BACKGROUND:Immune thrombocytopenic purpura (ITP) relapse following vaccination remains poorly reported in the adult population. OBJECTIVES:This report details real world data from the largest single-center cohort of ITP relapse following severe acute respiratory syndrome (SARS-CoV-2) vaccination. METHODS:The vaccination status of 294 patients under active follow-up was reviewed. A total of 17 patients were identified resulting in an incidence of ITP relapse following SARS-CoV-2 vaccination in this cohort of 6.6% and an incidence of newly diagnosed ITP following SARS-CoV-2 vaccination of 1.4%. RESULTS:Patients were noted to develop marked deviation of platelet count from baseline following vaccination (P =< .0001). Fourteen patients had a prior diagnosis of ITP and median follow-up following diagnosis was 4 years (range 0-45 years). Days from vaccination to presentation ranged from 2-42 (median 14) and the follow-up period was 34 weeks. Fifteen patients (88%) presented with symptoms and all 17 patients developed symptoms during the follow-up period. Nine patients (53%) received a second dose of vaccine during the follow-up period with seven patients (78%) requiring therapeutic support to facilitate second vaccination. Decision to treat patients was multi-factorial and aimed at decreasing bleeding symptoms and obtaining a platelet count >30 × 109 /L. Sixteen patients (94%) required therapeutic intervention and at the end of the follow-up period, four patients (24%) remained unresponsive to treatment with a platelet count <30 × 109 /L. CONCLUSION:Vaccination of ITP patients continues to have important clinical benefit; however, recommendations for patients who relapse remain lacking. This report outlines the real-world patient outcomes in the era of widespread SARS-CoV-2 vaccination.

Objectives Primary immune thrombocytopenia (ITP) is a bleeding disorder characterised by an isolated thrombocytopenia in the absence of an alternative diagnosis. The condition is highly heterogeneous with some patients requiring multiple of therapy before achieving response. In this study, we collected data on a large cohort of primary ITP patients with the objective of identifying variables which may predict treatment requirements. Methods We collected data on 379 patients, 275 with a confirmed diagnosis of primary ITP included demographics, baseline laboratory results and treatments. These were compared against treatment responses and lines of therapy. Results Patients who presented with a platelet count of <30 x 10(9)/L or bleeding symptoms were observed to require more subsequent lines of therapy (P-value <0.001). 32% of patients (n = 87) received no treatment, and these patients had a significantly higher median count compared to those with required >2 lines of therapy (P-value <0.001). Superior response rates were demonstrated with thrombopoietin receptor agonists when compared with other agents irrespective of baseline characteristics. Conclusions Platelet counts at diagnosis are a potentially strong predictive indicator of subsequent lines of therapy. Patients with bleeding symptoms at diagnosis were more likely to have lower median platelets counts.

Objectives Primary immune thrombocytopenia (ITP) is a bleeding disorder characterised by an isolated thrombocytopenia in the absence of an alternative diagnosis. The condition is highly heterogeneous with some patients requiring multiple of therapy before achieving response. In this study, we collected data on a large cohort of primary ITP patients with the objective of identifying variables which may predict treatment requirements. Methods We collected data on 379 patients, 275 with a confirmed diagnosis of primary ITP included demographics, baseline laboratory results and treatments. These were compared against treatment responses and lines of therapy. Results Patients who presented with a platelet count of <30 x 10(9)/L or bleeding symptoms were observed to require more subsequent lines of therapy (P-value <0.001). 32% of patients (n = 87) received no treatment, and these patients had a significantly higher median count compared to those with required >2 lines of therapy (P-value <0.001). Superior response rates were demonstrated with thrombopoietin receptor agonists when compared with other agents irrespective of baseline characteristics. Conclusions Platelet counts at diagnosis are a potentially strong predictive indicator of subsequent lines of therapy. Patients with bleeding symptoms at diagnosis were more likely to have lower median platelets counts.

Abstract Background: For the majority of patients with acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (HCT) offers the best prospect of long-term survival. However both the risk of relapse and non-relapse mortality remain stubborn barriers to successful outcome. Remission status is one of the strongest predictors of outcome, and while conventional risk stratification models account for this, complete remission with incomplete count recovery (CRi) is typically ascribed the same predictive value as complete remission (CR). Methods: In this single center retrospective study we assessed the impact of incomplete count recovery on outcome of allogeneic HCT for AML. Patients' disease status was classified immediately prior to HCT as complete remission (CR), complete remission with incomplete count recovery (CRi) or no complete remission (no CR/CRi). The conventional definition of complete remission (<5% marrow blasts by morphology) was employed and incomplete count recovery was defined as platelet count <100 x 109/L and/or absolute neutrophil count < 1 x 109/L. Measurable residual disease (MRD) was defined by detectable disease by a contemporaneously accepted standard methodology at the time of transplant (e.g. PCR or immunophenotyping). The primary outcome measure was overall survival, and secondary endpoint of non-relapse mortality and relapse were also assessed. Results: Between January 2005 and December 2017, 155 patients underwent allogeneic HCT for AML in our institution. Disease status was defined as CR in 82 (53%), CRi in 54 (35%) and no CR/CRi in 19 (12%). No significant demographic or transplant characteristics were observed between the groups. With a median follow-up of 3.4 [0.1 - 12.8] years, survival at 3 years was 42.5% for the whole cohort with significant differences between the three groups: 54.3% for CR, 34.8% for CRi and 13.4% for no CR/CRi (p<0.001; fig 1A; HR 1.94 for CRi, and 3.4 for no CR). These differences remained after corrections for standard transplant risk factors. The significant differences in overall survival between CR and CRi groups were accounted for by increased non-relapse mortality (7.5% vs. 24.2% at 100 days and 28.7 vs 44.9% at 3 years (p=0.003), fig 1B). The overall cumulative incidence (CI) of relapse at 3 years was 32.4%, and while those patients transplanted not in CR/CRi has a significantly increased CI of relapse (55.3%, p=0.006), there were no significant differences between the CR and CRi groups (25.1 and 36.7% respectively (p=0.441; fig 1C). Patients without MRD (n=107) had a lower incidence of relapse compared to those with MRD (n=48, 21.9% vs. 48.1%, p=0.009), however MRD negative patients with incomplete recovery still had a significantly worse 3-year survival than those with complete recovery (37.5 vs 56.7, p=0.006) resulting from higher NRM (46.4% vs 30.4%%, p=0.003, fig 1D). Discussion: CRi patients have a poorer survival and higher NRM than CR patients with full marrow recovery, without evidence of increased relapse. While death from NRM is a competing risk for relapse, the increased incidence of relapse remains overtly demonstrable in those patients transplanted not in CR/CRi, despite an equally high NRM. Additionally, the persistently increased NRM in CRi patients without MRD, suggests that the poorer survival may result from poor fitness for transplant and increased susceptibility to transplant related complications rather than an imminent relapse. With the advent of increasingly sensitive MRD technologies, these data may suggest that further pre-transplant optimization to promote marrow recovery may be permissible in order to minimize NRM without risking increased risk of relapse in CRi patients. Figure 1. Figure 1. Disclosures Apperley: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Speakers Bureau.

Abstract Introduction: Ex-Vivo T-Cell Depletion (EX-TCD) has been shown, in multiple cohorts, to markedly decrease the incidence of graft-versus-host-disease (GvHD). This conditioning regime however, has been associated with high incidence of disease relapse. This single center, observational 34 year study, demonstrates outcomes of patients who underwent EX-TCD Allogeneic Hematopoietic Stem Cell Transplant (AHSCT) for Chronic Myeloid Leukemia (CML). The total cohort consisted of 62 patients; all underwent EX-TCD AHSCT between 1984 and 1988. 58% (n=36) of the total cohort relapsed and 53% of relapsed patients (n=19) went on to have a second AHSCT (non-T-cell depleted) or donor lymphocyte infusion (DLI) with the remaining 47% (n=17) receiving conservative management. Given these differences in management, we used a competing risk model to adjust for the second AHCST or DLI on survival outcomes (using a second AHSCT or DLI as a competing risk). The aim of this study was to determine from this cohort, which factors were associated with overall survival and survival following disease relapse. Methods: Within the relapsed cohort, univariate and multivariate standard Cox proportional hazard regression models were used to analyse various factors, which were hypothesized to be associated with survival. These included; age at relapse, gender and relapse grade. Competing risk model was used to analyse the contribution of a second AHSCT or DLI to survival. Results: The cohort underwent EX-TCD AHSCT for CML between 1984 and 1988. Age range of recipients was 15 to 53 years and all were sibling donors. At the 34 year follow-up mark, there was no difference in overall survival between those who relapsed (and received a second AHSCT or DLI) and those patients who did not relapse (p-value 0.86). Of the 26 % (n=16) of patients who remain alive, 50% (n=8) relapsed and received a second AHSCT or DLI. Most recent BCR-ABL polymerase chain reaction (PCR) confirm all patients remain in molecular remission (MR4 or below). For the whole cohort, relapse was not affected by; donor gender, recipient age, CMV status, GvHD grade, duration of disease prior to AHSCT, Sokal score at diagnosis or duration to relapse following AHSCT. No parameter had a statistically significant association with survival or relapse, suggesting heterogeneity of disease could be an important consideration. 22 % (n=2) of the non-relapsed group and 17% (n=6) of the relapsed group developed acute GvHD. 37% (n= 23) of patients from the whole cohort developed chronic GvHD. Known causes of death included; relapse (36%, n=22), infection (16%, n=10), chronic GvHD (11%, n=7), other (8%, n=5). 26% (n=16) of patients remain alive today and 3% (n=2) were lost to follow-up. Relapse was graded into 5 categories, mirroring monitoring methods at the time of relapse (prior to the development of BCR-ABL PCR). 6% (n=2) of patients developed a molecular relapse (grade 1), 58% (n=21) developed cytogenetic relapse (grade 2), 25% (n=9) developed hematological relapse (grade 3), 3% (n=1) relapsed as accelerated phase CML (grade 4) and 8% (n=3) relapsed with blast phase CML (grade 5). We divided patients into two groups; relapse grade <2 (cytogenetic or molecular relapse only) and grade >3 (hematological relapse or above). In a multivariate Cox proportional model, relapse grades were significantly associated with subsequent survival (log rank p-value 0.0057). Relapse grade >3 had an 11% increased hazard of death compared to relapse grade <2 (Hazard ratio (HR) 1.11; p-value 0.0068). 46% (6/13) of patients with relapse grade >3 underwent a second AHSCT or received DLI, compared with 56% (13/23) of patients with grade <2. In the competing risk analysis, those patients with relapsed grade <2 had a significantly improved survival with a second AHSCT or DLI (HR 1.34; 95% CI 1.06-13.70; p-value 0.03) whereas patients with a relapse grade >3 had no improvement in survival. (HR 0.96; 95% CI 0.93 to 6.8; p-value 0.07, Figure 1). Conclusion: In this cohort, EX-TCD was associated with high rates of relapse. However, patients remain alive from both the non-relapsed and relapsed cohorts. In the relapsed cohort, patients who received a second AHSCT or DLI had improved survival outcomes compared to conservative management. A competing risk analysis demonstrated that patients with lower relapse grades had a statistically significant improvement in survival after a second AHSCT or DLI. Disclosures Milojkovic: Incyte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Apperley:Novartis: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau.