ALBERT

Description: Introduction Hematopoietic stem-cell transplantation (HSCT) has demonstrated only curative potential for patients with myelodysplastic syndrome (MDS), still prognosis after HSCT are highly different in MDS patients. Over the past decade, several studies have demonstrated that outcomes after HSCT are influenced by clinical and molecular factors, which suggests that a prognostic model combining clinical and molecular-related factors are needed to be identified. Method A total of 138 MDS patients who underwent allogeneic HSCT between 2010 and 2018 at the Institute of Hematology and Blood Disease Hospital were considered for inclusion in this study. Median follow-up duration was 33 months. A Custom Amplicon panel targeting exons of 185 genes was used for deep sequencing before transplant. We used a LASSO Cox regression model to achieve shrinkage and variable selection from prognostic factors (P0.065, IPSS-R score, TERT, ANKRD26 and PDGFRB mutations were significantly associated with poor OS (P 〈 0.05). Five variables were incorporated in our scoring model by LASSO, including IPSS-R score, HCT-CI, TERT, PDGFRB, ANKRD26 mutation. A risk scoring model was developed incorporating the weighted coefficients of these variables. The risk score grouped patients into two subgroups: low risk (LR, score ≤1.7, n= 78) and high risk (HR, score 〉 1.7, n= 13) groups. The 3-year OS for LR and HR groups were 80.5% and 23.1% (P 〈 0.0001), and 3-year DFS were 73.9% and 23.1% (P 〈 0.0001), respectively (Figure A-B). The similar results were also observed in validation cohort (3-year OS 88.9% vs. 50.0%, P= 0.0032; 3-year DFS were 83.3% and 50.0%, P =0.016, Figure C-D). Concordance index [train: 0.682, 95% CI (0.63, 0.734), validation: 0.747, 95% CI (0.655, 0.839)] demonstrated well discrimination power and calibration plots showed that the nomograms did well compared with an ideal model. Conclusions Here we create a new model combining clinical and molecular-related factors provides better survival stratification for patients with MDS receiving HSCT, provide a useful tool to predict transplant outcomes for MDS patients before transplant. This could have important implications as it can help better identify MDS patients who will benefit the most from transplantation, and may impact the choice of intensity of preparative regimens for transplantation as well as post-transplant maintenance therapy. Additional independent cohorts and prospective studies are needed to externally validate our model before implementation into clinics. Figure 1 Disclosures No relevant conflicts of interest to declare.

Description: Background and Objectives: Invasive fungal diseases (IFDs) are major and lethal infectious complications for patients with neutropenia after chemotherapy for acute leukemia (AL). We aimed to compare the use of oral posaconazole vs. itraconazole in an intravenous-oral regimen for primary antifungal prophylaxis in terms of efficacy, adverse events and costs among neutropenic patients with AL after chemotherapy. Methods: This single-center, retrospective study enrolled patients with AL. Prophylaxis with oral posaconazole or intravenous-oral itraconazole (intravenous formulation × 2 days + oral suspension) was administered for patients recovering from neutropenia after chemotherapy. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results: Among 342 eligible episodes from 186 patients, 110 episodes received oral posaconazole and 110 episodes received itraconazole in sequential regimen had similar propensity scores and were included in the analyses. The incidence of breakthrough IFDs was 0.0% (0/110) and 0.0% (0/110) in the posaconazole group and itraconazole group, while the incidence of proven, probable and possible IFDs was 1.8% (2/110) and 8.2% (9/110), respectively (P=0.030). In clinical failure analysis, the failure rate of posaconazole group was lower as compared to the itraconazole group (2.7% vs. 10.9%, P=0.016). The proportion of patients who needed systemic antifungal treatment were lower in posaconazole group than that in itraconazole group (2.7% vs. 10.0%, P=0.027). Five cases (4.5%) experienced adverse events possibly associated with posaconazole and thirteen cases (11.8%) with itraconazole (P=0.049). There was no significant difference of survival between patients on posaconazole or itraconazole. The acquisition costs of posaconazole were higher than those of itraconazole (P=0.000). Conclusions: Both oral posaconazole and intravenous-oral itraconazole are effective in preventing IFDs for acute leukemia patients recovering from neutropenia after chemotherapy, while posaconazole is slightly better. Oral posaconazole is safer and more tolerable but costs higher than intravenous-oral itraconazole. Disclosures No relevant conflicts of interest to declare.

Description: Background: Patients with B cell acute lymphoblastic leukemia (B-ALL) relapsed after allogenic hematopoietic stem cell transplantation(alloHSCT) have poor prognosis and the median survival after relapse was 4 - 5.5 months, estimated 2-year post-relapse survival rates were 10 - 16%. Donor lymphocyte infusion (DLI) have shown limited success in the setting of relapse by a mere increase in median survival by 6 months and a significant risk of acute and chronic graft-versus-host disease (GVHD) and additional risk of marrow aplasia. The donor chimeric antigen receptor-T cell (CAR-T) for CD19 is a promising treatment for relapsed and refractory B-ALL, but the effectiveness and safety of donor-derived CD19 CAR-T cell infusion for relapsed B-ALL after alloHSCT have not been determined. Methods: Between July 2017 and Nov 2018, 10 adult patients with B-ALL relapsed (4 patients were hematologic relapsed, 3 patients were extramedullary relapse, the other 3 patients were bone marrow MRD-positive, Table) after alloHSCT were enrolled, including 9 sibling-matched stem cell transplantation and 1 haploidentical transplantation. About 100 - 200 ml venous blood form each donor was obtained and the T cells were separated. Then donor's T cells were infected with lentivirus carrying CD19 CAR plasmid which containing CD19 scfv (HI-19 clone) and 4-1BB-CD3ζ signaling domains to generate CAR-T cells. ALL the 10 Patients received FAC (fludarabine: 25-30mg/m2/d*3, cyclophosphamide:350mg/m2/d*2, cytosine arabinoside:100mg/m2/d*4) pretreatment and then a total of 5.01 × 106/kg (range, 3.39 - 6.53 × 106/kg) donor T cells including donor-derived anti-CD19 CAR-T cell (1.82 × 106/kg, (range, 1.26 - 4.67 × 106/kg)) was infused on 2 or 3 consecutive days for each patient. The levels of cytokines including IL-1,IL-2R,IL-6,IL-8,IL-10 and the percentage of the donor anti-CD19 CAR-T cells were monitored serially . Clinical manifest and the severity of cytokine release syndrome (CRS) were recorded and evaluated. The bone marrow examination was performed every 2 weeks after CAR T-cell infusion to assess the response for the first 2 months and then was performed every 1-3 months including bone marrow smear, MRD detection by flow cytometry, fusion gene detection by quantitative real-time polymerase chain reaction (qPCR), donor chimera rate by short tandem repeat(STR). Results: The median transduction efficiency of the final donor-derived CD19 CAR-T cells was 35.8%(range 25 - 70.6%). The peak of donor-derived anti-CD19 CAR-T cell expansion in the recipients was about 7 - 14days after infusion and then decreased rapidly. The serum cytokines levels varied differently: the serum IL-6 and IL-2R levels increased overtly and reached the peak during day 5 - day 7 in most of the patients, whereas the serum levels of IL-1, IL-8 and IL-10 did not vary obviously. one patient experienced Grade 3 CRS, 4 patients experienced Grade 2 CRS and the other 5 patients only experienced Grade 1 CRS. Four patients showed encephalopathy and 2 patients received glucocorticoid treatment. All the 10 patients achieved MRD negative remission and complete donor chimerism within 14days to 42days after donor's CAR-T cells infusion. No patients developed acute or chronic graft-versus-host disease (GVHD). After a median follow-up of 20.6 months (range, 13.4-30.3), 5 patients (including all the 3 patients with extramedullary relapse) relapsed with leukemia cells CD19-dim and 4 of them died due to disease progression. Only one patient received a successful secondary alloHSCT from a haplo-identical donor. The other 5 patients showed persistent complete donor chimerism with MRD negative remission(Figure). The estimated 2-year overall survival and leukemia-free survival were 68.6% and 48.0%, 2.5-year OS and LFS were 51.4% and 48.0%. Conclusion: Donor-derived CD19 CAR-T cell infusion seems to be an effective and safe treatment for B-ALL relapsed after alloHSCT, especially for those without extramedullary disease, which may be confirmed with more clinical studies. Disclosures No relevant conflicts of interest to declare.