Haploidentical α/β T-cell and B-cell depleted stem cell transplantation in severe mevalonate kinase deficiency.

Abstract

OBJECTIVE:

Mevalonic aciduria represents the most severe form of mevalonate kinase deficiency (MKD). Patients with mevalonic aciduria have an incomplete response even to high doses of anti-cytokine drugs such 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 α/β T-cell and B-cell depleted SCT. Both patients received a treosulfan-based conditioning regimen and one received a second haploidentical-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 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.

• Authors: Maura Faraci, Stefano Giardino, Marina Podestà, Filomena Pierri, Gianluca Dell'Orso, Andrea Beccaria, João Farela Neves, Stefano Volpi, Marco Gattorno
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 60 Issue 10 Pg. 4850-4854 (10 02 2021) ISSN: 1462-0332 [Electronic] England
• PMID: 33410495 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].

Topics

• Acute Disease
• B-Lymphocytes (transplantation)
• Female
• Humans
• Infant, Newborn
• Male
• Mevalonate Kinase Deficiency (therapy)
• Stem Cell Transplantation (methods)
• T-Lymphocytes (transplantation)
• Transplantation, Haploidentical (methods)