Minimal Residual Disease Assessment Is an Independent Prognostic Factor in Splenic Marginal Zone Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Ryu Lv ◽  
Yi Wang ◽  
Tingyu Wang ◽  
Xiong Wenjie ◽  
Huijun Wang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
B Cell Lymphoma ◽  
Independent Prognostic Factor ◽  
Disease Assessment ◽  
Splenic Marginal Zone Lymphoma ◽  
End Of Treatment ◽  
Minimal Residual

Purpose: Splenic marginal lymphoma (SMZL) is a rare indolent B-cell lymphoma with long survival. The minimal residual disease (MRD) detection in indolent B-cell lymphomas has shown power in predicting survival and even in guiding treatment duration in chronic lymphocytic leukemia. As almost all SMZL patients have bone marrow involvement (BMI) at diagnosis, we prospectively designed the MRD detection during treatment to study its prognostic value in SMZL. Methods: SMZL patients who needed chemotherapy would regularly monitor the MRD status until undetectable MRD by multiparameter flow cytometry (MFC). Patients with MRD under 0.01% were defined as uMRD. Other clinical factors were also analysed as prognostic factors. Results: In total, 71 patients with frontline therapy were enrolled in this study. There were 284 evaluable BM MRD samples. At end of treatment, 55 patients (77.4%) got uMRD, 10 patients had a MRD level of 0.01-1%, and 6 patients had a MRD level of ≥ 1%. The uMRD rate increased at the end of treatment. With a median follow-up of 50 (24-157) months, uMRD patients showed superior outcomes compared with MRD-positive patients. Patients with uMRD had a significant better progression free survival (PFS) compared to those with MRD. PR with positive-MRD after induction therapy was a significantly poor predictor for PFS and overall survival (OS). Multivariate prognostic analysis showed it was a powerful independent prognostic factor for PFS [HR=0.357 (95%CI 0.131-0.972), P=0.044]. Conclusion: uMRD in BM was an independent prognostic factor in SMZL patients, especially for the patients only achieving PR at the end of therapy. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals HashClone: a new tool to quantify the minimal residual disease in B-cell lymphoma from deep sequencing data

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Marco Beccuti ◽  
Elisa Genuardi ◽  
Greta Romano ◽  
Luigia Monitillo ◽  
Daniela Barbero ◽  
...  
Keyword(s):  
B Cell ◽  
Minimal Residual Disease ◽  
Deep Sequencing ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Sequencing Data ◽  
Deep Sequencing Data ◽  
Minimal Residual

scholarly journals Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3449-3457 ◽  
Author(s):  
JG Gribben ◽  
D Neuberg ◽  
AS Freedman ◽  
CD Gimmi ◽  
KW Pesek ◽  
...  
Keyword(s):  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Pcr Amplification ◽  
B Cell Lymphoma ◽  
Lymphoma Cells ◽  
Minimal Disease ◽  
Residual Lymphoma ◽  
Minimal Residual ◽  
Risk Of Relapse

Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl- 2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR- detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR- detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy.

scholarly journals Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3449-3457 ◽  
Author(s):  
JG Gribben ◽  
D Neuberg ◽  
AS Freedman ◽  
CD Gimmi ◽  
KW Pesek ◽  
...  
Keyword(s):  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Pcr Amplification ◽  
B Cell Lymphoma ◽  
Lymphoma Cells ◽  
Minimal Disease ◽  
Residual Lymphoma ◽  
Minimal Residual ◽  
Risk Of Relapse

Abstract Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl- 2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR- detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR- detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy.

scholarly journals CD19-CAR T Cells Treatment for Minimal Residual Disease in B-Cell Lymphoma with a Higher Response Rate and Fewer Adverse Reactions

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3714-3714
Author(s):  
Xia Xiao ◽  
Yanyu Jiang ◽  
Xiaoyuan He ◽  
Xin Jin ◽  
Cao Yaqing ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Response Rate ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Car T Cells ◽  
Car T ◽  
Minimal Residual

Abstract Background: Chimeric antigen receptor modified T cells directed against CD19 (CART19) has demonstrated efficacy in relapsed or refractory (r/r) B-cell lymphoma with durable complete remissions (CR). However, there are some patients with minimal residual disease (MRD) also need attention. Persistence or reappearance of minimal residual disease (MRD) after chemotherapy always results in relapse. MRD is an indicator of resistance to chemotherapy. Based on these considerations, a clinical retrospective trials with control and without random study (ChiCTR-ONN-16008911) was conducted to determine the efficacy and safety of CD19-CAR-T cells in MRD positive B-cell lymphoma patients, which is devoted to reduce the risk of recurrence. This paper will discuss the difference of efficacy and safety between minimal residual disease or partial remission and relapsed or refractory patients. The structural features of our CAR-T products include anti-CD19 scFv, a transmembrane domain, and a 4-1BB/CD3ζsignaling domain. Patients and Methods: This study enrolled B cell lymphoma in two cohorts. Cohort1 includes 10 patients with MRD persistence or reappearance after induction and consolidation therapy or patients acquired partial remission(PR). Cohort2 includes 12 patients with relapsed or refractory (r/r) B-cell lymphoma were included. We used autologous T cells expressing a CD19-CAR T cells to treat these patients. Patients were monitored for response to treatment, toxic effects, the expansion and persistence of CD19-CAR T cells. Results: 1. A total of 22 patients with B-cell lymphoma received CD19-CAR T cells, the median dose of CAR-T cells was 5.2×106/kg (2.0~10.0×106/kg). The infusions were safe, and no dose-limiting toxicities occurred. 2.The cohort1 overall response rate was 100%. Complete remission occurred in 8 of 10 patients (80%). The other 2patients with DLBCL were stable after CAR T cells treatment. The cohort2 overall response rate was 75%(9/12). Complete remission occurred in 2 of 12 patients (17%),partial remission occurredin 5 of 12 patients (42%).And another 2 patients got stable disease. 3. CD19-CAR T cells proliferated in vivo and were detectable in the blood of patients. The cohort1 and cohort2 peak time of CAR T cells proliferated was 12(5~19) days and 4.5(1~12) days after treatment respectively. And among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55% ~24.74%)and 4.02% (2.23%~28.60%) of T lymphocytes respectively. 4. The cohort1 patients achieved sustained remissions, and at a median follow-up of 10 months(3 ~18 months). None of all the patients relapsed and the median follow-up time was 10 months (3~18 months). However, 9 of the cohort2 patients who had a response maintain a good condition for 40-90 days. Except for one patient with following hematopoietic stem cell transplantation, the remaining patients developed disease progression in different degrees. 5. Cytokine-release syndrome(CRS) occurred in all patients, which in cohort1 were grade 1-2 CRS and in cohort 2 has one patient developed a grade 3 CRS. Conclusions: CAR-T cell therapy not only plays a role in the rescue treatment of relapsed and refractory patients, but also has a surprising effect in the consolidation and maintenance of B-cell lymphoma, and it is expected to become a treatment that benefits more patients.CD19-CAR T cells might be more effective in the treatment of MRD+/PR B-cell lymphoma patients than in the refractory or relapse patients. High response rate were observed, with fewer adverse reactions. CAR T treatment in MRD-positive B-cells lymphoma patients may be a therapeutic option to put off the progression to relapse and refractory lymphoma. Disclosures No relevant conflicts of interest to declare.

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