Survival and Outcome
Four of the six transplanted patients are alive with a median follow-up
of 7 (range 4-15) years; only two of the surviving patients (patients 1
and 4) have 100% donor chimerism, whereas patients 5 and 6 developed
secondary engraftment failure.
Patient 1 is now 15 years post-transplantation. During the first five
years post-transplantation, she complained of mild abdominal pain and
poor appetite necessitating the continuation of TPN for 10 years. Over
the last 5 years, without requiring TPN, she is progressively, although
slowly, gaining weight to her current weight of 43 kg and is seemingly
asymptomatic. Her peripheral neuropathy improved clinically and her
latest nerve conduction test, performed a year ago, is within normal
range. Brain MRI revealed slow progression of the white matter changes
over the years (Fig. 1C-E) but despite the MRI changes she has no
cognitive deterioration. Over a year ago she had a single episode of
loss of consciousness initially suspected to be a generalized seizure.
However, a subsequent EEG was normal and there have been no further
recurrent episodes. She graduated from high school and college and works
in her profession. She has hypergonadotropic hypogonadism, which can be
a secondary long-term endocrine complication in a female survivor of
HSCT, or a primary abnormal endocrine manifestation of MNGIE.
Patient 2, despite full donor chimerism, continued having recurrent
episodes of abdominal pain and vomiting necessitating daily usage of her
gastrostomy for stomach drainage was dependent on daily opioids for pain
treatment and TPN constantly for 7 years. She remained the same weight
as she was prior to transplantation. Six years following HSCT she was
admitted frequently with severe abdominal pain, partial bowel
obstruction, leukopenia, thrombocytopenia and increased inflammatory
markers. An abdominal abscess was found on CT and she was treated
conservatively with antibiotics, with temporary improvement. It was not
possible to determine if the abscess was a result of intestinal
diverticula or micro-perforation of the small intestine. In total, she
had 12 hospitalizations during the first 4 years after HSCT and 22
hospitalizations in the next 4 years. She succumbed to her disease seven
and a half years post-HSCT form septic shock and multiple organ failure.
Patient 3 died before engraftment on day+12 post-transplantation from
sepsis and multi organ failure.
Patient 4 is now 4 years after HSCT, with full donor chimerism and
biochemical correction. She still uses her gastrostomy and is TPN
dependent as her main nutritional support. She requires chronic opioid
treatment for pain management. During the last 2 years she was admitted
several times for central line infection. A recent attempt to stop TPN
failed with a subsequent 30% loss of her weight.
Patients 5 and 6 lost their graft during the first year following
transplantation. Clinically, patient 5 remained stable during the first
year after HSCT with rare and short episodes of abdominal pain and
vomiting and stable weight and a second transplant was considered.
However, when she was admitted for a thorough assessment before
repeating HSCT, is was clear that there was severe gastrointestinal
involvement with weight loss, daily vomiting, and distressful abdominal
pain. She had electrolytes abnormalities with hypokalemia and
contraction alkalosis. A gastrostomy was placed and for a while TPN was
given but was stopped due to technical issues and the family’s request.
Currently, she uses her gastrostomy daily for drainage and attempted
feeding via jejunostomy is currently ongoing. At this stage, she is not
considered a candidate for HSCT. Her youngest sister (patient 6) also
developed secondary engraftment failure and due to severe
gastrointestinal involvement, including daily usage of her gastrostomy
for stomach drainage and almost daily vomiting, the decision was made
not to proceed to a second transplant.