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Background: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL., Methods: Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells., Results: A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy., Conclusions: The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile., Trial Registration Numbers: ChiCTR1900025419 and NCT04690192., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL., Methods: A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results., Results: Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC)., Conclusions: The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Attaining undetectable minimal residual disease (MRD) is the current therapeutic goal for multiple myeloma. But there is a current lack of data regarding the clinical benefit of autologous stem cell transplantation (ASCT) for patients with myeloma achieving early MRD-negative status after induction treatment, in addition to the interaction of longitudinal MRD status with ASCT. The current study included 407 patients with transplant-eligible multiple myeloma with available MRD status from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199), of whom 147 (34.4%) achieved early undetectable MRD and 182 (44.7%) received ASCT. Early MRD-negative status was associated with a lower risk of disease progression [HR = 0.447; 95% confidence interval (CI), 0.333-0.600; P < 0.001] and death (HR = 0.473; 95% CI, 0.320-0.700; P < 0.001). Of note, patients who achieved undetectable MRD early still benefitted from ASCT, with a remarkable improvement in the median MRD-negative duration (33.5-58.0 months, P < 0.001), progression-free survival (PFS; 46.0-88.3 months, P < 0.001), and overall survival (OS; 76.4 months to not reached, P = 0.003). These clinical benefits were more pronounced in patients with aggressive features (high-risk cytogenetic abnormalities or high tumor burden) compared with standard-risk patients. Similar results were observed in patients with detectable MRD after induction treatment. In addition, we identified four MRD-status transformation patterns following ASCT, which were strongly correlated with diverse survival outcomes ( P < 0.001). Our study revealed the enhanced clinical significance of ASCT in patients with transplant-eligible myeloma, regardless of early MRD status, particularly for high-risk patients. Subsequent prospective trials are essential to validate these observations., Significance: Achieving and maintaining undetectable MRD is the current treatment goal for multiple myeloma. Our results emphasized the remarkable clinical benefit of ASCT on MRD-negative duration, PFS, and OS in patients with multiple myeloma regardless of early MRD status. These favorable impacts were more evident in patients with aggressive features. Importantly, dynamic MRD monitoring among ASCT could facilitate personalized stratification of therapeutic approaches., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Recently, the definition of primary plasma cell leukemia (pPCL) has been revised as the presence of circulating plasma cells (CPCs) ≥5% in peripheral blood smear. Consequently, the clinical features and prognosis of this aggressive disease can be truly identified by the larger patient cohort. Herein, we identified 158 new-defined pPCL patients among 2,266 MM patients (7.0%), and such prevalence doubled the previous estimate. Our study firstly provided solid support for the application of the new definition. We also found that cytopenias and adverse prognostic biomarkers were more common in new-defined pPCL compared with MM ( p  < 0.05). Besides, the patients receiving proteasome inhibitors based regimen in combination with stem cell transplantation could experience a considerable survival benefit. Strikingly, we showed that the presence of conventional high-risk cytogenetic abnormalities in pPCL didn't exert a great prognostic effect like MM, while elevated LDH reflecting tumor cells proliferation rate was the only independent predictor.

Objective: To evaluate the results of autologous hematopoietic stem cell transplantation (auto-HSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL)., Methods: From January 2000 to December 2007, the clinical data of auto-HSCT in adults Ph-ALL with complete remession (CR) 1 according to BDHALL2000/02 protocol were analyzed., Results: A total of 56 patients were enrolled and the probabilities of standard risk, intermediated risk and high-risk group were 41.1%, 33.9%, and 25.0%, respectively. After a median follow-up of 75 months (range 7-177 months), the 5-year overall survival (OS), events free survival (EFS) and relapse free survival (RFS) were (51.8 ± 6.7)%, (51.8 ± 6.7)%, and (60.5 ± 6.9)%, respectively. And the 5-year accumulative relapse rate was (39.1 ± 6.9)%. The 5-year OS of standard risk, intermediate risk, high-risk group were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 2.8)%, respectively. The 5-year RFS among three groups were (68.3 ± 9.9)%, (62.5 ± 12.1)%, and (44.9 ± 14.1)%, respectively. The 5-year EFS among three groups were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 12.8)%, respectively. The 5-year accumulative relapse rate among three groups were (31.7 ± 9.9)%, (37.5 ± 12.1)%, and (55.1 ± 14.1)%, respectively. There was no statistical significance of any survival rates between standard and intermediate risk groups, just as intermediate and high-risk groups. The OS and EFS in standard risk group were superior to those in high-risk group (P=0.040 and P=0.029, respectively), while there was no statistical significance of RFS and accumulative relapse rate between the two groups. The clinical factors listed below did not influenced the prognosis in the univariate analysis (P>0.05), including more than 5 weeks reaching to CR, WBC count at diagnosis, different immunophenotype (T or B cells), myeloid antigen expression, hyperdiploid chromosome karyotype, complex chromosome abnormality, conditioning regimen with or without TBI, duration between transplantation and diagnosis., Conclusion: Ph-ALL adults could achieve a satisfactory CR and better survial according to BDHALL2000/02 protocol followed by auto-HSCT, especially for the standard or intermediate risk group, and no-donors high-risk patients.

Objective: To assess the efficacy of dose-intensive immunochemotherapy with or without autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed young patients with medium/high risk diffuse large B-cell lymphoma (DLBCL)., Methods: The retrospective study was performed in 29 cases of young patients (≤ 60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3. All of them were treated with dose-intensive regimens (DA-EPOCH or Hyper-CVAD/MA) combined with Rituximab and some were consolidated with first-line ASCT. The efficacy and the potential predictors were evaluated., Results: The median age of 29 patients was 43 years old. Of them, 12 patients were consolidated with high-dose chemotherapy and ASCT. The complete remission (CR) rate was 69%, the partial remission (PR) rate 21% and the overall response rate 90%. After a median follow-up of 14 months, the estimated progression-free survival (PFS) and overall survival (OS) at two years were 64% and 70%, respectively. The median PFS and OS were significantly longer in CR patients than that in PR patients (P=0.015 and 0.061, respectively). Two patients achieved PR after induction therapy converted to CR after ASCT and were in continuous CR after follow-up above three years. In multivariate analysis, only bone marrow involvement (BMI) at diagnosis had an adverse influence in PFS (P=0.009), but not in OS. Based on whether there was BMI or not and the extent of BMI at diagnosis, the patients were divided into three groups as BM-0 (without BMI), BM-1 (the extent of BMI ≤ 10%) and BM-2 (the extent of BMI>10%). Patients in BM-2 group had significantly shorter PFS and OS than those in BM-0 and BM-1 groups (P=0.001 and 0.045, respectively). In multivariate analysis, the extent of BMI>10% was the independent poor prognostic factor for PFS and CNS relapse or prognosis., Conclusion: Dose-intensive immunochemotherapy followed by ASCT or not has significant effect on efficacy of first-line treatment for young and untreated patients with medium/high risk DLBCL. The extent of BMI>10% at diagnosis is an independent risk factor associated with poor PFS and increased CNS relapse or progression.

Objective: To investigate the treatment outcomes of autologous stem cell transplantation (ASCT) as first-line treatment in patients with high risk lymphoblastic lymphoma (LBL) and compare the effect of different induction regimen on prognosis., Methods: Thirty LBL patients in complete remission received ASCT from 1996 to 2012 in our hospital were retrospectively analyzed., Results: (1)Of the 30 patients, 25 were T-LBL and 5 B-LBL with a median age of 19(7-53) years old. Ratio of male to female is 23:7. Fourteen (46.7%) patients presented with bulky mediastinal masses and 15(50.0%) with bone marrow involvement. The distribution of stages was 2(6.7%), 5(16.7%) and 23 (76.6%)patients with stages II, III, and IV, respectively. The distribution according to age-adjusted international prognostic index (aaIPI) was 5(16.7%) patients in 1 score, 14(46.6%) in 2 scores and 11(36.7%) in 3 scores. (2)At a median follow-up of 32(range, 10-171) months, 17 patients were alive and 13 relapsed and died from LBL after ASCT. The estimated 5-year probability of DFS and OS was (50.4±10.7) % and (53.9 ±10.2)% for all the patients. (3)According to the treatment regimens before ASCT, the patients were divided into NHL-type group (n=12) and ALL-type group (n=18). In NHL-type group, 9 patients relapsed and died, the estimated 5-year probability of DFS and OS was (22.2 ±12.8) % and (33.3 ±13.6) %, respectively. Median DFS and OS time were 24 months and 36 months. In ALL-type group, 4 patients relapsed and died from lymphoma, the estimated 5-year probability of DFS and OS was (77.8 ± 9.8) % and (77.8 ± 9.8) %, respectively. Median DFS and OS time were not reached. For DFS and OS, ALL-type group were better than that of NHL-type group and the difference was significant (P=0.022 and P=0.049)., Conclusion: The results showed that complete remission with intensive first-line ALL-type regimens and followed by ASCT consolidation may significantly improve long-term outcome for high risk LBL patients.

Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon that occurs during the treatment of multiple myeloma (MM). The incidence, biological characteristics, and prognostic value of secondary MGUS in patients with MM remain undefined. We proceed with a retrospective systematic review of serum immunofixation electrophoresis studies performed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia. Secondary MGUS was more common in patients with myeloma who had undergone stem cell transplantation than in those who had not (17 [29.8%] of 57 versus 5 [1.4%] of 352, P < .001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The complete response rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (P < .01). For the cohort as a whole, secondary MGUS was associated with significantly prolonged progression-free survival (median, 52.0 months versus 22.5 months; P = .002) and overall survival (median, not reached versus 35.0 months; P < .001). The presence of secondary MGUS retained independent prognostic value with a moderate impact on overall survival (hazard ratio .128 [95% confidence interval .018 to .922]; P = .041) in the multivariate Cox regression model. However, when analysis was restricted to patients undergoing stem cell transplantation, no statistical differences in progression-free survival and overall survival were found. In conclusion, we observe that secondary MGUS was frequently observed in MM patients after transplantation and conferred a survival prolongation. The favorable survival in patients with secondary MGUS may be explained by beneficial effect from myeloablative therapy., (Copyright © 2014 American Society for Blood and Marrow Transplantation. All rights reserved.)

Multiple myeloma is a highly heterogenous plasma cell malignancy, commonly seen in older patients. Age is one of the important prognostic factors. However, nearly all the prognostic staging systems are based on clinical trials, where patients were relatively fit and young. It is unknown how the presence of biochemical or cytogenetic prognostic factors and their risk weights changes with older age. To further investigate this question, we retrospectively analyzed the data from a consecutive cohort of patients treated with either bortezomib or thalidomide-based therapy. This retrospective study was carried out on a cohort of 1125 newly diagnosed multiple myeloma patients, from January 2008 to December 2019. Patients received bortezomib or thalidomide-based induction and maintenance therapy. Patients accepted hematopoietic stem cell transplantation if eligible. Statistical analysis was conducted by Stata/MP 16.0 and SPSS 26.0. With age increasing, the proportion of patients with ISS 3, performance status score ≥2, and the incidence rate of gain(1q) significantly increased. We also found that ISS became less important in older patients. However, cytogenetic abnormalities exerted a consistently adverse impact on survival, both in young and old patients. Older patients had an inferior outcome than their young counterparts. All patients in our cohort benefitted more from bortezomib than thalidomide-based induction therapy, except for patients ≥71 years old. ISS may lose prognostic value in patients ≥71 years old. Older patients had an inferior outcome and needed more effective and less toxic treatment. Plain Language Summary Multiple myeloma is a type of blood cancer commonly seen in older people. To treat this disease, genetic abnormality, the poor physical status of patients and the abundance of tumor cells are the main difficulties. We often draw these conclusions from clinical trials. However, clinical trials always enrolled relatively younger patients, so the presence and significance of these factors may vary from clinical trials to the real world. We conducted the study to find out the real risk in both young and old patients. We found that older patients were more likely to have anemia, poor nutritional status and renal function. We also found older patients had more risk of relapse, progression or death than young patients. Frail physical status is the key obstacle to treating older patients, and tumor burden no longer impacts the outcome of these people. Bortezomib is a powerful drug to treat this disease, but patients ≥71 years old had less benefit than younger ones. More studies should focus on older or frail patients as these patients need more effective and less toxic treatment. [ABSTRACT FROM AUTHOR]