Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant

Abstract

Only 30% of patients who require an allogeneic hematopoietic cell transplant will have an HLA-matched sibling donor. A search for an unrelated donor will be undertaken for patients without a matched family donor. However, many patients, particularly patients of diverse racial and ethnic backgrounds, may not be able to rapidly identify a suitably matched unrelated donor. Three alternative graft sources, umbilical cord blood (UCB), haploidentical (haplo)-related donor, and mismatched unrelated donor (MMUD) are available. UCB is associated with decreased GVHD, but hematologic recovery and immune reconstitution are slow. Haplo-HCT is characterized by donor availability for transplantation and after transplantation adoptive cellular immunotherapy but may be complicated by a high risk of graft failure and relapse. A MMUD transplant may also be an option, but GVHD may be of greater concern. Phase 2 studies have documented advances in HLA typing, GVHD prophylaxis, and infection prevention, which have improved survival. The same patient evaluated in different transplant centers may be offered MMUD, UCB, or haplo-HCT depending on center preference. In this review, we discuss the rationale for donor choice and the need of phase 3 studies to help answer this important question. IntroductionPatient 1 is a 62-year-old woman of Hispanic and Native American descent with a history of breast cancer, treated with surgery and chemotherapy. She is in complete remission; 5 years later, she develops acute myelogenous leukemia (AML) with monosomy 7 karyotype. She attains a complete remission, has an Eastern Cooperative Oncology Group performance status of 1, and reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HCT) is recommended. She has 3 siblings, but none is a HLA full (8/8 HLA-A,-B,-C,-DR) match. One sibling is a haploidentical (haplo) match. Her HLA typing is entered into the National Marrow Donor Program (NMDP), but no fully matched donor is identified. An unrelated donor with a single allele level mismatch at HLA-B is identified. Search of the umbilical cord blood (UCB) registries reveals 2 HLA 4/6 (-A,-B, -DR matches) UCB units with a combined cell dose of 5.3 ϫ 10 7 nucleated cells/kg.Most transplant physicians would agree that the only curative therapy for therapy-related AML is allogeneic HCT, and many would favor an RIC regimen for this patient. However, this patient might be offered a haplo-HCT from her sibling at one transplant center, a double UCB transplant (dUCBT) at a different center, and a mismatched unrelated transplant (MMUD) in another part of the country. All of these options have curative potential but significant mortality and morbidity. How is this patient to decide? What can her hematologists do to assist her?Only 30% of patients will have a matched sibling donor. The NMDP was established in 1986 and now boasts more than 16 million volunteer donors. 1 Today, approximately 60% of white, but only 20% to 45% of black and other minority patients, will be able to find an ...

Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10‐HLAmatched donors and cord blood

“…In comparison with transplants from adult donors, UCB transplants offer the advantage of prompt availability for many recipients and a decreased risk of graft-versus-host disease (GVHD) [2,3], but such transplants are associated with a slower hematological and immune recovery, leading to a higher risk of infection [4,5]. Mismatched-unrelated donor transplants are associated in some studies with a lower risk of relapse, but a higher risk of GVHD [6,7], while haploidentical HSCT may be complicated by a high risk of relapse and delayed immune recovery [8][9][10].…”

How to select the best available related or unrelated donor of hematopoietic stem cells?

“…51 These different graft sources have not yet been compared directly in a randomized trial. High-dose cyclophosphamide treatment after non-myeloablative conditioning and T-cell-replete haploidentical HSCT has been shown to result in acceptable rates of graft rejection and acute GVHD.…”

Umbilical cord blood donation: public or private?

“…In addition, UCB licensure in the United States has increased the costs of public banking and unrelated donor UCBT. The options for donor sources for alternative donor hematopoietic cell transplant (HCT) have increased, with the increase in haploidentical HCT and mismatched unrelated donor HCT; 6 it is, therefore, appropriate and timely to review the data supporting private and public UCB banking options, current uses of UCBT for hematopoietic reconstitution as well as the potential use of UCB in the emerging fields of regenerative medicine and cellular therapies.…”