Risk Factors, Treatment, and Immune Dysregulation in Autoimmune Cytopenia after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients

• Published in: Biology of blood and marrow transplantation Vol. 24; no. 4; pp. 772 - 778
• Main Authors: Kruizinga, Matthijs D., van Tol, Maarten J.D., Bekker, Vincent, Netelenbos, Tanja, Smiers, Frans J., Bresters, Dorine, Jansen-Hoogendijk, Anja M., van Ostaijen-ten Dam, Monique M., Kollen, Wouter J.W., Zwaginga, Jaap J., Lankester, Arjan C., Bredius, Robbert G.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2018
• Subjects: Adolescent; Adrenal Cortex Hormones - administration & dosage; Adult; Alemtuzumab - administration & dosage; Allografts; Autoimmune cytopenia; Autoimmune Diseases - etiology; Autoimmune Diseases - immunology; Autoimmune Diseases - mortality; Autoimmune Diseases - therapy; Bortezomib - administration & dosage; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - etiology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - mortality; Cytomegalovirus Infections - therapy; Female; Hematopoietic Stem Cell Transplantation; Hemolysis; Humans; Immunoglobulins, Intravenous - administration & dosage; Infant; Infant, Newborn; Male; Neutropenia; Retrospective Studies; Risk Factors; Rituximab - administration & dosage; Stem cell transplantation; Th2 Cells - immunology; Thrombopenia; Autoimmune cytopenia; Hemolysis; Stem cell transplantation; Cytomegalovirus; Thrombopenia; Neutropenia
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2017.12.782

•Autoimmune cytopenia after stem cell transplantation is a rare complication.•Nonmalignant disease, alemtuzumab use, and CMV reactivation are risk factors.•The cytokine profile of AIC patients appears to favor a Th 2 response.•Rituximab, bortezomib, and sirolimus are promising step-up therapies. Autoimmune or alloimmune cytopenia (AIC) is a known rare complication of hematopoietic stem cell transplantation (SCT). AIC after SCT is considered difficult to treat and is associated with high morbidity and mortality. In this retrospective study in pediatric patients we evaluated incidence, outcome, potential risk factors, and current treatment strategies. A nested matched case-control study was performed to search for biomarkers associated with AIC. Of 531 consecutive SCTs at our center between 2000 and 2016, 26 were complicated by the development of AIC (cumulative incidence, 5.0%) after a median of 5 months post-SCT. Autoimmune hemolytic anemia was the most common AIC with 12 patients (46%). We identified nonmalignant disease, alemtuzumab serotherapy pre-SCT, and cytomegalovirus (CMV) reactivation as independently associated risk factors. The cytokine profile of patients at the time of AIC diagnosis appeared to skew toward a more pronounced Th 2 response compared with control subjects at the corresponding time point post-SCT. Corticosteroids and intravenous immunoglobulin as first-line treatment or a wait-and-see approach led to resolution of AIC in 35% of cases. Addition of step-up therapies rituximab (n = 15), bortezomib (n = 7), or sirolimus (n = 3) was associated with AIC resolution in 40%, 57%, and 100% of cases, respectively. In summary, we identified CMV reactivation post-SCT as a new clinical risk factor for the development of AIC in children. The cytokine profile during AIC appears to favor a Th 2 response. Rituximab, bortezomib, and sirolimus are promising step-up treatment modalities.