Influence of low absolute lymphocyte count of patients with nongerminal center type diffuse large B-cell lymphoma with R-CHOP therapy

Song, Moo-Kon; Chung, Joo-Seop; Seol, Young-Mi; Kim, S.-G.; Shin, Ho-Jin; Choi, Young–Jin; Cho, G.-J.; Shin, Donghun

doi:10.1093/annonc/mdp505

Cited by 53 publications

(38 citation statements)

References 17 publications

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“…We have also shown that a low lymphocyte count on its own appears to be a predictor of poor outcome. This confirms the findings of a number of recent studies that show that lymphopenia at diagnosis and also post-therapy is an adverse prognosticator [16,26,27]. There is also emerging data that the AMC may predict outcome in DLBCL [28].…”

Section: Discussionsupporting

confidence: 88%

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

Keane,

Gill,

Vari

et al. 2013

American J Hematol

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Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P 5 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD41 T-cell infiltration as the most significant predictor of outcome with 23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P 5 0.007) and OS (P 5 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD41 T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P 5 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP. Am. J.

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Section: Discussionsupporting

confidence: 88%

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

Keane,

Gill,

Vari

et al. 2013

American J Hematol

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“…The optimal cut-point for the ALC by receiver operating characteristic analysis was 1470/ml. However, as an ALC cutpoint of 1000/ml has been utilized in previous studies, 23,31,32 and failed to yield a significant difference in the ability to risk stratify patients by OS when compared with the cut-point selected by receiver operating characteristic analysis (data not shown), we chose to dichotomize the ALC using a cut-point of 1000/ml. The Cox proportional hazards model was used to evaluate the AMC and ALC as prognostic factors for PFS and OS and to adjust for other known prognostic variables included in the IPI.…”

Section: Discussionmentioning

confidence: 99%

“…For example, lymphopenia is a poor-risk feature in DLBCL patients treated with either CHOP or R-CHOP and in GCB-and non-GCB-type DLBCL. 23,31 More recently, the development of new-onset lymphopenia following autologousperipheral blood stem cell transplantation was associated with a significant increase in the risk of disease relapse. 32 Patients with an ALC o1000/ml following autologous-peripheral blood stem cell transplantation had an incidence of disease relapse of 92%, compared with a relapse rate of 19% among patients without lymphopenia.…”

Section: Discussionmentioning

confidence: 99%

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

et al. 2011

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Despite the use of modern immunochemotherapy regimens, almost 50% of patients with diffuse large-B-cell lymphoma will relapse. Current prognostic models, including the International Prognostic Index, incorporate patient and tumor characteristics. In contrast, recent observations show that variables related to host adaptive immunity and the tumor microenvironment are significant prognostic variables in non-Hodgkin lymphoma. Therefore, we retrospectively examined the absolute monocyte and lymphocyte counts as prognostic variables in a cohort of 366 diffuse large-B-cell lymphoma patients who were treated between 1993 and 2007 and followed at a single institution. The absolute monocyte and lymphocyte counts in univariate analysis predicted progression-free and overall survival when analyzed as continuous and dichotomized variables. On multivariate analysis performed with factors included in the IPI, the absolute monocyte and lymphocyte counts remained independent predictors of progression-free and overall survival. Therefore, the absolute monocyte and lymphocyte counts were combined to generate a prognostic score that identified patients with an especially poor overall survival. This prognostic score was independent of the IPI and added to its ability to identify high-risk patients.

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“…This discrepancy might be ascribed to the difference in the value of AMC at diagnosis between the two patient cohorts. While an ALC cutoff of 1.0 × 10 9 /l was used in previous studies, the optimal cutoff point for the AMC has not been determined [13,14]. It is plausible that reducing the AMC cutoff point would identify a larger proportion of patients with a dismal prognosis.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Impact of Absolute Lymphocyte and Monocyte Counts at Diagnosis of Diffuse Large B-Cell Lymphoma in the Rituximab Era

et al. 2013

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Background: A recent report showed that the combination of the absolute lymphocyte count (ALC) and the absolute monocyte count (AMC) at diagnosis gave a prognostic score in diffuse large B-cell lymphoma (DLBCL). However, this model requires validation in other patient cohorts. Methods: We retrospectively evaluated the prognostic impact of the combination of the ALC and the AMC at diagnosis in a cohort of 299 DLBCL patients who were treated in the rituximab era at a single institution. Results: In univariate analyses, an ALC ≤1.0 × 10⁹/l [4-year overall survival (OS) rate 47.0 vs. 79.4%; p < 0.001] and an AMC ≥0.63 × 10⁹/l (4-year OS rate 52.4 vs. 75.6%; p < 0.001) were associated with inferior OS, respectively. In multivariate analyses, an ALC ≤1.0 × 10⁹/l and an AMC ≥0.63 × 10⁹/l were significantly associated with inferior OS independently of the International Prognostic Index. Furthermore, the combination of ALC and AMC could identify patients with the dismal prognosis; the 4-year OS rates for patients with ALC ≤1.0 × 10⁹/l and AMC ≥0.63 × 10⁹/l were 18.8%. Conclusions: The combination of ALC and AMC at diagnosis may be useful for the prognostic stratification of patients with DLBCL.

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Influence of low absolute lymphocyte count of patients with nongerminal center type diffuse large B-cell lymphoma with R-CHOP therapy

Abstract: A low ALC in non-GC type DLBCL counteracted the beneficial effect of rituximab on survival.

Cited by 53 publications

References 17 publications

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

The Prognostic Impact of Absolute Lymphocyte and Monocyte Counts at Diagnosis of Diffuse Large B-Cell Lymphoma in the Rituximab Era

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Influence of low absolute lymphocyte count of patients with nongerminal center type diffuse large B-cell lymphoma with R-CHOP therapy

Abstract: A low ALC in non-GC type DLBCL counteracted the beneficial effect of rituximab on survival.

Cited by 53 publications

References 17 publications

CD4+ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

CD4+ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

The Prognostic Impact of Absolute Lymphocyte and Monocyte Counts at Diagnosis of Diffuse Large B-Cell Lymphoma in the Rituximab Era

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CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy

CD4⁺ Tumor infiltrating lymphocytes are prognostic and independent of R‐IPI in patients with DLBCL receiving R‐CHOP chemo‐immunotherapy