Non-remission Research Articles

Fibrinogen-albumin ratio predicts treatment response in phospholipase A2 receptor-associated membranous nephropathy with nephrotic syndrome

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

Allogeneic haematopoietic stem cell transplantation for adult T-lymphoblastic lymphoma: A real-world multicentre analysis inChina.

In this multicentre, real-world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in T-lymphoblastic lymphoma (T-LBL). A total of 130 Ann Arbor stage III or IV T-LBL patients (>16 years) treated with allo-HSCT across five transplant centres were enrolled. The 2-year cumulative incidence of disease progression, the probabilities of progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM) after allo-HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo-HSCT in NR were associated with disease progression. Thus, our real-world data suggested that allo-HSCT appeared to be an effective therapy for adult T-LBL patients with Ann Arbor stage III or IV disease.

Outcomes and prognosis of haploidentical haematopoietic stem cell transplantation in children with FLT3-ITD mutated acute myeloid leukaemia.

The presence of internal tandem duplication mutations in the FMS-like tyrosine kinase 3 receptor (FLT3-ITD) is a poor prognostic predictor in paediatric patients with acute myeloid leukaemia (AML). We evaluated the treatment outcomes and prognostic factors of 45 paediatric patients with FLT3-ITD AML who achieved complete remission before haploidentical haematopoietic stem cell transplantation (haplo-HSCT) at our institution from 2012 to 2021. Among the 45 patients, the overall survival (OS), event‑free survival (EFS), and cumulative incidence of relapse (CIR) rates were 74.9% ± 6.6%, 64.1% ± 7.2%, and 31.4% ± 7.1%, respectively, with 48.8 months of median follow-up. Univariate and multivariate analyses associated positive minimal residual disease (MRD) at pre-HSCT and non-remission (NR) after introduce 1 with inferior long-term survival. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 35.6% ± 5.2%, and that of grade III-IV aGVHD was 15.6% ± 3.0% The overall 4-year cumulative incidence of chronic graft-versus-host disease after transplantation was 35.7% ± 9.8%, respectively. In conclusion, haplo-HSCT may be a feasible strategy for paediatric patients with FLT3-ITD AML, and pre-HSCT MRD status and NR after introduce 1 significantly affected the outcomes.

Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis

ObjectiveTypically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. MethodWe conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson’s chi-square or Fisher’s exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. ResultsWe selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations.Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8––34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6– 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2––35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2––24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1––90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2––24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. ConclusionsIn our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.

Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia

To compare the short-term effect and adverse reaction of venetoclax (VEN) combined with azacitidine (AZA) versus "7+3" regimen in newly diagnosed elder patients with acute myeloid leukemia (AML). From January 2021 to January 2022, the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed, including VEN+AZA group (41 cases) and "7+3" group (38 cases). The propensity score matching(PSM) method was used to balance confounding factors， then response， overall survival(OS), progressionfree survival(PFS) and adverse reactions between the two groups were compared. The ORR of VEN+AZA group and "7+3" group was 68% and 84%, respectively, and the CRc was 64% and 72%, respectively, the differents were not statistically significant (P >0.05). In the VEN+AZA group, there were 5 non-remission (NR) patients, 4 with chromosome 7 abnormality (7q-/-7), and 1 with ETV6 gene mutation. Median followed-up time between the two groups was 8 months and 12 months, respectively, and the 6-months OS was 84% vs 92% (P =0.389), while 6-months PFS was 84% vs 92% (P =0.258). The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳ myelosuppression, and the incidence rate was not statistically different(P >0.05). The median time of neutrophil recovery in two groups was 27(11-70) d, 25(14-61) d （P =0.161）, and platelet recovery was 27(11-75) d, 25(16-50) d （P =0.270）, respectively. The infection rate of VEN+AZA group was lower than that of "7+3" group (56% vs 88%, P =0.012）. The rate of lung infections of two groups was 36% and 64%, respectively, the difference was statistically significant (P =0.048). The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

CD7 Chimeric Antigen Receptor T-Cell Therapy Bridging to Allogeneic Hematopoietic Stem Cell Transplantation Remarkably Improved Long-Term Disease-Free Survival in Refractory/Relapsed T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Introduction: The prognosis of refractory/relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) is poor, and salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) can only result in 20%-30% disease-free survival (DFS). Our previous clinical trials have shown that the patients with r/r T-ALL have achieved 90% complete remission (CR) with CD7 chimeric antigen receptor T cell (CART) therapy (Pan J. et al. JCO 2021), then quick received allo-HSCT to obtain 57% of 1-year DFS in 12 patients (Li ZH. et al. Transplantation and Cellular Therapy 2022). Objectives : In current study, the long-term outcomes of allo-HSCT in r/r T-ALL/LBL after CD7 CART therapy in larger cohort are investigated, and compared with that chemotherapy only before allo-HSCT simultaneously. The risk factors for prognosis after allo-HSCT in this setting are also analyzed. Methods: Between February 2018 and January 2023, total 90 patients with r/r T-ALL/LBL who underwent allo-HSCT in our hospital were included. The median age was 14 (2-65) years old. Somatic and germline gene mutations were detected by sequencing pre-transplant. Thirty-two (35.6%) patients were sensitive to chemotherapy and achieved CR before transplant (group A), and 58 (64.4%) cases were resistant to chemotherapy and in non-remission (NR) pre-HSCT. Forty-one of 58 patients in NR received CD7 CART before allo-HSCT (group B) and the rest 17 patients in NR underwent salvaged transplant (group C). Donor types included haploidential (60, 66.7%), unrelated (16, 17.8%) and identical sibling (14, 15.6%). Myeloablative conditioning regimens with either total body irradiation (TBI)/fludarabine (51, 56.7%) based or busulfan/fludarabine (39, 43.3%) based were applied. Antithymocyte globulin was used for haploidentical and unrelated transplants. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis. Results: All patients achieved durable engraftment. No significant difference was found in the incidences of acute GVHD (aGVHD), chronic GVHD (cGVHD) and infections in 3 groups (p=0.612, p=0.091, p=0.649). With a median follow-up of 25.5 (19.6-32) months, 2-year overall survival (OS) in group B was similar to that in group A (54.4% vs. 69.9%, p=0.33) and much higher than that in group C (35.3%, p=0.0065), and 2-year DFS in group B was similar to that in group A (51.0% vs. 61.1%, p=0.24) and much higher than that in group C (17.6%, p=0.0029). No statistical difference was seen on transplant-related mortality (TRM) (17.3% vs. 9.8% vs. 11.8%, p=0.65) among group B, A, C. Two-year cumulative incidence of relapse in group B (31.7%) was similar to group A (29.0%), and much lower than that in group C (70.5%). The risk for relapse and death decreased remarkably in group B (p=0.0047) and group A (p=0.0003) compared with that in group C. NR before transplant (p=0.0062), aGVHD (p=0.013) and viral infections (p=0.047) were risk factors for relapse-related death, but TBI-based conditioning (p=0.01) was positive impact factor on OS. The most common somatic gene mutations were NOTCH 1(55.7%), JAK 3 (18.0%), TP53 (16.4%), JAK1 (14.8%) and N R AS(14.8%). The most common germline gene mutations were EP300 (10.3%), ATM (8.6%), F7 (8.6%), KIT (8.6%) and N CF2 (8%). The patients with somatic TP53 or MED12 mutation had significantly higher risk for relapse and death (p=0.0018, p=0.0068). Germline gene mutations had no significant influence on prognosis post-transplant. Multivariate analysis had shown that CD7 CART (p=0.037), TBI-based conditioning (p=0.002) and cGVHD (p=0.004) were independent positive impact factors on OS, but aGVHD (p=0.034) and TP53 mutation (p=0.002) were independent negative impact factors for OS. Meanwhile, CD7 CART (p=0.005) and TBI-based conditioning (p=0.024) had positive impact on DFS, but TP53 mutation (p=0.02) also had negative impact on DFS. Conclusion s : Our study has demonstrated that CD7 CART followed by allo-HSCT has remarkably improved long-term DFS for chemotherapy-resistant T-ALL/LBL, and achieved comparable results in safety and efficacy with chemotherapy-sensitive disease post-transplant. Our study has also shown the profiles of somatic and germline gene mutations in r/r T-ALL/LBL, and identified some positive and negative impact factors for prognosis after transplant in this setting.

The Efficacy and Prognosis of Advanced Myelodysplastic Syndrome in Children

Pediatric myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell neoplasm with an annual incidence of 1-4 cases/million. The low incidence of advanced MDS in children and poor prognosis attract our attention. However, there are limited reports on the scheme and efficacy of pediatric advanced MDS. In this study, we retrospectively analyzed the efficacy of chemotherapy in pediatric advanced MDS and assessed the prognosis of patients. According to 2016 World Health Organization (WHO) classification of haematolymphoid tumours, 30 newly diagnosed pediatric advanced MDS patients during Dec 2007 to Apr 2022 from our single center were selected as the research object. The clinical data and prognosis were analyzed. The median age of patients is 8 years (range: 1-15years). The median bone marrow blast is 15.75% (range: 5-29.5%), while the median peripheral blood blast is 4% (range: 0-29%). Cytogenetic analysis was available for 29 patients, 69% (20/29) cases had abnormal karyotype. Monosomy 7 (37.9%) was the most common cytogenetic abnormality. Out of the total, 7 patients were treated with CAG/HAG regimen (C: aclarubicin 6mg d1-14, H: homoharringtonine 1mg/m 2d1-14, A: cytarabine 10mg/m 2 q12h d1-14, and G: Granulocyte Colony-stimulating Factor 200mg/m 2 d1-14 ), 8 patients with decitabine (20mg/m 2 d1-5), 11 patients with decitabine and CAG/HAG, 4 patients with AML-like chemotherapy (Daunorubicin+cytarabine+etoposide ) or other. The evaluation of response of therapy was available in 25 patients, 5 cases (20%) in partial remission (PR), 11 cases (44%) in complete remission (CR), 9 cases in(36%)non-remission (NR). The total response rate of chemotherapy is 60%, with CAG/HAG therapy 33%, decitabine therapy 43%, combined CAG/HAG and decitabine therapy 78%, AML-like chemotherapy 100%. The total complete remission rate of chemotherapy is 44%, with CAG/HAG therapy 17%, decitabine therapy 43%, combined CAG/HAG and decitabine therapy 56%, AML-like chemotherapy 67%. Patients receiving CAG/HAG in combination with decitabine had higher response rates compared to CAG/HAG or decitabine alone (OR=17.5, 95% CI 1.2-250.3, P=0.035). With a median follow-up of 20 months (range: 1-158months), 23 patients received HSCT after chemotherapy, and they had a higher 2-year overall survival rate compared to those who did not undergo transplantation (86% vs 0%, p<0.001). Decitabine combined with CAG/HAG improve the response rate of advanced pediatric MDS. Chemotherapy bridged hematopoietic stem cell transplantation significantly improves the prognosis of advanced pediatric MDS.

Clinical Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation Using Busulfan/Cyclophosphamide and Melphalan or Thiotepa As Conditioning Regimen in 37 Patients with Acute Megakaryoblastic Leukemia

Background Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of childhood AML and about 1% of adult AML. Patients with non-Down's syndrome AMKL (non-DS-AMKL) are often associated with a poor prognosis with a 3-year overall survival (OS) rate of less than 40%. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative therapy for AMKL. However, the long-term survival post-transplant needs to be improved. Here we conducted a single-center study to evaluate the long-term efficacy and safety of allo-HSCT in 37 non-DS-AMKL patients using an innovative conditioning regimen of Busulfan/Cyclophosphamide (Bu/Cy) and Melphalan (MEL) or Thiotepa (TT). Methods From August 2015 to July 2023, a total of 37 non-DS-AMKL patients (M/F 21:16) were treated consecutively in our hospital (Hebei Yanda Lu Daopei Hospital). The median age was 2 years (range 1-9 years). Chromosomal abnormalities were present in 24 cases, with fusion genes as follows CBFA2T3/GLIS2 (5 cases) 13.5%, NUP98-KDM5A (2 cases) 5.4%, MLL-AF10 (3 cases) 8.1%, MLL-AF9 (1 case) 2.7%. Gene mutations: WT1 (10 cases) 27%, JAK2 (7 cases) 18.9%, EVI1 (6 cases) 16.2%, TET2 (4 cases) 10.8%, ASXL1 (4 cases) 10.8%, PTPN11 (4 cases) 10.8%, NRAS (3 cases) 8.1%, GATA1 (2 cases) 5.4%. Before transplantation, in bone marrow (BM), 29 patients were in complete remission (CR), 3 were in partial remission (PR) and the rest 5 were in non-remission (NR). Thirty-three patients received the haploidentical transplantation (donors from parents n=31, siblings n=2) including 1 with the 3 rd transplant, and 4 received matched-unrelated donor transplantation. The stem cell sources were from BM and peripheral blood stem cells (PBSCs) among the 33 related donors, and PBSCs for the 4 unrelated donors. Patients received a median cell number of total mononuclear cells 20.15×10 8/kg (10.7-32.85), CD34+ cells 12×10 6/kg(4.05-27.14) and CD3+ cells 4.66×10 8/kg(1.81-19.38). The conditioning regimens administered were modified Bu/Cy (fludarabine 30 mg/m 2/d×5d; cytarabine 2g/m 2/d×5d; Bu 3.2 mg/kg/d×4d, Cy 1.8g/m 2/d×2d; etoposide 100mg/m 2/d×2d; antithymocyte globulin 1.5mg/kg/d×5d) in 2 patients, Bu/Cy+MEL (MEL 55mg/m 2/d×2d) in 31 patients, and Bu/Cy+TT (TT 2.5mg/kg/d×2d) in the rest 4 patients. Cyclosporine A (CSA)+ mycophenolate mofetil (MMF)+ short methotrexate (sMTX) were used as graft-versus-host disease (GVHD) prophylaxis. Results The median follow-up time was 24 months (2-84 months), and all 37 cases survived the graft, with a median leukocyte engraftment of +13 days (9-21 days), and a median platelet engraftment of +9 days (4-38 days). BM was assessed one month after transplantation, with all grafts fully donor-type. The 5-year OS was 54.1% (Figure 1). There was a significantly higher OS in the CR group (5-year OS 69%) than the PR or NR groups (P<0.001) (Figure 2). Among the CR patients, no significant difference was observed in the 3 different condition regimen groups with modified BU/CY group OS of 50%, BU/CY+MEL group OS of 69.6% and BU/CY+TT group OS of 75% (P=0.869) (Figure 3). After transplantation, 17 patients died including 11 from relapse, 4 from GVHD, 1 from gastrointestinal bleeding and 1from cerebral hemorrhage. The cumulative recurrence rate (CIR) was 29.7%, among which the CIR of the CR group was 17.2%, the PR group of 66.7% and the NR group of 80% (P<0.001). Post-transplant, the incidence of acute GVHD (aGVHD) was 35.13% (Grade II-IV), and severe aGVHD (Grade III-IV) incidence was 18.91%. And 51.35% of patients developed chronic GVHD. Other complication incidences were cystitis at 16.21%, cytomegalovirus at 5.94%, Epstein-Barr viremia at 13.5% and infections at 21.62%. Conclusions Our study indicates that the use of modified Bu/Cy +MEL or +TT conditioning regimens in allo-HSCT procedures presents a feasible and effective approach, demonstrating an improvement in overall survival for non-Down Syndrome AMKL patients. Crucially, it was observed that achieving CR prior to transplantation significantly contributes to better outcomes. Therefore, it is strongly recommended that allo-HSCT is performed in CR status. However, to corroborate these findings, it is essential to conduct long-term, large-scale clinical research across multiple centers.

Efficacy and Safety of Chimeric Antigen Receptor T Cells Therapy Strategy That Dual Targeting CD19 and CD22 to Treat Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults

Background: Chimeric antigen receptor T-cells (CAR-T) targeting CD19 therapy is reported to induce 83-93% response in relapsed/refractory acute lymphoblastic leukemia (r/r-ALL) in adults. However, 30-60% of patients relapse after CAR-T treatment, of which 14-25% CD19-negative relapse. In spite of CAR-T cells persistence, CD19 absent causing tumors that evade CAR-T cells mediated recognition and clearance. For CD19-negative relapse, it is necessary to explore more effective targets. There are some research proved that compared with single-targeted CARs, CD19/CD22 dual-targeted CARs induce more IFN-γ and IL-2 in vitro and eradicate patient-derived xenografts (PDX) produced with CD19-negative relapse of CD19-directing CAR-T treatment. Therefore, our study explored the efficacy and safety of clinical studies on mixture of CD19 CAR-T and CD22 CAR-T cells in the treatment of r/r ALL in adults. Patients and Methods: CD3 + cells were selected from the apheresis PBMC and activated before lentiviral CAR T cells infection. The cells were transduced with a caspase9-inducible, safety-engineered lentivector CAR containing anti-CD19 or -CD22 scFv fused with multiple intracellular signaling domains: CD28/CD27/CD3z-iCasp9. The quality of apheresis cells, gene transfer and T cell proliferation efficiencies, and effective CAR-T infusion dose were quantitatively scored and documented. All enrolled patients expressed CD19 and CD22 positively. All patients received fludarabine (FLU) and cyclophosphamide (CTX) conditioning chemotherapy (FLU 30mg/m 2, d1-3; CTX 500mg/m 2, d1-3) before CAR-T infusions. Results: The study included 16 r/r ALL patients, median age is 26 years, and median of previous theraples is 6, all of patient details can be found in the table (Fig.1). In the first month after CD19/CD22 CAR-T cells infusion, total of 93.8% (15/16) of patients achieved complete response (CR), 1 case (6.25%) was evaluated as non-remission (NR). In the evaluation of safety, 68.75% (11/16) of patients did not experience cytokine release syndrome (CRS), 25% of patients (4/16) occurred grade 1 CRS and 6.25% (1/16) of patients occurred grade 2 CRS, no case of severe CRS defined as≥grade 3 and no any immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. After a median follow-up of 9.9 months, 4 patients maintained CR, while other 11 patients were relapsed, with a duration of response (DOR) of 25% (4/16), median LFS was 6.1 months and median OS were not reached (Fig.2). Conclusions: In summary, CD19/CD22 exhibited a manageable safety but limited antileukemia activity. Our study showed that mixture of CD19 CAR-T and CD22 CAR-T cells infusion is fail to expected to compensate for the treatment of relapsed in r/r ALL and prolonging the leukemia-free survival of patients. The low-efficacy of dual-targeted CAR-T cells may be caused by the CAR19 and CAR22 cells interfere with each other and weaken the CAR-T amplification in vivo. From our data, it seems that the timing of treatment and tumor burden status may play a more important role rather than new targets CAR-T cells infusion for r/r ALL in adults.

A Modified Busulfan/Cyclophosphamide Preconditioning Regimen Incorporating Selinexor for Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Hematologic Malignancies

Objective: To investigate the safety and efficacy of a modified busulfan (Bu)/cyclophosphamide (Cy) conditioning regimen incorporating Selinexor for allogeneic hematopoietic stem cell transplantation in relapsed/refractory hematologic malignancies. Methods: We retrospectively evaluated the clinical outcomes of patients with hematologic malignancies who had received allo-HSCT with conditioning incorporating Selinexor at the Institute of Hematology and Blood Disease Hospital. Results: Between September 2022 and June 2023, 13 adult patients with high-risk hematologic malignancies were enrolled including 6 males and 7 females with a median age of 49 (13-58) years. There were 7 patients with acute myeloid leukemia (AML), 4 with myelodysplastic syndromes (MDS)/AML, 1 with multiple myeloma (MM) and 1 with extramedullary plasmacytoma. Six patients were in complete remission (CR), four in CR1, two in ≥CR2, five in non-remission (NR), and two patients were in a progressive disease status (PD) prior to conditioning. Three patients received matched-sibling donors transplant, while ten received related haploid hematopoietic stem cell transplantation. All patients had received myeloablative conditioning regimen incorporating Selinexor. Eleven patients received the conditioning: Bu (3.2mg/kg/d*2d); Melphalan (Mel, 60mg/m 2/d*2d), Fludarabine(Flu 30mg/m 2/d*3d) or CLA (5mg/m 2/d*3d), Cy (40mg/kg/d*2d), Selinexor 60mg/d*2d. The other 2 patients received the conditioning: Decitabine (DAC, 20mg/m 2/d*5d), Bu (3.2mg/kg/d*3d), Cy (40mg/kg/d *2d), Flu 30mg/m2/d*3d, Selinexor 60mg/d*2d. The median amount of infused mononuclear cell and CD34 + stem cell were 11.72×10 8/kg(range, 9.66 to 14) and 2.92×10 6/kg(range, 2.35 to 9.61), respectively. All the 13 patients achieved neutrophil engraftment with a median time of 12 (range, 9 to 18) days and 9 patients achieved platelet engraftment with a median time of 13 (range, 11 to 30) days. Four patients were still experiencing prolonged isolated thrombocytopenia. All patients achieved complete donor chimerism and minimal residual disease (MRD) negative at 30 days post-transplantation.The cumulative incidence of cytomegalovirus (CMV) reactivation was 15.4%, while Epstein-Barr virus (EBV) reactivation was not observed. Six patients (46.2%) experienced mucosal barrier injury, comprising three cases of oral mucosal ulcer, one case of digestive tract hemorrhage, and two cases of hemorrhagic cystitis. The cumulative incidence of II-IV and III-IV acute GVHD was 23.1% and 15.4%. The median follow-up for all the participants was 93 (40-316) days after transplantation. Only one patient was dead due to Thrombotic Microangiopathy (TMA) 78 days after transplant. One patient experienced molecular relapse 156 days after transplant, and another patient experienced hematology relapse 20 days after transplant. The two relapsed patients had received donor lymphocyte infusions after chemotherapy. The other 10 patients were still in CR with complete donor chimerism and MRD negative. The cumulative transplant-related mortality (TRM) and relapse rates are 7.7% (1 case) and 15.4% (2 cases), respectively. Conclusions: Incorporating Selinexor into the modified BU/CY conditioning regimen for allogeneic HSCT in patients with relapsed/refractory hematologic malignancies demonstrated a favorable safety profile. Ongoing prospective trials will provide valuable insights into the potential benefits of Selinexor in patients undergoing HSCT.

THU031 White Blood Cells (WBC) As Biological Markers Of Cortisol Status In Patients With Cushing's Disease (CD)

Abstract Disclosure: B.M. Mascarenhas-Nakano: None. P.F. Santos-Neto: None. L.C. Portari: None. S.R. Correa-Silva: None. J. Abucham: None. CD is a rare disease caused by ACTH-secreting pituitary adenomas and responsible for ∼80% of cases of endogenous hypercortisolism. Hypercortisolism affects all tissues, leading to several nonspecific and few specific anatomical and functional changes which are not always easy to recognize and quantify. Clinical suspicion is the first step in the diagnosis but is rather impressionistic. The influence of endogenous cortisol on WBC, recognized a long time ago, has been widely forgotten/ignored in clinical practice. In this study, we aimed to assess the potential of WBC as biological markers of cortisol status in patients with CD. Patients and Methods: We retrospectively compared Leukocyte (Le), Neutrophil (Ne), Lymphocyte (Ly), Monocyte (Mo), Eosinophil (Eo), and Basophil (Ba) counts at diagnosis in patients with proven CD (CDdx, n=64), at remission after treatment (pituitary surgery, adrenalectomy, or radiotherapy) (CDrem=36), and in a control group of patients with hypercortisolism suspected and ruled out using ES guidelines (CT, n=63). In addition, we retro-prospectively evaluated WBC in a subgroup of 33 patients before and after treatment [25 in remission (RE) and 8 in non-remission (NRE)]. Comparisons >2 groups: ANOVA followed by multiple comparison tests (MCT). Before vs after comparisons: paired tests. Variations (Δ= after-before) between different groups: unpaired tests. Associations: Fisher´s exact test. ROC curves were generated cut off values chosen by Youden index. Significance was set at 0.05. Results: At Diagnosis. Le, Ne, Ly, and Mo were increased and Ly decreased: CDdx vs CT (0.0075<P<0.0001), CDdx vs CDre (0.0015<P<0.0001), CDre vs CT (0.34<P<0.99). Eo and Ba showed no differences in CDdx vs CT (0.20<P<0.67). Diagnostic ROC curves were significant (0.047<P<0.0001) for all cells and various indexes (ratios and differences). AUC (0.8705), Youden index (0.696)(cut off 3,047), sensitivity (87.3%), specificity (82.26%), PPV (0.83) and NPV (0.86) were all highest for the difference Ne-Ly with overlapping confidence intervals with other indexes. At Remission. In paired analysis, most cells showed significant changes after remission. However, comparisons of Δs between RE and NRE groups were only significant for ΔLy and ΔNe% [nearly significant (P=0.06) for ΔNe%-Ly% and ΔLy%]. Remission was associated with ΔLy>-3 (P=0.0049) and ΔNe%<-12.5% (P=0.0463). Combining both parameters (ΔLy>-3 and/or ΔNe%<-12.5%), a stronger association (P= 0.0001) was found. Evaluation of cortisol status after treatment using the combined criterion was able to identify 21/25 (84%) patients in remission and 8/8(100%) innon-remission. Conclusions: Our results show that WBC, mainly Ne and Ly, are reliable biological markers of cortisol status and potentially useful in different steps of the diagnosis of endogenous hypercortisolism as well as in the follow up of patients with CD after treatment. Presentation: Thursday, June 15, 2023

Salvage hematopoietic stem cell transplantation for patients with higher leukemia burden in relapsed or refractory acute myeloid leukemia: a ten-year study.

Patients with relapsed and refractory acute myeloid leukemia (R-R AML), especially those in non-remission (NR) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to optimize the entire allo-HSCT process for R-R AML patients and identify potential factors affecting clinical outcomes after HSCT, we retrospectively analyzed 44 adult patients with R-R AML who underwent salvage allo-HSCT while in NR or with concomitant extramedullary leukemia at the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2022. The 1-year and 2-year overall survival (OS) of the 44 patients were 55.3% (95% confidence interval [CI], 41.1%-74.3%) and 44.4% (95%CI, 30.2%-65.4%), respectively. The 1-year and 2-year cumulative incidence of relapse (CIR) were 39.4% (95%CI, 38.0%-40.7%) and 53.0% (95%CI, 51.0%-55.1%), respectively, and the 1-year and 2-year leukemia-free survival (LFS) were 37.8% (95%CI, 24.8%-57.7%) and 20.3% (95%CI, 9.1%-45.3%), respectively. The 100-day, 1-year and 2-year treatment-related mortality (TRM) was 13.8% (95%CI, 13.3%-14.4%), 22.8% (95%CI, 21.9%-23.7%) and 26.7% (95%CI, 25.5%-27.8%), respectively. Multivariate analysis revealed that patients who developed chronic graft-versus-host disease (cGVHD) after transplantation had lower relapse rate. Our analysis also indicated that patients with blast counts in bone marrow (BM) <20% and those with ≥20% had comparable clinical outcomes after allo-HSCT. In conclusion, our study demonstrated that R-R AML patients in NR or with concomitant extramedullary leukemia can benefit from allo-HSCT, regardless of leukemia burden at the time of transplantation. Patients who experience cGVHD after allo-HSCT may have lower relapse rate due to enhanced graft-versus-leukemia (GVL) effects, but cGVHD should be controlled at mild to moderate level to avoid life-threatening complications.

Association of obesity under different metabolic status with adverse outcomes in patients with chronic myeloid leukemia: A retrospective cohort study.

Little is known about the association between abnormal metabolic obesity states and the outcomes of chronic myeloid leukemia (CML), especially in patients with obesity with different metabolic status. Here, we used the Nationwide Readmissions Database to assess the effects of metabolically defined obesity on adverse outcomes of CML. Of the 35 460 557 (weighted) patients, we included 7931 adults with discharge diagnoses of CML from January 1, 2018 to June 30, 2018. The study population was observed until December 31, 2018 and divided into four groups based on body mass index and metabolic status. The primary outcome was the adverse outcomes of CML, including nonremission (NR)/relapse and severe mortality risk. Multivariate logistic regression analysis was performed to analyze data. Metabolically unhealthy normal weight and metabolically unhealthy obesity were all risk factors for adverse outcomes of CML compared with metabolically healthy normal weight (all p < 0.01), and a significant difference was not found in the metabolically healthy obese. Female patients with metabolically unhealthy normal weight and metabolically unhealthy obesity had 1.23-fold and 1.40-fold increased NR/relapse risk, while male patients did not have this risk. Moreover, patients with a higher number of metabolic risk factors or with dyslipidemia were at higher risk of adverse outcomes, regardless of obesity status. Metabolic abnormalities were associated with adverse outcomes in patients with CML, irrespective of obesity status. Future treatment of patients with CML should consider the effects of obesity on their adverse outcomes under different metabolic status, especially in female patients.

Serum 25-hydroxyvitamin D as a predictive biomarker of clinical outcomes in patients with primary membranous nephropathy.

Primary membranous nephropathy (PMN) is an immune-related disease with increased morbidity and the most common cause of adult nephrotic syndrome (NS). The serum 25-hydroxyvitamin D [25(OH)D)], a biomarker of vitamin D (VD) status, tends to decline in patients with kidney disease. However, the relationship between 25(OH)D and PMN is still unclear. Therefore, this study aims to clarify the association between 25(OH)D and disease severity and therapy response of PMN. A total of 490 participants diagnosed with PMN by biopsy from January 2017 to April 2022 were recruited at the First Affiliated Hospital of Nanjing Medical University. The correlations between baseline 25(OH)D and manifestations of nephrotic syndrome (NS) or seropositivity of anti-PLA2R Ab were confirmed by univariate and multivariate logistic analyses. Spearman's correlations were used to examine the associations between baseline 25(OH)D and other clinical parameters. In the follow-up cohort, Kaplan-Meier analysis was used to assess remission outcomes among groups with low, medium, and high levels of 25(OH)D. Furthermore, the independent risk factors for non-remission (NR) were explored by COX regression analysis. At baseline, 25(OH)D was negatively related to 24-h urinary protein and serum anti-PLA2R Ab. The lower level of baseline 25(OH)D was associated with an increased risk for the incidence of NS in PMN (model 2, OR 6.8, 95% CI 4.4, 10.7, P < 0.001) and seropositivity of anti-PLA2R Ab (model 2, OR 2.4, 95% CI 1.6, 3.7, P < 0.001). Furthermore, the lower level of 25(OH)D during follow-up was demonstrated as an independent risk factor for NR even after adjusting age, gender, MBP, 24 h UP, serum anti-PLA2R Ab, serum albumin, and serum C3 [25(OH)D (39.2-62.3 nmol/L): HR 4.90, 95% CI 1.02, 23.53 P = 0.047; 25(OH)D < 39.2 nmol/L: HR 17.52, 95% CI 4.04, 76.03 P < 0.001); vs. 25(OH)D ≥ 62.3 nmol/L]. The Kaplan-Meier survival analysis also demonstrated that the higher level of follow-up 25(OH)D had a higher possibility of remission than the lower one (log-rank test, P < 0.001). Baseline 25(OH)D was significantly correlated with nephrotic proteinuria and seropositivity of anti-PLA2R Ab in PMN. As an independent risk factor for NR, a low level of 25(OH)D during follow-up might serve as a prognostic tool for sensitively identifying cases with a high probability of poor treatment response.

P416 The impact of remission on healthcare resource utilisation and costs amongst patients with inflammatory bowel disease in France, Germany, Italy, Spain, and the United Kingdom

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) with increasing healthcare resource utilisation (HCRU) and associated costs. Optimal management of CD and UC aims to induce and maintain remission which may subsequently lower HCRU and costs. This study reports on the potential impact on HCRU and associated direct HCRU costs (excluding drug costs) from achieving CD or UC remission in France, Germany, Italy, Spain and the United Kingdom (EU5). Methods Data were drawn from an Adelphi Real World IBD Disease Specific ProgrammeTM, a point in time survey collected from gastroenterologists and their IBD patients in EU5 in Sep 2020-Jan 2021. GEs completed a patient record form for their next 5-10 consulting IBD patients covering demographics, remission status, healthcare professional visits, tests used to diagnose and monitor CD/UC, hospitalisations and surgeries related to IBD. Patients were stratified into two groups based on GE stated remission status from set categories: remission (RE) vs non-remission (NR). Associated HCRU costs were sourced from published healthcare system reports per country. Outcomes and costs were compared between patients in RE vs NR using inverse probability weighted regression statistical analysis (α=0.05), adjusting for age, sex, BMI, smoking status, disease location, and current treatment. Results A total of 1,526 CD patients were analysed and split into patients in RE (n=1,021) and NR (n=505; Figure 1). Compared with CD patients in NR, patients in RE experienced a lower risk of at least one hospitalization (12.8% vs 29.8%; p&amp;lt;0.001) and surgery (13.8% vs 26.0%; p&amp;lt;0.0001) (Figure 2), and fewer visits to HCPs in the last 12 months (6.5 vs 7.4; p=0.005) (Figure 3). Furthermore, total HCRU cost was 53% less for patients in RE vs NR (€1410.4 vs €2153.4; p=0.0002), with 16% lower HCP visit and test costs (€637.1 vs €737.3; p&amp;lt;0.001) and 83% lower hospitalisation and surgery costs (€773.3 vs €1416.2; p=0.001) (Figure 3). In addition, 1,447 UC patients were analysed and split into patients in RE (n=968) and NR (n=479; Figure 1). Compared to UC patients in NR, patients in RE experienced a lower risk of at least one hospitalization (11.4% vs 24.3%; p&amp;lt;0.0001) and surgery (1.8% vs 5.0%; p=0.004 (Figure 1), and fewer HCP visits (6.0 vs 7.1; p&amp;lt;0.001) (Figure 3). Total HCRU cost trended lower amongst patients in RE vs NR (€1219.6 vs €1443.0; p=0.085), with 19% lower costs of HCP visit and test costs (€617.3 vs €734.7; p&amp;lt;0.0001). Conclusion Patients with IBD who achieve remission present lower HCRU burden, lower risk of hospital and surgery, and ultimately lower associated direct HCRU costs to healthcare systems in EU5.

Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study.

We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1). We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021. The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

The Efficacy and Safety of Modified Melphalan and Busulfan-Based Conditioning Regimen for Allogeneic-HSCT in Refractory/Relapsed or Persistent MRD Positive AML Patients

Background: Allogeneic stem cell transplantation (Allo-HSCT) is the only salvage option offering long-term survival opportunity for high-risk AML patients, as those patients respond insufficiently to chemotherapy. However, the overall survival (OS) rate after allo-HSCT is still frustrating. Great efforts have been made in improving the conditioning regimen, such as introducing two alkylating agent, busulfan (Bu) and Melphalan (Mel) to enhance the anti-leukemia efficacy. But high non-relapse mortality (NRM) is reported. In this study, we made refinements in the conditioning regimen with two alkylating agents, namely MCBC (the combination of melphalan, cladribine, busulfan, and cyclophosphamide). We aim to investigate the efficacy and safety of MCBC conditioning regimen for allo-HSCT in refractory/relapsed (R/R) and minimal residual disease (MRD) persistent positive AML patients. Methods: This prospective multi-center clinical trial enrolled R/R AML or AML with MRDpersistentpositivity, who underwent allo-HSCT from July 2020 to May 2022 (ChiCTR Registration ID: ChiCTR2000029936). The MCBC conditioning regimen consists of melphalan 60mg/m2/d, day -9~-8, cladribine 5mg/m2/d, day -7~-5, busulfan 3.2mg/kg/d, day -5~-3, cyclophosphamide 30mg/kg/d, day -2~-1. A post-transplantation maintenance therapy was provided whenever possible, including azacytidine, venetoclax, or FLT3 inhibitors. Results and Discussion: This study included a total 75 AML patients (65 R/R AML and 10 MRD+AML), with median age 37 years (ranged 13-56 years). More than half of patients (40/75) were evaluated as non-remission (NR), including 13 patients with leukemia blast over 20% or active extramedullary disease pre-HSCT. Haplo-identical-donor HSCT (HID-HSCT) was the predominance HSCT type (n=51, 68%). Mucositis was the main reported regimen-related toxicity, mostly were mild and well tolerated. No graft failure was documented. It is inspiring that all patients achieved hematology complete remission (CR) (100%) and 89.3% achieved MRD clearance on reconstitution day, indicating profound anti-leukemia capacity of MCBC regimen. The incidence of severe acute GVHD was 9.3%. With a median follow-up of 232（30-695）days, the estimated one-year overall survival (OS), relapse-free survival (RFS) and NRM of all patients were 72.1±6.3%, 71.4±6.0% and 7.1±3.5% respectively. Notably, patients with persistent MRD positivity obtained 100% OS and RFS. There were 13 patients in R/R AML group relapsed after HSCT, with a median time from HSCT to relapse was 120(75-218) days. The one-year cumulative incidence of relapse was 22.6±5.6%. Univariate analysis using by Kaplan-Meier method was performed. It indicated high blast burden (blast≥20%) pre-HSCT and absence of opportune maintenance therapy post HSCT were two independent risk factors with clinical significance. Competitive risk modal analysis for multivariate analysis also confirms the results. Conclusion: The preliminary data demonstrated profound anti-leukemic capacity and well acceptable toxicity of MCBC regimen for R/R or MRD persistent positive AML. Furthermore, for patients with high leukemia blast burden, opportune maintenance treatment led to significant improved OS and RFS. Figure Legend: Survival outcomes of patients enrolled. Kaplan-Meier curves for Overall survival (A), Disease-free survival (B), Cumulative relapse rate(C) and Non-relapse mortality(D) of patients receiving MCBC conditioning regimen after allo-HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Outcomes and Prognostic Factors of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

To investigate the clinical outcomes and prognostic factors of refractory/relapsed acute myeloid leukemia (AML) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 80 refractory/relapsed AML patients who received allo-HSCT from December 2013 to June 2020 were retrospectively analyzed, including the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate, incidence of transplant-related mortality (TRM), and the related risk factors were explored. Hematopoietic reconstitution was obtained in all 80 patients after transplantation, the 3-year OS and DFS rates were (48.8±6.3)% and (40.8±6.7)%, respectively. The 3-year cumulative incidence of relapse and TRM were 33.8% (95%CI: 0.254-0.449) and 15.0%(95%CI: 0.114-0.198), respectively. Univariate analysis showed that non-remission (NR) status before transplantation, DNMT3A R882 mutations and grade II-IV acute graft-versus-host disease (aGVHD) had negative effects on OS and DFS. Multivariate analysis indicated that the DNMT3A R882 mutations and grade II-IV aGVHD were independent risk factors for OS (HR=0.253, 95%CI: 0.092-0.695, P=0.008; HR=5.681, 95%CI: 2.101-15.361, P=0.001) and DFS (HR=0.200, 95%CI: 0.071-0.569, P=0.003; HR=7.117, 95%CI: 2.556-19.818, P<0.001). The 3-year cumulative incidence of relapse was 71.4%(95%CI: 0.610-0.836) in genetic high-risk group, which was higher than 23.3%(95%CI: 0.147-0.370) in intermediate-risk group and 23.5%(95%CI: 0.127-0.437) in favorable-risk group (P=0.006). Allo-HSCT is an effective and safe choice for refractory/relapsed AML patients. DNMT3A R882 mutations and grade II-IV aGVHD are negative prognostic factors of allo-HSCT for refractory/relapsed AML patients.

Non-diabetic urine glucose in idiopathic membranous nephropathy

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-β-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.

S240: CD7 CHIMERIC ANTIGEN RECEPTOR T CELLS BRIDGING TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IMPROVED DISEASE-FREE SURVIVAL IN REFRACTORY/RELAPSED T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

Background: Our previous clinical study has shown that the patients with refractory/relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL) have achieved 90% complete remission (CR) with donor-derived CD7 chimeric antigen receptor T cells (CART), but some cases have developed donor-recipient mixed chimerism and remarkable pancytopenia (Pan J. et al. JCO 2021). It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Aims: In current study, the safety and efficacy of allo-HSCT in r/r T-ALL after CD7-CART are investigated. Methods: From February 2018 to December 2021, total 57 patients with r/r T-ALL who underwent allo-HSCT in our hospital were included. The median age was 13(4-69) years old. Extramedullary disease (EMD) was found in 32 patients (56.1%). Somatic gene mutations (NOTCH 18, IL7R 3, JAK 2, FBXW7 2, WT1 2, NRAS 2) were detected in 17 patients. Eighteen patients who were resistant to chemotherapy received CD7-CART (CART group) before transplant, and all patients except one achieved CR. Thirty-nine r/r T-ALL patients were managed with chemotherapy before transplant (non-CART group), and 25 patients achieved CR (CR arm), 14 patients were in non-remission (NR) (NR arm) before transplantation. Conditioning regimens in CART group were either busulfan/fludarabine (n=12) or TBI/fludarabine (n=6). Conditioning regimens in non-CART group were either busulfan/fludarabine (n=11) or TBI/ fludarabine (n=28). ATG was used for haploidentical or unrelated transplants. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for GVHD prophylaxis. Results: In CART group, the median time of neutrophils and platelets engraftment were 15 (10-22) and 18 (8-50) days. With the median follow-up 283 (14-496) days, 13 patients survived and 5 patients died (infection 4, cerebral hemorrhage 1). Three of 18 (16.7%) patients relapsed (CD7- 1, CD7 + 2) after transplantation and have been receiving treatment so far. One-year overall survival (OS) and disease-free survival (DFS) were 77.8% and 61.2%. Transplantation-related mortality (TRM) was 16.6%. In non-CART group, the median time of neutrophils and platelets engraftment were 15 (10-22) and 15 (8-28) days. Total 25 patients survived and 14 cases died (relapse 3, infection 4, GVHD 1, multiple organ failure 6). Fifteen of 39 (38.5%) patients relapsed. In CR arm, with the median follow-up 637(9-1357) days, one-year OS and DFS were 71.0% and 59.2%. In NR arm, with the median follow-up 517 (7-513) days, one-year OS and DFS were 59.2% and 40%. TRM was 28.2%. Summary/Conclusion: Donor-derived CD7-CART followed by allo-HSCT has achieved similar survival (OS, DFS) and lower relapse rate and TRM compared with chemotherapy followed by allo-HSCT in r/r T-ALL. CD7-CART may result in better disease control which will translate into less disease recurrence after transplant.