CGRA4: VENO‐OCCLUSIVE DISEASE WITH IMMUNODEFICIENCY (VODI) TREATED WITH HAPLO‐IDENTICAL BONE MARROW TRANSPLANT

Abstract

Veno-Occlusive disease with Immunodeficiency (VODI) is a rare combined immunodeficiency. Mutations in SP110, have been described in the Lebanese population with VODI. Untreated, reported outcomes for VODI are 100% mortality at one year of life. Conservative management (PJP prophylaxis and Immunoglobulin) result in mortality of 75%. Bone marrow transplant has been demonstrated as the only definitive treatment, but has a high rate of complications. Haploidentical HSCT provides an opportunity for Stem Cell Transplantation in those where a matched donor is not available. Historically, Haploidentical HSCT has been limited by high rates of graft rejection, Graft-Versus-Host Disease (GVHD), Transplant-related mortality and poor immune reconstitution. We present the first case of VODI that has been managed with a TCR alpha/beta, CD19 depleted Haplo-identical HSCT. This patient, the first child to consanguineous Lebanese parents, presented at 4 months of age with a febrile illness, hepatomegaly and abdominal ascites. Immunoglobulins were undetectable and the patient had normal lymphocyte subsets. SP110 mutation was confirmed. Infections included CMV, confirmed on Whole Blood PCR, and Pneumocystis Jerovicii Pneumoniae (PJP) confirmed on Brochoalveolar Lavage PCR. The latter resulted in acute deterioration, for which the patient required High Frequency Oscillatory Ventilation prior to improvement with high-dose Bactrim. CMV infection was treated with Gancyclovir. Haploidentical HSCT was performed using a parent donor. Conditioning consisted of Treosulfan and Fludarabine. The patient engrafted on day 11. MMF was discontinued at day +35. Day +30 donor chimerism was 99%. The post-transplant course has been complicated by deranged liver function, presumed secondary to CMV as liver biopsy has demonstrated resolution of Veno-Occlusive Disease and no evidence of GVHD. This case highlights successful use of Haploidentical HSCT in treatment of VODI. Further evaluation is required with subsequent cases and long-term outcomes.