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.

Different Human Immune Lineage Compositions Are Generated in Non-Conditioned NBSGW Mice Depending on HSPC Source

“…Hematopoietic stem cell transplantation (HSCT) using autologous or allogeneic graft tissue sources is a potentially curative treatment for patients with malignant and nonmalignant blood diseases. However, the clinical value of HSCT remains limited by its high potential for complications, including graft-vs-host-disease (GVHD), delayed immune reconstitution, and graft failure (1,2). Recovery of neutrophil and platelet populations is a key indicator of engraftment success that usually occurs between 14 and 25 days posttransplant, with delays beyond this window increasing the chances of mortality due to infection (3,4).…”

“…Recovery of neutrophil and platelet populations is a key indicator of engraftment success that usually occurs between 14 and 25 days posttransplant, with delays beyond this window increasing the chances of mortality due to infection (3,4). Furthermore, the late reconstitution of other immune lineages, which can also demonstrate substantial variability, may carry longterm consequences for patient health, including influencing the likelihood of disease relapse (1)(2)(3)(4). Factors that impact the capacity of human hematopoietic stem and progenitor cells (HSPCs) to engraft and differentiate, and the resulting dynamics of human hematopoietic reconstitution remain poorly understood, underscoring the need for new research strategies.…”

“…Pre-transplant conditioning induces a variety of different inflammatory pathways and produces damage that may alter bone marrow microenvironment in ways that are still not fully understood (11). While pre-transplant conditioning is routinely used in clinical settings, there is substantial variation in the specifics of the regimens used, and the nature of the conditioning regimen is known to influence both the recovery of the immune compartment and the risk of GVHD (1)(2)(3)(4). Myeloablative conditioning is associated with the fastest engraftment, though this is balanced by an increased probability of GVHD (1,2,12).…”

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

“…Only approximately 25% of siblings are HLA-matched, and usually, the only alternatives are unrelated or haploidentical donors [39]. A recent study has reported that post-transplant cyclophosphamide in HLA-haploidentical HSCT is associated with low rates of severe graft-versus-host disease and its efficacy is comparable with HLA-matched HSCT [40].…”

“…Table S5 shows the number of patients with aGvHD for individual studies which report the grade and organs implicated (see Additional file, pp. [38][39][40]. Most of the included patients suffered grade III-IV (82.99%).…”