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).