Prognostic significance of absolute monocyte count and lymphocyte to monocyte ratio in mucosa-associated lymphoid tissue (MALT) lymphoma.

To investigate the prognostic significance of peripheral blood absolute monocyte count (AMC) and lymphocyte to monocyte ratio (LMR) in mucosa-associated lymphoid tissue (MALT) lymphoma, we retrospectively analyzed 316 newly diagnosed patients with MALT lymphoma. The best cut-off value of AMC was 0.6 × 109/L and LMR was 1.8 by x-tile according to progression-free survival (PFS). Multivariate analysis showed that MALT-IPI (p < 0.001), Eastern Cooperative Oncology Group performance status (ECOG PS) (p = 0.010), and LMR (p = 0.003) have independent prognostic significance for PFS, MALT-International Prognostic Index (MALT-IPI) (p = 0.018), ß2-microglobulin (ß2-MG) (p = 0.015), and LMR (p = 0.029) predicted poor overall survival (OS). Receiver-operator characteristic (ROC) curves were used to compare the prognostic prediction capability of MALT-IPI and MALT-IPI-M (MALT-IPI combined with LMR); area under the curves (AUCs) for MALT-IPI-M were larger than that for MALT-IPI both PFS (0.682 vs 0.654) and OS (0.804 vs 0.788). Our results indicated that that low level LMR at diagnosis was associated with inferior prognosis. The new prognostic index, MALT-IPI-M, enabled the risk stratification capability for MALT lymphoma survival.

Utilization of absolute monocyte counts to predict cardiovascular events in people living with HIV.

OBJECTIVES: Cardiovascular risk is increased in people living with HIV (PLWH). In HIV-uninfected populations, total absolute monocyte count (AMC) has been shown to be predictive of future cardiovascular events (CVEs). We sought to determine whether AMC predicts CVEs in PLWH independent of established and HIV-related cardiovascular risk factors. METHODS: We identified all PLWH within the Partners HIV Cohort without factors that could confound the monocyte count. CVE was defined as fatal or non-fatal acute myocardial infarction or ischaemic stroke. Baseline-measured AMC was defined as the average of all outpatient AMC counts a year before and after the baseline date. Multivariable Cox proportional hazards models were used to assess the association of baseline AMC with CVEs. RESULTS: Our cohort consisted of 1980 patients, with median follow-up of 10.9 years and 182 CVEs. Mean (± SD) age was 41.9 ± 9.3 years; 73.0% were male. Mean CD4 count was 506.3 ± 307.1 cells/µL, 48% had HIV viral load (VL) < 400 copies/mL, and 87% were on antiretroviral therapy. Mean AMC was 0.38 × 103  ± 0.13 cells/µL. In multivariable modelling adjusted for traditional CV risk factors, CD4 cell count, and HIV VL, AMC quartile 2 (Q2) (HR = 1.01, P = 0.98), Q3 (HR = 1.07, P = 0.76), and Q4 (HR = 0.97, P = 0.89) were not significantly predictive of CVE compared with Q1. DISCUSSION: Baseline AMC was not associated with long-term CVEs in PLWH. AMC obtained in routine clinical encounters does not appear to enhance CV risk stratification in PLWH.

Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia.

This study aimed to examine the prognostic significance of peripheral absolute monocyte count (AMC) in combination with absolute lymphocyte count (ALC) at the time of relapse in a cohort of 57 patients with early relapsed (first complete remission <12 months) acute myeloid leukemia (AML). Both univariate and multivariate Cox proportional hazard regression analyses revealed that normal AMC in combination with normal/high ALC (versus low/high AMC in combination with low ALC) was significantly associated with improved OS. We concluded that the combination of AMC and ALC could be used as a prognostic marker for survival outcomes in early relapsed AML.

The classic prognostic factors in advanced Hodgkin's lymphoma patients are losing their meaning at the time of Pet-guided treatments.

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.

Tumor-associated macrophages predict prognosis in diffuse large B-cell lymphoma and correlation with peripheral absolute monocyte count.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. The clinical prognostic implications of tumor-associated macrophages (TAMs) in DLBCL remain controversial and the correlation between TAMs and peripheral absolute monocyte count (AMC) has not yet been elucidated. METHODS: In 221 untreated, newly diagnosed patients with DLBCL, we evaluated the prognostic value of TAMs using immunohistochemical analysis, as well as the association of TAMs and AMC. RESULTS: We found that high CD68 or high CD163 expression was correlated with clinicopathological characteristics, high CD163 expression was an adverse predictor for both overall survival (OS) [hazard ratio (HR) = 2.265, P = 0.005] and progression- free survival (PFS) (HR = 1.925, P = 0.017) in patients with DLBCL. Patients with high CD68 or high CD163 expression had significantly poorer OS and PFS than those with low CD68 or low CD163 expression, respectively (CD68: OS: P<0.001, PFS: P<0.001; CD163: OS: P<0.001, PFS: P<0.001), even in the rituximab era. Moreover, high-risk patients could be further identified by the expression of CD68 or CD163, especially in those classified as low/intermediate risk by International Prognostic Index (IPI). Furthermore, the significant positive correlation was also detected between CD68 expression or CD163 expression and AMC (r = 0.256, P<0.001; r = 0.303, P<0.001). CONCLUSIONS: Patients with high expression of TAMs tend to have poorer OS and PFS, even in the rituximab era, and have positive correlation with AMC. Therefore, the peripheral AMC is a useful prognostic marker reflecting the status of the tumor microenvironment (TME) in DLBCL.

Absolute monocyte count is a predictor of overall survival and progression-free survival in nodal peripheral T cell lymphoma.

Nodal peripheral T cell lymphomas (nPTCL) present aggressive clinical course, and its heterogeneous nature and poor prognosis with current therapeutic strategies make it a target for the development of new prognostic markers. Thus, we investigated tumor-associated macrophages (TAM) according to the number of cells expressing CD68 in biopsies and the absolute monocyte count (AMC) in peripheral blood of 87 patients with nPTCL. The median overall survival (OS) was 3 years (95% CI 1.3-8.4 years) and estimate 5 years OS of 43.3% (95% CI 32.5-53.7%). The median progression-free survival (PFS) was 1.5 years (95% CI 0.8-2.6 years) with estimate 5 years PFS of 29.2% (95% CI 19.7-39.3%). The cutoff for AMC was 1.5 × 109/L and the median OS for patients with AMC ≥ 1.5 × 109/L was 0.83 years versus 3.7 years for those with AMC < 1.5 × 109/L (HR 2.32, 95% CI 1.03-5.22, p = 0.035). The median PFS for patients with AMC ≥ 1.5 × 109/L was 0.50 years versus 1.5 years for those with AMC < 1.5 × 109/L (HR 2.25, 95% CI 1.05-4.78, p = 0.031). CD68 was evaluated in 26/87 (29.8%) patients with a median expression of 34% and positivity cutoff of 43%. CD68 expression was not associated with OS or PFS either with AMC values. Our findings suggest that the AMC of ≥ 1.5 × 109/L at diagnosis in peripheral blood is associated with poor prognosis in nPTCL. Further investigations in a larger cohort are required to better validate our results.

Immunochemotherapeutic increase of peripheral absolute monocyte count predicts interstitial pneumonia in lymphoma patients.

Interstitial pneumonia (IP) is one of the potentially fatal adverse events for lymphoma patients undergoing immunochemotherapy. However, the risk factors and predictive markers remain unclear for this complication. This retrospective study aims to explore whether the change of absolute monocyte count (AMC) during immunochemotherapy is correlated with IP occurrence and progression. A total of 500 lymphoma patients receiving immunochemotherapy from 2014 to 2016 were enrolled in this investigation. Interstitial pneumonia was generally diagnosed as diffused pulmonary interstitial infiltrates on computed tomography images in conjunction with respiratory symptoms or pulmonary function test, which is also adopted as a diagnosing tool of IP in this study. Among the total 500 participating patients, 40 patients were diagnosed as IP, which account for 8% of the total subjects. The median number of chemotherapy cycles for those patients prior to IP occurrence is 4. This research suggests that the increase of peripheral AMC over 0.565 × 109 /L after 2 cycles of immunochemotherapy is a great potential to develop IP. Using the method of multivariate analysis, lymphoma lung involvement and high AMC after 2 cycles of immunochemotherapy were identified as independent risk factors for IP. Most IP patients with sustained AMC elevation (>0.575 × 109 /L at IP onset) accompanied severe pulmonary symptoms, while those with AMC fall-back might tolerate subsequent immunochemotherapy. Thus, this study concludes that early increase of AMC during immunochemotherapy in lymphoma patients with lung involvement suggested a great potential to develop IP. Dynamic changes in AMC may serve as a predictive marker for IP severity and a guide for treatment adjustment for both tumor and pulmonary injuries.

Prognostic Analysis of Absolute Lymphocyte and Monocyte Counts after Autologous Stem Cell Transplantation in Children, Adolescents, and Young Adults with Refractory or Relapsed Hodgkin Lymphoma.

Previous studies in adults have shown that peripheral blood absolute lymphocyte and monocyte count ratio (ALC/AMC) after autologous stem cell transplantation (ASCT) can predict outcome in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). We retrospectively reviewed all of our children, adolescent, and young adult (CAYA) patients (age ≤26) who underwent transplantation for R/R HL between 2004 and 2015. Seventy-six patients (median age, 21; range, 10 to 26 years) who reached day 100 disease free were analyzed; 33% of them had positron emission tomography (PET)-positive tumors before ASCT. Patients received high-dose carmustine, etoposide, cytarabine, and melphalan (n = 40) or gemcitabine/busulfan/melphalan (n = 36). Median follow-up after day 100 was 3.9 years (95% confidence interval [CI], 2.8 to 4.9). A day 100 ALC/AMC ratio >2.1 correlated with lower risk of relapse (hazard ratio, .097; 95% CI, .03 to .29; P <.0001). Patients with day 100 ALC/AMC ratios >2.1 and ≤2.1 had 4-year relapse-free survival rates of 93% and 33%, respectively (P = .0001) and 4-year overall survival rates of 96% and 76%, respectively (P = .0001). In addition, an ALC/AMC ratio increase >1.8 from day 15 to day 100 correlated with lower risk of relapse (hazard ratio, .24; 95% CI, .08 to 0.73; P = .01). Likewise, an ALC/AMC ratio change >.26 from day 30 to day 100 also correlated with a lower likelihood of relapse (hazard ratio, .20; 95% CI, .081 to .51; P = .0007). Multivariate analysis showed that a positive PET scan at ASCT, day 100 ALC/AMC ratio ≤ 2.1, and an ALC/AMC ratio change either ≤1.8 from day 15 to day 100 or ≤.26 from day 30 to day 100 were independent adverse predictors. In conclusion, our analysis confirms in CAYA patients prior observations in adults indicating a major prognostic effect of peripheral lymphocyte and monocyte counts at day 100 and earlier post-ASCT time points in R/R HL.

Prognostic impact of absolute lymphocyte count/absolute monocyte count ratio and prognostic score in patients with nasal-type, extranodal natural killer/T-cell lymphoma.

Nasal-type, extranodal natural killer/T-cell lymphoma is a heterogeneous disorder with poor prognosis, requiring risk stratification in this population. The combined value of baseline absolute lymphocyte count and absolute monocyte count provided prognostic information in some malignancies. However, the evidence requires validation in extranodal natural killer/T-cell lymphoma. Aiming to investigate the prognostic significance of absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score for extranodal natural killer/T-cell lymphoma, a retrospective research was carried out. A total of 264 patients with newly diagnosed extranodal natural killer/T-cell lymphoma were analyzed in this study. The patients' absolute lymphocyte count and absolute monocyte count tested at initial diagnosis were collected. Receiver operating curve analysis showed that the optimal cut-off values for absolute lymphocyte count and absolute monocyte count were 1.0 × 109 and 0.5 × 109L-1, respectively, and for absolute lymphocyte count/absolute monocyte count ratio was 2.85. After a median follow-up of 27 months (range 1-87 months), the 3-year overall survival and progression-free survival was 75.4% and 67.6%, respectively. Patients with absolute lymphocyte count/absolute monocyte count ratio ≥ 2.85 had better 3-year overall survival and progression-free survival than those with absolute lymphocyte count/absolute monocyte count ratio <2.85 (p < 0.001). According to absolute lymphocyte count/absolute monocyte count prognostic score, significant difference has been noticed in 3-year overall survival and progression-free survival (p < 0.001) and high absolute lymphocyte count/absolute monocyte count prognostic score was associated with poorer survival. The International Prognostic Index and Korean Prognostic Index were used for prognosis and showed no significant difference. When adding absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score to the International Prognostic Index and Korean Prognostic Index model, additional prognostic information was found. These results suggest that absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score might be useful prognostic factors in extranodal natural killer/T-cell lymphoma.

High post-treatment absolute monocyte count predicted hepatocellular carcinoma risk in HCV patients who failed peginterferon/ribavirin therapy.

Salient studies have investigated the association between host inflammatory response and cancer. This study was conducted to test the hypothesis that peripheral absolute monocyte counts (AMC) could impart an increased risk of hepatocellular carcinoma (HCC) development in hepatitis C virus (HCV)-infected patients after a failed peginterferon/ribavirin (PR) combination therapy. A total of 723 chronic HCV-infected patients were treated with PR, of which 183 (25.3 %) patients did not achieve a sustained virological response (non-SVR). Post-treatment AMC values were measured at 6 months after end of PR treatment. Fifteen (2.8 %) of 540 patients with an SVR developed HCC during a median follow-up period of 41.4 months, and 14 (7.7 %) of 183 non-SVR patients developed HCC during a median follow-up of 36.8 months (log rank test for SVR vs. non-SVR, P = 0.002). Cox regression analysis revealed that post-treatment AFP level (HR 1.070; 95 % CI = 1.024-1.119, P = 0.003) and post-treatment aspartate aminotransferase (AST)-to-platelet ratio index (APRI) ≥0.5 (HR 4.401; 95 % CI = 1.463-13.233, P = 0.008) were independent variables associated with HCC development for SVR patients. For non-SVR patients, diabetes (HR 5.750; 95 % CI = 1.387-23.841, P = 0.016), post treatment AMC ≥370 mm(-3) (HR 5.805; 95 % CI = 1.268-26.573, P = 0.023), and post-treatment APRI ≥1.5 (HR 10.905; 95 % CI = 2.493-47.697, P = 0.002) were independent risks associated with HCC. In conclusion, post-treatment AMC has a role in prognostication of HCC development in HCV-infected patients who failed to achieve an SVR after PR combination therapy.

[Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia]. / Az abszolút monocytaszám prognosztikus értéke krónikus lymphoid leukaemiában.

INTRODUCTION: The low peripheral absolute lymphocyte and high monocyte count have been reported to correlate with poor clinical outcome in various lymphomas and other cancers. However, a few data known about the prognostic value of absolute monocyte count in chronic lymphocytic leukaemia. AIM: The aim of the authors was to investigate the impact of absolute monocyte count measured at the time of diagnosis in patients with chronic lymphocytic leukaemia on the time to treatment and overal survival. METHOD: Between January 1, 2005 and December 31, 2012, 223 patients with newly-diagnosed chronic lymphocytic leukaemia were included. The rate of patients needing treatment, time to treatment, overal survival and causes of mortality based on Rai stages, CD38, ZAP-70 positivity and absolute monocyte count were analyzed. RESULTS: Therapy was necessary in 21.1%, 57.4%, 88.9%, 88.9% and 100% of patients in Rai stage 0, I, II, III an IV, respectively; in 61.9% and 60.8% of patients exhibiting CD38 and ZAP-70 positivity, respectively; and in 76.9%, 21.2% and 66.2% of patients if the absolute monocyte count was <0.25 G/l, between 0.25-0.75 G/l and >0.75 G/l, respectively. The median time to treatment and the median overal survival were 19.5, 65, and 35.5 months; and 41.5, 65, and 49.5 months according to the three groups of monocyte counts. The relative risk of beginning the therapy was 1.62 (p<0.01) in patients with absolute monocyte count <0.25 G/l or >0.75 G/l, as compared to those with 0.25-0.75 G/l, and the risk of overal survival was 2.41 (p<0.01) in patients with absolute monocyte count lower than 0.25 G/l as compared to those with higher than 0.25 G/l. The relative risks remained significant in Rai 0 patients, too. The leading causes of mortality were infections (41.7%) and the chronic lymphocytic leukaemia (58.3%) in patients with low monocyte count, while tumours (25.9-35.3%) and other events (48.1 and 11.8%) occurred in patients with medium or high monocyte counts. CONCLUSIONS: Patients with low and high monocyte counts had a shorter time to treatment compared to patients who belonged to the intermediate monocyte count group. The low absolute monocyte count was associated with increased mortality caused by infectious complications and chronic lymphocytic leukaemia. The absolute monocyte count may give additional prognostic information in Rai stage 0, too.

Infused autograft lymphocyte to monocyte ratio and survival in diffuse large B cell lymphoma.

Infused autograft absolute lymphocyte count is a prognostic factor for survival after autologous peripheral hematopoietic stem cell transplantation (APHSCT) for diffuse large B cell lymphoma (DLBCL). CD14(+) HLA-DR(low/neg) immunosuppressive monocytes affect tumor growth by suppressing host antitumor immunity. Thus, we set out to investigate if the infused autograft lymphocyte to monocyte ratio (A-LMR), as a biomarker of host immunity (ie, lymphocytes) and immunosuppression (ie, monocytes), affects survival after APHSCT. From 1994 to 2012, 379 DLBCL patients who underwent APHSCT were studied. The 379 patients were randomly divided into a training set (n = 253) and a validation set (n = 126). Receiver operating characteristic and area under the curve identified an A-LMR ≥1 as the best cut-off value, which was validated by the k-fold cross-validation in the training set. Multivariate analysis showed A-LMR to be an independent prognostic factor for survival in the training set. Patients with an A-LMR ≥ 1.0 experienced superior overall survival (OS) compared with patients with an A-LMR <1.0 (median OS: 167.2 versus 17.6 months; 5-year OS: 73% [95% confidence interval (CI), 63% to 80%] versus 30% [95% CI, 2% to 38%], P < .0001, respectively) in the training set. In the validation set, an A-LMR ≥ 1 showed a median OS of 181.2 months versus 19.5 months for an A-LMR <1, and 5-year OS rates of 67% (95% CI, 52% to 79%) versus 35% (95% CI, 25% to 47%), P < .0001, respectively. The A-LMR provides a platform to engineer immunocompetent autograft to improve clinical outcomes in DLBCL patients undergoing APHSCT.

Platelet-to-lymphocyte ratio and absolute monocyte count have prognostic potential in primary myelodysplastic neoplasms.

INTRODUCTION: The platelet-to-lymphocyte ratio (PLR), peripheral blood absolute monocyte count (AMC), and monocyte-to-lymphocyte ratio (MLR) are considered biomarkers of systemic immune and inflammation response. However, their prognostic potential in patients with myelodysplastic neoplasms (MDS) remains unclear. This study aimed to explore the predictive impact of PLR, MLR, and AMC on MDS outcomes. METHODS: In total, 334 patients with primary MDS were included between January 2016 and December 2021 and were retrospectively followed up until December 31, 2022. The prognostic significance of PLR, MLR, and AMC was assessed using univariate and multivariate analyses, and predictive models were generated to estimate MDS outcomes. The area under their receiver operating curves was computed to compare the predictive power of these models. RESULTS: Fifty-one patients had disease progression, and 103 patients died during follow-up. In multivariate analyses, a higher PLR was an adverse independent factor for overall survival (OS) (p = 0.011), whereas a higher AMC indicated shorter progression-free survival (p = 0.003). The prognostic model incorporating PLR, MLR, and AMC with the Revised International Prognostic Scoring System (IPSS-R) risk categorization showed higher performance in predicting OS than the model that only utilized the IPSS-R category. CONCLUSION: Elevated PLR and increased AMC had independent prognostic value for adverse outcomes in patients with MDS. PLR, MLR, and AMC enhanced the IPSS-R risk categorization for OS prediction in MDS.

Prognostic impact of monocyte count at presentation in mantle cell lymphoma.

An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

The Absolute Monocyte Count at Diagnosis Affects Prognosis in Myelodysplastic Syndromes Independently of the IPSS-R Risk Score.

The absolute monocyte count (AMC) is associated with mortality in a variety of medical conditions. Its prognostic impact in myelodysplastic syndromes (MDSs) is less well studied. Therefore, we investigated its potential prognostic value in a cohort from the Düsseldorf MDS registry in relationship to the revised international prognostic scoring system (IPSS-R). An AMC below the population's median (<0.2 × 109/L) was associated with several adverse disease features such as lower haemoglobin levels, lower count of neutrophils and platelets, and a higher percentage of blasts in the bone marrow. MDS patients with an AMC < 0.2 × 109/L had a significantly higher risk of progression into acute myeloid leukemia (AML). In a univariate, proportional hazards model the effect of the AMC as a continuous variable was modelled via p-splines. We found a U-shaped effect with the lowest hazard around 0.3 × 109/L. Accordingly, an AMC within the last quartile of the population (0.4 × 109/L) was associated with a reduced overall survival independently of IPSS-R, but not with the risk of secondary AML. Considering monocytopenia as a risk factor for AML progression in MDS may provide an additional argument for allogeneic transplantation or the use of hypomethylating agents in patients who are not clear candidates for those treatments according to current prognostic scoring systems and/or recommendations. Further studies are needed to assess the prognostic impact of the AMC in the context of prognostic scoring systems, considering the molecular risk profile, and to identify the mechanisms responsible for the higher mortality in MDS patients with a subtle monocytosis.

Dosimetric parameters and absolute monocyte count can predict the prognosis of acute hematologic toxicity in cervical cancer patients undergoing concurrent chemotherapy and volumetric-modulated arc therapy.

PURPOSE: To explore clinical and dosimetric predictors of acute hematologic toxicity (HT) in cervical cancer patients treated with concurrent chemotherapy and volumetric-modulated arc therapy (VMAT). METHODS AND MATERIALS: We retrospectively reviewed the clinical data of 184 cervical cancer patients who had concurrent chemotherapy and VMAT. Hematological parameters were collected during the treatment period. The total pelvic bone (TPB) was delineated retrospectively for dose-volume calculations. To compare the differences between two groups, the normality test findings were used to run a paired-samples t-test or Wilcoxon signed-rank test. Pearson's correlation analysis or Spearman's correlation was used to testing the correlation between the two variables. Binary logistic regression analysis was used to analyze associations between HT and possible risk factors. The receiver operating characteristic curve(ROC) was used to evaluate the best cut-off point for dosimetric planning constraints. RESULTS: The nadir of absolute monocyte count (AMC) was found to be positively correlated with the nadir of absolute white blood cells (WBC) count (r = 0.5378, 95% CI 0.4227-0.6357, P < 0.0001) and the nadir of absolute neutrophil count(ANC) (r = 0.5000, 95% CI 0.3794-0.6039, P < 0.0001). The AMC decreased and increased before the ANC and WBC. In multivariate logistic regression analysis, the chemotherapy regimens and the TPB_V20 were independent risk factors for developing grade ≥ 3 HT. The optimal TPB_V20 cut-off value identified by ROC curves and the Youden test was 71% (AUC = 0.788; 95% CI 0.722-0.845; P value < 0.001). CONCLUSIONS: The changing trend of AMC can be used as an effective predictor for the timing and severity of the ANC/WBC nadirs and prophylactic G-CSF administration. Maintain TPB_V20 < 71% and selecting single-agent cisplatin or carboplatin could significantly reduce grade ≥ 3 HT in cervical cancer patients undergoing concurrent chemoradiotherapy.

Monocytic Myeloid-Derived Suppressor Cells But Not Monocytes Predict Poor Prognosis of Acute Myeloid Leukemia

Objective: Some reports suggest that high absolute monocyte count (AMC) at diagnosis is an independent predictor of poor prognosis in acute myeloid leukemia (AML), but others disagree. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are immature monocytes. This study aimed to compare the value of monocytes and Mo-MDSCs in predicting the prognosis of AML. Materials and Methods: Peripheral blood samples from 107 newly diagnosed patients with AML and 47 healthy controls (HCs) were collected. We validated the clinical significance of AMC, monocyte count (CD14+CD45++), and Mo-MDSC count (CD14+HLA-DRlow/-CD45++) for initial induction therapy response, maintenance of treatment effects, and long-term survival. Results: Compared with HCs, the levels of AMC, monocyte count, and Mo-MDSC count were all significantly higher among patients with AML. However, only elevated Mo-MDSC count was significantly associated with lower complete remission rate, higher relapse/refractory rate, and poorer long-term survival. Conclusion: Mo-MDSCs but not monocytes predict the poor prognosis of AML.

Evaluating the Prognostic Role of Monocytopenia in Chemotherapy-Induced Febrile Neutropenia Patients Treated with Granulocyte Colony-Stimulating Factor.

OBJECTIVE: Chemotherapy-induced febrile neutropenia is a common and serious oncological emergency which carries a substantial mortality and morbidity. The main objective of this study is to evaluate the usage of absolute monocyte count (AMC) at presentation as a prognostic factor for patients with chemotherapy-induced febrile neutropenia who were subsequently treated with granulocyte colony-stimulating factor (G-CSF). STUDY DESIGN: The electronic medical records of our center were used retrospectively to identify patients diagnosed with unprecedented chemotherapy-induced febrile neutropenia treated with G-CSF between January 2010 to December 2020 and diagnosed with solid and hematological malignancies. Patient's demographics, disease characteristics and laboratory investigations were extracted. Disease progression measures were statistically compared between the study groups in the short-term period of follow-up (six days) including absolute neutrophil count (ANC), ANC difference compared to the baseline readings, hospitalization period, and mortality. RESULTS: A total of 80 patients were identified and categorized into two groups namely monocytopenia (n = 34) and non-monocytopenia (n = 46) with an AMC cutoff point of 0.1×109 cells/L. The monocytopenia group exhibited a worse prognosis with lower ANC values and slower improvement illustrated by the low ANC difference values at all follow up points (P-value ≤ 0.05) apart from day 5. A statistically significant lower hospitalization period was also observed in the non-monocytopenia group (P-value = 0.006). Linear regression analysis evaluated the association between AMC values at admission and ANC values at admission along with subsequent days of follow up which were found to be statistically significant (P-value ≤ 0.05). Receiver operating characteristic curves suggest a satisfactory predictability of ANC changes by AMC values at admission, days1, 2, 3, 4 and 6. CONCLUSION: Monocytopenia holds a worse prognosis in chemotherapy-induced febrile neutropenia patients treated with G-CSF. In addition, AMC values at presentation represents a potential risk factor that can predict short-term changes regarding ANC measures.

Relationship between the absolute lymphocyte count/absolute monocyte count ratio, soluble interleukin 2 receptor level, serum programmed cell death 1 level, and the prognosis of patients with diffuse large B-cell lymphoma.

BACKGROUND: To analyze the relationship between the peripheral blood absolute lymphocyte count (ALC)/absolute monocyte count (AMC) ratio, soluble interleukin 2 receptor (sIL-2R) level, serum programmed cell death 1 (PD-1) level, and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 78 patients with DLBCL admitted to hospital and 30 healthy controls were enrolled as the case group and control group between August 2019 and June 2020, respectively. The ALC/AMC ratio and the levels of sIL-2R and serum PD-1 between the 2 groups and among patients with different prognoses were compared. The evaluation efficiency of these 3 factors for the prognosis of DLBCL patients was analyzed by receiver operating characteristic (ROC) curves. The risk factors affecting the 1-year survival rate were analyzed by the Cox hazard model. RESULTS: The levels of sIL-2R, AMC, and PD-1 in the case group were significantly higher than those in the control group, while the ALC/AMC ratio was lower than that in the control group (P<0.05). The levels of sIL-2R and PD-1 in the poor prognosis group were significantly higher than those in the good prognosis group, while the ALC/AMC ratio was lower than that in the good prognosis group (P<0.05). The areas under the ROC curve (AUCs) of sIL-2R level, serum PD-1 level, and the ALC/AMC ratio in evaluating the prognosis of DLBCL patients were 0.805 (95% CI: 0.700-0.886), 0.825 (95% CI: 0.722-0.902), 0.792 (95% CI: 0.685-0.876), respectively. The critical values were 474.80 µg/L, 206.85 pg/mL and 3.01, respectively. The differences in the 1-year survival rate among DLBCL patients with different tumor sizes, B symptoms, sIL-2R levels, and ALC/AMC ratios were statistically significant (P<0.05). B symptoms (RR =1.721) and ALC/AMC ratio lower than 3.01 (RR =1.484) were independent influencing factors of the 1-year survival rate in DLBCL patients (P<0.05). CONCLUSIONS: The ALC/AMC ratio, sIL-2R level, and serum PD-1 level can effectively assess the prognosis of DLBCL patients. B symptoms and ALC/AMC ratio lower than 3.01 are risk factors affecting the 1-year survival rate of patients.

Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection.

BACKGROUND: SARS-CoV-2 infection is associated with thrombotic and microvascular complications. The cause of coagulopathy in the disease is incompletely understood. METHODS: A single-center cross-sectional study including 66 adult COVID-19 patients (40 moderate, 26 severe disease), and 9 controls, performed between 04/2020 and 10/2020. Markers of coagulation, endothelial cell function [angiopoietin-1,-2, P-selectin, von Willebrand Factor Antigen (WF:Ag), von Willebrand Factor Ristocetin Cofactor, ADAMTS13, thrombomodulin, soluble Endothelial cell Protein C Receptor (sEPCR), Tissue Factor Pathway Inhibitor], neutrophil activation (elastase, citrullinated histones) and fibrinolysis (tissue-type plasminogen activator, plasminogen activator inhibitor-1) were evaluated using ELISA. Tissue Factor (TF) was estimated by antithrombin-FVIIa complex (AT/FVIIa) and microparticles-TF (MP-TF). We correlated each marker and determined its association with severity. Expression of pulmonary TF, thrombomodulin and EPCR was determined by immunohistochemistry in 9 autopsies. FINDINGS: Comorbidities were frequent in both groups, with older age associated with severe disease. All patients were on prophylactic anticoagulants. Three patients (4.5%) developed pulmonary embolism. Mortality was 7.5%. Patients presented with mild alterations in the coagulogram (compensated state). Biomarkers of endothelial cell, neutrophil activation and fibrinolysis were elevated in severe vs moderate disease; AT/FVIIa and MP-TF levels were higher in severe patients. Logistic regression revealed an association of D-dimers, angiopoietin-1, vWF:Ag, thrombomodulin, white blood cells, absolute neutrophil count (ANC) and hemoglobin levels with severity, with ANC and vWF:Ag identified as independent factors. Notably, postmortem specimens demonstrated epithelial expression of TF in the lung of fatal COVID-19 cases with loss of thrombomodulin staining, implying in a shift towards a procoagulant state. INTERPRETATION: Coagulation dysregulation has multifactorial etiology in SARS-Cov-2 infection. Upregulation of pulmonary TF with loss of thrombomodulin emerge as a potential link to immunothrombosis, and therapeutic targets in the disease. FUNDING: John Hopkins University School of Medicine.