We report 7-year follow-up of haploidentical transplant in a patient with WAS, where alternative options were limited.

An 18-month-old boy, a first-born from a non-consanguineous marriage presented with congenital thrombocytopenia, recurrent eczematous lesions on the skin with recurrent ear infections and diarrhea. Evaluation revealed micro-thrombocytopenia (mean platelet volume-7.2 fl) and platelet counts ranging from 15- 40,000/cu.mm. Front typing of blood grouping showed A positive with absent Anti B during back typing suggesting IgM-deficiency. DNA studies revealed a novel mutation at exon 10 of X chromosome (343-344 del (-C) ProfsX444). A similar mutation was identified in the mother. HLA-typing noted that father was a 5/6 antigen match with incompatibility at the HLA B locus on low -resolution and later confirmed to be 7/10 on high-resolution typing.

As a curative option of treatment, the child underwent an allogeneic stem cell transplant (bone marrow as stem cell source) with a modified busulfan/cyclophos-phamide/Antithymocyte globulin (ATG) conditioning. ATG was scheduled with cyclophosphamide for an in vivo depletion of the donor T cells. Time to neutrophil engraftment and platelet engraftment was day 15 and day 23, respectively.

On day 26, he developed discrete erythematous maculopapular rash over face and head and neck area suggestive of skin graft versus host disease (GVHD). Later the skin lesions progressed to involve the scalp, face, extremities, trunk, palms and soles (BSA=75%) by day 53. Skin biopsy was suggestive of acute GVHD, Grade 3.

He did not have any evidence of liver or gut GVHD and there were no signs of chronic GVHD in any other organs. One month after the completion of immunosuppression (23 months post BMT), vaccination was initiated. Initially conditioning was planned as per one antigen mismatch, retrospective high resolution typing at 2 years post-transplant confirmed that it was a haploidentical transplant with more than 1 antigen mismatch.

This transplant was performed when 10 antigen typing, matched unrelated and cord blood transplant facilities were not widely available in India. Literature review of eight studies between 1979 and 2014, reported 17 haploidentical transplants in the age group of 2-12 years with 8 survivors. Conditioning regimens used were Cytosine arabinoside/Total body irradiation (2), Busulfan/Cyclophosphamide (5), Cyclophosphamide/TBI (3) and Fludarabine based (4). Stem cell source was bone marrow in majority (13) and the rest used peripheral blood stem cell products (4) and T cell depletion (TCD) was performed in most of the cases (12) [4-10]. Un-manipulated haplo-identical transplant has been reported from the Spanish group when no other HLA-identical donors were available [4].

This case highlights the feasibility of doing haplo-identical stem cell transplant with unmanipulated BM as the source from a parent using Bu/Cy/ATG conditioning protocol and severe GVHD could be successfully managed using multidisciplinary approach using systemic and local modalities.

Acknowledgment: Dr Eunice Singhvi from CMC Vellore for identifying the novel mutation.

Contributors; MJJ: planned the management and drafted the initial manuscript, CCP: reviewed the literature and helped in manuscript preparation. AM: edited the manuscript and reviewed the literature, AW: was involved in the case management and drafting of the manuscript, NK: case management and gave inputs into the manuscript. All authors approved the final version of the manuscript.

Funding: None; Competing interests; None stated.

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