Oct 15, 2018 Outcomes of stem cell transplants in gene mutation patients

Stem cell transplants can cure some people with STAT1 mutations, but outcomes need to be improved

Haematopoietic stem cell transplantation (HSCT) is more successful in younger patients with
mutations in the STAT1 gene, however, it can also carry high risks of failure and even death.

©  BSIP/UIG/Getty

While some patients with a specific protein mutation are cured with a stem cell transplant, other patients face a range of poor outcomes that can be life-threatening, shows an international study.

Transplanting blood cell-producing haematopoietic stem cells into the bone marrow of people with a protein mutation that leads to severe infections and/or autoimmune disorders can cure some cases, explains Satoshi Okada, of Japan’s Hiroshima University Graduate School of Biomedical & Health Sciences. Although haematopoietic stem cell transplantation (HSCT) is more successful in younger patients with this mutation, this treatment can also carry high risks of failure and even death.

The findings are the result of data analyses of 15 patients from various parts of the world, each with mutations in the STAT1 gene that lead to the over-functioning of the protein it encodes. These patients all underwent haematopoietic stem cell transplantation as a life-saving procedure for their conditions.

STAT1 is a protein that guides the transcription of specific sequences of genetic information from DNA onto RNA. Mutations in its gene can cause the protein to become overactive or underactive. Gain-of-function STAT1 mutations can make patients susceptible to fungal, bacterial and viral infections, which are treated by long-term antifungal, antibacterial and antiviral therapies. It can also lead to autoimmune disorders, which are often treated with immunosuppressants. However, some conditions resist treatment or become severe, in which case HSCT is considered. But there has been little known of the outcomes of this therapy in people with STAT1 gain-of-function mutations.

The 15 patients studied varied in age, the source of stem cells received (bone marrow, umbilical cord blood, or peripheral blood stem cells), and how well these stem cells were matched. The patients also received a variety of pre-transplantation preparatory regimes.

Of the 12 patients whose transplantation initially succeeded, four had their disease-related symptoms completely resolved. Another six transplantations eventually failed due to loss of donor cells, called secondary graft failure. Only one of these patients experienced almost full resolution of disease-related symptoms following a second transplantation. Of the 15 patients studied, nine died and five had complete resolution of their symptoms. A sixth patient had only partial transplantation success.

The team was surprised by the high rate of secondary graft failure, says Okada. Even so, “HSCT can be a curable treatment for patients with STAT1 gain-of-function mutations, but the outcomes need to be improved,” he says. Better outcomes could result from improving the pre-transplantation regimens, says Okada. The findings also suggest that transplantations are more successful in younger patients and before symptoms become too severe.

The team now wants to understand the molecular mechanisms underlying gain-of-function mutations. This could help find molecular targets for treating the associated conditions, says Okada.

The program-affiliated researchers contributing to this research are from Hiroshima University Graduate School of Biomedical & Health Sciences.


  1. Leiding, J. W., Okada, S., Hagin, D., Abinun, M., Shcherbina, A. et al. Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutation. Journal of Allergy and Clinical Immunology 141,704-717 (2018).| Article

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