Risk factor analysis of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation in children

Abstract

Autoimmune hemolytic anemia (AIHA) is a clinically relevant complication after allogeneic hematopoietic stem cell transplantation (HSCT). Currently, there is no established consensus regarding the optimal therapeutic approach. Whether AIHA contributes to increased mortality is still somewhat controversial.We investigated the incidence, risk factors, and outcome of post-transplant AIHA in 265 consecutive pediatric patients undergoing allo-HSCT over a 17-year period. Onset of AIHA was calculated from the first documented detection of AIHA by either clinical symptoms or positive direct agglutinin test. Resolution of AIHA was defined as normalization of hemoglobin and biochemical markers of hemolysis with sustained transfusion independence.We identified 15 cases of AIHA after allo-HSCT (incidence rate, 6%). Ten (67%) of these patients had a positive direct antiglobulin test. Data were obtained for 9 boys and 6 girls after a median follow-up of 53 months (range 4–102). The median age was 5.1 years (range 0.5–15.4) at the time of HSCT and the median time to emergence was 149 days (range 42–273). No significant risk factor for post-transplant AIHA has emerged from our data to date. In the majority (14 of 15; 93%) of AIHA patients, multiple agents for treatment were required, with 12 of 15 (80%) patients achieving complete resolution of AIHA. No splenectomy was performed in any of our patients.For various reasons, post-transplantation AIHA poses an extraordinary challenge to transplant physicians. Despite the advancements in diagnostic tools, therapeutic challenges remain due to the myriad interacting pathways in AIHA.

Autoimmune hemolytic anemia and immune thrombocytopenia following hematopoietic stem cell transplant: A critical review of the literature

“…There were 9 studies with available data for risk factor assessment . Table highlights risks factors evaluated for the development of post‐HSCT AIC.…”

“…Additional risk factors addressed in <3 of these studies that did not have a significant association with the development of AIC included Epstein–Barr virus reactivation, adenovirus infection/reactivation, absolute neutrophil count recovery time, platelet count recovery time, chimerism status, history of prior HSCT, remission status, T‐cell function, B‐cell function, CD3 cell dose, total nucleated cell dose, T‐cell depletion by elutriation, ATG containing regimen, T‐cell depletion, and time from HSCT . Herpes simplex virus status (OR 7.38; 95% CI, 0.92–59.5, P = 0.06), serotherapy (higher risk with of alemtuzimab, HR 2.5; 95% CI, 1.1–5.7, P = 0.28), and donor/recipient concordant gender (HR 3.5; 95% CI, 1.03–12.1, P = 0.45) were all found to be a significant risk factors after multivariate analysis in the reported studies; however, these were each investigated in 1 study only.…”

“…Only three patients underwent splenectomy. Additional reported treatment approaches included azathioprine, cyclosporine, 6‐mercaptopurine, mycophenolate mofetil, danazol, cytoxan and vincristine combination, bortezomib, sirolimus, and second BMT/stem cell boost . Response to these individual therapies could not be adequately assessed.…”

“…Only one paper looked at mixed chimerism as a risk factor and found no association; however, this was a mixed population of both malignant and nonmalignant conditions . Available data on nonmalignant patients who developed AIC showed that 82% (49 of 60) had chimerism >95% (range, 15–100%), although the timing of chimerism testing into relationship to AIC event was not always clear …”

“…There were 9 studies with available data for risk factor assessment. 5,8,10,11,14,15,[19][20][21] 19 total nucleated cell dose, 19 T-cell depletion by elutriation, 20 ATG containing regimen, 8 Tcell depletion, 5 and time from HSCT. 15 Herpes simplex virus status (OR 7.38; 95% CI, 0.92-59.5, P = 0.06), 15 serotherapy (higher risk with of alemtuzimab, HR 2.5; 95% CI, 1.1-5.7, P = 0.28), 5 and donor/recipient concordant gender (HR 3.5; 95% CI, 1.03-12.1, P = 0.45) 11 were all found to be a significant risk factors after multivariate analysis in the reported studies; however, these were each investigated in 1 study only.…”