Indolent Non-Hodgkin Lymphoma: Skeletal Muscle Density Predicts Overall Survival With Rituximab Based Chemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5078-5078
Author(s):  
Michael P Chu ◽  
Jessica Lieffers ◽  
Andrew R Belch ◽  
Neil Chua ◽  
Amelie Fontaine ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Overall Survival ◽  
Adipose Tissue ◽  
Risk Factor ◽  
Hodgkin Lymphoma ◽  
Poor Prognosis ◽  
Solid Organ ◽  
Radiation Attenuation ◽  
Muscle Density ◽  
Non Hodgkin Lymphoma

Abstract Introduction Sarcopenia is an adverse risk factor for solid organ malignancies. Recent evidence suggests sarcopenia confers a poor prognosis in diffuse large B-cell lymphoma, but further study is needed to evaluate its role in other Non-Hodgkin Lymphoma (NHL) subtypes. Low skeletal muscle density (SMD) has also been identified as a risk factor for poor prognosis; it is more prognostic than sarcopenia in renal cell carcinoma and melanoma. Low SMD is hypothesized to be a marker of inflammation that suggests more active disease. SMD can be approximated using computed tomography (CT) images and measuring muscle radiation attenuation in Hounsfield Units (HU). An average muscle SMD of <30 HU is considered to be poorly functioning muscle and has the appearance of ectopic fat production. This study examines sarcopenia and SMD in follicular lymphoma (FL). Methods FL patients from 2004-2009 who received rituximab-based chemotherapy at our institution were retrospectively reviewed. Aside from baseline information (stage, age, gender, height, weight, performance status, FL International Prognostic Index 1 score [FLIPI-1], chemotherapy regimen received), progression free survival (PFS) and overall survival (OS) was collected as primary endpoints. Sarcopenia and SMD were calculated using Slice-o-Matic (Tomovision, Montreal Canada) with patients’ pre-treatment CT images. Skeletal muscle was defined as between -29 to 150 HU, intramuscular adipose tissue -190 to -30 HU; and visceral adipose tissue -150 to -50 HU. Skeletal muscle surface area and average radiation attenuation at the L3 vertebral body level were measured. Sarcopenia was pre-defined using skeletal muscle surface area cut-offs outlined in prior solid organ malignancy studies and from the elderly DLBCL study. Results 145 FL patients were identified. Median age was 59 years (range 29-83 years), with a median FLIPI-1 score of 2, median stage III, 79 male, and 66 female. The majority of patients received R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) chemotherapy with a median 8 cycles received (range 1-8) and 87 patients given maintenance rituximab. Median PFS and OS were 44.7 and 56.8 months, respectively. Patients with sarcopenia failed to have significant differences in either PFS or OS. The PFS hazard ratio (HR) of 1.26 suggested a trend for poor outcomes in sarcopenic patients (p=0.17). A specific cut-off for sarcopenia was not identifiable. However, comparing patients with SMD below the median to those above yielded a PFS of 40.9 vs 49.7 months (HR 1.91; p=0.01), respectively. Significant differences in OS similarly occurred for below and above the median SMD with 52.8 vs 63.3 months (HR 2.61;p=0.01). A discernible cut-off parameter for SMD was identified at 36.61 HU. PFS for those with lower than this SMD was a more pronounced detriment at 39.3 vs 55.3 months (HR 2.76; p=0.0005), respectively. OS of 51.9 vs 64.7 months (HR 4.67; p=0.0001) was also more pronounced at levels below and above the SMD cut-off parameter, respectively. Multivariate analysis found OS (HR = 4.08; p=0.004) in favor of the higher SMD group and independent of FLIPI-1 or gender. Conclusions In FL, SMD is a strong prognostic marker independent of the FLIPI-1 scores while sarcopenia has less of a prognostic role. SMD can be used as an additional tool to stratify FL patients. Evaluation of SMD and its mechanistic link with inflammation requires further study. Disclosures: No relevant conflicts of interest to declare.

Aggressive Non-Hodgkin Lymphoma: Predictive Value Of Sarcopenia and Skeletal Muscle Density On Prognosis With Rituximab Containing Therapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3023-3023 ◽  
Author(s):  
Michael P Chu ◽  
Jessica Lieffers ◽  
Andrew R Belch ◽  
Neil Chua ◽  
Amelie Fontaine ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Elderly Patients ◽  
Surface Area ◽  
Poor Prognosis ◽  
Ct Images ◽  
Muscle Quality ◽  
Solid Organ ◽  
Radiation Attenuation ◽  
Muscle Density

Abstract Introduction Sarcopenia is an established adverse risk factor for solid organ malignancies. Recent evidence suggests sarcopenia predicts a poor prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL) independent of Revised International Prognostic Index (R-IPI) scores. Because of the focus on an elderly population, it is difficult to generalize to the DLBCL population as a whole. Newer evidence suggests low skeletal muscle density (SMD) is a more significant indicator of poor prognosis in renal cell carcinoma and melanoma than sarcopenia. SMD can be approximated using computed tomography (CT) images and measuring muscle radiation attenuation in Hounsfield Units (HU). An average muscle SMD of <30 HU is considered to be poorly functioning muscle and has the appearance of ectopic fat production. This study examines sarcopenia and SMD in DLBCL. Methods DLBCL patients from 2004-2009 who received rituximab-based chemotherapy through our institution were retrospectively reviewed. Aside from baseline information (stage, age, gender, height, weight, performance status, R-IPI score, chemotherapy regimen and cycles received), progression free survival (PFS) and overall survival (OS) were collected as primary endpoints. Sarcopenia and SMD were calculated using Slice-o-Matic (Tomovision, Montreal Canada) with patients’ pre-treatment CT images. Skeletal muscle was defined as between -29 to 150 HU, intramuscular adipose tissue -190 to -30 HU; and visceral adipose tissue -150 to -50 HU. Skeletal muscle surface area and average radiation attenuation at the L3 vertebral body level were measured. Sarcopenia was pre-defined using skeletal muscle surface area cut-offs outlined in prior solid organ malignancy studies and from the elderly DLBCL study. Results We identified 224 DLBCL patients. Median age at diagnosis was 62 years (range 21-88 years), with 124 male, and 100 female. Median stage at diagnosis was III with a median IPI score of 3. The majority received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with a median of 6 cycles (range 1-8). Median PFS and OS were 55.2 and 56.3 months, respectively. Patients with sarcopenia did not have a significant difference in either PFS or OS. In fact, the PFS hazard ratio (HR) of 0.70 would suggest sarcopenia as being protective but it was not statistically significant (p=0.19). Subgroup analysis of elderly DLBCL patients (defined as >70 years), found sarcopenia was protective for both PFS and OS yielding HRs of 0.24 and 0.45, respectively (p=0.002 and 0.05). A statistically insignificant PFS improvement by SMD was seen above and below the median SMD with 61.0 and 52.8 months, HR 1.28 (p=0.32), respectively. However, OS was significantly better in those above the median SMD at 65.5 vs 51.4 months, HR 2.02 (p=0.006). A cut-off point in SMD was noticeable at 26.63 HU where PFS was significantly worse in those that had lower SMD with 53.3 vs 56.3 months, HR 1.74 (p=0.03). OS was also significantly poorer with SMD lower than this cut-off, 51.9 vs 59.2 months, HR 1.92 (p=0.01), respectively. This difference though failed to maintain significance in multivariate analysis taking into consideration R-IPI and gender. Conclusions Contrary to recent evidence suggesting sarcopenia as a poor prognostic factor in elderly patients with DLBCL, our study demonstrates that sarcopenia may in fact be protective. Perhaps patients with lower lean body mass may be exposing their disease to relatively higher concentrations of chemoimmunotherapy. SMD is more prognostic than sarcopenia in DLBCL patients. While these findings suggest muscle mass and muscle quality play a strong role in the disease process, factors captured in the R-IPI score predict clinical course more strongly. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR) and Risk of Thromboembolism in Patients with Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3649-3649
Author(s):  
Darko Antic ◽  
Natasa Milic ◽  
Vladimir Otasevic ◽  
Tanja Virijevic Salak ◽  
Vladislava Djurasinovic ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Factor ◽  
T Cell ◽  
Hodgkin Lymphoma ◽  
Roc Curve ◽  
Response To Therapy ◽  
Neutrophil To Lymphocyte Ratio ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Non Hodgkin Lymphoma

Background: Thromboembolism (TE) is one of major causes of morbidity and mortality in patients with malignancy. Pathophysiological connection between TE and inflammation has been established and it is being thoroughly studied recently. The neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) are biomarkers for systemic inflammation and might represent a yet unrecognized risk factor for development of venous thromboembolism in lymphoma patients having in mind chronic inflammatory milieu specific for lymphomas. Aims: We aimed to investigate the association between NLR, PLR and future risk of TE, in a prospective cohort of lymphoma patients receiving chemotherapy. Methods: We prospectively included 630 patients with B cell non Hodgkin lymphoma /indolent and agressive/, T cell non Hodgkin lymphoma and Hodgkin lymphoma who were diagnosed and treated (period 2014-2019.) at the Clinic for Hematology, Clinical Center of Serbia. Data for newly diagnosed patients, who had completed a minimum of one chemotherapy cycle, were collected for venous TE events from time of diagnosis to 3 months after the last cycle of therapy. NLR and PLR were calculated according to the CBC with differential count. TE complications were diagnosed based on clinical examination, laboratory evaluation and radiographic studies (duplex venous ultrasound, contrast-enhanced computed tomography scan, magnetic resonance imaging (MRI)). Response to therapy was assessed according to Cheson criteria. Logistic regression analysis and ROC curve were performed to assess the association of NLR and PLR with TE and therapy response. Cox regression and Kaplan Meier analysis were used to assess overall survival. Results: The mean age in our group of patients was 53 years (range, 18-89 years) while 52.8% were males. Most patients had advanced stage disease: clinical stage III 20.6% and stage IV, 41.5%. A total of 327 patients (51.9%) had aggressive NHL; 175 (27.8%) had indolent NHL; 102 (16.2%) had HL; 26 (4.1%) had T cell NHL. 51 (8.2%) patients developed thromboembolic events. NLR and PLR were significantly higher in TE patients compared to patients without TE (p=0.001 and p=0.002, respectively). The NLR was positively associated with PLR (p&lt;0.001). A positive NLR was considered 3 or higher, while a positive PLR was a ratio of 10 or more. The ROC curve analysis demonstrated acceptable specificity and sensitivity of NLR and PLR in predicting TE. NLR and PLR were found to be prognostic factors for the TE (relative risk [RR] = 2.9, 95% confidence interval [CI] = 1.6-5.3, p=0.001 and RR=2.7, 95% CI =1.4-5.1, p=0.002, respectively) as well as for overall response to therapy (RR=2.7, 95%CI=1.7-5.7, p&lt;0.001 and RR=2.0, 95%CI=1.1-3.4, p=0.015, respectively). Regarding the overall survival, in univariate analysis there was an association of the development of TE and decreased survival, while in multivariate model NLR was found to be an independent risk factor for overall survival in lymphoma patients (HR=1.8, 95%CI=1.1-2.9, p=0.024) (Figure 1). Summary/Conclusion: NLR could represent useful clinical predictor of TE complications in patients with lymphoma without additional costs to the national health systems. Our research showed that NLR is also predictive for response to therapy and overall survival of lymphoma patients. Simplicity, cost effectiveness, and rapid turn around qualify this new tool for routine prognostic assessment in lymphoma patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals BMI-1 and survivin expression with clinicopathological correlation and prognostic impact in B and T/NK- cell non-Hodgkin lymphoma

2019 ◽  
Vol 9 (2) ◽  
pp. 11
Author(s):  
Nahed Ahmed Soliman ◽  
Lamia M Abdalkader ◽  
Doaa Shams
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Nk Cell ◽  
Survivin Expression ◽  
Polycomb Group ◽  
Clinicopathological Parameters ◽  
Prognostic Impact ◽  
Non Hodgkin Lymphoma ◽  
Significant Difference ◽  
Well Correlation

Background: The pathogenesis of non-Hodgkin lymphoma is a complex process that involves several molecular changes. Alterations in polycomb group proteins as well as Survivin have been described but details are still lacking particularly in T/NK-cell lymphomas. Polycomb proteins have a big role in cell cycle and differentiation. Survivin is another recently recognized player in non-Hodgkin lymphoma.Objective: To study the pattern of Bmi-1 and Survivin in different categories of B- and T/NK- cell non-Hodgkin lymphomas, their association with the clinicopathological parameters, and their impact on the prognosis of non-Hodgkin lymphomas.Material& methods: Immunohistochemical staining was used to study paraffin samples of 267 patients’ biopsies. We used tonsils and reactive lymph node as normal control.Results: Both Bmi-1 and Survivin showed significant upregulation in several subtypes B- (P = .000-.02 for Bmi-1 and .00- .03 forSurvivin) and T/NK cell lymphomas (P= .009-.03 for Bmi-1 and 0.008- 0.009 for Survivin) compared to normal tissue. Significantpositive correlation between Bmi-1 and Survivin was detected in both B- (Co= 0.539**, P = .00) and T - cell lymphomas (Co= 0.560**, P = .000). A statistically significant difference between overall survival and expression of both BMI-1 and Survivin was detected (P = .00 for BMI-1and survivin).Conclusion: Bmi-1 and Survivin show significant upregulation as well correlation with clinicopathological parameters and overall survival of non-Hodgkin lymphomas.

Secondary Neoplasms Subsequent to Berlin-Frankfurt-Muenster (BFM) Therapy of Non-Hodgkin Lymphoma of Childhood: Significantly Higher Risk for Patients with Lymphoblastic Lymphoma Compared to Other NHL-Subtypes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 232-232 ◽  
Author(s):  
Olga Wachowski ◽  
Martin Zimmermann ◽  
Birgit Burkhardt ◽  
Olaf Determann ◽  
Ulrike Meyer ◽  
...  
Keyword(s):  
Risk Factor ◽  
Brain Tumors ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Cumulative Risk ◽  
Lymphoblastic Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin Lymphoma

Abstract We evaluated the rate and type of second malignant neoplasms (SMN) after BFM treatment of children with Non-Hodgkin lymphoma (NHL). Between January 1981 and February 2003 2451 patients (pts) &lt;15 years (y) of age at diagnosis were enrolled into the subsequent trials NHL-BFM 81, 83, 86, 90, and 95. Pts with lymphoblastic lymphoma (LBL) (n=547) or non-anaplastic peripheral T-cell lymphoma (n=97) received acute lymphoblastic leukemia (ALL)-type therapy including cumulative doses of cyclophosphamide (max. 3g/m2), daunorubicine/doxorubicin (max. 280mg/m2), but, except few pts, no etoposide. Prophylactic cranial radiotherapy (CRT) was given in stage III/IV (omitted in NHL-BFM95). Pts with mature B-cell neoplasms (n=1597), or anaplastic large cell lymphoma (n=210) received B-type therapy, consisting of 2–8, 5-day courses including cumulative doses of cyclophosphamide (max. 7g/m2), ifosfamide (max. 8g/m2), doxorubicine max. 150mg/m2 (in trial 81 max. 200mg/m2), and etoposide (max. 1.4g/m2). CRT was omitted since trial NHL-BFM86. With a median follow-up of 6.9 (range 0.2–22.6) years the probability of survival at 15 y was 83+1%. By June 2005, 47 SMN were documented, including 16 acute myeloid leukemias/myelodysplastic syndromes (AML/MDS), 11 NHL, 2 ALL, 1 Hodgkin’s lymphoma, 7 brain tumors, and 10 other SMN. All SMN occurred in first remission after a median time of 2.9 (range: 0.4–12.3) years from diagnosis of NHL. The cumulative incidence of SMN at 15 y was 4.0% (95% confidence interval [CI]: 1.9%–6.1%) for the total group. The cumulative incidence of SMN was significantly higher among pts with LBL receiving ALL-type therapy (6.3% at 15 y [95%CI: 2.4%–10.3%] (13 AML/MDS, 2 NHL, 3 brain tumors, and 3 other SMN), as compared to pts with other NHL-entities receiving B-type therapy (3.4% at 15 y [95% CI: 0.5–6.4%] (3 AML/MDS, 9 NHL, 2 ALL, 1 Hodgkin’s lymphoma, 4 brain tumors, and 7 other SMN), p=0.002. There was no significant difference of cumulative incidence of SMN in pts who received CRT compared to pts not receiving CRT. However, 5 of 7 pts, who developed brain tumor, received CRT of 12–24 Gy. Also, there was no significant correlation between the incidence of SMN and the cumulative doses of drugs, except for anthracyclines. For pts receiving a cumulative dose of anthracyclines of &gt;160mg/m2 (almost exclusively pts with LBL receiving ALL-type therapy) the cumulative risk for SMN at 15 y was 6.5% (95% CI: 1.5-11.5%), as compared to 2.0% (95% CI: 1.1–2.9%) for pts with lower doses, p=0.007. Exposure to etoposide was not a risk factor for secondary AML/MDS (11 of 16 pts with sec. AML/MDS did not receive etoposide). In a Cox regression analysis only diagnosis of LBL remained a significant risk factor for SMN (RR 2.5, 95% CI 1.4–4.4). Our analysis revealed a cumulative risk for SMN of 4% at 15 y after successful treatment of childhood NHL. The cumulative incidence of SMN was significantly higher in LBL-pts than in other pts. AML/MDS were the most frequent SMN following LBL while second lymphoid malignancies were the most frequent SMN following non-LBL.

Secondary Central Nervous System Lymphoma: A Single Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5181-5181
Author(s):  
Gregory M. Cote ◽  
Yang Feng ◽  
Aliyah R. Sohani ◽  
Zachary J. Roberts ◽  
Anna Colpo ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
Non Hodgkin Lymphoma ◽  
Cns Relapse ◽  
Pathologic Features ◽  
Systemic Lymphoma

Abstract Abstract 5181 Background: Secondary CNS non-Hodgkin lymphoma (SCNSL) is estimated to occur in ∼5% of patients with non-Hodgkin lymphoma, and it carries a poor prognosis. Early CNS relapse (i.e. during treatment or within the first 6 months following chemotherapy) may represent subclinical CNS lymphoma present at the time of diagnosis. DLBCL is the most common histology seen in SCNSL and primary CNS (PCNSL) lymphoma. PCNSL DLBCL is usually characterized by an activated B-cell like (ABC) phenotype; it is unknown whether SCNSL follows the same pattern or if it includes germinal center B-cell (GCB) and non-ABC/non-GCB phenotypes. Methods: We queried our IRB approved clinicopathologic database of hematologic malignancies for patients with lymphoma diagnosed between 1999 and July 2011 who had brain or spine MRI, head CT, lumbar puncture or intrathecal chemotherapy. Clinical data and patient characteristics were extracted. We also obtained pathologic features of tumors including immunohistochemistry and cytogenetics, when available. Descriptive statistics were used to characterize patients at baseline. Overall survival (OS) is defined as the time from time from systemic lymphoma diagnosis (i.e. disease outside of the CNS) to death (event), or censored at last known date of survival. Overall survival curves were obtained using the Kaplan-Meier method with 95% confidence intervals calculated using Greenwood's formula. We did an analysis of CNS lymphoma diagnosis within the first 6 months from systemic lymphoma diagnosis (Early CNS involvement) versus greater than 6 months from systemic lymphoma diagnosis (Late CNS relapse), based on Multivariable logistic regression. The associations between potential risk factors and OS after CNS relapse have been explored using the stepwise Cox regression models. Results: One-hundred and twelve patients met the criteria of systemic lymphoma with CNS relapse/involvement with 68% DLBCL and the remainder including Mantle Cell lymphoma (5%), BL (5%), CLL/SLL (4%) and others. Of the DLBCL patients, 25/76 (33%) were GCB type, 20/76 (26%) were non-GCB, and the remaining unclassifiable with the data available. The median OS for all patients was 23 mo (95% CI=11–41), and 6.7 mo (95% CI=4.6–9.9) after CNS lymphoma diagnosis. Sixty-one of 112 patients (54%) were found to have CNS lymphoma within 6 mo of systemic lymphoma diagnosis including 40 patients (36%) where CNS involvement was present at the time of, or within the first month of, systemic diagnosis, suggesting that these are concurrent presentations. Median OS for patients with early (i.e. concurrent systemic and CNS lymphoma and early CNS relapse patients) v. late CNS relapse was 8.5 mo (95% CI=5.5–10.4) compared to 57.8 mo (95% CI=33.2–94.7), (p < 0.003). The OS after CNS diagnosis was similar between the two groups at 5.5 mo (95% CI=2.85–11) and 8.2 mo (95% CI=3.9–9.7), respectively (p=0.5). Regression analysis of clinical and pathological features (e.g. age, sex, stage, IPI score, LDH, histology, cytogenetics, immunohistochemistry, initial treatment and others) was performed to determine if there were factors associated with early versus late CNS lymphoma involvement and none were significant or clinically relevant. Hazard ratios (HR) for OS after CNS relapse favored patients who obtained a CNS complete response (CR1, HR=0.18, p=<0.01, 95% CI=0.08–0.40) or partial response (PR1, HR=0.31, p=0.004, 95% CI=0.14–0.68). Fifteen patients underwent autologous stem cell transplantation (ASCT) for CNS lymphoma therapy; the median OS after CNS relapse was over 1000 days (HR=0.19, p=0.002, 95% CI=0.07–0.56), suggesting a benefit for intensive therapy in selected patients. HR's for OS after CNS relapse were worse for DLBCL patients with non-GCB phenotype (HR=5.61, 95% CI=2.85–11) and those with an elevated LDH and >1 site of EN disease (HR=2.50, p=0.004, 95% CI=1.34–4.68) at the time of systemic diagnosis, perhaps reflecting more aggressive disease at initial presentation. Conclusion: The prognosis of secondary CNS lymphoma remains poor, though selected patients who undergo high-dose chemotherapy with ASCT may enjoy prolonged remissions. In contrast to PCNSL, both GCB and non-GCB DLBCL relapse in the CNS, with the non-GCB subtype associated with an inferior prognosis. For patients at high-risk of CNS involvement, efforts must be directed at prophylactic strategies and novel therapeutic approaches. Disclosures: No relevant conflicts of interest to declare.

Clinical Outcome of Therapy-Related Acute Myeloid Leukemia Is Strongly Related to Cytogenetic Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1401-1401
Author(s):  
Croix Fossum ◽  
Rhett P. Ketterling ◽  
Lindsey E. Roeker ◽  
Ajoy L. Dias ◽  
Michelle Elliott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Alkylating Agent ◽  
De Novo ◽  
Disease Course ◽  
Primary Malignancy ◽  
Non Hodgkin Lymphoma ◽  
Cytogenetic Profile ◽  
De Novo Aml

Abstract Background: Treatment-related AML (t-AML) accounts for 10 to 20% of all AML cases and carries an especially poor prognosis (Kayser et al. 2011, Godley et al. 2008). Patients diagnosed with t-AML are likely to have abnormal cytogenetic profiles with chromosome changes that are predictive of an aggressive malignancy, poor response to therapy, and decreased overall survival(Smith et al. 2003). The simultaneous use of multiple chemotherapeutic agents of different classes makes it increasingly difficult to predict risk for developing t-AML and determining disease course. An updated analysis of predictive factors for t-AML is needed so clinicians can more accurately inform patients of their prognosis. The aim of this study was to classify t-AML according to primary malignancy, previous chemotherapy exposure, and cytogenetic profile. Methods: A retrospective chart review of patients that were diagnosed with AML at Mayo Clinic from 7/1/1990 to 5/13/2015 was performed following IRB approval. AML patients found to have a previous malignancy treated with chemotherapy were classified as t-AML. Chemotherapeutics were classified as alkylating agents, antimetabolites, anti-tubulin agents, and topoisomerase II inhibitors. Patients diagnosed with a myelodysplastic or myeloproliferative disorder prior to development of AML were excluded from this study. Previous chemotherapy exposures, duration of chemotherapy exposure, complete blood count, chromosome abnormalities, and survival data were collected for t-AML cases. Cytogenetic changes were classified as favorable, intermediate, and adverse according to the system used by Kayser et al. 2011. JMP 10.0 was used for statistical analysis. Results: Out of 584 patients, 64 patients (11%) had a primary malignancy that was treated with chemotherapy prior to being diagnosed with AML. The most common primary malignancies were breast cancer (31%), non-Hodgkin lymphoma (27%), colorectal cancer (8%), and Hodgkin lymphoma (8%). Laboratory findings showed median hemoglobin 9.6 g/dL (4.7-13.8), median white blood cells 3.2 x109 (0.6-126), median platelets 50x109 (3-320), median peripheral blood blasts of 8% (0-91), and median bone marrow blasts 38% (1-94). 95% of patients diagnosed with t-AML had been previously treated with an alkylating agent. Additional exposure to an anti-metabolite trended towards a more adverse cytogenetic profile (χ2=5.0, p=0.08) but there was not a statistically significant decrease in overall survival (KM analysis, p=0.31). The median overall survival for patients diagnosed with t-AML was 10.2 months compared to 19.2 months for patients with de-novo AML (KM analysis, p=0.04). Adverse cytogenetic profiles were associated with decreased survival (KM analysis, p <0.0001). However, there was no difference in overall survival between patients with t-AML that had intermediate cytogenetics and those with de-novo AML (KM analysis, p=0.36). None of the chemotherapy classes other than antimetabolites were associated with poor cytogenetics or survival when combined with an alkylating agent. Conclusion: Over half of all patients classified as having t-AML in this study received prior chemotherapy for breast cancer or non-Hodgkin lymphoma. Cytogenetic classification of t-AML into favorable, intermediate and adverse groups is useful in predicting disease course. Interestingly, t-AML patients with intermediate risk cytogenetics had similar overall survival to patients with de-novo AML. This suggests that the poor outcomes observed in patients with t-AML is predominantly due to the subset with adverse cytogenetics. Thus, cytogenetic analysis remains the best indicator of overall survival regardless of chemotherapy exposure. Additional work is needed to delineate the risk associated with the aforementioned chemotherapy classes. Disclosures Al-Kali: Celgene: Research Funding.

Association of lymphocyte to monocyte ratio with clinical response and survival in patients with relapsed, aggressive non-Hodgkin lymphoma treated with axicabtagene ciloleucel CAR-T.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3028-3028 ◽  
Author(s):  
Abdullah S. Al Saleh ◽  
Sangeetha Gandhi ◽  
Tuan Truong ◽  
Arushi Khurana ◽  
Eva Brandes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Hodgkin Lymphoma ◽  
Strong Predictor ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Monocyte Count ◽  
Non Hodgkin Lymphoma ◽  
Response Predictors ◽  
Car T

3028 Background: Chimeric antigen receptor T-cell (CAR-T) therapy induces complete remission (CR) in 30-40% of patients with non-Hodgkin lymphoma (NHL). However, for patients who do not achieve CR as their first response, predictors for achieving CR as best response can guide management between careful observation or early intervention. Increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC) predicts better response rates and survival in NHL patients receiving chemotherapy and/or autologous stem cell transplant. We evaluated the prognostic impact of ALC/AMC in CAR-T therapy for NHL. Methods: This was a retrospective review of patients who received CAR-T for NHL from June 2016-August 2019. ALC/AMC was assessed at the start of lymphodepletion (LD) chemotherapy. The receiver operator curve (ROC) was used to determine the best cutoff for ALC/AMC in predicting CR at 3 months. Event-free survival (EFS) was defined from time of CAR-T infusion to relapse or death, whichever occurred first. Overall survival (OS) was defined from time of infusion to death of any cause. Results: Forty-seven patients received axicabtagene ciloleucel, with a median follow-up of 14 months. By ROC, ALC/AMC > 0.8 before LD chemotherapy was predictive of achieving CR at 3 months. Baseline characteristics were similar between the high (n = 30) and low (n = 17) ALC/AMC groups. Patients with an ALC/AMC > 0.8 at the time of LD chemotherapy were more likely to achieve CR at 3 months (46% vs. 12%, p = 0.01), 6 months (52% vs. 0%, p < 0.0005), and 12 months (42% vs. 0%, p = 0.01). Correspondingly, the EFS and OS were significantly shorter in patients with ALC/AMC≤0.8 vs. those > 0.8 (median EFS: 2 vs. 13 months, P < 0.0001) and (median OS: 15 months vs. not reached, P = 0.03), respectively. Association between ALC/AMC ratio and EFS and OS remained consistent in multivariate Cox models after adjusting for other prognostic variables, including abnormal lactate dehydrogenase and increased ferritin level at infusion day. Conclusions: ALC/AMC > 0.8 before lymphodepletion chemotherapy is a strong predictor for complete remission as well as improved event-free and overall survival for axicabtagene ciloleucel in NHL.

Skeletal muscle density as a positive predictive factor for nivolumab therapy in patients with metastatic renal cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17107-e17107
Author(s):  
Meltem Ekenel ◽  
Murat Sari ◽  
Samil Aliyev ◽  
Mert Basaran
Keyword(s):  
Skeletal Muscle ◽  
Renal Cell Carcinoma ◽  
Adipose Tissue ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Predictive Factor ◽  
Renal Cell ◽  
Intermediate Risk ◽  
Second Line ◽  
Muscle Density

e17107 Background: Immunotherapy has shown promising clinical responses in patients with metastatic Renal Cell Carcinoma (mRCC) at second-line therapy. Since objective response rates are highly variable, it is utmost important to identify patients who may benefit from immunotherapy to avoid unnecessary adverse effects and costs. Therefore, predictive as well as prognostic markers need to be studied extensively. To our knowledge, none of the body composition measurements such as fat content or skeletal muscle density have been assessed for this purpose. The objective of the current study is to analyze whether skeletal muscle (either muscle mass or muscle density) and adipose tissue play a prognostic role in patients with mRCC who were treated with immunotherapy at second line. Methods: We retrospectively analyzed 14 patients with mRCC who were progressed after tyrosine kinase inhibitor therapy and treated with Nivolumab between March 2016 and September 2019. Skeletal muscle density (SMD), skeletal muscle and adipose tissue were assessed with computed tomography imaging. Overall Survival (OS) and Progression Free Survival (PFS) were estimated by using the Kaplan-Meier method. Results: The median OS was 13,1 months and it was strongly associated with SMD; the median OS was significantly longer in patients with high SMD compared to patients with low SMD (6,9 months vs 18,5 months; P < 0,05). Also in our analysis, SMD separated the intermediate-risk group into 2 groups with different median OS periods, ranging from 8,1 months (95% confidence interval [95% CI], 5,1 months-11,1 months) in patients with intermediate-risk Heng score and low SMD to 21,5 months (95% CI, 14 months-27 months) in patients with an intermediate-risk Heng score and high SMD. Other parameters calculated for adipose tissue or skeletal muscle did not cause any significant change in survival analysis. Conclusions: High SMD appears to be associated with improved outcome in our small patient population. It could be a predictive factor when immunotherapy, Nivolumab, is considered for therapy of mRCC patients at second line.

Comparative analysis of characteristics, survival trends, and associated malignancies of B-cell and T-cell prolymphocytic leukemia: A surveillance, epidemiology, and end results (SEER) based study1998 to 2016.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7558-7558
Author(s):  
Doaa Attia ◽  
Sara Aly Attia
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
T Cell ◽  
B Cell ◽  
Survival Time ◽  
Hodgkin Lymphoma ◽  
Median Survival ◽  
Prolymphocytic Leukemia ◽  
Non Hodgkin Lymphoma

7558 Background: Prolymphocytic leukemia (PLL) compromises two subsets; B-cell and T-cell, accounting for less than 2% of mature lymphocytic leukemia. Both of them are rare lymphoid neoplasms with a very aggressive clinical course and poor prognosis. Methods: We used SEER program dataset between 1998 and 2016. We divided the patients into 2 groups: B-PLL and T-PLL and identified them using ‘ICD-O-3 histology recode: 9833/3 and 9834/3 respectively. We used SPSS software (version 26, IBM, NY, USA) to calculate overall survival using Kaplan-Meier methods and compare the survival between the two subtypes using the log-rank test. We also used multivariable covariate-adjust cox models to determine the impact of age, sex, race, cause of death, and associated primary malignancies on survival in both types. Results: A retrospective cohort study of 783 patients (295 B-PLL and 488 T-PLL) with overall survival rate of 22.5% (30.2% B-PLL and 18% T-PLL). The overall median survival for PLL was 16 months (95 CI, 13.745-18.255). The median survival of B-PLL (25 months, 95%CI, 15.733-34.267) was much better than T-PLL (14 months, 95%CI, 11.922-16.078). The mean age was 68.7±15.3. Patient age was an independent factor in determining the survival and inversely associated with survival time in both types (p < 0.0001). The survival rate was worst ) among age groups older than 79, between 70-79 years (8.9%, 18.9%) respectively. Although white male patients were more affected in both types, neither sex nor race significantly affected survival (P 0.554, 0.062 respectively). 64.7% of PLL patients died due to cancer. Patients with cancer-related death had significantly shorter survival time in both T-PLL group (HR = 0.351, 95% CI 0.241-0.512) and B-PLL group (HR = 0.682, 95% CI 0.491-0.945). We also found that 24.4% of B-PLL and 19% of T-PLL patients have another associated primary malignancy. Among hematological malignancies, non-hodgkin lymphoma was the commonest. Although associated solid tumors were less common, Prostate cancer and breast cancer were the commonest for both types and lung/bronchus malignancies were more associated with T-PLL. Conclusions: T-PLL subtype has worse prognosis. Age is the most important independent predictor of survival in both types. Although most of affected patients were white males, race and gender have no impact on survival. Non-hodgkin lymphoma is the commonest primary associated malignancy followed by breast and prostate cancer in both types.

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