VPS 45-associated primary infantile myelofibrosis--successful treatment with hematopoietic stem cell transplantation.

PMF of infancy is a recently described autosomal recessive disorder presenting with severe bone marrow failure, accelerated neutrophil apoptosis, and significant platelet dysfunction, caused by a mutation in the VPS45 gene. In this study, we update our group of patients with PMF, highlighting different aspects of this disease, and evaluating the effectiveness of HSCT for the treatment of this disorder. Update of clinical data, hematological features, molecular studies, treatment and final outcome of four children diagnosed with VPS 45-associated PMF of infancy. The patients described had clinical and hematological findings consistent with MF. Molecular studies showed that all patients were homozygous for the Thr224Asn mutation in the VPS 45 gene. HSCT was carried out in three patients and was successful in two. VPS 45-associated MF is a novel primary immune deficiency that can be successfully corrected by HSCT if applied early in the course of disease using appropriate conditioning. The diagnosis of VPS 45-associated PMF should be considered in all children presenting with SCN with subsequent development of pancytopenia. Long-term follow-up of these patients is necessary to identify extra-hematological manifestations of VPS45 deficiency.