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There are many indications for hematopoietic stem cell transplantation. In addition to hematologic malignancies, transplants are performed in certain non-hematologic malignancies, for marrow disorders such as Sickle Cell Anemia, and for various inherited disorders such as SCID. Traditionally, transplants have been performed between donors and recipients that are a complete HLA match (typically matched siblings). That is, patients have identical HLA alleles on both copies of chromosome 6. HLA alleles code for major histocompatibility complex molecules, which are the proteins that cause transplant rejection when a mismatch between donor and recipient is present. Thus, matched transplants have been historically favored in order to avoid both rejection of the graft by the recipient, as well as disease in the recipient due to graft vs. host disease (GVHD) in which the donor immune cells attack the host’s tissues.

However, matched transplants have several disadvantages. First, only about 30% of patients requiring a transplant have a matched sibling available as a donor. For the remaining 70%, the search for an unrelated matched donor can be time consuming, expensive, and especially difficult for patients of minority racial and ethnic groups. Many conditions requiring transplant are so acute that patients often die during the search for a donor. Accordingly, several institutions pioneered the research and implementation of haploidentical transplants as a viable option.

A haploidentical transplant refers to the situation when the recipient and donor have identical alleles on one copy of chromosome 6, but not on the other. In terms of advantages, haploidentical transplants greatly increase the pool of available donors since biological parents are by definition haploidentical to all of their children, and there is a much greater chance that a sibling will be a half match than a full match. Additionally, haploidentical transplants allow for a critical Graft vs. Tumor effect (GVT), whereby the donor’s immune cells attack the recipient’s cancer cells because of the HLA mismatch present. The caveat, however, is that this mismatch also promotes GVHD that can be lethal. Accordingly, different institutions have attempted various methods of manipulating the donor graft to try and maximize the GVT effect while minimizing GVHD. Jefferson’s regimen is one such method that has had success thus far.