HAPLOIDENTICAL α/β T-CELL AND B-CELL STEM CELL TRANSPLANTATION IN SEVERE MEVALONATE KINASE DEFICIENCY.

OBJECTIVE Mevalonic aciduria (MA) represents the most severe of mevalonate kinase deficiency (MKD). Patients with MA have an incomplete response even to high doses of anti-cytokine drugs as anakinra or canakinumab and stem cell transplantation (SCT) represents a possible therapy for this severe disease. METHODS We report the first two children affected by severe MKD who received haploidentical (haplo) α/β T cell and B cell depleted SCT. Both patients received treosulfan based conditioning regimen and one received a second haplo-SCT for secondary rejection of the first. RESULTS Both patients obtained a stable full donor engraftment with a complete regression of clinical and biochemical inflammatory signs, without acute organ toxicity or acute and chronic GvHD. In both, the urinary excretion of mevalonic acid remained high in post transplant in the absence of any inflammatory signs. CONCLUSION Haploidentical α/β T cell and B cell depleted SCT represents a potential curative strategy in patients affected by MKD. The persistence of urinary excretion of mevalonic acid after SCT, probably related to the ubiquitous expression of MVK enzyme, suggests that these patients should be carefully monitored after SCT to exclude MKD clinical recurrence. Prophylaxis with anakinra in the acute phase after transplant could represent a safe and effective approach. Further biological studies are required to clarify the pathophysiology of inflammatory attacks in MKD in order to better define the therapeutic role of SCT.