aGvHD,   GvHD Prophylaxis,  cGvHD

Educational theme: Impact of the stem cell source on GvHD

Graft-versus-host disease (GvHD) is one of the main causes of death in patients who receive allogeneic stem cell transplantation (allo-SCT). GvHD is an immune condition where the transplanted donor cells consider the recipient tissues as foreign and attack the body. Clinically it can present either as acute (aGvHD) or chronic (cGvHD) depending on how long after the allo-SCT it happens.

For allo-SCT to be performed there is a need for a stem cell donor. Ideal donors are human leukocyte antigen (HLA)-matched related donor (MRd; from siblings) or an HLA-matched unrelated donor (MUd). However, approximately 70% of patients will not have a matched sibling donor and a MUd might not be available.1 Alternative stem cell sources can be from an HLA-mismatched unrelated donor (MMUd), an HLA-partially matched haploidentical donor (family member) or umbilical cord blood samples (UCB). To reduce the risk of GvHD after transplantation, cyclophosphamide (PTCy) is commonly administered to suppress the T cells of the host. 1

Very few randomized phase III clinical trials have compared the impact of all the above stem cell sources on GvHD incidence, as patients receiving allo-SCT represent a very heterogeneous sample (such as different hematological conditions). Clinicians are thus left to decide the stem cell donor without solid evidence on which one is better for each patient subgroup.

Below are some highlights of content that the GvHD Hub has previously published to enhance knowledge on the effect of stem cell source on GvHD risk and help clinicians make an informed decision when it comes to donor choice.

Post-transplant cyclophosphamide use in matched HLA donors

Riad El Fakih from the King Faisal Hospital & Research Center, Riyadh, SA, and colleagues published a literature review on the use of PTCy in MUd and MRd transplants. PTCy is widely used after haploidentical transplants but there is limited data on its use following MUd and MRd allo-SCT. The authors reviewed a number of studies which are presented in a summary table here and concluded that the use of PTCy seems to reduce the incidence of both aGvHD and cGvHD without affecting relapse rates.

Furthermore, Irene García-Cadenas from the Hospital de la Santa Creu I Sant Pau, Barcelona, ES, discussed at the 2019 EBMT meeting the role of incorporating PTCy-based prophylaxis as standard of care in MRd or MUd transplants for patients with an increased risk of GvHD. The study concluded that reduced-intensity conditioning allo-SCT with PTCy in combination with tacrolimus or sirolimus as immunosuppressive drugs are a good option for patients at high risk of GvHD. Read more about this study in this summary published by the GvHD Hub.

Haploidentical vs haplo-cord transplant in adults receiving fludarabine and melphalan conditioning

In this retrospective study, the use of UCB as the donor source for allo-SCT (haplo-cord) was compared to haploidentical transplants in terms of efficacy and GvHD incidence. The results of the trial showed that the incidence of GvHD was lower, and neutrophil and platelet recovery was quicker after haplo-cord than haploidentical transplant. Nevertheless, similar efficacy results were obtained for the two groups with no differences in progression-free survival (PFS) or overall survival (OS). Moreover, despite PTCy-based prophylaxis, GvHD remained a serious side effect of haploidentical transplantations. The authors concluded that both haploidentical and haplo-cord transplants are good alternatives to patients without MRd or MUd donors and that the choice between these two should be based on the patient’s fitness, the availability of cord blood, as well as the cost and strain on hospital resources according to the clinicians’ discretion.

Arnon Nagler | EBMT 2019 | Haploidentical hematopoietic transplantation: current status and future perspectives

Prof. Arnon Nagler from Sheba Medical Center, Tel Aviv, IL, spoke to the GvHD Hub during the 2019 EBMT meeting, about the current advances with haploidentical allo-SCT and its future clinical perspectives. He highlighted the major development in the field of haploidentical transplants, which is the use of PTCy that enabled a significantly lower transplant-related mortality when compared to previous strategies. Moreover, Prof. Nagler mentioned that in a study they performed comparing haploidentical to MRd transplants in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) there were no differences in efficacy or safety between the regimens. Nevertheless, according to his clinical experience, MRd remains the best stem cell source for allo-SCT in the AML and ALL setting.

Clinical features of cGvHD following cord blood infused haploidentical transplantation

In this multicenter, non-randomized prospective trial, summarized by the GvHD Hub, the clinical features of cGvHD following haploidentical transplant with cord blood infusion was assessed. Multivariate analysis showed that GvHD overall survival (GOS) was associated with relapse, thrombocytopenia, bronchiolitis obliterans syndrome, and steroid-refractory cGvHD. Interestingly, the infused CD34+ cells from the haploidentical grafts were a protective factor for GOS.

Although there is limited prospective clinical evidence comparing different allo-SCT donor sources and their impact on GvHD, the advances in the field of haploidentical transplant provide hope that in the future the incidence of GvHD will be further reduced with fewer patients dying from GvHD-related toxicities. The quick access feature of a haploidentical donor is a crucial benefit for patients with hematological conditions, as a delay in transplantation due to donor issues can result in poor patient outcomes.

The GvHD Hub is constantly up-to-date with all the latest advances and most recent publications in the field and this month’s focus will be content on the role of the stem cell source in GvHD. Stay tuned!

References
  1. Kekre N. & Antin J.H. Hematopoietic stem cell transplantation donor sources in the 21st century: Choosing the ideal donor when a perfect match does not exist. Blood, Vol. 124, pp. 334–343. 2014. DOI: 10.1182/blood-2014-02-514760
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