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1.
Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis
Berning, P., Schmitz, N., Ngoya, M., Finel, H., Boumendil, A., Wang, F., Huang, X. J., Hermine, O., Philippe, L., Couronné, L., et al
Leukemia. 2023;:1-10
Abstract
Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. Patients (pts) with relapsed/refractory disease after Asparaginase (ASPA)-based chemotherapy have a dismal prognosis. To better define the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), we conducted a retrospective analysis of data shared with the European Society for Blood and Marrow Transplantation (EBMT) and cooperating Asian centers. We identified 135 pts who received allo-HSCT between 2010 and 2020. Median age was 43.4 years at allo-HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) Asian. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% previous auto-HSCT, and 74.1% ASPA-containing regimens prior to allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. With a median follow-up of 4.8 years, 3-year progression-free(PFS) and overall survival were 48.6% (95%-CI:39.5-57%) and 55.6% (95%-CI:46.5-63.8%). Non-relapse mortality at 1 year was 14.8% (95%-CI:9.3-21.5%) and 1-year relapse incidence 29.6% (95%-CI:21.9-37.6%). In multivariate analyses, shorter time interval (0-12 months) between diagnosis and allo-HSCT [HR = 2.12 (95%-CI:1.03-4.34); P = 0.04] and transplantation not in CR/PR [HR = 2.20 (95%-CI:0.98-4.95); P = 0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased GVHD nor impacted survival. We demonstrate that allo-HSCT can achieve long-term survival in approximately half of pts allografted for NKTCL.
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2.
Identification of the Predictive Models for the Treatment Response of Refractory/Relapsed B-Cell ALL Patients Receiving CAR-T Therapy
Gu, J., Liu, S., Cui, W., Dai, H., Cui, Q., Yin, J., Li, Z., Kang, L., Qiu, H., Han, Y., et al
Frontiers in immunology. 2022;13:858590
Abstract
BACKGROUND/AIMS: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion. METHODS Univariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed. RESULTS The predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06). CONCLUSIONS We have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.
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3.
Comparation of CART19 and autologous stem-cell transplantation for refractory/relapsed non-Hodgkin's lymphoma
Li, C., Zhang, Y., Zhang, C., Chen, J., Lou, X., Chen, X., Kang, L., Xu, N., Li, M., Tan, J., et al
JCI insight. 2019;5
Abstract
BACKGROUND Autologous stem-cell transplantation (ASCT) is the standard treatment for R/R B-NHL, while chimeric antigen receptor T (CAR-T) therapy targeting CD19 emerges as an alternative strategy. Here we report a comparative analysis of the two strategies in a single center. METHODS We performed a prospective single-arm study of CAR-T therapy in 29 patients with R/R B-NHL and compared the outcomes with contemporaneous 27 patients who received ASCT. NHL was diagnosed by histopathological assessments, and the safety and efficacy were compared. RESULTS The CAR-T group exhibited better rates of CR (48.0% vs. 20.8%, P=0.046) and one-year OS (74.4% vs. 44.5%, P=0.044) compared with the ASCT group. Subpopulation analysis showed that patients with IPI scores ≥ 3 achieved significantly higher ORR and CR rates in the CAR-T group than in the ASCT group (ORR: 72.0% vs. 10.0%, P=0.002; CR: 38.9% vs 0% P=0.030, respectively). The most common severe adverse events in the CAR-T group were cytokine release syndrome, neurotoxicity and infection compared with cytopenia, gastrointestinal toxicity and infection in the ASCT group. Additionally, the incidence of non-hematologic severe adverse events (SAEs) was markedly lower in the CAR-T group than in the ASCT group (20.7% vs. 48.1% P=0.030). CONCLUSION CAR-T therapy exhibited superior clinical outcomes in safety and efficacy over ASCT in patients with R/R B-NHL, suggesting CAR-T may be a recommended alternative to ASCT.
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4.
Modified BuCy is an alternative conditioning regimen for lymphoma patients undergoing autologous stem cell transplantation
Huang, H., Zhang, L., Jiang, Y., Liu, S., Jin, Z., Chen, J., Xiao, X., Ruan, J., Zhang, X., Wu, D.
Annals of hematology. 2019
Abstract
The aim of this study is to determine whether the modified BuCy (semustine, cytarabine, busulfan, and cyclophosphamide, mBuCy) conditioning regimen can be safely used as an alternative to the SEAM (semustine, etoposide, cytarabine, and melphalan) regimen by comparing the efficacy and toxicity of the mBuCy and SEAM regimens. We matched 34 pairs of patients with regard to disease status at the time of autologous stem cell transplantation (auto-SCT). We found no significant difference in the time of platelet engraftment between the two groups. Furthermore, neutrophil engraftment was somewhat faster in the mBuCy group than in the SEAM group (median: 9 days vs 10 days, p = 0.015). With regard to toxicity, the incidence of nausea/vomiting, hepatic impairment, renal impairment, pulmonary infection, and treatment-related mortality (TRM) was similar between the two groups. In addition, compared to patients conditioned with SEAM, patients conditioned with mBuCy were less likely to develop mucositis and diarrhea (p = 0.027; p = 0.050). The 2-year progression-free survival (PFS) rates in the mBuCy and SEAM groups were 79% and 70% (p = 0.378), respectively, and the 2-year overall survival (OS) rates were 81% and 78.0%, respectively (p = 0.789). These analyses showed that the mBuCy conditioning regimen was well tolerated and can be used as an alternative to the SEAM regimen for lymphoma.
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5.
Plerixafor and granulocyte-colony-stimulating factor for mobilization of hematopoietic stem cells for autologous transplantation in Chinese patients with non-Hodgkin's lymphoma: a randomized Phase 3 study
Zhu, J., Huang, H., Chen, H., Zhang, X., Li, Z., Wu, D., Zhou, D., Song, Y., Hu, Y., Liang, Y., et al
Transfusion. 2017
Abstract
BACKGROUND This Phase 3 randomized, double-blind study evaluated the efficacy and safety of plerixafor plus granulocyte-colony-stimulating factor for the mobilization of hematopoietic stem cells in Chinese patients with non-Hodgkin's lymphoma. STUDY DESIGN AND METHODS Adults (ages 18-75 years) with non-Hodgkin's lymphoma in first or second complete or partial remission, without previous hematopoietic stem cell mobilization or autologous transplant, were included. Patients received granulocyte-colony-stimulating factor 10 micro g/kg/day from Days 1 through 4 before they were randomized (1:1) to receive either plerixafor 0.24 mg/kg/day or placebo subcutaneously on Days 4 through 7 plus continued granulocyte-colony-stimulating factor on Days 5 through 8. Apheresis began on Day 5 and continued for no more than 4 days. The primary endpoint was collection of 5 x 106 CD34+ cells/kg or greater over no more than 4 days of apheresis. Other endpoints included the collection of 2 x 106 CD34+ cells/kg or greater and safety. RESULTS Overall, 101 patients were enrolled, and 50 were randomized to each group. More patients in the plerixafor group achieved 5 x 106 CD34+ cells/kg or greater (62 vs. 20%; p<0.0001) or 2 x 106 CD34+ cells/kg or greater (88 vs. 66%) and underwent transplantation (88 vs. 68%) compared with those in the placebo group. The most common plerixafor-related adverse events were nausea (7.8%) and diarrhea (3.9%). CONCLUSION Plerixafor plus granulocyte-colony-stimulating factor is superior to placebo plus granulocyte-colony-stimulating factor for the mobilization of CD34+ cells for autologous transplantation and is generally well tolerated in Chinese patients with non-Hodgkin's lymphoma.
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6.
Outcome of Allogeneic and Autologous Hematopoietic Cell Transplantation for High-Risk Peripheral T Cell Lymphomas: A Retrospective Analysis From a Chinese Center
Huang, H., Jiang, Y., Wang, Q., Guo, L., Jin, Z., Fu, Z., Han, Y., Sun, A., Liu, W., Ruan, J., et al
Biology of Blood & Marrow Transplantation. 2017;23(8):1393-1397
Abstract
Peripheral T cell lymphomas (PTCLs) often carry poor outcomes with conventional chemotherapy, and hematopoietic cell transplantation (HCT) can benefit patients with PTCL. We conducted a retrospective review of 67 patients with PTCL who underwent autologous HCT (autoHCT, n=43; median age, 40 years) or allogeneic HCT (alloHCT, n=24; median age, 36.5 years) from 2004 to 2016. With a median follow-up of 27 months, 5-year progression-free survival (PFS) and overall survival (OS) of autoHCT patients were 49% and 57%, respectively. Among alloHCT recipients, the 5-year PFS and OS were 54% and 55%, respectively. When considering incidence of disease relapse or progression (CIR) and nonrelapse mortality (NRM), the 5-year CIR and 1-year NRM of alloHCT recipients were 38% and 18%, respectively, and 58% and 7% for autoHCT patients, respectively. There were no differences between autoHCT and alloHCT in 5-year PFS (P=.499), OS (P=.566), CIR (P=.555), and NRM (P=.202). When specifically examining recipients in primary refractory disease, 3-year PFS rates of autoHCT and alloHCT were 20% and 49% (P=.054); 3-year OS rates were 20% and 53% (P=.042), respectively. Based on these results, we favor proceeding to alloHCT in patients with PTCL in primary refractory disease.
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7.
Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission
Cowan, A. J., Stevenson, P. A., Cassaday, R. D., Graf, S. A., Fromm, J. R., Wu, D., Holmberg, L. A., Till, B. G., Chauncey, T. R., Smith, S. D., et al
Biology of Blood & Marrow Transplantation. 2016;22(2):380-5
Abstract
Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.