The Efficacy and Safety of Allogeneic Stem Cell Transplantation in Mevalonate Kinase Deficiency

Overview

Journal Pediatr Rheumatol Online J

Publisher Biomed Central

Specialty Pediatrics

Date 2022 Jul 29

PMID 35906690

Authors

Jerold Jeyaratnam

Maura Faraci

Andrew R Gennery

Katarzyna Drabko

Mattia Algeri

Akira Morimoto

Tiarlan Sirait

Arjan C Lankester

Michael Albert

Benedicte Neven

Joost Frenkel

Affiliations

Soon will be listed here.

Abstract

Objectives: Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome. Several reports have described allogeneic hematopoietic stem cell transplantation in severely affected patients, sometimes with promising results. In view of the scarcity of data, this study aims to analyse the efficacy and safety of allogeneic hematopoietic stem cell transplantation (HSCT) to give a more complete overview of this treatment.

Methods: This multicentre retrospective study on behalf of the European Society for Blood and Marrow Transplantation aimed to include all MKD patients who had undergone allogeneic HSCT. All centres related to EMBT and centres that have reported cases of allogeneic HSCT in the literature were contacted via the EBMT data office.

Results: We analyzed 9 patients (5 male). Treosulfan based conditioning was the most frequently used conditioning regimen. Engraftment occurred in all but one patient. Source of stem cells was cord blood (n = 2), peripheral blood stem cells (n = 4) and bone marrow (n = 5). Two patients needed a second transplantation due to an incomplete response or primary graft failure. Seven patients went into complete remission after stem cell transplantation. At final follow-up these patients reported no symptoms of MKD. Four patients suffered from grade II-IV acute graft-versus-host disease (GvHD). During follow-up two patients died due to transplantation related complications.

Conclusion: In conclusion, allogeneic stem cell transplantation represents an effective treatment for the most severely affected MKD patients. However, treatment-related morbidity and mortality are significant. Transplantation may be justified in patients with a severe disease course on conservative therapy.

Citing Articles

Intrauterine intestinal obstruction in a preterm infant with severe mevalonate kinase deficiency - a case report.

Hoermann H, Franzel J, Tautz J, Oommen P, Lainka E, Mayatepek E Matern Health Neonatol Perinatol. 2025; 11(1):8.

PMID: 40038796 PMC: 11881282. DOI: 10.1186/s40748-025-00207-w.

Mevalonate kinase deficiency: an updated clinical overview and revision of the SHARE recommendations.

Lengvari L, Takacs K, Lengyel A, Palinkas A, Wouters C, Kone-Paut I Front Immunol. 2024; 15:1466844.

PMID: 39600705 PMC: 11590122. DOI: 10.3389/fimmu.2024.1466844.

Tocilizumab effectively reduces flares of hyperimmunoglobulin D syndrome in children: Three cases in China.

Li C, Chen X, Tang X, Zeng H, Zhou J Mol Genet Metab Rep. 2024; 40:101105.

PMID: 38983106 PMC: 11231588. DOI: 10.1016/j.ymgmr.2024.101105.

Isolated neurological presentations of mevalonate kinase deficiency.

Hoytema van Konijnenburg E, Oussoren E, Frenkel J, van Hasselt P JIMD Rep. 2023; 64(1):53-56.

PMID: 36636591 PMC: 9830010. DOI: 10.1002/jmd2.12348.

References

Shiraki M, Williams E, Yokoyama N, Shinoda K, Nademi Z, Matsumoto K . Hematopoietic Cell Transplantation Ameliorates Autoinflammation in A20 Haploinsufficiency. J Clin Immunol. 2021; 41(8):1954-1956. DOI: 10.1007/s10875-021-01124-1. View

van der Hilst J, Bodar E, Barron K, Frenkel J, Drenth J, van der Meer J . Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore). 2008; 87(6):301-310. DOI: 10.1097/MD.0b013e318190cfb7. View

De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman H . Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med. 2018; 378(20):1908-1919. DOI: 10.1056/NEJMoa1706314. View

Bader-Meunier B, Florkin B, Sibilia J, Acquaviva C, Hachulla E, Grateau G . Mevalonate kinase deficiency: a survey of 50 patients. Pediatrics. 2011; 128(1):e152-9. DOI: 10.1542/peds.2010-3639. View

Hashem H, Kumar A, Muller I, Babor F, Bredius R, Dalal J . Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2. Blood. 2017; 130(24):2682-2688. PMC: 5731089. DOI: 10.1182/blood-2017-07-798660. View

Ter Haar N, Jeyaratnam J, Lachmann H, Simon A, Brogan P, Doglio M . The Phenotype and Genotype of Mevalonate Kinase Deficiency: A Series of 114 Cases From the Eurofever Registry. Arthritis Rheumatol. 2016; 68(11):2795-2805. DOI: 10.1002/art.39763. View

Neven B, Valayannopoulos V, Quartier P, Blanche S, Prieur A, Debre M . Allogeneic bone marrow transplantation in mevalonic aciduria. N Engl J Med. 2007; 356(26):2700-3. DOI: 10.1056/NEJMoa070715. View

Ter Haar N, Lachmann H, Ozen S, Woo P, Uziel Y, Modesto C . Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis. 2012; 72(5):678-85. DOI: 10.1136/annrheumdis-2011-201268. View

Laberko A, Burlakov V, Maier S, Abinun M, Skinner R, Kozlova A . HSCT is effective in patients with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. J Allergy Clin Immunol. 2020; 148(1):250-255.e1. DOI: 10.1016/j.jaci.2020.11.043. View

10.

Mori T, Saburi M, Hagihara M, Mori M, Yamazaki R, Kato J . Long-term remission of cryopyrin-associated periodic syndrome after allogeneic haematopoietic stem cell transplantation. Ann Rheum Dis. 2020; 80(4):542-543. DOI: 10.1136/annrheumdis-2020-218695. View

11.

Yildiz H, Bailly S, Van den Neste E, Yombi J . Clinical Management of Relapsed/Refractory Hemophagocytic Lymphohistiocytosis in Adult Patients: A Review of Current Strategies and Emerging Therapies. Ther Clin Risk Manag. 2021; 17:293-304. PMC: 8056168. DOI: 10.2147/TCRM.S195538. View

12.

Giardino S, Lanino E, Morreale G, Madeo A, Di Rocco M, Gattorno M . Long-term outcome of a successful cord blood stem cell transplant in mevalonate kinase deficiency. Pediatrics. 2014; 135(1):e211-5. DOI: 10.1542/peds.2014-2553. View

13.

Erdol S, Cekic S, Caki Kilic S, Saglam H, Kilic S . Massive ascites in a canakinumab resistant case with MVA leading to bone marrow transplantation. Rheumatol Int. 2016; 36(7):1011-3. DOI: 10.1007/s00296-016-3456-9. View

14.

van der Meer J, Vossen J, Radl J, van Nieuwkoop J, Meyer C, Lobatto S . Hyperimmunoglobulinaemia D and periodic fever: a new syndrome. Lancet. 1984; 1(8386):1087-90. DOI: 10.1016/s0140-6736(84)92505-4. View

15.

Mandey S, Kuijk L, Frenkel J, Waterham H . A role for geranylgeranylation in interleukin-1beta secretion. Arthritis Rheum. 2006; 54(11):3690-5. DOI: 10.1002/art.22194. View

16.

Faraci M, Giardino S, Podesta M, Pierri F, DellOrso G, Beccaria A . Haploidentical α/β T-cell and B-cell depleted stem cell transplantation in severe mevalonate kinase deficiency. Rheumatology (Oxford). 2021; 60(10):4850-4854. DOI: 10.1093/rheumatology/keaa912. View

17.

van der Burgh R, Ter Haar N, Boes M, Frenkel J . Mevalonate kinase deficiency, a metabolic autoinflammatory disease. Clin Immunol. 2012; 147(3):197-206. DOI: 10.1016/j.clim.2012.09.011. View

18.

Nassereddine S, Rafei H, Elbahesh E, Tabbara I . Acute Graft Host Disease: A Comprehensive Review. Anticancer Res. 2017; 37(4):1547-1555. DOI: 10.21873/anticanres.11483. View

19.

Arkwright P, Abinun M, Cant A . Mevalonic aciduria cured by bone marrow transplantation. N Engl J Med. 2007; 357(13):1350. DOI: 10.1056/NEJMc072018. View

20.

Prieur A, Griscelli C . [Nosologic aspects of systemic forms of very-early-onset juvenile arthritis. Apropos of 17 cases]. Sem Hop. 1984; 60(3):163-7. View