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.