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.