HSCT is effective in patients with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome.
Adaptor Proteins, Signal Transducing
/ immunology
Child, Preschool
Cytokines
/ immunology
Cytoskeletal Proteins
/ immunology
Female
Genetic Diseases, Inborn
/ immunology
Graft Rejection
Graft vs Host Disease
/ immunology
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immunosuppressive Agents
/ immunology
Infant, Newborn
Inflammation
/ immunology
Male
Myeloid Cells
/ immunology
Transplantation Conditioning
/ adverse effects
Transplantation, Homologous
/ adverse effects
Hematopoietic stem cell transplantation
PSTPIP1
autoinflammatory disorder
hypercalprotectinemia and hyperzincemia
macrophage activation syndrome
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
23
09
2020
revised:
06
11
2020
accepted:
12
11
2020
pubmed:
19
12
2020
medline:
13
10
2021
entrez:
18
12
2020
Statut:
ppublish
Résumé
Proline-serine-threonine phosphatase-interacting protein 1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a novel genetic disorder, causing hypercalprotectinemia and hyperzincemia with inflammatory complications accompanied by cytopenia. Immunosuppressive and/or anticytokine therapy is of limited effect. Because of cytokine production in nonhematopoietic tissues, the potential therapeutic effect of allogeneic hematopoietic stem cell transplantation (HSCT) in autoinflammatory disorders, including PAMI syndrome, has remained uncertain. Five patients with PAMI syndrome underwent allogeneic HSCT with myeloablative (4) or reduced-intensity (1) conditioning regimens. Lack of PAMI disease control served as indication for the HSCT in 4 patients and myelodysplastic syndrome development in 1. All 5 patients engrafted; however, 1 patient at day +13 developed hemophagocytic syndrome, followed by graft rejection at day +17. After 5.5 months, a second HSCT was performed from an alternative donor. A further patient at day +116 developed an intense inflammatory syndrome with significant serositis and severe mitral and aortic valve regurgitation, controlled with adalimumab, tacrolimus, and prednisone. No other noninfectious inflammatory episodes, or acute or chronic graft-versus-host disease, occurred in any patient. At the last follow-up (median, 2.2 years), all 5 patients have predominantly or complete donor chimerism and adequate immune recovery and are free of any PAMI symptoms. Allogeneic HSCT seems to be an effective option to cure cytopenia and severe autoinflammation in PAMI syndrome and may be a curative option for other proline-serine-threonine phosphatase-interacting protein 1-associated inflammatory disorders with poor therapeutic control.
Sections du résumé
BACKGROUND
Proline-serine-threonine phosphatase-interacting protein 1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a novel genetic disorder, causing hypercalprotectinemia and hyperzincemia with inflammatory complications accompanied by cytopenia. Immunosuppressive and/or anticytokine therapy is of limited effect.
OBJECTIVES
Because of cytokine production in nonhematopoietic tissues, the potential therapeutic effect of allogeneic hematopoietic stem cell transplantation (HSCT) in autoinflammatory disorders, including PAMI syndrome, has remained uncertain.
METHODS
Five patients with PAMI syndrome underwent allogeneic HSCT with myeloablative (4) or reduced-intensity (1) conditioning regimens. Lack of PAMI disease control served as indication for the HSCT in 4 patients and myelodysplastic syndrome development in 1.
RESULTS
All 5 patients engrafted; however, 1 patient at day +13 developed hemophagocytic syndrome, followed by graft rejection at day +17. After 5.5 months, a second HSCT was performed from an alternative donor. A further patient at day +116 developed an intense inflammatory syndrome with significant serositis and severe mitral and aortic valve regurgitation, controlled with adalimumab, tacrolimus, and prednisone. No other noninfectious inflammatory episodes, or acute or chronic graft-versus-host disease, occurred in any patient. At the last follow-up (median, 2.2 years), all 5 patients have predominantly or complete donor chimerism and adequate immune recovery and are free of any PAMI symptoms.
CONCLUSIONS
Allogeneic HSCT seems to be an effective option to cure cytopenia and severe autoinflammation in PAMI syndrome and may be a curative option for other proline-serine-threonine phosphatase-interacting protein 1-associated inflammatory disorders with poor therapeutic control.
Identifiants
pubmed: 33338535
pii: S0091-6749(20)31764-4
doi: 10.1016/j.jaci.2020.11.043
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Cytokines
0
Cytoskeletal Proteins
0
Immunosuppressive Agents
0
PSTPIP1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
250-255.e1Informations de copyright
Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.