Autoimmune hemolysis and immune thrombocytopenic purpura after cord blood transplantation may be life-threatening and warrants early therapy with rituximab

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) transplanted for hematologic malignancies with myeloablative or non-myeloablative conditioning and calcineurin-inhibitor (CNI)/ mycophenolate mofetil. With a median 5.2 year (range 1.6–9.7) 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 ≤ 6 g/dl and/ or platelets < 20 × 109/L). All AH patients were direct anti-globulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute graft-versus-host disease. 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.

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

“…AH/ITP can be both abrupt in onset and life-threatening 109–111 . High rates of immune cytopenias have been reported in pediatric patients undergoing CBT in the first year of life 112 .…”

“…High rates of immune cytopenias have been reported in pediatric patients undergoing CBT in the first year of life 112 . Early intervention with corticosteroids and rituximab at diagnosis is effective and early rituximab administration is a corticosteroid sparing strategy in patients with severe disease 111 .…”

Autoimmune hemolytic anemia and immune thrombocytopenia following hematopoietic stem cell transplant: A critical review of the literature

“…When identified early, initiation of first‐line therapy with corticosteroids is appropriate. Patients who do not respond to steroids should receive treatment with rituximab . Long‐term courses of corticosteroids should be avoided to minimize long‐term side effects, which may be more intensified in this patient population with significant underlying comorbidities and concomitant therapies.…”

“…Patients should be monitored long‐term for these complications and prompt treatment should be initiated when identified. Early use of rituximab may reduce the long‐term complications of corticosteroid use and is successful in about 60% of patients . Further research is still needed, however, to better understand the immunology behind these conditions and determination of more targeted therapeutic options.…”

“…HSCT characteristics associated with the development of AIHA and immune thrombocytopenia Diagnosis (malignant vs nonmalignant)4,7,9,10,13,14,19 4.33, 2.84-6.61 Nonmalignant disease Transplant type (related vs unrelated) 4,7,9,10,18 2.97, 1.76-5.00 Unrelated transplant TBI containing conditioning (yes vs no) 7,9,13,18 1.82, 1.01-3.26 No history of TBI exposure cGvHD 4,13,14,18 1.97, 1.23-3.16 cGvHD .23-3.16), presence of cGvHD (OR 1.97; 95% CI, 1.23-3.16), and peripheral or cord blood stem cell source (OR 1.88; 95% CI, 1.25-2.82) were all more likely to develop AIC. Additional risk factors addressed in <3 of these studies that did not have a significant association with the development of AIC included Epstein-Barr virus reactivation, 5 adenovirus infection/reactivation, 5 absolute neutrophil count recovery time, 5 platelet count recovery time, 5 chimerism status, 5 history of prior HSCT, 8 remission status, 8 Tcell function, 21 B-cell function, 21 CD3 cell dose,…”