Incidence and Outcomes of Immune Thrombocytopenia (ITP) Following Hematopoietic Stem Cell Transplantation (HCT).
Authors: Elimelakh Milena , Eastlund Ted , Reding Mark , DeFor Todd , Burns Linda 
Published: October 2019

While thrombocytopenia is common following HCT, and has been associated with delayed engraftment, disease relapse, infections and drugs, autoantibody mediated ITP is rarely observed. In one series of non-Hodgkin’s lymphoma patients, development of ITP following autologous HCT (autoHCT) was associated with long-term disease free survival (Hequet et al. Bone Marrow Transplant2003; 32:89). Limited data is available on occurrence and prognosis of ITP following allogeneic HCT (alloHCT). Here we report the incidence and outcomes of ITP in 1700 adults who underwent autoHCT (n=749) and alloHCT (n=951) between January 1990 and December 2004. Of the alloHCT recipients, 531 patients received stem cells from a sibling donor (SD), 268 from an unrelated donor (URD), and in 147 patients umbilical cord blood (UCB) was used as the stem cell source. ITP was defined according to the American Society of Hematology guidelines for diagnosis of ITP (Ann Intern Med1997; 126:319). In addition, a confirmatory bone marrow examination demonstrating adequate megakaryocyte numbers and morphology and absence of CMV viremia were required. Patients receiving interferon therapy around the time of ITP diagnosis were excluded. Recovery from ITP was defined as a sustained increase in platelet count to 140 x 109/liter (l). Ten patients (median age 37 years [range 25–51]), including 7 alloHCT and 3 autoHCT recipients developed ITP at a median 15 months (range 4–76) post transplant, with an overall cumulative incidence of 0.8% at 5 years (95% confidence interval [CI] 0.3–1.6%). Of the alloHCT recipients, four patients received one or two antigen mismatched UCB HCT, two received matched HCT from an URD and one a SD HCT. The overall cumulative incidence of ITP at 5 years was highest among UCB HCT recipients (3%; 95% CI 0–6%) as compared to SD (0.2%; 95%CI 0–0.5%) and URD (0.7%; 95% CI 0–1.7%) HCT recipients (p<0.01). Nine (7 alloHCT and 2 autoHCT) recipients were transplanted for hematologic malignancy and one autoHCT patient for metastatic breast cancer. Nine of ten patients received myeloablative conditioning regimen. Six of the seven alloHCT recipients received cyclosporin for graft versus host disease (GVHD) prophylaxis. ITP was severe, with a nadir platelet count of 10 x 109/l in all patients. Platelet antibodies were present in 50% (3 of 6) of patients tested. Nine of the ten patients were in complete remission from their underlying malignancy at the time of ITP diagnosis. ITP was steroid refractory in the majority of patients, and required multiple treatment modalities. All alloHCT recipients with ITP developed chronic GVHD and systemic viral infections. While nine patients recovered, one autoHCT recipient died of multi-organ hemorrhage at 76 months post HCT. At a median follow-up of 61 months, seven patients are still alive and disease free, while two additional patients died (one from relapsed acute myeloid leukemia 32 months and one from pulmonary Aspergillosis 154 months post HCT). In summary, we found ITP to be a rare complication of HCT, with the highest incidence in recipients of UCB HCT. While the majority of patients eventually recovered from ITP and achieved long-term overall survival, the illness was severe, associated with chronic GVHD and serious viral infections. Degree of antigenic disparity, immune dysregulation, development of autoimmunity and its contribution to maintenance of disease control after transplantation may be implicated in pathogenesis of ITP following HCT.