Benefits of Haploidentical Transplantation from the Development of Unmanipulated Grafts

Selma Romanoff^*
*Correspondence: Dr. Selma Romanoff, Department of Experimental Hematology, University of Groningen, Groningen, Netherlands, Email:

Editorial Note

Recently, the practise of haploidentical transplantation has benefited from the development of platforms of unmanipulated grafts. Based on a Bone Marrow (BM) graft source and a protracted pharmacologic GvHD prevention, Chinese centres have offered pivotal experiences. Huang et al. exhibited a significant number of G-CSF primed BM and PB cells, Antithymocyte Globulin (ATG) conditioning, and a potent GvHD prophylaxis after transplantation. Busulfan, cyclophosphamide, and thymoglobulin were used as part of the conditioning regimen prior to HSCT. For GvHD prevention, the patients were given CsA, mycophenolate mofetil, and short-term MTX.

All of the patients had 100% donor myeloid engraftment; the median time for myeloid engraftment was 12 days, while the median time for platelet engraftment was 18 days. The use of a potent GvHD prophylactic regimen using CSA, MTX, and MMF, as well as an intensified conditioning regimen that adds busulfan to CTX+ATG, the combination of G-BM and G-PB grafts that work synergistically to enhance engraftment, and the use of a potent GvHD prophylactic regimen using CSA, MTX, and MMF, all contributed to full engraftment in Patients who survived had an overall survival rate of 64% and a median follow-up length of 746 days. The incidence of chronic GvHD, on the other hand, was observed to be 56 percent. Zhang recently analysed the clinical data of 18 children with SAA who were treated between 2010 and 2014, with a median follow-up duration of 2 years and 23.5 months (range, 3-52 months).

The overall survival rate was 66.7 percent; however, GvHD occurred in 15/18 of the HHCT patients, with five cases of grade III or above. Lu compared haplo-SCT to transplantation from an Unrelated Donor (UD-HSCT). Between 2012 and 2014, 26 SAA patients had UD-HSCT and 24 patients underwent haplo-SCT as part of a cohort of 50 patients. With a median follow-up of 9 months, the OS rate was 91.3 percent. Haplo-SCT developed a significant high incidence of aGvHD and cGvHD in this study (37 percent).

In Baltimore and Seattle, clinical trials based on post-BM transplantation cyclophosphamide targeting activated donor or host alloreactive T cells were developed, and 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with posttransplant Cy were reported from Brazil.

BM (N=13) and PBSCs (N=3) were used as stem cell sources. The percentage of neutrophil and platelet engraftment was 94 percent and 75 percent, respectively. Two patients experienced secondary graft failure, but were able to be saved with a new transplant.

Three patients had acute GvHD, and five of them died, with a 1- year survival rate of 67 percent (95 percent confidence interval: 36.5-86.4 percent). Clay et al. published pilot results of haplo-SCT with reduced-intensity conditioning and postgraft highdose cyclophosphamide in eight patients with IST-refractory SAA or as a salvage treatment in patients who had previously refused a UD or cord blood transplant. Despite rigorous pre-HSCT desensitisation with plasma exchange and rituximab, six of eight patients engrafted; graft failure was linked to donor-directed HLA antibodies. Only one patient had grade II skin GvHD, indicating that PT-Cy was highly successful in GvHD prophylaxis [1-5].

This preliminary study established the importance of donordirected HLA antibodies in the outcome of haplo-SCT in patients with SAA; routine HLA antibody screening is recommended prior to transplantation, and if antibodies are found, an alternative donor lacking HLA antigens against which recipient HLA antibodies are directed should be used. In the setting of hematologic malignancy, PBSCs have recently been employed for reducedintensity haplo-HSCT with postgraft CY, with no deleterious effects on GvHD or survival as compared to BM.

In order to promote a rapid posttransplant immunological recovery with a preferential buildup of regulatory T lymphocytes, a calcineurin inhibitor-free GvHD prophylaxis based on rapamycin, Mycophenolate Mofetil (MMF), and anti-T lymphocyte globulin (ATG-Fresenius) was investigated (Tregs). Rapamycin is an immunosuppressive medication that, unlike calcineurin inhibitors, encourages the production of natural Treg cells. GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab facilitated a quick immune reconstitution skewed toward Tregs in this preliminary trial, permitting the infusion of unmanipulated haploidentical PBSC grafts in patients with advanced malignancies. The viability of PBSC grafts followed by PTCy and sirolimus-based GvHD prophylaxis (Sir-PTCy) was recently studied, and low rates of GvHD and NRM, as well as a positive immune reconstitution profile, were described.

For patients who do not have an HLA-identical donor, haploidentical transplantation is still considered an experimental treatment, and such transplants should only be performed in the context of controlled clinical trials. The majority of haploidentical transplants have been performed in patients with advanced stages of refractory hematologic malignancies after myeloablative conditioning, with promising results in adult patients with AML, paediatric patients with ALL158, and children with acute leukaemia using CD34+ positively selected grafts. Another study compared the effects of HLA-identical sibling transplantation with unmanipulated haploidentical blood and marrow stem cells [6-10].

Non-myeloablative techniques using unmanipulated HLA 2-3 antigen-mismatched haploidentical stem cells have been used in addition to myeloablative conditioning regimens, with encouraging results. With CD3/CD19-depleted PBSC and a non- TBI based less severe conditioning regimen, fast engraftment and low toxicity have been demonstrated in people with high-risk or refractory illness. Low toxicity and infection rates were linked to less intensive conditioning regimens and CD3/CD19-depleted PBSC.

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