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

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 3832-3840 ◽  
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.

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

Blood ◽  
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.

Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia (AML)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7015-7015
Author(s):  
F. P. Santos ◽  
W. Qiao ◽  
J. E. Cortes ◽  
D. Jones ◽  
F. Ravandi ◽  
...  
Keyword(s):  
Risk Group ◽  
Cox Model ◽  
Tyrosine Kinase Domain ◽  
P Value ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Poor Risk ◽  
Flt3 Mutations ◽  
The Impact ◽  
Good Risk

7015 Background: Mutations of the FLT3 gene (in special internal tandem duplication -ITD) are common in normal karyotype AML (NK-AML) and are associated with shorter relapse free and overall survival (OS). The frequency of FLT3 mutations is lower in other cytogenetic subgroups and the impact on outcome is unclear. Methods: The records of patients (pts) with newly diagnosed AML (from 2003 to 2007) were reviewed. Pts were divided among three cytogenetic subgroups: Good-risk (t(8;21), Inv(16)/t(16;16)) Intermediate-Risk (Diploid,-Y) and Poor Risk (-5,-7, 11q abnormalities). FLT3 ITD and tyrosine kinase domain (TKD) mutations were determined on baseline DNA samples by a PCR based method with 1% sensitivity. Since the frequencies of FLT3 mutations were lower in good- and poor-risk subgroups, ITD/TKD mutations were considered together in the analysis, while in the intermediate risk group they were analyzed separately. Survival curves stratified by FLT3 mutation were estimated by Kaplan Meier plots and compared by logrank test. A Cox model was fit for OS, and non-significant variables were eliminated in a step-down fashion with a p- value cut-off of p = .10. Results: A total of 481 pts were included (65 pts=good risk, 272 pts=intermediate risk and 144 pts= poor risk). Prevalence of FLT3 mutations is shown in the Table. No difference was found in median OS between FLT3-mutated and FLT3- wild type pts in the good risk group (not reached (NR) vs NR, P = 0.57) nor in the poor risk group (55 vs 24 weeks, P = 0.44). In intermediate risk, OS was worse in FLT3-ITD positive pts (33 vs 89 weeks, P < 0.0001) but not in FLT3-TKD positive pts (77 vs 70 weeks, P = 0.89). In the Cox model, FLT3 mutations were prognostic for OS only in intermediate risk pts with FLT3-ITD (HR 2.63, P < 0.0001). Conclusions: In our cohort of pts, FLT3 mutations did not have a prognostic impact in AML with good and poor risk karyotype. [Table: see text] No significant financial relationships to disclose.

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 ◽  
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.

scholarly journals Clinical Prognostic Models in Diffuse Large B-Cell Lymphoma Patients Are Still Essential in the Rituximab Era

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3057-3057
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Renata Oliveira Costa ◽  
Abrahão Elias Hallack Neto ◽  
Sheila Siqueira ◽  
Rodrigo Santucci ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Risk Categories

Abstract Introduction: To evaluate a new enhanced IPI proposed by the National Comprehensive Cancer Network (NCCN-IPI) in DLBCL patients, we compared the international prognostic index (IPI), R-IPI and NCCN-IPI in DLBCL patients treated with rituximab, cyclophosphamide, hidroxydaunorubicin, vincristine and prednisone (R-CHOP). Methods: From June 2008 to November 2011 we retrospectively evaluated 146 DLBCL patients treated with R-CHOP-21 referred for cancer treatment in a single university institution in Brazil. Patient's clinical data were assessed to calculate the IPI, R-IPI and NCCN-IPI. Results: Patient's median age was 58.9 years (range 16 – 86); 85 (57.8%) were female. According to IPI, risk categories were low (n=41, 28.1%), low-intermediate (n=43, 29.5%), high-intermediate (n=37, 25.3%) and high (n=25, 17.1%). Using R-IPI, risk categories were very good (n=19, 13%), good (n=65, 44.5%) and poor (n=62, 42.5%). According to NCCN-IPI, risk categories were low (n=12, 8.2%), low-intermediate (n=52, 35.6%), high-intermediate (n=62, 42.5%) and high (n=20, 13.7%). At 30 months (median follow up 17.7 months - range 0.6-58.2 months) the overall survival (OS) was 75.5%. The progression-free survival (PFS) at a median follow-up of 16.3 months (range 0.6-52.4) was 68.3% for all patients. Using IPI, the OS at 30 months did not differ between low and low-intermediate risk patients (96.8% vs. 82.2%; p=0.136); however, it was higher than the OS of high-intermediate risk (n=37; 96.8% vs 74.1% p=0.11) and high-risk (n=25; 96.8% vs 41% p < 0.001) patients (Figure 1). The NCCN-IPI demonstrated significant differences in OS (p < 0,001) and PFS (p<0.001) among low-intermediate, high-intermediate, and high risk groups, with the high-risk group exhibiting worse OS (32.1% in 30 months) (Figure 2). According to IPI, the OS in high-risk patients was 41%. Figure 1: OS and PFS according to International Prognostic Index (IPI) Figure 1:. OS and PFS according to International Prognostic Index (IPI) Figure 2: OS and PFS according to NCCN-IPI Figure 2:. OS and PFS according to NCCN-IPI Figure 3 Figure 3. Conclusion: In our study the NCCN-IPI, but not the IPI or R-IPI was able to discriminate a high-risk group of DLBCL patients treated with R-CHOP with worse OS. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2658-2658 ◽  
Author(s):  
Branimir Spassov ◽  
Donka Vassileva ◽  
Georgi Michaylov ◽  
Gueorgui Balatzenko ◽  
Margarita Guenova
Keyword(s):  
Risk Group ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Prognostic Information ◽  
Poor Risk ◽  
Risk Patients ◽  
Good Risk

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.

The Follicular Lymphoma International Prognostic Index (FLIPI) Predicts Treatment Outcome in Patients with Advanced Stage Follicular Lymphoma Treated Front-Line with Rituximab and the Combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 925-925 ◽  
Author(s):  
Christian Buske ◽  
Eva Hoster ◽  
Martin Dreyling ◽  
Joerg Hasford ◽  
Michael Unterhalt ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Relative Risk ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Intermediate Risk ◽  
Advanced Stage ◽  
Front Line

Abstract Background: The Follicular Lymphoma International Prognostic Index (FLIPI) has been developed to predict prognosis and to allow risk adapted treatment decisions in patients with follicular lymphoma (FL) before the widely use of Rituximab. However, the addition of Rituximab to standard induction chemotherapy with its long-term beneficial effects has profoundly changed the treatment outcome in patients with advanced stage FL and has become the new standard in the first line therapy of this disease. Therefore, we addressed the question, whether the prognostic value of the FLIPI could be reconfirmed in patients with advanced stage FL treated initially with a rituximab/chemotherapy combination. Methods: The FLIPI index was tested in patients treated with Rituximab and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone, R-CHOP) in a prospective multicenter phase 3 trial of the GLSG using the time to treatment failure (TTF) as target parameter. Results: 362 Patients treated with R-CHOP were evaluable for TTF. Of the 338 patients evaluable for all FLIPI risk factors, 14% of patients were classified as low, 41% as intermediate and 45% as high risk. After a median follow-up time of 20 months, patients with low risk and intermediate risk FLIPI had almost identical TTF (2-years TTF 92% vs 90%, 95% C.I., 83% to 100% and 84% to 96%, respectively). In contrast, the TTF was significantly shorter in the high risk FLIPI group (2-years TTF 67%, 95% C.I., 58% to 76%) as compared to the combined low/intermediate risk FLIPI group (relative risk 3.0, 95% C.I., 1.7 to 5.1; p &lt; 0.0001). In addition, responding patients with high risk FLIPI had a significantly shorter progression free survival as compared to the low/intermediate risk group (relative risk 3.3, 95% C.I., 1.8 to 6.0; p &lt; 0.0001). When postremission treatment was taken into account, the FLIPI separated the high risk group from the low/intermediate risk group in 65 patients treated with autologous stem cell transplantation (relative risk 6.0, 95% C.I., 1.4 to 25.2) as well as in 242 patients who had received IFN-α maintenance or no postremission therapy (relative risk 3.2, 95% C.I., 1.8 to 5.8). As the FLIPI was able to separate the high from the low/intermediate risk group in patients with advanced follicular lymphoma treated initially with Rituximab and CHOP we next performed a multivariate analysis to determine the impact of the individual parameters incorporated in the FLIPI on the TTF. The serum LDH level greater than the upper normal limit (relative risk 2.6, 95% C.I., 1.5 to 4.5) and the hemoglobin level below 12 g/dl (relative risk 2.5, 95% C.I., 1.4 to 4.3) were independently associated with a shorter TTF in these patients, whereas the age and the number of nodal areas were not discriminant. Conclusion: Taken together, these data indicate that the FLIPI is a valid prognostic index for identifying high-risk patients in FL, also after front-line combined immuno-chemotherapy. The index will remain an important tool to adjust treatment decisions in individual patients according their risk profile and to design clinical trials for the different risk groups in the era of antibody-based therapy.

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

Blood ◽  
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.

Hammersmith Score Is Able to Identify Chronic Myeloid Leukemia Patients with Poor Prognosis Before Treatment with Second-Generation TKIs.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3409-3409
Author(s):  
Massimo Breccia ◽  
Roberto Latagliata ◽  
Fabio Stagno ◽  
Antonella Gozzini ◽  
Elisabetta Abruzzese ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Second Generation ◽  
Cytogenetic Response ◽  
Risk Category ◽  
Intermediate Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Poor Risk ◽  
Risk Patients ◽  
Good Risk

Abstract Abstract 3409 A score aiming at early identification of CML patients showing sensitivity to second generation TKIs was proposed by the Hammersmith group. The score was created by analizing 80 patients and was based on 3 prognostic factors: previous cytogenetic response to imatinib, Sokal risk and recurrent neutropenia during imatinib. Subsequently, the score was validated in a small series of 28 patients. Aim of our study was to confirm the validity of this score and to establish its strength on a large group of CML patients resistant to imatinib and treated with second generation TKIs. One hundred twenty-seven patients were collected from 6 different Italian hematologic centers. There were 66 males and 61 females, median age 54 years (range 25–80). Twenty-seven patients received interferon before imatinib. Thirty patients had primary resistance, whereas 97 patients received second-generation TKI after acquired resistance to imatinib. The application of Hammersmith score was possible in 118 patients with available data: 52 patients were identified as good risk, 27 patients as intermediate risk and 38 patients as poor risk. The 1-year cumulative incidence of complete cytogenetic response (CCR) was 73% in good risk patients, 40% in intermediate risk patients and 23% in poor risk patients (p=0.0001). Similarly, the cumulative incidence of major molecular response (MMR) was 52% in good risk, 28% in intermediate risk and 13% in poor risk category (p=0.001). In the evaluation of event-free survival (EFS), events were considered loss of hematologic or cytogenetic response, disease progression, death for any cause, toxicity: the estimated 2-year event-free survival (EFS) was 89% in good risk, 70% in intermediate risk and 55% in poor risk group (p=0.0001). Progression-free survival (PFS) was defined as survival without evidence of accelerated or blastic phase: the estimated 2-year PFS was 97% in good risk, 93% in intermediate risk and 87% in poor risk category (p=0.05). Kaplan Meier estimated 2-year overall survival (OS) was 100% in the good risk, 93% in the intermediate risk and 82% in the poor risk category (p=0.001). In conclusion, as suggested by Milojkovic et al, some prognostic factors before starting second generation TKIs might predict cytogenetic response and outcome. As far as we known, the so-called Hammersmith score was not yet validated in large series of patients: we demonstrated that this score was able to discriminate patients at high risk of failure and consequent progression before treatment with second generation TKIs. Disclosures: No relevant conflicts of interest to declare.

Cause of death in patients with newly diagnosed chronic lymphocytic leukemia (CLL) stratified by the CLL-International Prognostic Index (CLL-IPI).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8026-8026
Author(s):  
Yucai Wang ◽  
Sara J Achenbach ◽  
Kari G. Rabe ◽  
Tait D. Shanafelt ◽  
Timothy Call ◽  
...  
Keyword(s):  
High Risk ◽  
Cause Of Death ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Second Malignancies ◽  
Very High

8026 Background: CLL progression and CLL-related complications (infections and second malignancies) were the leading cause of death (COD) in a prospective cohort of CLL patients (Strati, BJH 2017). The CLL-IPI integrates major clinical and molecular prognostic factors and stratifies patients into 4 risk groups with distinct prognosis. It is unknown if COD differs according to CLL-IPI risk group in patients with newly diagnosed CLL. Methods: Patients diagnosed with CLL between 1/2000-12/2019 and seen within 1 year of diagnosis were identified from the Mayo Clinic CLL database. Cumulative incidences of cause-specific death were analyzed using Gray’s test, with deaths from different causes treated as competing events and deaths from unknown causes excluded. Results: 1276 patients were included in this study. The median age at diagnosis was 63 years (range 24-92), and 880 (69%) were male. Based on CLL-IPI score, 449 (35%) had low risk disease, 443 (35%) had intermediate risk disease, and 384 (30%) had high/very high risk disease. Median follow-up time for the study was 6 years; 286 deaths occurred. The COD was CLL progression in 99 (35%), infection in 16 (6%), second malignancy in 47 (16%), CLL-unrelated in 59 (21%), and unknown in 65 (23%) patients. The rates of death due to CLL progression were higher (17.3% at 5 years; 30.3% at 10 years) than the rates due to CLL-related complications (5.7% at 5 years; 12.9% at 10 years) or due to CLL-unrelated causes (8.6% at 5 years; 16.9% at 10 years) in the CLL-IPI high/very high risk group, but not the CLL-IPI low or intermediate risk group (Table). A higher CLL-IPI risk group was associated with a higher rate of death due to CLL progression ( P < 0.001), as well as a higher rate of death due to CLL-related complications ( P = 0.013), and CLL-unrelated causes ( P < 0.001). Conclusions: Causes of death in newly diagnosed CLL patients differ according to their CLL-IPI risk group. In patients with high/very high risk CLL, improving CLL disease control with novel agents seems justified. In patients with low/intermediate risk CLL, there should be increased efforts to reverse immune dysfunction to reduce infections and second malignancies. [Table: see text]

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