Hematopoietic stem cell transplantation in patients with chronic granulomatous disease in the Czech Republic and Slovakia (2007-2019)
Abstract
Objective: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency with X-linked or autosomal recessive inheritance caused by defects in the genes encoding phagocyte oxidase subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. This complex is responsible for the respiratory burst inside the cell, which leads to the killing of microbes ingested by phagocytic cells.
NADPH oxidase also plays key role in regulating immunity and therefore CGD is also characterized by autoimmune and autoinflammatory manifestations. Hematopoietic stem cell transplant (HSCT) is the only definitive curative treatment.
Here we present the outcome of patients with CGD who from 2007 till 2018 underwent allogeneic HSCT at pediatric transplant centers in Prague and Bratislava. Methods: Fourteen patients with chronic granulomatous disease received first hematopoietic stem cell transplant at a medium age of 6.4 years (1.0-17.8).
CYBB gene mutation (X-linked) was identified in thirteen of them. The stem cell source was bone marrow (n=10) or peripheral stem cells (n=4) from a human leukocyte antigen identical unrelated (n=13) or healthy sibling (n=1) donor.
Results: Primary engraftment was obtained in all 14 patients. Five patients, who later lost the primary graft, were successfully re-grafted following second HSCT.
One patient died six months after HSCT due to cerebral bleeding following repeated surgery for cerebral aspergilloma, one developed secondary acute myeloid leukemia eight years after HSCT and 12 months ago underwent second transplant. 13/14 patients are alive with median follow-up 6.1 (range 0.1-12.2) years after the last HSCT. Conclusions: Allogeneic HSCT were safely performed without serious transplant-related complications.
Early indication, pre-transplant organ involvement, donor selection and conditioning regimens remain the key points with the aim to decrease the risk of late graft failure and need for re-HSCT.