Abstract B046: Immune repertoire sequencing enables complete B-cell and T-cell clonality determination and minimal residual disease assessment

Author(s):  
Chen Song ◽  
Luo Sun ◽  
Pingfang Liu ◽  
Bradley Langhorst ◽  
Andrew Barry ◽  
...  
Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5020-5020
Author(s):  
Natalia G. Chernova ◽  
Yulia V. Sidorova ◽  
Natalia V. Ryzhikova ◽  
Svetlana Yu. Smirnova ◽  
Hunan L. Julhakyan ◽  
...  

Abstract Introduction: Peripheral T-cell lymphoma, unspecified (PTCL, NOS) is a tumor of mature T-lymphocytes characterized by aggressive course and low response rate to CHOP-like therapy. Bone marrow involvement in PTCL, NOS is detected by histological investigation in about 20-40% of patients and it is considered to be a poor prognostic factor. Importance of T-cell clonality examination in bone marrow as a prognostic and staging factor has been insufficiently studied. Aim: In order to evaluate the significance T-cell receptor gene γ- and β-chains (TCRG and TCRB) rearrangements for identification of bone marrow involvement; to estimate its value for staging and prognosis; to evaluate the significance of T-cell clonality persistence in bone marrow after initial therapy in patients with PTCL, NOS. Patients and methods: Bone marrow samples of 27 patients with primary PTCL, NOS (median age 62 years, range 32-77) have been obtained from 2006 till 2014 and were analyzed retrospectively. Morphological examination was performed for all bone marrow samples. Detection of T-cell clonality by revealing rearrangements of TCRB and TCRG were performed by PCR in bone marrow samples of patients before and after initial chemotherapy. Results: Bone marrow involvement was revealed by histological investigation in 22 (81%) of patients. T-cell clonality was detected by rearrangements of TCRG or TCRB in 26 (96%) patients, including 4 of 5 patients without bone marrow involvement by histology. Rearrangements of TCRG and TCRB were detected in 24 (89%) and 26 (96%) of patients, respectively. Rearrangements of TCRB were observed without rearrangements of TCRG in 2 cases. Interestingly, we detected more than 2 clonal rearrangements present simultaneously in 33% of cases. For monitoring minimal residual disease the examination of T-cell clonality in bone marrow samples was performed in 15 of 27 patients after initial therapy; all these 15 patients achieved complete remission. Persistence of T-cell clonality was observed in 14 of 15 patients after treatment, disease progression was noted in 1-3 months in all these cases. Conclusion: The examination of T-cell clonality in the bone marrow seems to be important and necessary for staging, monitoring minimal residual disease. Detection of T-cell clonality in bone marrow allows revealing its involvement even without morphological features in primary patients with PTCL, NOS. Persistence of clonal rearrangements in bone marrow after initial therapy shows continuing lesion and necessity for timely therapy escalation for patients with PTCL, NOS. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Ryu Lv ◽  
Yi Wang ◽  
Tingyu Wang ◽  
Xiong Wenjie ◽  
Huijun Wang ◽  
...  

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie L. Rellick ◽  
Gangqing Hu ◽  
Debra Piktel ◽  
Karen H. Martin ◽  
Werner J. Geldenhuys ◽  
...  

AbstractB-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.


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