How we perform haploidentical stem cell transplantation with posttransplant cyclophosphamide

Abstract

HLA-haploidentical hematopoietic stem cell transplantation is now one of the most commonly employed alternative donor techniques, with most centers applying T-cell-replete strategies such as that developed by the Baltimore group using high-dose posttransplant cyclophosphamide. HLA-haploidentical hematopoietic stem cell transplantation using posttransplant cyclophosphamide is associated with low rates of severe graft-versus-host disease and nonrelapse mortality and does not require graft manipulation or storage, which results in a low graft acquisition cost. Its remarkable safety when used with reduced-intensity conditioning has been demonstrated in patients up to 75 years old with outcomes similar to those of patients in their 50s. Several large, registry-based retrospective studies have confirmed the efficacy of HLA-haploidentical hematopoietic stem cell transplantation with posttransplant cyclophosphamide, achieving results comparable to those of HLA-matched hematopoietic stem cell transplantation. In this article, we describe our approach to this rapidly available and clinically simple platform and address some of the key clinical questions associated with its use.

Figure 1.

Family pedigree of the patient in the clinical case. An HLA-haploidentical donor has inherited one HLA haplotype in common with the recipient and is mismatched for anywhere between 0 and 5 HLA genes on the unshared haplotype. Biological parents and biological children always share an HLA haplotype with the recipient, unless a rare genetic rearrangement has occurred. In this pedigree analysis, the patient has 3 siblings, none of whom are HLA-matched, but 2 are partially matched related (haploidentical) donors, whereas 1 brother is disparate. Other potential HLA-haploidentical donors include half-siblings, aunts, uncles, nieces, nephews, cousins, or grandchildren.

Figure 2.

Rationale for using an alternative donor for second allogeneic transplantation. The patient’s 2 HLA haplotypes are shown in blue and red. The first donor shares a common blue haplotype with the recipient and a distinct yellow haplotype. At relapse, the leukemic blasts lose the mismatched red haplotype, which results in loss of cell surface expression of that mismatched HLA molecule. After relapse and subsequent chemotherapy to induce a remission, a second haploidentical donor is selected because they share the red haplotype with the patient, but lack the blue haplotype. This will allow the second donor’s immune system to recognize these disparate HLA molecules on the leukemic blasts to potentially elicit graft-versus-leukemic effects. Figure concept was influenced by two prior publications.