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PROGNOSTIC SIGNIFICANCE OF ABSOLUTE MONOCYTE COUNT AND LYMPHOCYTE TO MONOCYTE RATIO IN MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA
Author(s): ,
Yue Li
Affiliations:
Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Chine;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Cina;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical U
,
Chunyu Shang
Affiliations:
Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Chine;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Cina;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical U
,
Yimin Ren
Affiliations:
Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Chine;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Cina;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical U
,
Li Wang
Affiliations:
Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Chine;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Cina;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical U
,
Jianyong Li
Affiliations:
Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Chine;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Cina;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical U
Wei Xu
Affiliations:
Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Chine;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Cina;Hematology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,China;Hematology,the First Affiliated Hospital of Nanjing Medical U
(Abstract release date: 05/12/22) EHA Library. Li Y. 06/10/22; 357978; P1118
Yue Li
Yue Li
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1118

Type: Poster presentation

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background
 Extranodal marginal zone B-cell lymphoma of the MALT lymphoma is a unique type of indolent lymphoma. It usually presents with local disease and exhibit an indolent clinical course, but some patients have disseminated systemic symptoms and require systemic treatment. Monocytes, as part of the important immune cells in tumor microenvironment, are closely linked to the pathogenesis and progression of malignancies. In recent studies, the absolute monocyte count (AMC) and lymphocyte to monocyte ratio (LMR) are shown to reflect the host systemic immunity states and have prognostic significance in different kinds of lymphoma.

Aims
Our study aims to explore the prognostic significance of AMC and LMR in MALT lymphoma, and to propose a more accurate prognostic index based on MALT-IPI.

Methods
Baseline clinical characteristics collected from the medical records at diagnosis. PFS and OS were analyzed with the Kaplan-Meier method and compared using the log-rank test. X-tile analysis was performed to identify cut-off value. Chi-square test was performed for comparisons between groups. Cox proportional-hazards regression models were used for univariate and multivariate analysis. Statistical analyses were performed with MedCalc 19.5.6, SPSS software 26.0, R software version 4.0.4 and Graphpad Prism 9.0.

Results
316 MALT lymphoma patients were enrolled in this study. A statistically evident dominance showed that LMR was related to age, LDH level, β2-MG level, B symptom, ECOG PS and systemic therapy. With a median follow-up time of 39.1 months (1–237 months), median PFS was 146.4 months and median OS was not reached, estimated PFS rate at 3 years and 5 years were 84.1% and 79.6%, estimated OS rate at 3 years and 5 years were 94.9% and 92.4%, respectively. According to Figure 1, high AMC group (>0.6×109/L) and low LMR group (<1.8) were associated with poor outcomes. We performed Cox proportional-hazards regression for PFS and OS, MALT-IPI, ECOG PS and LMR were identified to have independent prognostic significance for PFS while MALT-IPI, β2-MG and LMR were independently associated with poor OS. Figure 2A showed that low level of LMR in subgroup was related to a poor PFS. The prognostic value of low level of LMR for PFS was more significant in age (p value for interaction =0.020). Across a subgroup analysis of OS (Figure 2B), the prognostic value of low level of LMR was consistent. Since we have confirmed AMC showed prognostic significance in MALT lymphoma survival. We combined MALT-IPI and AMC to generate a new prognostic index named ‘MALT-IPI-M’, which included four parameters: age≥70 years, Ann Arbor stage III or IV, serum LDH level >UNL, and LMR <1.8. MALT-IPI-M classified patients into low-risk group (the MALT-IPI-M=0), intermediate-risk group (the MALT-IPI-M=1) and high-risk group (the MALT-IPI-M≥2), the proportions of different stratifications in our cohort are 52.5%, 32.9% and 14.6%, respectively. As shown in Figure 3, we generated Receiver-operator characteristic (ROC) curves to compare the prognostic prediction capability of MALT-IPI and MALT-IPI-M. The area under the curves (AUCs) for MALT-IPI-M were 0.682 for PFS and 0.804 for OS, which was larger than AUCs for MALT-IPI, 0.654 for PFS and 0.788 for OS. This illustrated that MALT-IPI-M has a better capability of distinguishing MALT patients with different risk.

Conclusion
In conclusion, our findings suggest that low level LMR at diagnosis might be associated with inferior PFS and OS in patients with MALT lymphoma. Incorporating LMR into MALT-IPI may permit a more accurate risk assessment of disease progression. 

Keyword(s): Absolute lymphocyte count, Lymphocyte, MALT lymphoma, Prognosis

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1118

Type: Poster presentation

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background
 Extranodal marginal zone B-cell lymphoma of the MALT lymphoma is a unique type of indolent lymphoma. It usually presents with local disease and exhibit an indolent clinical course, but some patients have disseminated systemic symptoms and require systemic treatment. Monocytes, as part of the important immune cells in tumor microenvironment, are closely linked to the pathogenesis and progression of malignancies. In recent studies, the absolute monocyte count (AMC) and lymphocyte to monocyte ratio (LMR) are shown to reflect the host systemic immunity states and have prognostic significance in different kinds of lymphoma.

Aims
Our study aims to explore the prognostic significance of AMC and LMR in MALT lymphoma, and to propose a more accurate prognostic index based on MALT-IPI.

Methods
Baseline clinical characteristics collected from the medical records at diagnosis. PFS and OS were analyzed with the Kaplan-Meier method and compared using the log-rank test. X-tile analysis was performed to identify cut-off value. Chi-square test was performed for comparisons between groups. Cox proportional-hazards regression models were used for univariate and multivariate analysis. Statistical analyses were performed with MedCalc 19.5.6, SPSS software 26.0, R software version 4.0.4 and Graphpad Prism 9.0.

Results
316 MALT lymphoma patients were enrolled in this study. A statistically evident dominance showed that LMR was related to age, LDH level, β2-MG level, B symptom, ECOG PS and systemic therapy. With a median follow-up time of 39.1 months (1–237 months), median PFS was 146.4 months and median OS was not reached, estimated PFS rate at 3 years and 5 years were 84.1% and 79.6%, estimated OS rate at 3 years and 5 years were 94.9% and 92.4%, respectively. According to Figure 1, high AMC group (>0.6×109/L) and low LMR group (<1.8) were associated with poor outcomes. We performed Cox proportional-hazards regression for PFS and OS, MALT-IPI, ECOG PS and LMR were identified to have independent prognostic significance for PFS while MALT-IPI, β2-MG and LMR were independently associated with poor OS. Figure 2A showed that low level of LMR in subgroup was related to a poor PFS. The prognostic value of low level of LMR for PFS was more significant in age (p value for interaction =0.020). Across a subgroup analysis of OS (Figure 2B), the prognostic value of low level of LMR was consistent. Since we have confirmed AMC showed prognostic significance in MALT lymphoma survival. We combined MALT-IPI and AMC to generate a new prognostic index named ‘MALT-IPI-M’, which included four parameters: age≥70 years, Ann Arbor stage III or IV, serum LDH level >UNL, and LMR <1.8. MALT-IPI-M classified patients into low-risk group (the MALT-IPI-M=0), intermediate-risk group (the MALT-IPI-M=1) and high-risk group (the MALT-IPI-M≥2), the proportions of different stratifications in our cohort are 52.5%, 32.9% and 14.6%, respectively. As shown in Figure 3, we generated Receiver-operator characteristic (ROC) curves to compare the prognostic prediction capability of MALT-IPI and MALT-IPI-M. The area under the curves (AUCs) for MALT-IPI-M were 0.682 for PFS and 0.804 for OS, which was larger than AUCs for MALT-IPI, 0.654 for PFS and 0.788 for OS. This illustrated that MALT-IPI-M has a better capability of distinguishing MALT patients with different risk.

Conclusion
In conclusion, our findings suggest that low level LMR at diagnosis might be associated with inferior PFS and OS in patients with MALT lymphoma. Incorporating LMR into MALT-IPI may permit a more accurate risk assessment of disease progression. 

Keyword(s): Absolute lymphocyte count, Lymphocyte, MALT lymphoma, Prognosis

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