1.
Immune Cytopenias After Ex-Vivo CD34+ Selected Allogeneic Hematopoietic Cell Transplantation
Scordo, M., Hsu, M., Jakubowski, A. A., Shah, G. L., Cho, C., Maloy, M. A., Avecilla, S. T., Papadopoulos, E., Gyurkocza, B., Castro-Malaspina, H., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Immune mediated cytopenias (IC), such as immune thrombocytopenia (ITP) and immune hemolytic anemia (IHA), are among the adverse events after allogeneic hematopoietic cell transplantation (allo-HCT). Previous reports suggest that in-vivo T-cell depletion may increase the incidence of IC after allo-HCT. We evaluated whether a strategy that reduces functional donor T-cells via ex-vivo CD34(+)-selection associates with the development of IC in a cohort of 408 patients who underwent allo-HCT for hematologic malignancy. The cumulative incidence of IC at 6, 12, and 36 months after the 30-day landmark post-HCT, respectively, was 3.4%, 4.9%, and 5.8%. Among 23 patients who developed IC, 7 died of relapse-related mortality and 4 of non-relapse mortality. A median 2 types of treatment (range 1-5) was required to resolve IC, and there was considerable heterogeneity in the therapies used. In univariable analyses, a hematologic malignancy Disease-Risk Index (DRI) score of 3 was significantly associated with an increased risk of IC compared to a DRI of 1 or 2 (hazard ratio [HR] 4.12, P =.003), and IC (HR 2.4, P =.03) was associated with increased risk of relapse. In a multivariable analysis that included DRI, IC remained significantly associated with increased risk of relapse (HR 2.4, P =.03). Our findings show that IC events occur with relatively similar frequency in patients after ex-vivo CD34(+)-selected allo-HCT compared to unmodified allo-HCT, suggesting that reduced donor T-cell immunity is not causative of IC. Moreover, we noted a possible link between its development and/or treatment and increased risk of relapse.
2.
Risk Factors, Treatment, and Immune Dysregulation in Autoimmune Cytopenia after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients
Kruizinga, M. D., van Tol, M. J. D., Bekker, V., Netelenbos, T., Smiers, F. J., Bresters, D., Jansen-Hoogendijk, A. M., van Ostaijen-Ten Dam, M. M., Kollen, W. J. W., Zwaginga, J. J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018;24(4):772-778
Abstract
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.
3.
Autoimmune hemolysis and immune thrombocytopenic purpura after cord blood transplantation may be life-threatening and warrants early therapy with rituximab
Bhatt, V., Shune, L., Lauer, E., Lubin, M., Devlin, S. M., Scaradavou, A., Parameswaran, R., Perales, M. A., Ponce, D. M., Mantha, S., et al
Bone Marrow Transplantation. 2016;51(12):1579-1583
-
-
Free full text
-
Abstract
Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10.4 months (range 5.8-24.5) post CBT for a 7% cumulative incidence 3 years after the day 100 landmark. Six patients presented with severe disease (hemoglobin 6g/dL and/or platelets <20 x 109/L). All AH patients were direct antiglobulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute GVHD. All 10 patients received rituximab 2-18 days after diagnosis, and corticosteroids combined with rituximab within <7 days was the most effective. No patient died of AH/ITP. AH/ITP occurs infrequently after CBT but may be life-threatening requiring emergency therapy. Rituximab combined with corticosteroids at diagnosis is warranted in patients with severe disease.