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

Introduction: While AH & ITP are recognized after CBT, the incidence, severity, treatment response, & prognosis of these complications is not established. Methods: We evaluated AH/ ITP in a day 100 landmark analysis of 152 double-unit CBT recipients (median age 38 years, range 0.9-70) who were transplanted for hematologic malignancies, engrafted & disease-free. Results: Nine patients [median age 42 years (range 2-54), median follow-up 50.6 months (range 7.6-105.4) have developed autoimmune cytopenias (7 AH, 1 ITP, 1 both) for a 6% (95%CI: 3-11) 3-year cumulative incidence [median onset 8.6 months (range 5.8-24.5), Figure]. Six patients had severe disease (Hb < 6 gm/dl &/or platelets < 20). Their lowest counts (Hb 2.6-6.8 & platelets 0-4) were a median of 1 day (range 0-94) after diagnosis. Six had grade II-IV acute GVHD prior to AH/ ITP, and all 9 patients developed AH/ ITP in the context of immunosuppression taper. There was no association between AH/ ITP and age, diagnosis, regimen intensity, or recipient CMV serostatus. Treatment in the first week was IVIg/ corticosteroids/ rituximab in 3 patients, whereas CSA dose was increased in 1, 2 had IVIg only, 2 rituximab only, and 1 received corticosteroids/ IVIg. Overall, all 9 patients received rituximab at 2-18 days (4-6 doses) after diagnosis. Early rituximab (≤ 7 days) reduced time to CR (Hb ≥ 8 &/or platelets ≥ 100): median 13 days (7-49 days) if early rituximab in 4 patients versus 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 at 28-393 days but all achieved CR with further treatment. Drug therapy was well tolerated whereas 2 of 3 patients who underwent splenectomy with initial therapy or with relapse had complications. Eight of 9 AH/ ITP patients are alive & disease free. Seven of them are in CR from AH/ ITP at a median of 30 months (range 9-102) follow-up after AH/ ITP diagnosis whereas one has recurrent AH requiring therapy. Conclusions: While AH/ ITP is infrequent it can have sudden onset and be life-threatening. The mechanism is likely transient B-cell immune dysregulation during immunosuppression taper, and thus patient monitoring and prompt recognition during this period are warranted. Early rituximab treatment is both mandated at presentation in severe disease and will likely reduce corticosteroid exposure & could avoid splenectomy.

Figure