- STAT1 gene
mutation leads to dysfunction of the immune system making the person
susceptible to fungal, viral and certain bacterial infections.
- Current study
conducted to assess response of patients to hematopoietic stem cell transplant
(HSCT) for this condition indicates it is curative but associated with
stem cell transplant (HSCT) can cure severe STAT1 gene mutation but results
could be disappointing if many of the limiting factors are not addressed
according to the team of scientists which included Dr.
Satoshi Okada (Hiroshima University), Professor Jennifer Leiding (University of
Florida), Professor Tomohiro Morio (Tokyo Medical and Dental University), and
Professor Troy Torgerson (University of Washington).
is the Need to Assess Outcome of HSCT in STAT1 Gene Mutation
gain of function mutation leads to an immunodeficiency/autoimmune
increased susceptibility to fungal infections such as Candida, viral infections
including herpes simplex encephalitis and bacterial infections such as
tuberculosis. The symptoms can range from mild to severe and life threatening.
The condition was first described by Dr
Okada in 2011
‘Lessons learnt from current study might help improve outcomes of stem cell transplant for STAT1 gene mutation in the future.’
medications to treat the infections do not address the mutation
and immunosuppressive medications such as steroids actually worsen
the disease by damaging the already frail immune system.
is believed that if hematopoietic stem cell transplant found to
be safe and effective could offer the hope of a cure and relief from suffering
for many of these patients.
Hematopoietic stem cell transplant has been tried in a
few patients with severe disease
and shown to be curative at least in one instance in published literature. However, the overall efficacy, safety and outcomes following HSCT
in this condition have not been established
study hopes to determine patient
response to HSCT in a worldwide study
across many centers taking into
consideration factors such as donor
engraftment, graft versus host disease, overall patient survival
and other transplant related complications
. Response to HSCT In STAT1 Gene Mutation - Study Details
Possible Reasons Why Response To HSCT Was Average -
- The study involved 15 young
patients, from nine different countries, with varying degree of
complications caused by the STAT1 mutation.
- Patients were enrolled for the study
through appeals to various transplant centers and consortia.
- The age of participants ranged from
13 months to 33 years.
- A diagnosis of STAT1 gain of
function mutation was confirmed by the research team and established as
the source of their illness.
- Centers across the world carried out
- Before HSCT was done, patients were
administered chemotherapy to destroy the bone marrow which was the source
of the disease causing STAT1 mutation.
- Following this, stem cell cultures
obtained from healthy donors was transplanted into the patients in the
hope of making the marrow healthy and disease free.
- The results were rather disappointing in that only 6 out of the 15
(40%) survived the HSCT; the only
heartening factor was that 5 of these were completely cured and
disease free at the end of the study.
possible reasons for the rather average 40 percent positive outcome could be as
Proposals Made To Improve HSCT Response In STAT1
- Over time the transplanted healthy cells decreased in number and
the marrow went back to the pre-transplant state with the mutation.
Subsequently the donor transplant was rejected.
- Strong and high dose chemotherapy to destroy diseased marrow also
damaged host tissue causing failure of multiple organs including the
immune system leading to severe life threatening infections.
- Younger patients fared better, probably because the cumulative
effects of the disease, in particular infections might have been lesser.
- Only patients with severe symptoms should be considered for HSCT as
the benefits may outweigh the risks
- Dose of chemotherapy needs to be reduced to decrease damage to host
tissue, but diseased marrow has to be eradicated for the transplant to be
successful. A fine balance has therefore to be maintained.
- Low dose chemotherapy may need to be supplemented with other
treatments to neutralize host antibodies and prevent immune attack on
donor stem cells and to prevent donor stem cell graft rejection.
- HSCT should be considered at an younger age itself since outcomes
have been better.
advancements in understanding of the disease and early diagnosis possible, it
is quite possible that HSCT with due refinements and precautions as
appropriate, would see better outcomes and offer hope of a cure for persons
suffering from this devastating disease.
- Hematopoietic stem cell transplantation in patients with Gain of Function STAT1 Mutation - (http://www.jacionline.org/article/S0091-6749(17)30916-8/pdf)
- STAT1 gene - (https://ghr.nlm.nih.gov/gene/STAT1#conditions)