Successful haploidentical stem cell transplantation in a 3-month-old child with reticular dysgenesis using post-transplant cyclophosphamide: A case report & literature review from Pakistan

Abstract

Abstract Reticular dysgenesis is the most severe and rarest form of primary immunodeficiency disorder. Children with severe combined immunodeficiency mainly have lymphopenia. But this rare variant has an additional feature of neutropenia not responding to growth factor. There should be a high index of suspicion for this disease if any infant is presenting with recurrent infections with persistently low myeloid and lymphoid cell lines. A late preterm and low birth weight baby was found to have bi cytopenia incidentally. Presumed sepsis was treated but there was persistent lymphopenia and neutropenia. He had recurrent infections that raised the suspicion of immunodeficiency. He was a product of consanguineous marriage. He was diagnosed with reticular dysgenesis on whole exome sequencing homozygous mutation in mitochondrial AK2 gene variant c.94-2A > G. At 3.5 months of age, he underwent a haploidentical bone marrow transplant using myeloablative conditioning. He had neutrophil and platelet engraftment on post-transplant day + 14 and day + 16 respectively. He maintained full donor chimerism (> 90%) at post-transplant D + 30, + 60 and + 120. Nine months after the transplant his blood counts dropped and he developed severe neutropenia not responding to GCSF. He was given a CD34 booster dose (6.6 x 10^6 cells per kg/recipient body weight). Then eventually his blood count recovered. After, twenty months of transplant, he presented with grade 3 chronic GVHD of nails. At post-transplant 2.5 years both T and B cell immune reconstitution have been achieved with full donor chimerism. Any child with repeated infections and combination of lymphopenia and neutropenia should have high index of suspicion for reticular dysgenesis.