HSCT is effective in patients with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome.

Abstract

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.

• Authors: Alexandra Laberko, Vasiliy Burlakov, Sarah Maier, Mario Abinun, Roderick Skinner, Anna Kozlova, Deepti Suri, Kai Lehmberg, Ingo Müller, Dmitry Balashov, Galina Novichkova, Dirk Holzinger, Andrew R Gennery, Anna Shcherbina
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 148 Issue 1 Pg. 250-255.e1 (07 2021) ISSN: 1097-6825 [Electronic] United States
• PMID: 33338535 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Cytokines
• Cytoskeletal Proteins
• Immunosuppressive Agents
• PSTPIP1 protein, human

Topics

• 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)