Predicting Early Mortality in Diffuse Large B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5411-5411
Author(s):  
Jamie M Maddox
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Early Mortality ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Non Hodgkin Lymphoma ◽  
Risk Patients ◽  
Large B Cell

Abstract It is difficult to find figures for the expected rate of early mortality in diffuse large B-cell non-Hodgkin lymphoma (DLBCL) as many of the patients who are destined to die early do not enter clinical trials. Our own rate of early mortality (death within 100 days of the diagnostic test being performed) was higher than we had anticipated (23%). We undertook a study to look at risk factors for early mortality, and to see if there were any factors which could be improved by altering our investigation and initial management. Our haematology database has baseline demographic and prognostic information on all cases of haematological malignancy diagnosed in our centre. A two year period was chosen retrospectively from 1st January 2013 until 31st December 2014. This gave 97 registered patients with DLBCL. Early mortality was significantly related to the patient age, Eastern Cooperative Oncology Group (ECOG) performance status, lactase dehydrogenase value, presence of 2 or more sites of extranodal disease and the presence of B-symptoms. We did not see a significant relationship to the presence of marrow disease or the presence of disease bulk. As the majority of the relevant factors are already part of validated prognostic scoring systems, we evaluated the (International Prognostic Index) IPI, the R-IPI (revised International Prognostic Index) and the NCCN-IPI (enhanced International Prognostic Index) to see which was the best predictor of early mortality. The IPI gave the chance of 100 day mortality as 4% for low or low-intermediate risk patients, 16% for high-intermediate risk patients and 53% for high risk patients. The R-IPI gave the chance of 100 day mortality as 0% for low risk patients, 5% for intermediate risk patients and 48% for high risk patients. The NCCN-IPI gave the chance of 100 day mortality as 0% for low or low-intermediate risk patients, 13% for high-intermediate risk patients and 57% for high risk patients (figure 1). By six months, the mortality rate in high risk NCCN-IPI patients had reached 71% while the low and low-intermediate groups remained at 0%. Some patients were included who were not considered for potentially curative chemotherapy. Even with these patients excluded, the risk of 100 day mortality was still 50% in the high risk NCCN-IPI group. Some of the risk factors for mortality will likely worsen if the diagnosis or initial treatment are delayed. We therefore looked at the overall pathway from referral until first treatment. We found that those with early mortality tended to have a shorter time course until receiving their first treatment, likely reflecting the fact that they were more unwell when they first presented. Disclosures Maddox: Janssen: Other: Funding to attend ASH 2016 (travel, accommodation, registration); Boehringer-Ingelheim: Other: Funding to attend ASH 2014 (travel, accommodation, registration).

The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1504-1508 ◽  
Author(s):  
Christian Buske ◽  
Eva Hoster ◽  
Martin Dreyling ◽  
Joerg Hasford ◽  
Michael Unterhalt ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Intermediate Risk ◽  
Advanced Stage ◽  
Front Line ◽  
High Risk Patients ◽  
Risk Patients

The Follicular Lymphoma International Prognostic Index (FLIPI) was developed to predict prognosis of patients with follicular lymphoma (FL). However, it was based on different protocols, none of which included rituximab. The current analysis aimed at evaluating the predictive value of the FLIPI for treatment outcome in 362 patients with advanced-stage FL treated front-line with rituximab/CHOP in a prospective trial of the German Low Grade Lymphoma Study Group. According to the FLIPI, 14% of the patients were classified as low-risk, 41% as intermediate-risk, and 45% as high-risk patients. With a 2-year time to treatment failure (TTF) of 67%, high-risk patients had a significantly shorter TTF as compared with low- or intermediate-risk patients (2-year TTF of 92% and 90%, respectively; P < .001). Our data demonstrate that the FLIPI is able to identify high-risk patients with advanced-stage FL after first-line treatment with rituximab/chemotherapy.

scholarly journals Follicular lymphoma: are we ready for a risk-adapted approach?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 358-364 ◽  
Author(s):  
Brad S. Kahl
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Randomized Clinical Trials ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Predictive Biomarkers ◽  
Western Hemisphere ◽  
Ongoing Research ◽  
High Risk Patients ◽  
Risk Patients

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.

Age-adjusted International Prognostic Index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 1989-1996 ◽  
Author(s):  
Paul A. Hamlin ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Jing Qin ◽  
Jaya M. Satagopan ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intermediate Risk ◽  
Second Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Second-line chemotherapy followed by high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) cures less than half of the patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Prognostic models capable of predicting outcome are essential. In 3 sequential clinical trials, conducted from January 1993 to August 2000, we treated 150 patients with relapsed or primary refractory DLBCL with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy followed by HDT/ASCT for patients with chemosensitive disease. We evaluated the age-adjusted International Prognostic Index at the initiation of second-line therapy (sAAIPI) as a predictor of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 4 years, the PFS and OS are 28% and 34% by intention to treat and 39% and 45% for only those patients with chemosensitive disease. Three risk groups with different PFS and OS were identified by the sAAIPI: low risk (0 factors), 70% and 74%; intermediate risk (1 factor), 39% and 49%; and high risk (2 or 3 factors), 16% and 18% (P &lt; .001 for both PFS and OS). The sAAIPI also predicts the PFS and OS for patients with ICEchemosensitive disease: low risk, 69% and 83%; intermediate risk, 46% and 55%; and high risk, 25% and 26% (P &lt; .001 PFS and OS). The sAAIPI predicts outcome for patients with relapsed or primary refractory DLBCL in both intent-to-treat and chemosensitive populations. This powerful prognostic instrument should be used to evaluate new treatment approaches and to compare results of different regimens.

scholarly journals A risk model for relapsed/refractory aggressive NHL integrating clinical risk factors and pretransplant Deauville score

2020 ◽  
Vol 4 (22) ◽  
pp. 5762-5771
Author(s):  
Ho-Young Yhim ◽  
Yael Eshet ◽  
Ur Metser ◽  
Chae-Hong Lim ◽  
Katherine Lajkosz ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Salvage Chemotherapy ◽  
Low Risk ◽  
Clinical Risk Factors ◽  
Intermediate Risk ◽  
Clinical Risk ◽  
Deauville Score

Abstract There are limited data regarding the combined value of the pretransplant Deauville score (DS) from a positron emission tomography scan and clinical risk factors in patients with relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). We performed a retrospective analysis to assess the prognostic role of pretransplant DS in patients with relapsed/refractory aggressive NHL who underwent salvage chemotherapy and autologous stem cell transplantation (ASCT). We identified 174 eligible patients between January 2013 and March 2019. In multivariable analysis, pretransplant DS, B symptoms, and secondary International Prognostic Index (sIPI) were independent risk factors for event-free survival (EFS). These variables were used to derive an integrated risk score that categorized 166 patients with available information for all risk factors into 3 groups: low (n = 92; 55.4%), intermediate (n = 48; 28.9%), and high (n = 26; 15.7%). The new prognostic index showed a strong association with EFS (low-risk vs intermediate-risk hazard ratio [HR], 3.94; 95% confidence interval [CI], 2.16-7.17; P &lt; .001; low-risk vs high-risk HR, 10.83; 95% CI, 5.81-20.19; P &lt; .001) and outperformed models based on clinical risk factors or DS alone. These results were validated in 60 patients from an independent external cohort (low-risk vs intermediate-risk HR, 4.04; 95% CI, 1.51-10.82; P = .005; low-risk vs high-risk HR, 10.49; 95% CI, 4.11-26.73; P &lt; .001). We propose and validate a new prognostic index that risk-stratifies patients undergoing salvage chemotherapy followed by ASCT, thereby identifying patients at high risk for posttransplant treatment failure.

Randomized, phase III study of early intervention with venetoclax and obinutuzumab versus delayed therapy with venetoclax and obinutuzumab in newly diagnosed asymptomatic high-risk patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): EVOLVE CLL/SLL study (SWOG S1925, NCT#04269902).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7567-TPS7567
Author(s):  
Deborah Marie Stephens ◽  
Anna Moseley ◽  
Brian T. Hill ◽  
John M. Pagel ◽  
Mazyar Shadman ◽  
...  
Keyword(s):  
Early Intervention ◽  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Free Survival ◽  
High Risk Patients ◽  
Asymptomatic Patients ◽  
Risk Patients

TPS7567 Background: Currently, asymptomatic patients with CLL/SLL are observed without treatment until development of symptoms or cytopenias. Historically, early intervention studies with chemoimmunotherapy have not resulted in an overall survival (OS) benefit and have resulted in toxicity. The introduction of targeted therapies, such as venetoclax and obinutuzumab (VO), have provided tolerable/efficacious options for CLL patients. In the CLL14 study, symptomatic CLL patients receiving frontline therapy with VO had longer progression-free survival (PFS) and deeper remissions [more minimal residual disease-undetectable (MRDu)] compared with those receiving chlorambucil and obinutuzumab (Fischer 2019). The CLL-International Prognostic Index (CLL-IPI; Table) is a validated prognostic model to predict which patients are highest risk for a shorter time to first therapy and shorter OS. We aim to use VO as early intervention in asymptomatic, high-risk patients with CLL to potentially lengthen OS and thus alter the natural history of the disease. Methods: On 12/14/20, we activated the S1925 study for adult patients with CLL or SLL, who were diagnosed within 12 months of enrollment. Eligible patients have a CLL-IPI score ≥ 4 (Table) or complex cytogenetics (≥3 cytogenetic abnormalities) and do not meet any criteria for initiation of treatment by the International Working Group for CLL (IWCLL; Hallek 2018) guidelines. Enrolled patients are randomized in a 2:1 manner to early versus delayed (at the time IWCLL indication for treatment is met) therapy with VO. VO is administered for a fixed duration of 12 months as previously described (Fischer 2019). The primary endpoint is OS. We hypothesize that early intervention with VO will improve the rate of 6-year OS from 60% to 80%. This design requires 222 eligible patients for 88% power (2-sided α=0.05) for the primary comparison. To allow for 10% ineligibility, we will enroll 247 patients. Estimated accrual time is 4 years. Secondary endpoints include: rates of response, PFS, and relapse-free survival; safety; time to 2nd CLL-directed therapy; and quality of life (FACT-Leukemia total score). The primary translational objective is to evaluate the prognostic association between OS and peripheral blood MRD status at 15 months after treatment initiation by flow cytometry. Additional exploratory objectives include the association of other clinical outcomes, baseline prognostic factors, and IWCLL-defined response with MRD status at multiple timepoints. Currently, enrollment is open. Clinical trial information: NCT04269902. [Table: see text]

scholarly journals A Novel Prognostic Index for Sporadic Burkitt Lymphoma in Adult Patients: A Real-Word Multicenter Study

2021 ◽  
Author(s):  
Mei-ting Chen ◽  
Fei Pan ◽  
Wei Zhang ◽  
Hui-juan Lv ◽  
Yong-chang Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Survival Rate ◽  
High Risk ◽  
Burkitt Lymphoma ◽  
Prognostic Model ◽  
Prognostic Index ◽  
Adult Patients ◽  
Inflammatory Biomarkers ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. Methods: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n=229) and validation cohort (n=107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models.Results and Conclusions: Univariate and multivariate analyses revealed that platelets<254×109/L, albumin<40g/L, lactate dehydrogenase≥334U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1%, 72.4%, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell’s concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

scholarly journals A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Mei-ting Chen ◽  
Fei Pan ◽  
Yung-chang Chen ◽  
Wei Zhang ◽  
Hui-juan Lv ◽  
...  
Keyword(s):  
Risk Factors ◽  
Survival Rate ◽  
High Risk ◽  
Burkitt Lymphoma ◽  
Prognostic Model ◽  
Prognostic Index ◽  
Adult Patients ◽  
Inflammatory Biomarkers ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL. Methods We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm. Results and conclusions Univariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell’s concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON)

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2759-2766 ◽  
Author(s):  
Leo F. Verdonck ◽  
Annelise Notenboom ◽  
Daphne D. de Jong ◽  
Marius A. MacKenzie ◽  
Gregor E. G. Verhoef ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Optimal Dose ◽  
Intermediate Risk ◽  
Free Survival ◽  
Younger Patients ◽  
Non Hodgkin Lymphoma ◽  
Risk Patients

Abstract Optimal dose and timing of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for aggressive non-Hodgkin lymphoma (NHL) is still an unresolved issue. We assessed whether dose intensifications with cyclophosphamide and doxorubicin might improve outcome in younger patients with intermediate-risk aggressive NHL. Previously untreated patients were assigned to receive either 8 courses of standard CHOP (n = 239) or 6 courses of intensified (I)–CHOP (n = 238). Although there was a tendency in favor of I-CHOP for overall survival (OS), disease-free survival (DFS), and event-free survival (EFS), the differences were not significant. However, although these analyses were not planned, when the intermediate-risk group was divided into low-intermediate- and high-intermediate-risk patients according to the International Prognostic Index (IPI), low-intermediate-risk patients had improved 6-year OS (67% vs 52%; P = .05), DFS (58% vs 45%; P = .06), and EFS (41% vs 30%; P = .21) when they were treated with I-CHOP compared with standard CHOP. On the other hand, high-intermediate-risk patients seem to have no benefit from I-CHOP. Although clinically relevant side effects occurred more often in the I-CHOP arm, treatment-related mortality was similar. These data suggest that I-CHOP might be preferable to standard CHOP in younger patients with low-intermediate-risk aggressive NHL.

Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma

Blood ◽  
2002 ◽  
Vol 99 (4) ◽  
pp. 1136-1143 ◽  
Author(s):  
Sharon L. Barrans ◽  
Ian Carter ◽  
Roger G. Owen ◽  
Faith E. Davies ◽  
Russell D. Patmore ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Large B Cell

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P &lt; .0001) and bcl-2 (R = 0.14, P = .0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = −0.025, P = .02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2− group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.

Sign in / Sign up

Export Citation Format

Share Document