Patient 3:
A ten-year-old girl (born to consanguineous parents) was diagnosed as
DOCK8 deficiency due to atopic dermatitis, food allergies (egg and
milk), elevated Ig E levels and elder brother’s DOCK8 diagnosis at 6
months old. Although she was on regular IVIG treatment and antibiotic
prophylaxis, she experienced multiple bronchitis, otitis and sepsis even
disseminated BCG infection (an abscess in the right popliteal fossa with
bilateral inguinal and axillary lymphadenopathies, fever, and weight
loss). She also had comorbidities like esophageal papillomas,
esophagitis, hepatic fibrosis, choledochal cysts, bronchiectasis and
pulmonary nodules. Because of her elder brother’s complicated
transplantation course and the unavailability of a matched donor, she
couldn’t be transplanted. Finally, we decided to transplant her from her
haploidentical father because of her severe malnutrition, recurrent
sepsis episodes, non-healing skin wounds, chronic diarrhea,
cryptosporidium infection and EBV viremia. She was transplanted
following an RIC regimen consisting of Rituximab (375
mg/m2), Treosulfan (42g/m2),
Fludarabine (150mg/m2) and ATG (20mg/kg) at age of ten
years and eight months. Tacrolimus, MMF (iv) and Post-transplantation
Cyclophosphamide were preferred for GvHD prophylaxis. Her
transplantation course was also challenging from the outset. On the
post-transplant first day, she had catheter sepsis due to Klebsiella
pneumonia requiring extended anti-microbial therapy. On the
11th day, diarrhea occurred due to cryptosporidium
parvum. On the 14th day, a widespread maculopapular
rash appeared. Skin biopsy revealed Grade 2 acute skin GvHD.
Methylprednisolone (2 mg/kg) and subsequently infusions of MSC (x4,
weekly) were added to treatment During steroid taper, on the
30th day, diarrhea with epigastric pain and vomiting
occurred supporting intestinal GvHD. Endoscopic and colonoscopic
biopsies revealed Grade IV GvHD. Because of her infectious background,
we decided to use oral budesonide and AAT. Although she received 8 doses
of AAT, bloody diarrhea occurred. Tocilizumab (x1) was added to the
treatment. (Table 3) Unfortunately, she had septic shock due to
pancreatitis requiring multiple inotropes and had respiratory distress,
so she was transferred to ICU on the 78th day. During
follow-up in ICU, her clinical status was deteriorated, she was
intubated on the 85th day with TAMOF diagnosis.
Despite all intensive treatments (plasma exchange, haemodialysis, an
additional dose of MSC, etc.), she passed away on the
102nd day.