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.

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

Faraci M.;Dell'Orso G.;Beccaria A.;Volpi S.;Gattorno M.
2021-01-01

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.
File in questo prodotto:
File Dimensione Formato  
2021_Haploidentical αβ T-cell.pdf

accesso chiuso

Tipologia: Documento in versione editoriale
Dimensione 159.13 kB
Formato Adobe PDF
159.13 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1078870
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 0
social impact