Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide for Primary Immunodeficiencies and Inherited Disorders in Children

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some inherited disorders, including selected primary immunodeficiencies (PIDs). In the absence of a well-matched donor, HSCT from a haploidentical family donor (HIFD) may be considered. In adult recipients high-dose post-transplant cyclophosphamide (PTCY) is increasingly used to mitigate the risks of graft failure and graft-versus-host disease (GVHD). However, data on the use of PTCY in children (and especially those with inherited disorders) are scarce. We reviewed the outcomes of 27 children transplanted with an HIFD and PTCY for a PID (n = 22) or osteopetrosis (n = 5) in a single center. The median age was 1.5 years (range, .2 to 17). HSCT with PTCY was a primary procedure (n = 21) or a rescue procedure after graft failure (n = 6). The conditioning regimen was myeloablative in most primary HSCTs and nonmyeloablative in rescue procedures. After a median follow-up of 25.6 months, 24 of 27 patients had engrafted. Twenty-one patients are alive and have been cured of the underlying disease. The 2-year overall survival rate was 77.7%. The cumulative incidences of acute GVHD grade II, chronic GVHD, and autoimmune disease were 45.8%, 24.2%, and 29.6%, respectively. There were 2 cases of grade III acute GVHD and no extensive cGVHD. The cumulative incidences of blood viral replication and life-threatening viral events were 58% and 15.6%, respectively. There was evidence of early T cell immune reconstitution. In the absence of an HLAidentical donor, HIFD HSCT with PTCY is a viable option for patients with life-threatening inherited disorders.

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

“…At present, there are no published PTCy-based haplo transplant approaches for patients with PID that similarly avoid serotherapy, radiation, and/or myeloablation for direct comparison to this platform. Approaches that do include 1 or more of these factors have resulted in high engraftment rates with haplo donors in patients with PID [23,35,40,41]. Regardless, further improving engraftment without sacrificing the favorable aspects of this platform is desirable.…”

Sustained Remission After Haploidentical Bone Marrow Transplantation in a Child With Refractory Systemic Juvenile Idiopathic Arthritis

“…The procedure was very effective in controlling SJIA activity within a few months, similarly as for most patients previously treated by intensive immunosuppressive conditioning regimens followed by autologous HSCT (16) or allogenic HSCT from HLA-matched related or unrelated donors (13) ( Table 2). The achievement of long-lasting, complete SJIA remission off-steroids or other immunosuppressive therapy in our patient and other SJIA patients who successfully underwent allogenic HSCT offers hope of de nitive cure, which is speci c to this peculiar therapeutic procedure, although a longer follow-up is required.…”

“…As there are more and more innovative therapeutic options in SJIA, as witnessed by several currently ongoing trials with new biologics and Janus Kinase inhibitors, only a tiny minority of SJIA patients should be proposed allogenic HSCT. However, the feasibility and safety of this therapeutic approach is also regularly improving, thanks to the increasing experience of haploidentical HSCT in other non-malignant diseases, particularly in patients with primary immunode ciencies (16).…”

Hematopoietic Stem Cell Transplantation for Combined Immunodeficiencies, on Behalf of IEWP-EBMT

“…In the absence of a matched-donor, decision to transplant needs to be balanced. Transplantation from an alternative donor is more challenging even though most recent results show increasingly successful survival, allowing to consider transplant early in the disease course (43)(44)(45)(46). At the end, the final decision about transplant will depend on a conjunction of factors such as immunological parameters, the severity of past and current clinical manifestations, i.e., severity of infections, autoimmunity, need of immunosuppressive treatment to control the manifestations related to immune dysregulation and donor compatibility.…”

“…Haplo-HSCT strategies without ex vivo graft manipulation, but using posttransplant cyclophosphamide (PTCY) as GVHD prophylaxis, have been increasingly used to treat adult patients with malignant diseases. Data on PTCY in children with PIDs and CIDs are still limited but encouraging (43,44). All these alternative approaches need to be prospectively compared in the context of CIDs.…”