AUTHOR=Neely Jessica A. , Dvorak Christopher C. , Pantell Matthew S. , Melton Alexis , Huang James N. , Shimano Kristin Ammon 

TITLE=Autoimmune Cytopenias in Pediatric Hematopoietic Cell Transplant Patients

JOURNAL=Frontiers in Pediatrics

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2019.00171

DOI=10.3389/fped.2019.00171

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Autoimmune cytopenias (AICs) are potentially life-threatening complications following hematopoietic cell transplantation (HCT), yet little is understood about the mechanism by which they develop. We hypothesized that discordant B cell and T cell recovery is associated with AICs in transplant patients, and that this might differ based on transplant indication.</p><p><bold>Methods:</bold> In this case control study of children who underwent HCT at our institution, we evaluated the clinical and transplant characteristics of subjects who developed AICs compared to a control group matched by transplant indication and donor type. In cases, we analyzed the state of immune reconstitution, including B cell recovery, T cell recovery, and chimerism, immediately prior to AIC onset. Subjects were stratified by primary indication for transplant as malignancy (<italic>n</italic> = 7), primary immune deficiency (PID, <italic>n</italic> = 9) or other non-malignant disease (<italic>n</italic> = 4). We then described the treatment and outcomes for 20 subjects who developed AICs.</p><p><bold>Results:</bold> In our cohort, cases were older than controls, were more likely to receive a myeloablative conditioning regimen and had a significantly lower prevalence of chronic GVHD. There were distinct differences in the state of immune recovery based on transplant indication. None of the patients (0/7) transplanted for primary malignancy had T cell recovery at AIC onset compared to 71% (5/7) of patients with PID and 33% (1/3) of patients with non-malignant disease. The subset of patients with PID and non-malignant disease who achieved T cell reconstitution (6/6) prior to AIC onset, all demonstrated mixed or split chimerism. Subjects with AIHA or multi-lineage cytopenias had particularly refractory courses with poor treatment response to IVIG, steroids, and rituximab.</p><p><bold>Conclusions:</bold> These results highlight the heterogeneity of AICs in this population and suggest that multiple mechanisms may contribute to the development of post-transplant AICs. Patients with full donor chimerism may have early B cell recovery without proper T cell regulation, while patients with mixed or split donor chimerism may have residual host B or plasma cells making antibodies against donor blood cells. A prospective, multi-center trial is needed to develop personalized treatment approaches that target the immune dysregulation present and improve outcomes in patients with post-transplant AICs.</p>