Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study.

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.

Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure.

Background and aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005). Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.

The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma.

Objective: The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. Methods: The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. Results: Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively (P < 0.01). The median progression-free survival was 16.3 (2.6-24.5) months, and the median overall survival was 19.3 (6-24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS (P < 0.01) and OS (P < 0.01). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome (≥grade 3 ICANS) and cytokine release syndrome (≥grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. Conclusion: The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.

The value of ultrasound-guided fine needle aspiration in the diagnosis of diffuse large B-cell lymphoma: A single center experiment.

OBJECTIVES: Flow cytometry (FC) is a critical diagnostic approach for guiding targeted chemotherapy and cellular immunotherapy for relapsed and refractory lymphoma patients. The aim of the study was to investigate the value of ultrasound-guided fine needle aspiration (FNA) to improve the quality of FC specimens in relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL). METHODS: Twenty patients with R/R DLBCL after standard treatment were included. The primary lesions of all cases were confirmed by pathology. FNA and core needle biopsy (CNB) were both used for ultrasound-guided puncture, the specimens obtained by FNA are directly examined by FC, and the specimens by CNB were subjected to FC after grinding. The accuracy of FC with the two methods were evaluated using histopathology as the gold standard. RESULTS: Of the 20 R/R DLBCL cases, 19 were diagnosed as DLBCL pathologically and one was diagnosed as inflammatory granuloma. Among the specimens obtained by CNB, 14 cases examined by FC after grinding showed abnormal mature B cells, five cases were missed, all cases are not misdiagnosed. Among the specimens obtained by FNA, 18 cases showed FC-confirmed abnormal mature B cells, one case was missed, all cases are not misdiagnosed. The sensitivity, specificity, and accuracy of FC with CNB and FNA were 73.68 % (14/19) vs 94.73 % (18/19), 100 % (1/1) vs 100 % (1/1), and 75 % (15/20) vs 97.14 % (19/20), respectively. The sensitivity of the two puncture methods of FC of DLBCL was statistically different (p < 0.001). CONCLUSION: Sampling with ultrasound-guided FNA is of great value to improve the quality of FC specimens. FNA can significantly improve the sensitivity and accuracy of FC diagnosis in R/R DLBCL.

[Imatinib Combined with VP Low Dose Regiment for Treating Newly Diagnosed Adult Patients with Ph-positive ALL].

OBJECTIVE: To investigate the inductive therapeutic effects of imatinib combined with VP low dose regiment on adult patients with Ph-positive acute lymphoblastic leukemia (Ph(+) ALL). METHODS: Fourteen newly diagnosed adult patients with Ph(+) ALL were treated with VP regimen, and imatinib (400 mg/d) was added at the 8(th) day. VP regimen would be stopped when neutropenia lasted for 1 week or complicated with infection, fever, etc. Therapeutic effects were assessed by bone marrow morphology and quantitative analysis of BCR/ABL:ABL at the 28(th) - 33(rd) day. Patients could be treated with imatinib combined with chemotherapy for consolidation and maintenance therapy or were treated with allogeneic hematopoietic stem cell transplantation after complete remission. RESULTS: Fourteen cases obtained CR1 after first course of treatment, the median decline of BCR/ABA:ABL was 55.89 (10.25 -180.97) %; during the induction chemotherapy, pulmonary infection occurred in 3 patients, diarrhea in 1 patients, facial edema in 3 patients, however, all these patients were cured after symptomatic treatment, only 1 patient died of relapse after transplantation. CONCLUSION: In the period of tyrosine kinase inhibitor (TKI), inductive chemotherapy combined with imatinib and low dose VP can obtaine satisfactory CR rate and decrease the toxicity of the traditional drugs. It is suggested that TKI combined with VP regimen chemotherapy can achieve CR1 and make possible for allo-HSCT, from which patients can achieve the long-term survival.

Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL) in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]). The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. METHODS: In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30) years. Overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years) were enrolled, including those with BCR/ABL transcripts 190 (n = 52), 210 (n = 25), and 230 (n = 2); BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT), and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008), the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012), and also higher than those with TKI salvage administration (P = 0.004). BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each). CONCLUSIONS: The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.

[Analysis of clinical characteristics and prognosis of 13 cases of acute erythroleukemia].

The aim of this study was to investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL, AML-M6). The clinical features and results of morphologic, immunophenotypic, cytogenetic and molecular biologic detections were retrospectively analyzed in 13 cases of AEL from 305 acute leukemia patients hospitalized between October 2007 and October 2012. The results showed that the expression of erythroid and non-erythroid cells increased at the same time. The myeloid antigens mainly expressed CD13/CD33/CD117/CD34, while the erythroid antigens expressed Gly and CD71. The karyotypic detection indicated that there were 1 case with normal karyotype, 3 cases with simple karyotypic abnormality and 2 cases with complex karyotypic abnormality, the other cases were not detected. The molecular biological detection found that the poor prognosis gene existed in 5 cases [38.5% (5/13)], including 3 cases with MLL-MLL fusion gene, 1 case with MLL mutation, and 1 cases with NRAS gene mutation, the abnormal genes were not detected in remainder 8 cases. After chemotherapy with decitabine, the complete remission (CR) rate achieved 53.5% (7/13), partial remission (DR) rate achieved 15.4% (2/13). Finally, 8 patients received allo-HSCT, the median overall survival (OS) was 20.7 months, 3 year survival rate was 79%, 3 year disease-free survival rate was 78%. It is concluded that the acute erythroleukemia is a rare subtype of AML, which is transformed from MDS and has harmful genes and poor prognosis. Allo-HSCT and treatment with decitabine may enhance the survival rate of AEL.

[Autologous hematopoietic stem cell transplantation for patients with diffuse large B-cell lymphoma: a retrospective study].

The purpose of this study was to investigate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with diffuse large B-cell lymphoma (DLBCL), and analyse the factors influencing prognosis. The clinical data of 67 patients with DLBCL received auto-HSCT from 1996 to 2011 and cumulative overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), and relapse rate were retrospectively analyzed. The results showed that the median follow-up time was 40 months after transplantation. Three-year cumulative OS and PFS were 70.6% and 66.4% respectively, 5-year cumulative OS and PFS were 70.6% and 63.8% respectively, and TRM was 7.2%. One-year and three-year cumulative relapse rate were 16.5% and 23.7% respectively. Univariate analysis revealed that the age and pre-transplant disease status were significantly associated with poor prognosis (P < 0.05). It is concluded that auto-HSCT is a safe and effective therapeutic option for patients with DLBCL, especially for the young patients or patients with better remission.

[Clinical significance of rapid detecting bone marrow BCL2/IGH and BCL6/IGH fusion genes in patients with diffuse large B cell lymphoma by multiplex PCR].

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL), characterized by great heterogeneity in clinical manifestations and molecular genetics. This study was aimed to explore the clinical significance of applying multiplex PCR to detect BCL2/IGH and BCL6/IGH fusion genes in DLBCL. Multiplex PCR was used to detect bone marrow samples from 80 cases of DLBCL. The results showed that 12 patients (15%) carried BCL2/IGH or BCL6/IGH fusion genes, BCL2/IGH was found in 6 patients (7.5%), and BCL6/IGH in another 6 patients (7.5%). The patients with different molecular markers displayed different clinical features and outcomes. It is concluded that multiple PCR is rapid and accurate method to identify gene abnormalities in DLBCL, but further studying a quantitative or semi-quantitative assay for the expression of fusion genes is needed.

[Application of multiplex nested RT-PCR to detecting 10 fusion genes related with MLL gene in myelodysplastic syndrome].

This study was aimed to investigate the clinical value of multiplex nested reverse transcription PCR (RT-PCR) in detecting MLL-related fusion genes in myelodysplastic syndrome (MDS). Ten MLL-related genes (dupMLL, MLL-ELL, MLL-ENL, MLL-AF6, MLL-AF9, MLL-AF10, MLL-AF17, MLL-CBP, MLL-AF1P, MLL-AF1Q) in 221 MDS cases were detected by multiplex nested RT-PCR. The results indicated that 20 patients were detected with positive result among 221 patients and the positive rate was 9.05%. The number of the positive cases and positive rates of the above mentioned 10 fusion genes were in order: 7 (3.16%), 2 (0.9%), 1 (0.45%), 1 (0.45%), 2 (0.9%), 2 (0.9%), 1 (0.45%), 2 (0.9%), 1 (0.45%), 1 (10.45%). It is concluded that the multiplex nested RT-PCR has been confirmed to be able to detect 10 fusion genes in MDS patients, which can provide important evidences for assessing diagnosis and treatment, and give related necessary information about minimal residual disease and its prognosis.