Serum Albumin and Peripheral Blood Lymphocyte/Monocyte Ratio at Diagnosis May Provide Additional Prognostic Information in R-IPI Good Risk Diffuse Large-B-Cell Lymphoma Patients Treated with R-CHOP

Abstract Background and Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Currently, the standard of care in DLBCL patients (pts) is rituximab-CHOP immunochemotherapy (R-CHOP) and the prognostic stratification is performed by the Revised International Prognostic Index (R-IPI), identifying 3 distinct prognostic groups with a very good, good and poor outcome. A lot of new prognostic markers have been introduced into the clinical practice to perform better pts' stratification. Particular prognostic relevance has been attributed to serum albumin (SA), β2-microglobulin (B2M), peripheral blood lymphocyte/ monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR) etc. However the data of these prognostic factors across the different R-IPI prognostic groups are limited. Therefore, we decided to access whether SA, B2M, LMR and NLR were predictors of overallsurvival (OS) across the different R-IPI groups of R-CHOP treated DLBCL pts. Patients and Methods: We retrospectively reviewed the clinical outcome of 281 R-CHOP treated DLBCL pts with median age 58 years and 51.8 % male. According to the R-IPI score, the pts in very good, good and poor risk were 24.2%, 54.8% and 21%, respectively. Laboratory levels of albumin, absolute lymphocyte, monocyte and neutrophil count were recorded, and LMR and NLR - calculated. Serum B2M levels were measured by radioimmunoassay. A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of SA, B2M, LMR and NLR to predict OS by Kaplan-Meier method. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models. Results: The estimated 5-year OS was 87.1%, 74% and 31% for R-IPI very good, good and poor-risk patients, respectively. The median values of SA, B2M, LMR and NLR were 40.7 g/L, 2.9 mg/L, 2.95 and 2.86, respectively. Our data showed that on univariate analysis inferior OS was associated with decreased SA (≤39.4 g/L; 95% confidence interval (CI) 0.70-0.82, p=<0.001), elevated B2M (>2.6 mg/L; 95% CI 0.68-0.80, p=<0.001), reduced LMR (≤2.16; 95% CI 0.71-0.81, p=<0.001) and increased NLR (>2.61; 95% CI 0.66-0.77, p=<0.001), presented as dichotomized variables. On multivariate analysis the independent prognostic significance was confirmed only for SA and LMR, with hazard ratios of 0.23 (95% CI 0.11-0.49, p<0.001) and 0.41 (95% CI 0.21-0.81, p=0.011), respectively. Based on the dichotomized SA and LMR values a SA/LMR prognostic index (PI) was created stratifying patients into 3 risk groups: very good (SA >39.4 g/L and LMR >2.16; n=75), good (SA ≤39.4 g/L or LMR ≤2.16; n=52) and poor-risk (SA ≤39.4 g/L and LMR ≤2.16; n=41) populations. The estimated 5-year OS was 88.7% for very good, 51.7% for good, and 8.8% for poor SA/LMR PI group (p<0.001). Median OS for poor-risk patients was 1.1 years (95% CI 1.03-1.72 years) and not reached for both the very good and good-risk groups. We sought to determine whether the SA/LMR PI may provide additional prognostic information within the R-IPI risk groups. Due to low number of deaths - 4.4% (3/68), no statistics could be calculated in very good R-IPI risk group. Within the R-IPI good risk patients SA/LMR PI allowed us to discriminate 3 subgroups, characterized by significant differences in 3-year and median OS (Figure 1): a SA/LMR PI poor risk subgroup (n=18) with 10.4% 3-years OS and 1.13 years (95% CI 0.82-1.44 years) median OS; a SA/LMR PI good risk subgroup (n=32) with 59.5% 3-years OS and median not reached; and a SA/LMR PI very good risk subgroup (n=50) with not reached median OS and 91.3% 3-years OS comparable to the OS in R-IPI very good patients (p=0.229). Only SA retained its independent prognostic significance in R-IPI poor risk group. Conclusion: SA and LMR are independent prognostic markers to predict survival in DLBCL pts. Adding these variables to prognostic models such as the R-IPI score might improve their predictive ability, providing particularly relevant information within the R-IPI good risk group. A subgroup of R-IPI good risk pts with a very good SA/LMR PI was identified, comparable to the R-IPI very good risk category in terms of OS. Figure 1. Overall survival of R-CHOP treated R-IPI good risk DLBCL patients according to SA and LMR at diagnosis Figure 1. Overall survival of R-CHOP treated R-IPI good risk DLBCL patients according to SA and LMR at diagnosis Disclosures No relevant conflicts of interest to declare.

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Charlson Comorbidity Index Is An Independent Prognostic Factor Among Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v114.22.3923.3923 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3923-3923

Author(s):

Jin Takeuchi ◽

Atsuko Hojo

Keyword(s):

Elderly Patients ◽

Charlson Comorbidity Index ◽

Conflicts Of Interest ◽

Risk Group ◽

International Prognostic Index ◽

B Cell Lymphoma ◽

Poor Risk ◽

Risk Patients ◽

Comorbidity Index ◽

Good Risk

Abstract 3923 Poster Board III-859 Introduction Wide use of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has improved the clinical outcome for elderly patients with DLBCL; however, a higher prevalence of coexisting disorders remains a problem. Correlation between their comorbidities and prognosis has not yet been well investigated. Patients and methods We retrospectively analyzed all patients over 65 years old who had been newly diagnosed with DLBCL at our institution from 2001 to 2008. To assess their comorbid medical status, we calculated the Charlson Comorbidity Index (CCI) for patient excluding primary disease. Prognostic factors were identified by Cox proportional hazards regression model. We classified patients into a low CCI group (CCI 0-1) and a high CCI group (CCI 2 or higher). Kaplan-Meyer curves for each group were evaluated by logrank test. Results A total of 80 patients were enrolled in this analysis. The median age was 73 (range 66-90) and the median observation period was 28 months (range 4-90 months). 62 patients (77.5%) were treated with R-CHOP, 15 (18.6%) underwent some other regimen, and 3 (3.8%) were given best supportive care only. According to revised International Prognostic Index (r-IPI), 43 patients were in the good risk group and the others were in the poor risk group. The estimated 3 year over all survival (OS) rate for these groups were 90% and 45% (p<0.0001). As for CCI, 14 patients (17.5%) were assigned to the high CCI group. Multivariate analysis revealed high CCI was associated with worse OS, while independent of r-IPI [Hazard Ratio (HR) 3.20, 95% Confidence interval (CI) 1.28-7.41, p=0.0145]. Among r-IPI poor risk patients, the high CCI group was inferior to the low CCI group for the 3 year OS rate (14% vs 56% p=0.0358), whereas this was not significant among r-IPI good risk patients (69% vs 94% p=0.0617). Conclusions Among elderly patients with DLBCL, high CCI is independently associated with poor survival. Patients having both poor r-IPI and high CCI may need discrete strategies. Disclosures: No relevant conflicts of interest to declare.

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The Absolute Monocyte and Lymphocyte Counts at Diagnosis Predict Survival and Identify High-Risk Patients In Diffuse Large-B-Cell Lymphoma

Blood ◽

10.1182/blood.v116.21.3088.3088 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3088-3088

Author(s):

Ryan A. Wilcox ◽

Kay Ristow ◽

Thomas M. Habermann ◽

David James Inwards ◽

Ivana Micallef ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Confidence Interval ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Hazard Ratio ◽

Poor Risk ◽

Large B Cell Lymphoma ◽

Risk Patients ◽

Good Risk

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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Serum Albumin and Peripheral Blood Neutrophils at Diagnosis May Provide Additional Prognostic Information in Primary Nodal Diffuse Large-B-Cell Lymphoma Patients Treated with R-CHOP

Blood ◽

10.1182/blood.v128.22.5304.5304 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5304-5304

Author(s):

Branimir Spassov ◽

Donka Vassileva ◽

Georgi Mihaylov ◽

Gueorgui Balatzenko ◽

Margarita Guenova

Keyword(s):

Multivariate Analysis ◽

Cell Lymphoma ◽

Univariate Analysis ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

Prognostic Impact ◽

Prognostic Information ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background and Aim: Diffuse large B-cell lymphoma (DLBCL) can present both as a primary nodal or extranodal neoplasm. Some studies claimed a separate origin for nodal and extranodal lymphomas and it has been even suggested that these could be regarded as separate nosological entities. However, the standard of care in DLBCL patients (pts) is rituximab-CHOP immunochemotherapy (R-CHOP), and the prognostic stratification is performed by the Enhanced Revised International Prognostic Index (NCCN-IPI), identifying 4 distinct [low (L), low-intermediate (LI), high-intermediate (HI) and high (H)] risk groups (RGs). A lot of new prognostic markers such as serum albumin (SA), serum β2-microglobulin (B2M), hemoglobin level (Hb), absolute neutrophil (ANC), lymphocyte (ALC), monocyte (AMC) and platelet counts etc. have been introduced into the clinical practice to perform better pts' stratification. However, data on the importance of these factors particularly in primary nodal (PN) DLBCL pts are still limited. Therefore, we aimed to access the prognostic impact of these markers regarding overallsurvival (OS) across the different NCCN-IPI RG of R-CHOP treated PN-DLBCL pts. Patients and Methods: We retrospectively reviewed the clinical outcome of 174 R-CHOP treated PN-DLBCL pts at a median age 58.4 years. Pts were stratified using NCCN-IPI into L (24.1%), LI (43.1%), HI (24.7%) and H (8.1%) RGs. Laboratory levels of SA, B2M, Hb, ANC, ALC, AMC and PC were recorded, and LMR and NLR - calculated. A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of SA, B2M, Hb, ANC, ALC, AMC, PC, LMR and NLR to predict OS by Kaplan-Meier method. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models. Results: The estimated 5-year OS was 79.4%, 51.5%, 20.1% and 16.2% for NCCN-IPI L, LI, HI and H-risk pts, respectively (p<0.001). Univariate analysis showed that inferior OS was associated significantly with decreased SA (≤39.4 g/L), elevated B2M (>3.2 mg/L), elevated ANC (>5.19 x 109), reduced ALC (≤1.38 x 109), elevated AMC (>0.515 x 109), decreased LMR (≤1.77), increased NLR (>2.97), lower Hb level (≤134 g/L), presented as dichotomized variables. Multivariate analysis confirmed the independent prognostic impact only for SA (p<0.001) and ANC (p=0.011). Based on the dichotomized SA and ANC values a SA/ANC prognostic index (PI) was created stratifying pts into 3 RG: favorable (F) [SA >39.4 g/L and ANC ≤5.19 x 109], intermediate (I) [SA ≤39.4 g/L or ANC >5.19 x 109] and poor (P) - risk [SA ≤39.4 g/L and ANC ≤5.19 x 109] populations. The estimated 5-year OS differed significantly in SA/ANC PI RG, as follows: 92.8% in F-RG, 48.4% in I-RG, and 0% in P-RG (p<0.001). Median OS for I- and P- SA/ANC PI RG was 2.54 and 1.13 years, respectively and not reached for the F-risk pts. We sought to determine whether the SA/ANC PI may provide additional prognostic information within the NCCN-IPI RG. No statistics could be calculated within the L-RG due to the low number of deaths - 9.5% (4/42), and in the H-RG due to the low number of patients (n=14), respectively. However, within the LI-RG the SA/ANC PI allowed us to discriminate 3 subgroups, characterized by significant differences in the OS (p<0.001): no patient within the P-RG was alive at 5years and the median OS was only 1.13 years; while 5-years OS was 77% and 87.7% in the I-RG and F-RG, respectively, and the median was not reached in both RG. Similarly, within the NCCN-IPI HI-RG the application of SA/ANC PI allowed us to discriminate 3 subgroups, characterized by significant differences in OS: no patient within the P-RG was alive at 5 years and the median OS was 1.29 years; while 5-years OS was 30.6% (median OS - 1.66 yrs) in the I-RG and 100% (median OS not reached) in the F-RG. The introduction of the SA/ANC PI allowed for defining favorable subgroups within the IPI LI- and HI RGs with 5-yrs OS comparable to IPI L-RG. Conclusion: The present study provided evidence for the independent prognostic significance ofSA and ANC in regard to survival in patients with PN-DLBCL. Adding these variables to prognostic models such as the NCCN-IPI score might improve the predictive ability, particularly within the NCCN-IPI LI and HI risk groups, where the introduction of SA/LMR PI allowed for identifying favorable subgroups comparable to the NCCN-IPI L-RG in terms of OS. Disclosures No relevant conflicts of interest to declare.

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AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy

Blood ◽

10.1182/blood-2005-09-3600 ◽

2006 ◽

Vol 107 (10) ◽

pp. 3832-3840 ◽

Cited By ~ 92

Author(s):

Nicolas Mounier ◽

Michele Spina ◽

Jean Gabarre ◽

Martine Raphael ◽

Giuliano Rizzardini ◽

...

Keyword(s):

Risk Group ◽

Cox Model ◽

International Prognostic Index ◽

Prognostic Index ◽

Intermediate Risk ◽

Intensive Chemotherapy ◽

Poor Risk ◽

Cell Counts ◽

Risk Patients ◽

Good Risk

We aimed to compare AIDS risk–adapted intensive chemotherapy in AIDS-related lymphoma (ARL) patients before and after the advent of highly active antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years were randomly assigned to chemotherapy after stratification according to an HIV score based on performance status, prior AIDS, and CD4+ cell counts below 0.10 × 109/L (100/mm3). A total of 218 good-risk patients (HIV score 0) received ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177 intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90 poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The 5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47% for CHOP (P = .85); in the intermediate-risk group, 28% for CHOP versus 24% for Ld-CHOP (P = .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS (P = .14). The time-dependent Cox model demonstrated that the only significant factors for OS were HAART (relative risk [RR] 1.6, P < .001), HIV score (RR 1.7, P < .001), and the International Prognostic Index (IPI) score (RR 1.5, P < .001) but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV score, IPI score, and HAART affect survival but not the intensity of the CHOP-based chemotherapy.

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Postremission Therapy in Adult Acute Myeloid Leukemia (AML): A Randomized Comparison of Intensified Consolidation Therapy without Maintenance Therapy Against Conventional Consolidation with Maintenance Therapy -JALSG AML-97 Trial-.

Blood ◽

10.1182/blood.v104.11.868.868 ◽

2004 ◽

Vol 104 (11) ◽

pp. 868-868 ◽

Cited By ~ 1

Author(s):

Shuichi Miyawaki ◽

Hisashi Sakamaki ◽

Shigeki Ohtake ◽

Fumiharu Yagasaki ◽

Kinuko Mitani ◽

...

Keyword(s):

Maintenance Therapy ◽

Induction Therapy ◽

Risk Group ◽

Randomized Study ◽

Risk Groups ◽

Consolidation Therapy ◽

Poor Risk ◽

Short Course ◽

To Receive ◽

Good Risk

Abstract Between 1997 and 2001, JALSG conducted a randomized study to assess the optimal post remission therapy for adult AML in the first CR. The JALSG AML97 enrolled 809 previously untreated AML patients (pts) aged 15–64 yrs. Induction therapy consisted of cytarabine (100mg/m2 day1–7) and idarubicin (IDR 12mg/m2 day1– 3). If the patients did not achieve remission after the first induction therapy, the same therapy was given once more. Pts were categorized into good, intermediate or poor risk groups by risk factors based on the previous JALSG AML studies. All CR pts were randomized to receive either the intensified short course post remission regimen (arm A) or the conventional JALSG’s post remission regimen for AML including maintenance therapy (arm B). Arm A: 1) AraC 200mg/m2 day1–5+ Mitoxantrone (MTZ) 7mg/m2 day1–3, 2) AraC 200mg/m2 day1–5+Daunorubicin (DNR) 50mg/m2 day1–3, 3) AraC 200mg/ m2 day1–5+ Aclacinomycin (ACR) 20mg/m2 day1–5, 4) AraC 200mg/m2 day1–5+ Etoposide (ETP) 100mg/m2 day1–5 + Vincristine (VCR) 0.8mg/m2 day 8 + Vindesine (VDS) 2 mg/m2 day10. Arm B: 1) AraC 200mg/m2 day1–5 + MTZ 7mg/m2 day1–3, 2) Behenoyl AraC (BHAC) 200mg/m2 day1–7 + ETP 100mg/m2 day1–5 + DNR 50mg/m2 day1–3 + 6 mercptopurine (6MP) day1–7, 3) BHAC 200mg/m2 day1–7 + ACR 14mg/m2 day1–7, and then 6 courses maintenance therapy: 1) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1,4+6MP day1–7, 2) BHAC 170mg/m2 day1–5 + MTZ 5mg/m2 day1–3, 3) BHAC 170mg/m2day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8, 4) BHAC 170mg/m2 day1–5 + ACR 14mg/m2 day1–4 + 6MP day1–7, 5) BHAC 170mg/m2 day1–5 + DNR 50mg/m2 day1–4 + 6MP day1–7, 6) BHAC 170mg/m2 day1–5 + ETP 80mg/m2 day1,5,7 + VDS 2mg/m2 day1,8. Result: Of the 809 pts registered, 789 pts (median age: 45 years) were evaluable. 621 pts (78.7%) achieved CR after one or two courses of induction therapy. The 5-year OS rate of arm A was 45.6% and of arm B 53.2% (p=0.3259). The 5-year DFS rate of CR patients was 34.8% in arm A and 28.9% in arm B (p=0.4978). Among the good risk group, the 5-year OS rate of arm A was 62.1% and of arm B 70.2% (p=0.5068), and the 5-year DFS rate of arm A was 53.4% and of arm B 42.0% (p=0.3719). Among the intermediate risk group, the 5-year OS rate of arm A was 35.6% and of arm B 45.5% (p=0.4776), and the 5-year DFS rate of arm A was 26.0% and of arm B 26.1% (p=0.9653). Among the poor risk group, the 5-year OS rate of arm A was 29.7% and of arm B was 33.4% (p=0.6523), and the 5-year DFS rate of arm A was 20.4% and of arm B was 13.5% (p=0.6339). In conclusion: JALSG’s conventional post remission therapy consisting of 3 courses of consolidation and 6 courses of maintenance therapy could be replaced by a shorter duration of intensified consolidation therapy.

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Conditional survival (CS) for patients with metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy (TT): Results from the International mRCC Database Consortium.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.358 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 358-358

Author(s):

Toni K. Choueiri ◽

Wanling Xie ◽

Lauren Christine Harshman ◽

Georg A. Bjarnason ◽

Jennifer J. Knox ◽

...

Keyword(s):

Risk Group ◽

Risk Groups ◽

Vascular Endothelial ◽

Conditional Survival ◽

Prognostic Information ◽

Poor Risk ◽

The Poor ◽

Changes Over Time ◽

Endothelial Growth Factor ◽

Over Time

358 Background: Survival estimates for patients with mRCC are traditionally reported from the time of TT initiation. These survival projections, however, may not be applicable to patients who have already survived a period of time after initiating therapy. CS accounts for elapsed time since starting therapy, providing more relevant prognostic information. Methods: Data on 1673 patients treated with first-line VEGF TT between 4/7/2003 and 10/12/2010 was analyzed. Median follow up for patients still alive is 20.1 months. Conditioned survival was calculated on the set of patients alive or on TT at 3 months and using 3 months increments for up to 18 months. Results: The 2-year CS probability tends to slightly improve from 44 to 51% when conditioned on having already survived 0 to18 months since initiation of TT, respectively. The Heng et al (JCO 2009) risk criteria (defined at therapy initiation) retains prognostic ability over time independent of previous survival time or previous time on TT up to 18 months (p<0.0001 for all comparisons). In the subgroup analysis stratified by Heng risk groups, 2-year CS minimally changes over time in the favorable (FAV) and in the intermediate (INT) groups, but in the poor risk group, the 2-year CS improves from 11% initially to 33% after 18 months. When conditioned on time on TT, 2-year CS improves from 44% to 68% overall, from 74% to 90% in the FAV risk group, 49% to 57% in the INT risk group and 11% to 73% in the poor-risk group. Conclusions: Conditional survival may be a more relevant measure of prognosis for those who have already survived or have been on TT for a period of time. The largest improvement was seen in patients in the poor risk group. [Table: see text]

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Risk Stratification for Diffuse Large B-Cell Lymphoma by Integrating Interim Evaluation and International Prognostic Index: A Multicenter Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.754964 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xue Shi ◽

Xiaoqian Liu ◽

Xiaomei Li ◽

Yahan Li ◽

Dongyue Lu ◽

...

Keyword(s):

High Risk ◽

Risk Stratification ◽

Risk Group ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

High Risk Group ◽

Stratification System ◽

Risk Stratification System

The baseline International Prognostic Index (IPI) is not sufficient for the initial risk stratification of patients with diffuse large B-cell lymphoma (DLBCL) treated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The aims of this study were to evaluate the prognostic relevance of early risk stratification in DLBCL and develop a new stratification system that combines an interim evaluation and IPI. This multicenter retrospective study enrolled 314 newly diagnosed DLBCL patients with baseline and interim evaluations. All patients were treated with R-CHOP or R-CHOP-like regimens as the first-line therapy. Survival differences were evaluated for different risk stratification systems including the IPI, interim evaluation, and the combined system. When stratified by IPI, the high-intermediate and high-risk groups presented overlapping survival curves with no significant differences, and the high-risk group still had >50% of 3-year overall survival (OS). The interim evaluation can also stratify patients into three groups, as 3-year OS and progression-free survival (PFS) rates in patients with stable disease (SD) and progressive disease (PD) were not significantly different. The SD and PD patients had significantly lower 3-year OS and PFS rates than complete remission and partial response patients, but the percentage of these patients was only ~10%. The IPI and interim evaluation combined risk stratification system separated the patients into low-, intermediate-, high-, and very high-risk groups. The 3-year OS rates were 96.4%, 86.7%, 46.4%, and 40%, while the 3-year PFS rates were 87.1%, 71.5%, 42.5%, and 7.2%. The OS comparison between the high-risk group and very high-risk group was marginally significant, and OS and PFS comparisons between any other two groups were significantly different. This combined risk stratification system could be a useful tool for the prognostic prediction of DLBCL patients.

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Comparison of Matched/Mismatched Unrelated Donor Stem Cell Transplantation to Autologous Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission: A Study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v126.23.3216.3216 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3216-3216

Author(s):

Francesco Saraceni ◽

Myriam Labopin ◽

Norbert Claude Gorin ◽

Didier Blaise ◽

Reza Tabrizi ◽

...

Keyword(s):

Stem Cell ◽

Myeloid Leukemia ◽

Risk Group ◽

Unrelated Donor ◽

Cell Transplant ◽

Intermediate Risk ◽

Poor Risk ◽

Risk Patients ◽

Matched Sibling ◽

Good Risk

Abstract Background. Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is still matter of debate. Allogeneic Stem Cell Transplant (allo-HSCT) is the most effective treatment to prevent leukemia relapse, and for patients who lack a sibling donor transplantation from a matched or mismatched unrelated donor (URD) is usually the preferred alternative. However, increase in donor-recipient HLA mismatch, patient age and comorbidity scores lead to higher non relapse mortality (NRM) rates; moreover incidence of chronic GVHD is rather high after transplant from unrelated donors. Autologous Stem Cell Transplant (ASCT) has several advantages compared to allo-HSCT including low NRM, no GVHD risk, less late effects and better quality of life. The aim of the current study was to compare the outcome of allo-HSCT from matched (10/10 URD) or mismatched unrelated donor at a single HLA-locus (9/10 URD) to ASCT in patients with AML in first CR. Patients and methods. We performed a retrospective analysis of 2689 AML patients receiving 10/10 URD (n=1260), 9/10 URD-HSCT (n=356) or ASCT (n=1073) in first CR between 2005 and 2013 and reported to the ALWP of the EBMT. Results. Median FU was 35, 27 and 27 months for ASCT, 10/10 and 9/10 URD, respectively (p<10-4); median age was 48.7, 50.8, 48.7 years, respectively (p=10-3). Time from diagnosis to transplant was longer for URD compared to ASCT (p<10-4); patients who received URD had more frequently poor risk cytogenetics (p<10-4), were more likely to get a TBI-based conditioning (p<10-4) and were transplanted more recently (p<10-4), compared to patients who received ASCT. The 2-year cumulative incidence of relapse (RI) for ASCT, 10/10 and 9/10 URD were 46.3±3%, 24.9±3% and 27.7±5%, respectively (p<10-5), while the 2-year NRM rates were 3.1±2%, 16.4±4% and 20.5±4%, respectively (p<10-5). The 2-year KM estimates of leukemia-free survival (LFS) were 50.6±3% for ASCT, 58.7±3% for 10/10 URD and 51.8±6% for 9/10 URD (p=0.002), while the 2-year overall survival (OS) rates were 68.2±3, 63.6±3% and 55.1±6%, respectively (p<10-4). ASCT showed significantly higher RI compared to URD independently of cytogenetic risk (good risk: p<10-4, intermediate and poor risk: p<10-5); accordingly, 2y LFS was significantly better for URD compared to ASCT in all risk groups (good risk: p=0.034, intermediate risk: p=0.0007, poor risk: p=0.021). ASCT and URD showed similar OS in good and poor risk patients, while in intermediate risk group ASCT resulted in similar OS compared to 10/10 URD and better OS compared to 9/10 URD (66.2±4% for ASCT, 65.8±5% for 10/10 URD, 55.4±7% for 9/10 URD, p=0.012) (Fig 1). Within intermediate cytogenetic risk group, FLT3-ITD mutational status affected outcome; in patients harboring FLT3-ITD 10/10 URD showed the best LFS and OS (LFS: 36.3±11% for ASCT, 58.4±7% for 10/10 and 34±13% for 9/10 URD, p=10-3; OS: 51.7±12%, 62.2±7% and 41.4±14%, respectively, p=0.02). Conversely, in patients with wild type FLT3-ITD URD showed better LFS compared to ASCT (51.3±8% for ASCT, 66.7±7% for 10/10 URD, 64±13% for 9/10 URD, p=0.008), while no difference was observed in OS. Multivariate analysis confirmed significantly lower RI for 10/10 (HR 0.36, p<10-5, 95% CI:0.29-0.44) and 9/10 URD (HR 0.43, p<10-5, 95% CI:0.32-0.57) and higher NRM for 10/10 URD (HR 3.88, p<10-5, 95% CI:2.37-6.33) and 9/10 URD (HR 4.89, p<10-5, 95% CI:2.84-8.43) compared to ASCT. URD-SCT was associated with better LFS compared to ASCT (HR 0.57, p<10-5, 95%, CI:0.47-0.67 for 10/10 URD; HR 0.69, p=0.002, 95% CI:0.55-0.87 for 9/10 URD). 10/10 URD was associated with better OS compared to ASCT (HR 0.81, p=0.031, 95% CI:0.66-0.98) but no difference in OS was observed between 9/10 URD and ASCT (HR 1.02, p=0.87, 95% CI:0.79-1.31). Conclusion. In AML patients lacking an HLA-matched sibling donor URD-HSCT significantly reduces relapse risk and improves LFS. 10/10 URD showed better OS compared to ASCT in MV analysis in our series, while 9/10 URD impact on LFS didn't translate in better OS. In intermediate risk patients, in the absence of an HLA fully matched sibling or unrelated donor, autologous transplant may be considered as a valid option as ASCT results seem to overlap 10/10 URD outcome and to provide better survival compared to mismatch URD. Analysis is ongoing to better define which subpopulation of patients might benefit from each approach. Figure 1. OS in patients with intermediate risk cytogenetics. Figure 1. OS in patients with intermediate risk cytogenetics. Disclosures Craddock: Celgene: Consultancy, Honoraria, Research Funding; Pfizer: Speakers Bureau; Sunesis: Honoraria; Johnson and Johnson: Consultancy.

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Concurrent Elevations of VEGF, Osteopontin and MCP-1 Serum Levels Are Independent Predictors of Survival in Patients with Diffuse Large B-Cell Lymphoma

Acta Haematologica ◽

10.1159/000444624 ◽

2016 ◽

Vol 136 (1) ◽

pp. 52-61 ◽

Cited By ~ 4

Author(s):

Antica Duletić-Načinović ◽

Vedrana Gačić ◽

Toni Valković ◽

Ksenija Lučin ◽

Elizabeta Fišić ◽

...

Keyword(s):

B Cell ◽

Univariate Analysis ◽

International Prognostic Index ◽

Eastern Cooperative Oncology Group ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Risk Groups ◽

Serum Levels ◽

Response To Therapy ◽

Large B Cell

Background: Diffuse large B-cell lymphomas (DLBCL) are heterogeneous diseases, and the identification of additional DLBCL risk factors is especially important. Methods: In this pilot study, we determined pretreatment serum levels of vascular endothelial growth factor (VEGF), osteopontin (OPN) and macrophage chemotactic protein-1 (MCP-1) in 67 newly diagnosed DLBCL patients before treatment with standard chemoimmunotherapy and in 30 healthy persons. Results: Serum levels of all three cytokines were significantly elevated in untreated patients compared to controls. VEGF and OPN concentrations were higher in patients with advanced Ann Arbor stage, B symptoms, Eastern Cooperative Oncology Group score ≥2, International Prognostic Index (IPI) ≥3 and partial/no remission. A high MCP-1 level was associated with advanced stage, increased IPI and bone marrow infiltration. In univariate analysis, elevated OPN and VEGF, and concurrent elevation of all three biomarkers, were identified as significant predictors of poor survival. Multivariate Cox analysis revealed that elevated OPN combined with elevated VEGF levels was one of the best parameter subsets predicting poorest survival. Conclusion: According to our preliminary results, serum levels of VEGF and OPN before treatment predict response to therapy and survival after chemoimmunotherapy, and may help to further stratify DLBCL patients into risk groups.

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Deep Phenotypic Analysis Reveals a Monocyte Subpopulation Predictive of Relapse/Refractory Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-119756 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2863-2863

Author(s):

Edward Truelove ◽

Frances Seymour ◽

Janet Matthews ◽

John G. Gribben

Keyword(s):

Peripheral Blood ◽

Research Funding ◽

B Cell Lymphoma ◽

Peripheral Blood Monocyte ◽

Blood Monocyte ◽

Phenotypic Analysis ◽

Poor Risk ◽

Large B Cell Lymphoma ◽

Risk Patients ◽

Good Risk

Abstract Background: Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma subtype with up to two thirds of patients achieving cure following standard immuno-chemotherapy. However, approximately 10-15% will be primary refractory and a further 20-30% relapse. There is an urgent need for improved biomarkers to identify these poor risk patients at diagnosis who are destined to fail standard therapy so that novel approaches can be considered. The diagnostic peripheral blood monocyte count is known to be predictive of outcome in DLBCL, with higher counts identifying patients with worse outcome but mechanistic understanding is currently lacking. The aim of this study was to investigate the peripheral blood monocyte population driving this phenomenon and we present here a deep phenotypic analysis of the monocyte compartment at diagnosis in patients with extremes of outcome following immuno-chemotherapy. Methods: We identified 112 immuno-chemotherapy treated DLBCL patients with viably cryopreserved peripheral blood mononuclear cells (PBMCs) in our tissue bank. The diagnostic absolute monocyte (AMC) and lymphocyte counts (ALC) were examined as prognostic variables. For phenotypic analysis a subset of 20 patients, 10 with relapse/refractory disease within 12 months of therapy (Poor risk) and 10 with continued complete remission >24 months post therapy (Good risk), were selected. PBMCs from these patients were stained with a panel of 29 metal-tagged antibodies designed to identify immune populations and characterize the monocyte compartment and analyzed using cytometry by time-of-flight (CyTOF2TM). Samples were acquired in batches run with the same healthy donor control PBMCs to ensure consistency of staining. Normalized data were subjected to traditional Boolean gating in Cytobank (www.mrc.cytobank.org) to identify CD45+ live single cells and further analyzed using FlowSOM and CITRUS. Results: In the full 112 patient cohort, a higher diagnostic AMC (≥0.6 x 109/L) predicted worse outcome (5-year OS, 59% vs 74%, p=0.047*). The lymphocyte to monocyte ratio (LMR) was more discriminatory, with a low LMR (<2.6) predicting worse outcome (5-year OS, 49% vs 81%, p=0.0009*). CyTOF analysis of the CD45+ events from all 20 DLBCL patients were clustered in an unsupervised manner with FlowSOM and visualized according to the tSNE algorithm. This identified all expected immune populations with further subdivision into multiple clusters / sub-populations based on protein marker expression. Repeating the FlowSOM analysis by outcome revealed clusters with clear differences between the 2 groups, including striking changes to the monocyte compartment (Figure 1). CITRUS, an algorithm for automated biomarker discovery, was used to further assess the differences in the monocyte compartments between poor risk and good risk DLBCL patients. This identified a monocyte subset, representing approximately 10% of non-lymphoid CD45+ PBMCs, with increased abundance in poor risk patients with relapsed/refractory disease (p=0.0028*, Figure 2). This subset expressed markers including HLA-DR, CD11b, CD13, CD14, CD33, SIRPα (CD172a), CCR2 (CD192, monocyte chemo-attractant protein receptor), CD206 and PD-L1 (CD274). Conclusions: We confirmed the previous finding that the diagnostic AMC is predictive of outcome in our cohort of DLBCL patients and have identified differences in the peripheral blood monocyte compartment between patients with good and poor risk disease. Unsupervised analysis using FlowSOM identified monocyte clusters with greater abundance in poor risk patients. A second high-dimensional single cell data analysis algorithm, CITRUS validated this finding by revealing a stratifying monocyte sub-population that was enriched in poor risk patients. This phenotype of peripheral blood monocytes may account for the adverse nature of a higher AMC at diagnosis. We are now functionally characterizing these monocytes and evaluating their relationship to differences between the lymphoid populations of good and poor risk patients. Disclosures Seymour: Celgene: Research Funding. Gribben:Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria; Abbvie: Honoraria; Kite: Honoraria; Acerta Pharma: Honoraria, Research Funding; Wellcome Trust: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; NIH: Research Funding; Unum: Equity Ownership; Roche: Honoraria; Novartis: Honoraria; Cancer Research UK: Research Funding; Medical Research Council: Research Funding; TG Therapeutics: Honoraria.

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