Autoimmune Hemolysis & Immune Thrombocytopenic Purpura after Cord Blood Transplantation (CBT) May be Life-Threatening & Warrants Early Therapy with Rituximab

![Graphic][1] Introduction: Autoimmune hemolysis (AH) & immune thrombocytopenic purpura (ITP) are recognized complications of CBT. However, the incidence, severity, treatment response, & prognosis of these autoimmune cytopenias are not established. Methods: We evaluated AH/ITP after CBT in a landmark analysis of 152 patients who received double-unit grafts, had sustained donor engraftment, & were disease-free at 100 days post-transplant. This landmark was chosen as no patient has developed AH/ITP prior to day 100. CBT recipients (median 38 years, range 0.9-70) were transplanted for hematologic malignancies with myeloablative (MA) or non-myeloablative (NMA) conditioning and calcineurin-inhibitor (CNI)/mycophenolate mofetil immunosuppression. Results: With a median follow-up of survivors in this cohort of 50.6 months (range 7.6-105.4) post-CBT, 9 patients [median age 42 years (range 2-54), 5 MA & 4 NMA conditioning] have developed autoimmune cytopenias (7 AH, 1 ITP, 1 both). All AH patients were IgG Direct Antiglobulin Test (Coombs) positive and ITP diagnosis was made by standard criteria. The cumulative incidence of AH/ITP is 6% (95%CI:3-11) at 3-years after the day 100 landmark with a median onset of 8.6 months (range 5.8-24.5) post-CBT (Figure). Six patients presented with severe disease (Hb 8 &/or plts >100): median 13 days (7-49 days) in 4 early rituximab patients vs 58 days (19-98 days) in 5 without early rituximab. Moreover, an initial IVIg/corticosteroids/rituximab combination was best (CR 7-13 days). Four patients flared after CR at 28-393 days & all patients achieved CR with further therapy. Three patients underwent splenectomy (2 with initial therapy & 1 with flare). Eight/9 AH/ITP patients are alive & disease-free (one patient died of GVHD in remission from AH). Seven/8 surviving patients are in CR from AH/ITP (median 30 months after AH/ITP diagnosis, range 9-102) & 1 has recurrent AH requiring therapy. Treatment was well tolerated although 4 patients required intermittent IVIg & 4 had transient neutropenia. Conclusions: AH/ITP occurs infrequently after CBT but is associated with sudden onset and may be life-threatening. The onset during immunosuppressant taper suggests the mechanism may be due to transient immune dysregulation at this time-point, and investigation of whether AH/ITP can be predicted from analysis of B-cell immune reconstitution is underway. IVIg/corticosteroid/rituximab combination is appropriate initial therapy in severe disease & our data suggests this is the most effective although the role of IVIg is unclear. Earlier treatment with Rituximab may reduce corticosteroid exposure & avoid early splenectomy. While the optimal treatment regimen is not established, our series suggests rituximab is essential to achieve & maintain CR & has an excellent safety profile. Finally, survival was high in AH/ITP patients with no deaths from this complication although this was likely contingent on aggressive supportive care in these patients. ![Figure 1][2] Figure 1 Disclosures No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif [2]: pending:yes