Absolute lymphocyte count as a prognostic biomarker for overall survival in patients with advanced melanoma treated with ipilimumab

Background/Aim: To investigate the utility of peripheral blood biomarkers – absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) – for predicting outcomes in eribulin-treated patients with metastatic human epidermal growth factor receptor type 2 (HER2)-negative breast cancer. Patients and Methods: ALC, NLR, and PLR were retrospectively obtained from pre-treatment blood sampling results of 120 patients and stratified according to means. Univariate and multivariate analyses were performed to investigate the association of clinicopathological factors, including these values, with overall survival (OS) and progression-free survival (PFS). Results: The ALC, NLR, and PLR cut-off points were 1,285/μl, 3.3, and 235, respectively. No biomarkers were associated with PFS. However, univariate analysis showed ALC (p=0.044) and PLR (p=0.044) to be significantly associated with OS. Conclusion: ALC and PLR can predict eribulin efficacy in terms of OS, reflecting the antitumour immune response in the microenvironment and indicating eribulin’s effectiveness.

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Baseline neutrophil-to-lymphocyte ratio and absolute lymphocyte count in patients with HER2-negative breast cancer treated with eribulin may predict overall survival.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13005 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13005-e13005

Author(s):

Shigeto Maeda ◽

Keisei Anan ◽

Kenichiro Koga ◽

Sayaka Kuba ◽

Hiroshi Yano ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Lymphocyte Count ◽

Group Performance ◽

Absolute Lymphocyte Count ◽

Neutrophil To Lymphocyte Ratio ◽

Rank Test ◽

Lymphocyte Ratio ◽

Log Rank Test

e13005 Background: In Japan, eribulin has been approved for inoperative or recurrent breast cancer, following treatment with an anthracyclines and a taxanes. We reported the efficacy and safety of eribulin as a first-line to third-line treatment in patients with advanced/metastatic breast cancer (MBC) previously treated with anthracylinsanthracyclines and taxanes (Breast 2017). Briefly, the main inclusion criteria were as follows: no history of eribulin administration; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2,; human epidermal growth factor receptor 2 (HER2)-negative,; 20–75 years; ≥4 weeks from the last dose of chemotherapy, or ≥2 weeks from the last dosing of endocrine or radiation therapy; measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1; sufficient organ function; life expectancy of ≥3 months; and no significant abnormalities on electrocardiogram. Patients in this clinical trial were enrolled between December 1, 2011, and November 30, 2013. Eribulin was administered intravenously at a dose of 1.4 mg/m2 during a 2-5 min infusion on days 1 and 8 every 3 weeks. In contrast, baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) were reported to predict progression-free survival (PFS) or overall survival (OS). However, these reports were mainly retrospective analysis. Therefore, retrospective evaluation of NLR/ALC in a prospective clinical trial is important to understand the association between NLR/ALC and OS/PFS. Methods: Of 47 prospectively enrolled patients in a previous trial, 45 patients were retrospectively evaluated for baseline NLR/ACL and at the time of 3 cycles of eribulin. The association between NLR/ALC and OS/PFS was also were analyzed for association with OS/PFS. The Kaplan-Meier method was used to estimate the OS/PFS distribution. The cut-off values for baseline NLR and ALC were set at 3 and 1500 /ul, respectively. Results: The median OS of patients with a baseline NLR < 3 was significantly longer than that of patients with a baseline NLR ≥ ≧3 (769 days vs. 409 days; log-rank test p = 0.0333). The median OS of patients with a baseline ALC ≥ ≧1500 was also significantly longer than that of patients with a baseline ALC < 1500 (964 days vs.vs 427 days; log-rank test p = 0.0425). Association between baseline NLR/ALC and PFS were not seen, and also association between at the time of 3 cycles of NLR/ALC and OS/PFS were not seen neither. Conclusions: Baseline NLR and ALC in the patients with HER2- negative breast cancer who plan to treat eribulin may predict overall survival. Clinical trial information: UMIN000007121.

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Impact of Day 28 Absolute Lymphocyte Count on Outcome of Adult Patients with Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v124.21.5256.5256 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5256-5256

Author(s):

Naresh Bumma ◽

Jing Ai ◽

Xuefei Jia ◽

Sean Hobson ◽

Donna Abounader ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Board Of Directors ◽

Lymphocyte Count ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Absolute Lymphocyte Count ◽

Advisory Committees ◽

The Impact ◽

Acute Myeloid

Abstract Introduction: Lymphocyte recovery after induction chemotherapy (IC) predicts outcome in adult patients (pts) with acute myeloid leukemia (AML) (Behl et al. Leukemia 2006; 20: 29-34). However, it is unknown whether absolute lymphocyte count (ALC) recovery after IC predicts outcome in those pts who are then treated with allogeneic hematopoietic stem cell transplant (AHCT) in first complete remission (CR1). We hypothesized that the prognostic impact of ALC might be nullified by AHCT in CR1 due to the abrogation of normal immunologic recovery. In this study, our aims were to (1) evaluate the impact of Day 28 ALC on all AML pts receiving IC and (2) to specifically, evaluate the impact of Day 28 ALC on the subset of AML pts proceeding to AHCT in CR1. Methods: A retrospective chart review of 180 adult AML pts (≥ 18 years of age) who were treated with IC during the years 2001- 2012 at the Cleveland Clinic was performed. Institutional Review Board approval was obtained. Pts with acute promyelocytic leukemia were excluded . Ninety-four of the 180 pts received AHCT in CR1. A total of 141 AML pts receiving IC and a total of 66 pts receiving IC and then receiving AHCT in CR1 were eligible for data analysis because Day 28 ALC was missing in the remainder of the pts. Prior studies in AML identified an ALC of < 500/ µL at Day 28 of IC as predictive of overall survival. We stratified Day 28 ALC into the following categories: (a)< 250/ µL (b) < 350/ µL (c) < 500/ µL and (d) < 500/ µL for Max ALC [Max ALC was defined as the maximum ALC value between days 26 and 30 after the initiation of IC]. Other variables collected included age at diagnosis, WBC at diagnosis, and cytogenetic (CG) risk. CG risk was ascribed by CALBG criteria. The Kaplan-Meier method was used to summarize overall survival (OS) and relapse-free survival (RFS), which were measured for all pts from the time of diagnosis. The log-rank test was used for univariate analysis of categorical factors and the Cox proportional hazards model was used for measured factors and multivariate analysis. We performed two separate analyses : one for all AML pts (n=141); and a second analysis only focusing on those receiving AHCT in CR1 (n=66). Results: Pt characteristics for the entire AML cohort: The median age was 58.0 years (20.0-80.0); 46.1% female. The median WBC at diagnosis was 11.6 K / µL (range 0.7-220.7) and median Day 28 ALC was 400/ µL (0-2.4). Twenty-seven pts (19.7%) had favorable CG, 84 (61.3%) intermediate, and 26 (19.0%) unfavorable. Most pts (91%) received "7+3" IC and 93 (66%) also received at least 1 cycle of post-remission chemotherapy. On univariate analysis, age ≥60 (HR 2.72, p< 0.001), CG risk (HR 2.13, p < 0.001), Day 28 ALC < 250/ µL (HR 1.60, p=0.022), Day 28 ALC < 350/ µL (HR 1.57, p=0.029), and max ALC < 500/ µL (HR 1.54, p=0.035) were associated with a worse OS from the initiation of treatment. Low ALC was associated with both a higher incidence of refractory disease and death during induction (p=0.015). In our second analysis of pts undergoing AHCT in CR1, although not statistically significant, max ALC < 500/ µL (during IC) was associated with a trend towards decreased OS from the start of treatment on both univariate (HR 1.88,p= 0.13) and multivariate (HR 2.16, p=0.075) analysis. Conclusions: Max ALC < 500/ µL is predictive of outcome in AML pts undergoing IC, and there is a suggestion that this effect may not be abrogated by AHCT. A larger study will be needed to further confirm these findings. Therapies to improve lymphocyte recovery may be important in the treatment of AML. Disclosures Sekeres: Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees.

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A Retrospective Single Center Comparison of Cyclophosphamide Plus G-CSF Versus G-CSF Alone for Peripheral Blood Stem Cell (PBSC) Mobilisation Following First Line Therapy in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.1898.1898 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1898-1898

Author(s):

Richard S Whitmill ◽

David J Lewis ◽

David John Sutton ◽

Jahanzeb Khawaja ◽

Georgina Mayer ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Lymphocyte Count ◽

Progression Free Survival ◽

Absolute Lymphocyte Count ◽

Initial Therapy ◽

Single Center ◽

Free Survival ◽

Neutropenic Sepsis ◽

Cd34 Cells

Abstract Introduction Autologous transplantation is considered standard therapy for young and fit myeloma patients after initial therapy. Cyclophosphamide+ G-CSF is considered standard therapy for collection even though there is evidence for minimal anti-myeloma effect of cyclophosphamide, some increased short term toxicity and potential concerns regarding long term toxicity. There have been a few retrospective comparisons and one randomized study comparing cyclophosphamide based and G-CSF alone based PBSC collection. To our best knowledge they have not reported any impact in progression free survival (PFS) or overall survival (OS). We have compared here our myeloma patient cohort to explore these important endpoints. Patients and methods 89 patients (55 male and 34 female) who underwent first autologous transplant for myeloma between 2003 and 2010 were analysed in our study. Mobilization was with G-CSF alone in 45 patients (median age 58 yrs, range 38-70 yrs.) and cyclophosphamide and G-CSF in 44 (median age 58 yrs, range 41-74 yrs.). Cyclophosphamide was used at 3g/m2 and in both cases G-CSF used was lenogastrim at 10mcg/kg. There were 7 patients with ISS stage 3 in the G-CSF only group as compared to 10 in the Cyclophosphamide group. Prior chemotherapy was cyclophosphamide, thalidomide and dexamethasone in majority of cases (n=55) with no difference across both groups. Data regarding high risk genetics and pre-transplant response was unavailable. We collected data progression free survival, overall survival, harvest dose and engraftment kinetics. Data was analyzed using SPSS and log rank test. Results The median dose of stem cells collected with G-CSF alone was 3.59×106 CD34 cells/kg (range 1.84-8.09) where as with cyclophosphamide and G-CSF it was 3.8×106 CD34 cells/kg (range 1.6-13). There was no difference in engraftment between the two groups with median neutrophil engraftment (Absolute neutrophil count>0.20×109/L) at day 14 and platelet engraftment (>50×109/L) at day 15 and 16 respectively. Progression free survival was significantly better in G-CSF alone cohort (46 months vs. 38 months, P=0.016) (fig. a) Overall survival was better in the GCSF only group as well (113 months vs. 75 months, P=0.029) (fig b). In the 17 high risk patients PFS was much better in the G-CSF group (60months vs. 22 months, P=0.02) (Fig c). There were 4 (9%) admissions in the cyclophosphamide group due to neutropenic sepsis as compared to none in the G-CSF group. Discussion Cyclophosphamide and G-CSF may be associated with slightly higher stem cell yields but this margin is becoming smaller and not significant in the era of liberal plerixafor usage. In addition some patients are hospitalized due to neutropenic sepsis with this regimen. Our data shows anti-myeloma effects of cyclophosphamide +G-CSF is not demonstrated. There are ongoing studies from the Finland group which show no difference in the number of CD34+ cells collected after initial therapy with lenalidomide. The only difference is the number of days required for apheresis. In addition to above our single center experience shows both PFS and OS benefit for G-CSF only PBSC mobilization. . This may partially be explained by the slight difference in ISS risk stages in our patients but on censoring for ISS stage 3 these results were more pronounced. This is the first time we have seen any report point out towards a PFS and OS difference between two widely used mobilization regimens. This needs testing in a large randomized multi-center study to see if there is a difference and if so is this due to a change in milieu of lymphocytes. We have previously reported that absolute lymphocyte count on day 15 post autograft was reflective of a higher lymphocyte count in the apheresis bag in case of G-CSF only mobilizations as compared to cyclophosphamide +G-CSF. The absolute lymphocyte count on day 30 was a predictor for better OS. Figure 1. Progression free Survival Figure 1. Progression free Survival Figure 2. Overall survival Figure 2. Overall survival Figure 3. progression free survival for ISS score 3 Figure 3. progression free survival for ISS score 3 Disclosures Sutton: bayer: Honoraria. Paneesha:Janssen: Consultancy. Nikolousis:Alexion: Honoraria. Kishore:Jazz pharma: Honoraria; Celgene: Honoraria.

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Interim Absolute Lymphocyte Count (ALC) As a Predictor of Survival in Hodgkin Lymphoma

Blood ◽

10.1182/blood.v126.23.2640.2640 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2640-2640

Author(s):

Tarsheen K. Sethi ◽

Van T Nguyen ◽

David S Morgan ◽

John P. Greer ◽

Nishitha M Reddy

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Lymphocyte Count ◽

Absolute Lymphocyte Count ◽

Disease Stage ◽

Predictive Score ◽

Advanced Stage ◽

Bulky Disease ◽

Nodular Sclerosis

Abstract Introduction: Patients with Hodgkin lymphoma (HL) have excellent response to current chemotherapy, however, up to 20% may have relapsed/refractory disease. Lymphocytopenia at diagnosis has been found to be predictive of survival in patients with advanced stage HL. An ALC of <600/μlat diagnosis as part of the Hasenclever predictive score is associated with a poorer prognosis. Furthermore, lymphocyte count at the time of apheresis and at day 15 after autologous SCT has been found to be predictive of survival in patients of HL. ALC is considered a surrogate indicator for the tumor microenvironment as well as immune recovery post treatment. There are no large studies evaluating the clinical significance of ALC recovery in patients with HL during initial chemotherapy treatment. In this study, we evaluated the role of lymphocyte recovery during and after standard chemotherapy in patients with HL. Patients and Methods: We analyzed 183 patients with Classical Hodgkin lymphoma treated at our institution between 1996 and 2014 following IRB approval. Complete data was available for 115 patients. We evaluated the absolute lymphocyte count at diagnosis, interim staging (after 2 cycles, Òinterim ALCÓ), at time of completion of chemotherapy and at 6 weeks and 3 months post completion of chemotherapy. Patients were categorized into two groups based on ALC where lymphocytopenia was defined as an ALC of <1x103/µl for adults based on standard criteria. Differences between the two groups were analyzed using Chi- square and t -Student tests. Statistical significance was set at P <0.05. Kaplan Meier method was used to calculate the Progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. Statistical analysis was performed using SPSS.22 software. Results: The median age of patients was 31 years (yrs.) (range: 17-76 yrs.) and 53% of patients were male. 100% patients had an ECOG status of 0-1. 48% patients presented with B symptoms, 42% had advanced stage disease (Stage III and IV) and 22% had bulky disease (defined as a mass > 10 cm or mediastinal mass >1/3 of diameter of thorax at T5-T6). In terms of histology, 68% patients had classical nodular sclerosis HL, 19% syncytial variant of nodular sclerosis HL, 8% mixed cellularity HL and 5% Classical HL (NOS). 90% patients received ABVD as their initial chemotherapy, 2% received Stanford V and 1% received MOPP. The remaining patients were treated on a clinical trial. In the analysis of the 115 patients for whom the lymphocyte data was available, at a median follow up of 40 months, 57% in the ALC <1x103/µl group versus 66% in the ALC >1x103/µlgroup had not progressed. The median overall survival was not reached in the two groups. In the multivariate analysis, for PFS, interim ALC predicted survival independent of the interim staging response. The ALC at the time of interim staging scan (interim ALC) was associated with a significantly superior PFS in the group with ALC>1x103/µl(HR=4.16, 95% CI 2.37 to 7.28, P=0.024). There was no difference in overall survival between the groups (Fig. 1&2,P=0.28). For ALC at other time points, no statistically significant differences in PFS or OS were found in the two groups based on ALC at diagnosis, completion of therapy, six weeks and three months post therapy. Discussion: In summary, our results suggest that for patients across all stages and histopathologic subtypes of classical HL receiving first line chemotherapy, interim ALC >1x103/µl (after 2 cycles) is associated with a superior PFS as compared with ALC <1 x103/µl and this is independent of the interim staging response. This did not translate into a difference in OS. Further studies are underway to determine the role of immune effector cells in the context of newer therapeutic agents. Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Disclosures Reddy: Gilead: Other: Speaker; Seattle Genetics: Consultancy; ImmunoGen: Consultancy; PCYC: Consultancy; Celgene: Consultancy, Research Funding.

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Absolute lymphocyte count as predictor of overall survival for patients with multiple myeloma treated with single autologous stem cell transplant

Leukemia & Lymphoma ◽

10.3109/10428194.2014.1003057 ◽

2015 ◽

Vol 56 (9) ◽

pp. 2668-2673 ◽

Cited By ~ 12

Author(s):

Victor H. Jimenez-Zepeda ◽

Donna E. Reece ◽

Suzanne Trudel ◽

Christine Chen ◽

Norman Franke ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Lymphocyte Count ◽

Stem Cell Transplant ◽

Absolute Lymphocyte Count ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

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Prognostic Value of Absolute Lymphocyte count, Lymphocyte percentage, Serum albumin, Aberrant Expression of CD7, CD19 and the Tumor Suppressors (PTEN and p53) in Patients with Acute Myeloid Leukemia

Asian Pacific Journal of Cancer Biology ◽

10.31557/apjcb.2020.5.4.131-140 ◽

2020 ◽

Vol 5 (4) ◽

pp. 131-140

Author(s):

Nadia Ali Sadek ◽

Suzan M Abd-eltawab ◽

Nagwa Mohamed Assem ◽

Hoda A-M Hamdy ◽

Fatma M. EL- sayed ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Serum Albumin ◽

Tumor Suppressors ◽

Lymphocyte Count ◽

Myeloid Leukemia ◽

Prognostic Value ◽

Absolute Lymphocyte Count ◽

Aberrant Expression ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) is a hematopoietic neoplasm. Tumor suppressors have a magnificent role in preventing the AML process. The absolute lymphocyte count is a simple yet statistically powerful estimate in patients with acute leukemia besides the lymphocyte’s percentage. Aim: Investigating the prognostic value of absolute lymphocyte count, lymphocyte percentage, serum albumin, the aberrant expression of CD7and CD19 and the tumor suppressor genes (PTEN and p53) in patients with AML. Methods: 35 de novo AML patients were included. They received the standard induction chemotherapy (3+7 protocol) and were followed up for one year after treatment. 15 normal healthy individuals, age and sex matched constituted the controls.Results: The mean overall survival of patients with lymphocyte percentage ≤25 was low compared to those with high lymphocyte percentage (>25%) (χ2 =5.808, P=0.016). AML patients with low levels of ALC showed significantly shorter overall survival than patients with high levels (χ2 =4.587, P= 0.032). AML patients with low serum albumin were of low overall survival compared to those with normal level (χ2 =8.698, P=0.003). Patients with aberrant CD7 expression showed short survival and unresponsiveness to treatment than CD7 negative patients. PTEN gene expression and p53 protein level were significantly lower in AML patients compared to the control group.Conclusion: The decrease in ALC, lymphocyte percentage, albumin concentration and the increase in monocyte percentage indicates bad prognosis in AML patients. The Aberrant CD7 expression, very low expression of PTEN and low level of p53 could estimate the unresponsiveness to standard chemotherapy.

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