METHODS
This retrospective cohort study was approved by the Institutional Review Board at Boston Children’s Hospital and included patients undergoing HSCT between January 2003 and June 2019. All patients who underwent allogeneic transplant at Boston Children’s Hospital in this time period (n=868) were identified through an HSCT program research database. Patients met inclusion criteria if they had a positive direct antiglobulin test and clinically significant hemolysis, defined by both a decrease in hemoglobin and evidence of at least one additional laboratory feature of hemolysis, including reticulocytosis, low haptoglobin, indirect hyperbilirubinemia, and/or elevated lactate dehydrogenase. The date of AIHA diagnosis was defined as the date on which the patient met these criteria. The study population included patients 0-25 years old who had AIHA following their first transplant. Patients who developed AIHA after a second transplant or who underwent autologous gene therapy were excluded.
Demographic features, clinical characteristics, laboratory data, transplant types, conditioning regimen, GVHD prophylaxis, and treatments were obtained by chart review. Neutrophil engraftment date was defined as the first of three consecutive days of absolute neutrophil count greater than 0.5 x 109/L.[12] Acute and chronic GVHD were staged using Center for International Blood & Marrow Transplant Research definitions.[13] Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections were defined as a detectable blood CMV or EBV polymerase chain reaction (PCR) test on two consecutive tests. Laboratory response to AIHA treatment was defined as a complete response if hemoglobin increased to prior baseline with no evidence of hemolysis by labs while on AIHA treatment, and partial response if hemoglobin increased but evidence of ongoing hemolysis was present while on AIHA treatment.[2, 10, 14] Non-response was defined as any response not meeting complete or partial response. Remission was defined as complete remission if the patient had no evidence of hemolysis while off all treatment for AIHA, partial remission if there was no evidence of hemolysis but patient remained on treatment for AIHA, and not in remission if there was ongoing evidence of hemolysis.
After identification of the cases, controls were identified in a 2:1 ratio through the HSCT program research database and matched for age, recipient sex, and malignant versus non-malignant diagnosis (Supplemental Table S1).