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Background Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. Patients and Methods We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. Results Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). Conclusions cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.

Background Haplo-HCT emerged as a reliable option for patients with high risk hematological malignancies with no HLA-matched related or unrelated donors available. Retrospective registry data suggest comparable outcomes to HLA-matched donors; however, relatively little is known regarding predictors of disease relapse following haplo-HCT. We hypothesize that attainment of full-donor CD3 and CD33 chimerism at day 30 (D30) and 100 (D100) is associated with lower incidence of relapse after haplo-HCT. Methods We undertook a retrospective analysis of 78 patients who underwent haplo-HCT at the Ohio State University James Cancer Hospital between January 2013 and December 2017. The associations between patient characteristics including CD3/CD33 donor chimerisms and the cumulative incidence rate (CIR) of relapse were evaluated using proportional sub-distribution hazards model, treating death without relapse as the competing risk. The models were built adopting a landmark analysis approach at D30 and D100. Progression-free survival (PFS) was estimated using the method of Kaplan-Meier. Results Median age at haplo-HCT was 56 (20-74) years and 68% were males. 50% had acute myeloid leukemia/myelodysplastic syndrome, and 54% had intermediate disease risk index (DRI). Most patients (85%) received reduced-intensity conditioning and 50% received bone marrow (BM) grafts. Complete (100%) CD3 donor chimerism was observed in 63 (84%) patients at D30, and subsequently 59 (95%) patients at D100. Complete CD33 donor chimerism was observed in 67 (89%) patients at D30, and subsequently 56 (88%) patients at D100. In univariable D30 landmark analysis, the CIR of relapse was significantly lower in patients who achieved complete CD3 (and CD33) chimerism compared with patients with less than complete chimerism (Figure 1A; p Conclusions Complete CD3 and CD33 donor chimerisms at D30 and D100 predict a patient's risk for relapse following haplo-HCT. We observed a strong association between CD3 chimeric status at D30 with DRI, as well suggestive that high risk disease may be associated with impaired immune reconstitution after transplant and perhaps a less robust graft vs disease effect.

Introduction Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Preventing GVHD without impairing the graft-versus-tumor effect remains an important goal for successful allo-HSCT. Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as aGVHD prophylaxis. The influence of TAC has proved effective for preventing aGVHD after allo-HSCT. There is also variability in the serum concentrations of TAC and very little is known on the impact of early (first 4 weeks) TAC levels on aGVHD incidence. Methods Data were analyzed for 707 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002- 2016. All patients received standard prophylaxis with TAC daily and methotrexate on days +1, +3, +6, and +11 post allo-HSCT. Tacrolimus dose was adjusted to achieve a target serum level of 5-12 ng/ml. Fine and Gray's proportional hazard models accounting for competing risks were used to evaluate the association between TAC levels and outcome of aGVHD, cGVHD, GVHD-free/relapse-free survival (GRFS),and relapse. Cox proportional hazard models were used for the association with OS. Results The mean weekly TAC concentrations at weeks 1, 2, 3 and 4 were 8.0, 9.7, 11.3 and 10.5 ng/mL, respectively. The cumulative incidence of grades II–IV aGVHD was 40% at day 100 and 45% at day 180 post HSCT. In univariable analysis, high TAC level at week 1 was associated with lower grade II-IV aGVHD (Hazard ratio (HR), 0.96; p = 0.006). We examined the effect of week 1 TAC levels categorized into tertiles ( 8.95 ng/ml). Higher level of TAC (>8.95 ng/ml) was associated with lower risk of aGVHD (Figure 1a). In multivariable analysis, week 1 TAC levels > 5.85 ng/ml remained associated with a lower risk of grade II-IV aGVHD. However, only levels of 5.85-8.95 ng/ml were associated with statistically significant lower risk with HR=0.75, p=0.04 compared to the lower group ( 7.2 ng/ml (HR: 0.78, p=0.03). The CI of cGVHD was 41% at 1 year post-allo-HSCT. Week 2 TAC level >10.6 ng/ml was associated with an increased risk of relapse (HR, 1.37, p=0.043) (Figure 1b). The cumulative incidence of relapse at 1, 3 and 5 year post allo-HSCT was 33%, 38% and 40%, respectively. TAC levels at weeks 1, 2, 3 and 4 were not associated with OS. The 1, 3 and 5 year GRFS was 21%, 14% and 12%.TAC levels at any week were not associated with GRFS. Conclusion Achieving mean whole-blood level of tacrolimus between 6.0-9.0 ng/ml within the first week post-allogenic bone marrow transplantation may reduce the risk of aGVHD.

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have poor treatment outcomes when treated with traditional chemoimmunotherapy. Superior outcomes have been observed with the 2 CAR-T cell products approved by the US FDA; tisagenlecleucel (CTL109) and axicabtagene ciloleucel (Axi-cel) with 12 months overall survival rates of 49% and 59% respectively. The 2 major acute toxicities of these therapies are cytokine release syndrome (CRS) and neurotoxicity. The incidence of grade 3 or higher neutropenia, anemia, and thrombocytopenia was 78%, 43%, and 38% in patients treated with axi-cel. Little is known regarding the patterns and outcomes of these cytopenias. Here we present our preliminary experience on the patterns and outcomes of cytopenias in 32 patients who received commercially-available CAR-T cell therapy at our institution. We retrospectively reviewed all DLBCL patients receiving either CTL109 or axi-cel between January and September 2018 at our institution. All patients received a conditioning regimen of low-dose cyclophosphamide and fludarabine, followed by CAR-T infusion. Persistent cytopenias were defined as incomplete absolute neutrophil count ( The median age of patients was 59 years (range, 23-80); 63% were male, 4 patients (13%) received CTL109 and 28 (87%) received axi-cel. Twenty-two patients (69%) had a 3 month follow up imaging for assessment of response, of whom 7 patients (32%) achieved complete response (CR), 6 patients (27%) achieved partial response (PR), and 9 patients (41%) had progressive disease (PD). Persistent neutropenia was observed in 3 patients (9%), while persistent thrombocytopenia was seen in 21 cases (65%) and persistent anemia was the most common with a frequency of 72% (23/32 cases). Median time to neutrophil, platelet and Hb recoveries were 11 days (range, 5-218 days), 59.5 days (range, 4-241 days), and 76 days (range, 0-218 days), respectively. Filgrastim was used in 15 (47%) patients to facilitate neutrophil recovery. Twenty-three patients (72%) experienced neurotoxicity, of whom 11 (34%) had grade 3-4 toxicity. The frequency of CRS was 94% (29 out of 32 patients), with grade 3-4 CRS observed in 4 cases (12.5%). We observed no significant association between CRS and persistent cytopenias. In our preliminary series of 32 patients, persistent anemia and thrombocytopenia were more common than neutropenia after CAR-T cell therapy. However, most of these patients required growth factor support for neutrophil recovery. Longer duration of follow up is necessary to determine the impact of persistent cytopenias on outcomes and survival after CAR-T cell therapy.

Introduction Autologous stem cell transplant patients (ASCT) are at risk for bacterial. Antibacterial prophylactic strategy is variable among centers. Fluoroquinolone prophylaxis in ASCT patients has not been found to add a survival benefit. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. Methods At our institution, patients undergoing ASCT for multiple myeloma (MM) receive levofloxacin 500 mg daily as prophylaxis, while lymphoma patients do not. We retrospectively examined MM or lymphoma patients undergoing ASCT between July of 2015 and 2018 for bacteremia episodes. MM patients received melphalan and lymphoma patients received BEAM. All patients received growth factor support. Clinical and microbial data was recorded and analyzed using SPSS. Results In total, 172 patients underwent ASCT for lymphoma and 343 for MM. Seventeen percent (30/172) of lymphoma patients and 5.5% (19/324) of MM patients had febrile neutropenic episodes associated with bacteremia. Relative risk was 3.1 [1.83 – 5.43, p Discussion Fluoroquinolone prophylaxis resulted in less blood stream infection episodes but more breakthrough infections with resistant isolates. There was no statistically significant difference between the rates of CDI infections despite a trend to lower incidence in the prophylaxis group. Bacteremia was more difficult to treat for the resistant isolates. There were two infection-related mortalities in the prophylaxis group. In the era of antimicrobial resistance, further reevaluation of the utility of fluoroquinolone prophylaxis should be carefully weighed against the risks.