Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

Yao, Z.; Deng, Lijuan; Xu-Monette, Zijun Y.; Manyam, Ganiraju C.; Jain, Preetesh; Tzankov, Alexandar; Visco, Carlo; Bhagat, Govind; Wang, J; Dybkær, Karen; Tam, Wayne; Hsi, Eric D.; Krieken, J. Han van; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael; Winter, Jane N.; Piris, Miguel Á.; Fayad, Luis; Liu, Y; Song, Yongping; Orłowski, Robert Z.; Kantarjian, Hagop M.; Medeiros, L. Jeffrey; Li, Y; Cortes, Jorge; Young, Ken H.

doi:10.1038/leu.2017.222

Cited by 43 publications

(46 citation statements)

References 47 publications

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“…In our series of 189 patients treated with R-CHOP-like, we observed that high-grade BM involvement had a significantly unfavorable effect on PFS, independent of R-IPI, even considering only stage IV patients. This finding is in accordance with the results reported by Sehn et al [2] from larger series and, in agreement with these observations, a recent study published by Yao et al [18] has suggested that patients with DLBCL and concordant BM involvement should be considered a distinct entity due to a more aggressive course and poor prognosis in terms of both PFS and OS. However, in our series, concordant involvement had no independent prognostic influence on OS in the multivariate analysis, probably due to the small number of patients with concordant infiltration and to the relatively high efficacy of the salvage therapies employed, including autologous and allogeneic stem cell transplantation.…”

Section: Discussionsupporting

confidence: 93%

“…In both studies, the number of events was small and the multivariate analysis was limited to the IPI or CNS-IPI score, so larger studies are needed to confirm these results. In the recent and previously mentioned analysis from Yao et al [18], investigators do not describe a higher incidence of CNS relapse in patients with concordant BM infiltration. However, CNS prophylaxis, including systemic high dose methotrexate (MTX) and cytarabine or intrathecal MTX, were administered to 61.8% of patients.…”

Section: Discussionmentioning

confidence: 88%

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Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma

Alonso‐Álvarez

Alcoceba

García‐Álvarez

et al. 2020

Cancers

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The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans’ algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 88%

Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma

Alonso‐Álvarez

Alcoceba

García‐Álvarez

et al. 2020

Cancers

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“…Concordant bone marrow involvement of DLBCL disease is a risk factor for short OS, but not for discordant bone marrow involvement of DLBCL disease. The OS period for patients with discordant bone marrow involvement is comparable to those without bone marrow involvement of disease 32,33 . In this study, only patients with concordant bone marrow involvement of disease was categorised in positive bone marrow group.…”

Section: Discussionmentioning

confidence: 92%

Extranodal site of diffuse large B‐cell lymphoma and the risk of R‐CHOP chemotherapy resistance and early relapse

Ting

Gan

Ong

et al. 2020

Int. J. Clin. Pract.

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Background About 20%‐30% of diffuse large B‐cell lymphoma (DLBCL) patients experience early disease progression despite R‐CHOP chemotherapy treatment. Revised international prognostic index (R‐IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R‐CHOP therapy or experience early relapse. Aims of the Study To analyse pre‐treatment clinical features of DLBCL patients that are predictive of R‐CHOP therapy resistance and early disease relapse after R‐CHOP therapy treatment. Methods Used to Conduct the Study A total of 698 lymphoma patients were screened and 134 R‐CHOP‐treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R‐CHOP resistance/early relapse group and R‐CHOP sensitive/late relapse group. Results of the Study 81 of 134 (60%) were R‐CHOP sensitive/late relapse, while 53 (40%) were R‐CHOP resistance/early relapse. The median follow‐up period was 59 months ± standard error 3.6. Five‐year overall survival rate of R‐CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R‐CHOP resistance/early relapse [odds ratio = 5.268 (1.888‐14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll‐lV), raised pre‐treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2‐4) and high R‐IPI score (3‐5) showed no significant association with R‐CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05). Conclusion and Clinical Implications DLBCL patients with more than one extranodal site are 5.268 times more likely to be R‐CHOP therapy resistance or experience early disease relapse after R‐CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.

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“…Literatürde kemik iliği tutulum sıklığı, yaklaşık %10-20 olarak bildirilmiş olup, çalışmamız %11,6 oranı ile benzerdi. Kemik iliği tutulumu, genel sağkalımın daha kötü olacağını öngörmektedir (16,17) .…”

Section: Discussionunclassified

Prognostic Significance of Clinicopathological and Immunophenotypic Properties of Diffuse Large B Cell Lymphoma Patients

Kahraman¹,

Diniz²,

Ceylan³

2019

TERH

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Objective: Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of non-Hodgkin lymphoma (NHL) in adults. In our study, the clinicopathological features of patients with DLBCL were evaluated retrospectively. Methods: The study included 43 patients with the diagnosis of DLBCL between 2009-2016. Clinical and histopathological features of the patients were collected from the archive of our hospital. Results: The mean age of the patients was 62.5 (23-86) years. Twenty-four of them (55.8%) were male and 19 (44.2%) were female. Twenty-five patients (58.1%) had B symptoms. Early stage (I and II) disease was seen in 21 (48.8%) patients, while advanced stage (III and 1V) disease was seen in 22 (51.2%) patients. Bone marrow involvement was present in 5 (11.6%) patients. Nodal involvement was present in 39.5% and extranodal involvement in 60.5% of the patients. The most commen involved node was cervical lymph node and the most involved extranodal site was gastrointestinal system and especially stomach. Immunohistochemically, BCL2 and BCL6, which had prognostic significance, were expressed as 46.5% (n=20) and 27.9% (n=12) of the cases, respectively. A significant relationship was found between Bcl6 protein expression and gender (p<0.001, almost all female patients) and extranodal involvement (p=0.009). The patients were in a low risk group with a rate of 58.1% and a high risk of 41.9% according to the İnternational Prognostic Index (IPI). Twenty-seven out of 43 patients exited. The mean survival rate was 37.2 percent. Conclusion: In this study, there was no correlation between the histopathological features and mean life span, but an inverse relationship was found with IPI score. In our study, clinical and immunophenotypic features and significant prognostic parameters of DBBHLs were emphasized.

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Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

Cited by 43 publications

References 47 publications

Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma

Biological Features and Prognostic Impact of Bone Marrow Infiltration in Patients with Diffuse Large B-cell Lymphoma

Extranodal site of diffuse large B‐cell lymphoma and the risk of R‐CHOP chemotherapy resistance and early relapse

Prognostic Significance of Clinicopathological and Immunophenotypic Properties of Diffuse Large B Cell Lymphoma Patients

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