by the extensive degree of compatibility required and the relative rarity of TM- or SCD-prone ethnic groups in donor registries or cord blood banks. Last but not least the cost issue: the search and identification of an unrelated donor or a cord blood unit may cost over 50,000 USD. At present the chance of a child from a TM or SCD ethnic group who does not have a compatible brother or sister to find a suitably matched unrelated donor is less than 30%.
The ability to use partially compatible (haploidentical) family members, typically the mother, as stem cell donors has been a long-sought holy grail of bone marrow transplant specialists. Even though early studies suggested that maternal marrow transplantation was feasible1–3, toxicities and costs where prohibitive. A recent simple and very inexpensive modification of transplant protocols, namely the administration of some chemotherapy after transplantation aiming at selectively killing unwanted immune cells activated in the early post-BMT phase, has made a major revolution opening up opportunities for safe, effective and inexpensive BMT for over 95% of children who have a biological mother, father or semicompatible sibling4. What mother would not gladly (and free of cost) donate bone marrow to save the life of her child? Thanks to this critical advance partially matched related donors have now been used for both leukemia and SCD with very encouraging outcomes5,6, and, most importantly, with a simple methodology which may be applicable in settings with more limited resources where the great majority of children with TM or SCD live.
Dr Lawrence Faulkner, our medical coordinator, is one of the pioneers in the field of maternal bone marrow transplant for thalassemia.
2.Tamaki, S. et al. Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts. Bone Marrow Transpl. 28, 375–380 (2001).
3.Sodani, P. et al. Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia. Blood 115, 1296 – 1302 (2010).
4.Luznik, L., Engstrom, L. W., Iannone, R. & Fuchs, E. J. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 8, 131–138 (2002).
5.Bolaños-Meade, J. et al. HLA-haploidentical bone marrow transplantation with post-transplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood (2012). doi:10.1182/blood-2012-07-438408
6.Bashey, A. et al. T-Cell–Replete HLA-Haploidentical Hematopoietic Transplantation for Hematologic Malignancies Using Post-Transplantation Cyclophosphamide Results in Outcomes Equivalent to Those of Contemporaneous HLA-Matched Related and Unrelated Donor Transplantation. J. Clin. Oncol. 31, 1310–1316 (2013).