Mismatched related vs matched unrelated donors in TCRαß/CD19-depleted HSCT for primary immunodeficiencies.

TCRαß+/CD19+ graft depletion effectively prevents graft-versus-host disease (GVHD). In the current study, we compared the outcomes of hematopoietic stem cell transplantation (HSCT) with TCRαß+/CD19+ depletion from matched unrelated donors (MUDs) and mismatched related donors (MMRDs) in patients with primary immunodeficiency (PID). A total of 98 pediatric patients with various PIDs underwent HSCT with TCRαß+/CD19+ graft depletion from MUDs (n = 75) and MMRDs (n = 23). All patients received a fludarabine-/treosulfan-based conditioning regimen, with 73 also receiving a second alkylating agent. For GVHD prophylaxis, all but 2 received serotherapy (antithymocyte globulin) before HSCT and a short course of posttransplant immunosuppression. Neutrophil and platelet engraftment in both the MUD and MMRD groups occurred on days 14 and 13, respectively. The incidence of secondary graft failure was 0.16 and 0.17 (P = .85), respectively. The cumulative incidence of acute GVHD grade 2 to 4 was 0.17 in the MUD group and 0.22 in the MMRD group (P = .7). The incidence of cytomegalovirus (CMV) viremia was 0.5 in the MUD group and 0.6 in the MMRD group (P = .35). The frequency of CMV disease was high (17%), and the most common manifestation was retinitis. The kinetics of immune recovery was similar in both groups. The overall survival was 0.86 in the MUD group and 0.87 in the MMRD group (P = .95). In our experience, there was no difference in the outcomes of HSCT performed from MUD and MMRD. Hence, given the immediate availability of donors, in the absence of HLA-identical siblings, HSCT with TCRαß+/CD19+ graft depletion from MMRDs can be considered as the first choice in patients with PID.

Serious Hemorrhagic Complications After Successful Treatment of Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy With Defibrotide in Pediatric Patient With Myelodysplastic Syndrome.

Background: Transplant-associated thrombotic microangiopathy (TAM) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). There is some evidence of endothelial injury playing a significant role in TAM development. The efficacy of defibrotide was demonstrated for prophylaxis and treatment of another HSCT-associated endothelial damage syndrome-liver veno-occlusive disease. The data for defibrotide usage in TAM are limited. Case Description: A 9-year old boy underwent HSCT from a matched unrelated donor for monosomy seven-associated myelodysplastic syndrome treatment. A myeloablative preparative regimen and post-transplant immunosuppression with cyclophosphamide on days +3 and +4 and a combination of tacrolimus with mycophenolate mofetil from day +5 were used. From day +61, sustained fever with progressive neurologic impairment and no evidence of infection was observed. On day +68, the patient developed severe TAM with acute kidney injury requiring renal replacement therapy (RRT). Defibrotide therapy 25 mg/kg/day was administered for 7 days with resolution of TAM symptoms. It was followed by multiple hemorrhagic episodes-epistaxis, hemorrhagic cystitis, and renal hemorrhage, which are presumed to be the complications of defibrotide therapy. Conclusion: Defibrotide could be an effective therapy for TAM, but adequate doses, duration of therapy, and drug safety profile both for pediatric and adult patients need to be evaluated by randomized prospective studies.