Successful Reduced Intensity Conditioning Alternate Donor Stem Cell Transplant for Wiskott-Aldrich Syndrome

Abstract

There are very few reports of reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) with alternate donor for Wiskott-Aldrich syndrome (WAS) and there is no report of RIC with posttransplant cyclophosphamide (PTCy) in WAS. There is only 1 report of T cell receptor αβ and CD19-depleted haploidentical HSCT for WAS. Here we report successful outcome in 3 children with WAS who underwent successful RIC alternate donor HSCT of whom 2 (matched unrelated donor and T-cell replete haploidentical) received PTCy and 1 underwent T cell receptor αβ and CD19-depleted haploidentical HSCT. We modified conditioning used by Luznik for haploidentical HSCT by adding thiotepa 8 mg/kg and Campath or rabbit antithymoglobulin for 2 cases who received PTCy. In third case we gave fludarabine, thiotepa, and treosulfan-based conditioning. The mean duration of follow-up for these patients was 23.6 months posttransplant (range, 21 to 26 mo). All 3 patients are transfusion independent. Acute graft versus host disease (GVHD) grade I occurred in 1 and none had chronic GVHD. Chimerism of all 3 was fully donor (>95% donor) at D+30 and D+100 posttransplant. All are alive, healthy, and doing well. Our 3 cases highlight that with newer conditioning and GVHD prophylaxis approach alternate donor HSCT in WAS can become a safe and effective treatment option.

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

“…This prospective study demonstrates promising outcomes with a novel RIC-BMT platform, enabling the use of alternative donors and unmanipulated, T-cell-replete grafts across a range of diseases in high-risk PID patients, with partial to complete phenotype reversal in all surviving patients, overall low toxicity, indication that thymic function and gonadal function may be preserved, and markedly low rates of GVHD. The platform and patient population differ from previously published, largely retrospective reports of other promising RIC-BMT approaches for PID [23][24][25][26][27][28] in that our conditioning was radiation free, there was no in vivo T cell depletion with serotherapy or ex vivo graft manipulation, and both pediatric and adult patients were included. The rates of graft failure, GVHD, and TRM seen here are lower than other reports of RIC-BMT outcomes for PID where 1 or more of these complications were more frequent [29][30][31].…”

Posttransplant cyclophosphamide for haploidentical stem cell transplantation in children with Wiskott–Aldrich syndrome

“…HSCT is the only available curative treatment for WAS and there are some reports of HSCT with a family donor combined with PTCy for this disease. 13,14 15 In our pilot study, using modified PTCy, our patients did Recently, there have been only two case reports of three patients with WAS transplanted with a haploidentical donor with PTCy. 13,14 The benefit of haplo-HSCT with PTCy is the selective suppression of alloreactive T cells in the graft, which can reduce GVHD and preserve T-regulatory and memory cells, facilitating successful engraftment.…”

“…HSCT is the only available curative treatment for WAS and there are some reports of HSCT with a family donor combined with PTCy for this disease . In this prospective phase II clinical trial of family donor bone marrow transplant (BMT) with PTCy, five patients achieved a complete platelet reconstitution of their refractory WAS with minimal toxicity.…”

“…Recently, there have been only two case reports of three patients with WAS transplanted with a haploidentical donor with PTCy . The benefit of haplo‐HSCT with PTCy is the selective suppression of alloreactive T cells in the graft, which can reduce GVHD and preserve T‐regulatory and memory cells, facilitating successful engraftment.…”

Acute GvHD prophylaxis with posttransplant cyclophosphamide after hematopoietic stem cell transplantation (HSCT) for non-malignant disorders

“…A higher risk of non-engraftment in cases of haploidentical donorship could be decreased due to myeloablative conditioning regimens. The recruitment of haploidentical donors for HSCT in children with primary immune deficiencies and sickle-cell anemia have been described in present studies [9,10,11]. PtCy prophylaxis was applied in all these cases showing its clinical efficiency.…”