scholarly journals Validation of FLIPI1, FLIPI2, PRIMA and POD24 in Patients with Extranodal Follicular Lymphoma: A Cohort from Two Cancer Centers in Peru

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4505-4505
Author(s):  
Jule F Vasquez ◽  
Alonso Diaz ◽  
Any S Mendoza ◽  
Carlos Barrionuevo ◽  
Cesar Samanez-Figari
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Latin American ◽  
Nodal Involvement ◽  
Bulky Disease ◽  
Cancer Centers ◽  
Overall Response

Abstract Background Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma subtype, being nodal involvement its main characteristic. However, data about Extranodal (EN) involvement is not reported in Latin American patients. Our aim was to evaluate the clinical features, treatment patterns outcomes of Peruvian patients with ENFL from two cancer centers and validate FLIPI1, FLIPI2, PRIMA and POD-24 prognostic index in our cohort. Methods: This is a retrospective study, including all patients with a pathological diagnosis of FL grade 1 to 3A treated at the National Institute of Neoplastic Diseases and Oncosalud, both in Lima, Peru from 2010 to 2019. All cases were reviewed by specialized pathologists. Baseline clinical and pathological data were collected. Responses were assessed based on the Lugano criteria. Overall survival (OS) was estimated using the Kaplan-Meier method. Differences were compared with the log-rank test. Results A total of 86 patients were evaluated. The median age was 61 years (30-91), 43% were male, 20% had bulky disease (≥6 cm in diameter), 51% had stage III/IV disease, 31% had hemoglobin <12 g/dl, 11% had serum albumin <3 g/dl, 25% had elevated serum LDH, 31% had B2-microglobulin ≥3,5 mg/l, 27% had bone marrow involvement and 19% had lymph node sites >4. The most frequent EN sites were gastrointestinal, bone marrow, cutaneous and breast with 22%, 21% and 9%, and 6%% respectively. Low, intermediate and high-risk FLIPI1 was seen in 56%, 23% and 21% of patients, respectively. Low, intermediate and high-risk FLIPI2 was seen in 28%, 58% and 14% of patients, respectively. Low, intermediate, and high PRIMA was seen in 57%, 10% and 33%, respectively. 55 patients (64%) received any treatment, 47% received CHOP ± rituximab (R), 16% CVP ± R, 22% radiotherapy alone, 9% CHOP, 15% other treatments. Response data were available in 44 patients with complete response in 45%, partial response in 43% and no response in 12%, for an overall response rate of 88%. From patients who received CHOP/CVP ± R, 13% patients had disease progression within 24 months of first treatment initiation (POD24). For the entire cohort (N=88) the median follow-up time was 2.1 years (interquartile range [IQR] 0.08-11.3), median overall survival was 8.25 years (IQR 4.4-not reached [NR]). 5y OS was71.7% (95% CI 55.3-82.9), figure 1. For the FLIPI group 5y OS for low, intermediate and high FLIPI were 86.9% (95% CI 64.7-95.6), 60.1% (95% CI 24.4-83.2) and 75.7% (95% CI 30.4-93.7), respectively (p=0.07; Figure 2). For the FLIPI2 group (N=58) 5y OS for low, intermediate and high FLIPI2 were 79.5% (95% CI 39.3-94.5), 77% (95% CI 55.3-89.2) and 86% (95% CI 33.4-97.8), respectively (p=0.86). For the PRIMA group (N=38) 5y OS for low, intermediate and high PRIMA was 86% (95%55.6-96.6), 100% (95% CI 100), and 80% (95% CI 42-95), respectively (p=0.80). Patients who had and did not have POD24 had median OS of NR (IQR 0.6-NR) and NR (IQR 2.69-NR), respectively. 5y OS for patients who had and did not have POD24 was 71.2 % (95% CI 48-85) and 75% (12.7-96), respectively (p<0.87). Conclusion: Peruvian patients with ENFL showed a higher rate of female patients. Gastrointestinal involvement was the most common primary site. The OS rates is similar to our nodal involvement cohort. Chemoimmunotherapy is the standard approach to FL patients, which is associated with high rates of overall response. In our study FLIPI, FLIPI2, PRIMA and POD24 were not predictors for OS, but larger cohorts and longer follow-up are needed to find more accurate predictors of survival in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

scholarly journals High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2780-2786 ◽  
Author(s):  
AS Freedman ◽  
JG Gribben ◽  
D Neuberg ◽  
P Mauch ◽  
RJ Soiffer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplantation ◽  
Follicular Lymphoma ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Autologous Bone

We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT. Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest. After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months. Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR. This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow-up will be necessary to determine potential impact on overall survival.

Rituximab - Inmunotherapy Combined with Chemotherapy, CHOP for the Treatment of Patients with Difusse Large B - Cell Lymphoma (DLBCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4745-4745
Author(s):  
Jorge H. Milone ◽  
Fernando Bezares ◽  
Maria del Carmen Ardaiz ◽  
Dardo Riveros ◽  
Luis Palmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
High Risk Group ◽  
Hematologic Toxicity ◽  
Gastric Bleeding ◽  
Bulky Disease ◽  
Free Survival

Abstract Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL. We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS). Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84). They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %. Elevated LDH was present en 14 patients, bulky disease > 7 cm in 50% of cases. During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient. Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%). With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained. The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.

Cytogenetic Progression in Patients with Multiple Myeloma As Assessed By Serial Bone Marrow Biopsy Is Associated with Worse Outcome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4209-4209
Author(s):  
Catherine Randall Paschal ◽  
Jens C Eickhoff ◽  
Aric C Hall ◽  
Jennifer Laffin ◽  
Natalie Scott Callander ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
High Risk ◽  
Risk Group ◽  
Clonal Evolution ◽  
Intermediate Risk ◽  
Disease Course ◽  
Cytogenetic Abnormalities ◽  
Standard Risk

Abstract Background:Multiple Myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal, mutated plasma cells, which ultimately leads to multi-organ damage and in most cases death. Despite improved treatments, clinical heterogeneity remains, with some patients succumbing to disease within 1-2 years. Certain cytogenetic and FISH abnormalities at diagnosis confer a higher likelihood of poor outcomes (Mikhael et al., 2013). Still, the utility of repeated cytogenetic assessment over the course of disease is unknown. Methods: We performed a retrospective review to identify MM patients with cytogenetics (CG) performed at diagnosis who had two or more bone marrow (BM) examinations performed during follow up over a five year period at UW Carbone Cancer Center. We reviewed the pathology and CG results from each BM sample. CG data was categorized into risk groups using the mSMART stratification criteria: High risk - deletion 17p13, t(14;16), t(14;20); intermediate risk - t(4;14), hypodiploid, deletion 13, gain of 1q21; standard risk - hyperdiploidy and all other abnormalities, and normal CG. CG progression over disease course was categorized based on stability or change in CG risk group. We measured survival from date of diagnosis to death or last follow up. Results: 130 patients with CG at diagnosis were identified over the five year period of the study. These patients had 365 follow-up bone marrow (BM) aspirates, 341 with repeat CG study. Initial cytogenetics were as follows: 90 (69%) of 130 patients had normal CG at diagnosis, 13 (10%) standard risk CG, 16 (13%) intermediate risk CG, and 11 (8%) high risk CG. Serial CG studies showed both development of new CG abnormalities in patients with previously normal studies, and clonal evolution with CG abnormal patients acquiring additional abnormalities on repeat testing. 24 (27%) of 90 patients with normal CG at diagnosis developed abnormal CG during disease course: 12 had intermediate risk CG and 9 high risk CG, the latter all due to p53 deletion. Clonal evolution and drift among initially CG abnormal patients were also common. Of the 34 patients with abnormal CG results on diagnosis and subsequent bone marrow samples, clonal evolution was identified in 19 patients (56%) and 4 (12%) patients developed new CG abnormalities unrelated to the prior clone, while 11 (32%) showed stable CG. Despite this high rate of change, only two patients with abnormal CG at diagnosis moved from a lower to a higher cytogenetic risk group. When we correlated CG at diagnosis with survival, we found that patients with high risk CG at diagnosis appeared to have shorter median overall survival at 3.8 yrs (range 1-12 yrs) compared with 7.4 yrs (range 2-12 yrs) for intermediate risk, 8.5 yrs (range 2-9 yrs) for standard risk, and 8.2 yrs (range 1-12 yrs) for normal CG. Comparison among all four groups was not statistically significant however, possibly due to the small proportion of high risk CG patients. When we examined the effect of acquiring CG abnormalities, we found that development of abnormal CG in patients with normal CG at diagnosis was associated with shorter median OS (4.0 yrs) compared to either persistent normal CG (11.3 yrs) or any CG abnormality at diagnosis (7.4 yrs), overall comparison p = 0.0048. Conclusion: Our longitudinal study of 130 unselected patients with MM revealed a cohort who showed cytogenetic progression. In patients with normal CG at diagnosis, the presence of cytogenetic abnormalities in follow-up BM specimens was associated with inferior overall survival. This finding indicates that serial testing may facilitate the detection of a higher risk patient cohort. Further analysis is underway to identify clinical parameters that underlie a higher risk of clonal evolution or development of new cytogenetic abnormalities. The results of our study will help elucidate the optimal prognostic utility of cytogenetic analysis in patient care. Disclosures No relevant conflicts of interest to declare.

Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin's disease treated with alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy.

1990 ◽  
Vol 8 (7) ◽  
pp. 1173-1186 ◽  
Author(s):  
D J Straus ◽  
J J Gaynor ◽  
J Myers ◽  
D P Merke ◽  
J Caravelli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Prognostic Factors ◽  
High Risk ◽  
Disease Progression ◽  
Striking Difference ◽  
Dose Radiation ◽  
Intermediate Dose

The initial promising results with alternating chemotherapy regimens (mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine [MOPP/ABVD]; lomustine, melphalan, and vindesine [CAD] plus MOPP plus ABV) combined with intermediate-dose radiation therapy (RT) have been sustained with further follow-up; 82.2% of patients (152 of 185) achieved a complete remission (CR), and overall survival is 71.7% +/- 4.4% at 8 years (median follow-up is 55 months among the survivors). No statistically significant differences were found in CR percentage, CR duration, or survival between stages IIB, IIIB, and IV patients. For that reason, stepwise Cox regression analyses to identify the important prognostic factors were performed on overall survival, tumor mortality, freedom from disease progression, and survival following disease progression. Pretreatment characteristics were also tested for association with the probability of achieving CR, CR duration, and death due to other causes. Characteristics that were consistently associated with an independently unfavorable prognosis were low hematocrit, high serum lactic acid dehydrogenase (LDH), age more than 45 years, inguinal node involvement, mediastinal mass greater than .45 of the thoracic diameter, and bone marrow involvement. Patients with two or more unfavorable characteristics were much more likely to fail treatment (median survival, 62.4 months) than those with none or only one unfavorable factor (greater than 95% survival). This striking difference between the low- and high-risk groups remained even if the comparison was restricted to patients less than or equal to 45 years of age. These results provide a basis for selecting the young patients at high risk of failure for more intensive initial treatment with either autologous bone marrow rescue or hematopoietic growth factors.

scholarly journals The PRIMA-Prognostic Index (PI) Is Valid in Follicular Lymphoma (FL) Patients with Rituximab Chemo-Free First-Line Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4150-4150 ◽  
Author(s):  
Eva Kimby ◽  
Sandra Lockmer ◽  
Harald Holte ◽  
Björn E Wahlin ◽  
Hans Hagberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Risk Group ◽  
Bone Marrow Involvement ◽  
First Line ◽  
Advisory Committees

Abstract Background: Follicular lymphoma (FL) is a heterogenous disease. The optimal timing, sequence and choice of therapy remain matters of debate and there is no optimal prognostic tool. The FLIPI (Follicular Lymphoma International Prognostic Index) is based on five bio-clinical parameters and is widely used, but not as guide for choice of treatment. Recently a new prognostic score (PRIMA-PI), based solely on two parameters, bone marrow involvement and serum beta2 microglobulin (ß2m) was proposed for patients treated with immunochemotherapy (Bachy E., Blood 2018). The Nordic Lymphoma Group (NLG) performed two randomized trials including patients with symptomatic/progressive indolent CD20+ lymphoma, with rituximab monotherapy or rituximab in combination with interferon (IFN)-α2a as primary treatment, without maintenance (Kimby E., 2008, 2015). The 10 years follow-up of these patients showed a good survival with no major safety issues and no need for later chemotherapy in 38% of FL patients (Lockmer S, JCO 2018). Aim/Purpose: To evaluate two different prognostic systems (the new PRIMA-PI and the FLIPI), for overall survival (OS) and time to treatment failure (TTF) in a cohort of symptomatic/progressive FL patients treated with a rituximab-containing first-line regimen without chemotherapy. Methods: Previously untreated patients with a confirmed FL diagnosis (n=269) or indolent lymphoma not otherwise specified (n=22, most FLs with insufficient material for grading), treated in the NLG randomized trials with two cycles rituximab (375 mg/m2 x 4 weeks), with or without IFN-α2a, were classified into the three PRIMA-PI categories: high-risk: ß2m> 3mg / L, intermediate-risk: ß2m ≤ 3 mg / L with bone marrow involvement and low-risk: ß2m ≤ 3 mg / without bone marrow involvement. The FLIPI scores were also assessed. TTF, defined as the interval between randomization and either initiation of new lymphoma therapy due to relapse or intolerance, or death from any cause, as well as OS were estimated using the Kaplan Meier method. The log-rank test was used for comparison between risk groups. Results: Out of 291 patients, 252 had complete data on PRIMA-PI and FLIPI (at the time of randomization in the original trials) and were available for analyses of TTF and OS. Patient characteristics are shown in Table 1. PRIMA-PI seemed to identify a true high-risk group of 47 patients, 32 of them being high risk also according to FLIPI, while a larger patient group (n=117) was classified as FLIPI high-risk. After a long follow-up time, median 9.9 years (0.4 -18.8) from randomization, median 10.6 years for the 214 patients (74%) still alive, 76 patients (26%) were failure-free and 108 (37%) without need of any chemotherapy, Patients with PRIMA-PI high showed a shorter TTF compared to PRIMA-PI intermediate and low (Fig 1a), whereas the FLIPI risk-groups were not significantly separated (Fig 1b). Evidence of transformation to aggressive disease was seen in 55 patients, with no significant difference in frequency between the PRIMA-PI groups, nor between FLIPI groups. Both PRIMA-PI and FLIPI were of significant value for predicting OS, most evident after a long follow-up time (Fig 1c and d). In 41 patients the cause of death was progressive disease or therapy complications, regarded as lymphoma-related death, whereas 21 died of other causes. The lymphoma-specific survival was related to the PRIMA-PI (log-rank p=0.03), but not to the FLIPI (n.s). Prognosis was worse for the PRIMA-PI high-risk group than the for the low-risk, also when adjusted for sex, high age (>60 years), diagnosis, stage, ECOG and FLIPI risk-group; TTF HR 1.82 (95% CI 1.16-2.85, p=0.01) and OS HR 2.3 (95% CI 1.00-5.38, p=0.05). Conclusion: FL patients included in two NLG trials with complete clinical data and a median follow-up of >10 years after randomization have been assessed for validation of different prognostic indices. In these patients, all with chemo-free first-line therapy, the PRIMA-PI was shown a valid predictor of both TTF and OS and seemed more useful than the FLIPI. The PRIMA-PI high risk identified a group of patients (19% of all) with true poor prognosis. Disclosures Kimby: Roche: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Roche, Norway: Research Funding. Wahlin:Roche: Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Hagberg:Roche: Honoraria.

scholarly journals VEGF 2578 c>a, a Functional Angiogenic Polymorphism, Is Associated with Aggressiveness and Clinical Outcome of Follicular Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3022-3022
Author(s):  
Guilherme Rossi Assis de Mendonça ◽  
Angelo Borsarelli Carvalho Brito ◽  
Rodrigo de Andrade Natal ◽  
Marcia T Delamain ◽  
Carmino Antonio De Souza ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Small Sample ◽  
Low Risk ◽  
Bone Marrow Infiltration ◽  
Aggressive Form ◽  
Kaplan Meier ◽  
Ann Arbor

Abstract Introduction: Follicular lymphoma (FL) is the second most prevalent non-Hodgkin lymphoma worldwide, and is characterized by an indolent course and frequent relapses. Better understanding of FL has shown that angiogenesis (AG) has an important role in its progression to a more aggressive form. The most important mediator of AG is the vascular endothelial growth factor (VEGF), which is encoded by a polymorphic gene. It is already known that allele C of the VEGF 2578C/A polymorphism (rs699947) is related to higher serum concentration of VEGF compared to the A allele. The roles of this genetic polymorphism in clinical manifestations and outcome of FL are still unknown, and therefore these were the aims of the present study. Methods: Our analysis included 86 consecutive FL patients seen at diagnosis at the university hospital. The patients were treated with 6 to 8 cicles of R-CHOP. The clinical data of these patients were obtained from medical records. Genomic DNA was extracted from peripheral blood samples, and genotyping of the VEGF -2578C/A (rs699947) polymorphism was performed with real-time qPCR. Overall-survival (OS) was defined as time from diagnosis until death from any cause or last follow-up. The differences between groups were analyzed by the logistic regression model. Kaplan-Meier and log-rank analyses were used to assess survival information from the patients’ data. Furthermore, we examined survival data using univariate Cox proportional hazards regression, with the respective hazard ratios (HR) and 95% Confidence Intervals (CIs). Adjustement of Cox regression for clinical features was also performed. A p-value smaller than 0.05 was used to denote statistical significance. Results: The FL patients had a mean age of 56.2 years at diagnosis. The majority of the patients were caucasians (87.6%), and there was an equivalent distribution between genders: 43 male and 43 female patients (50% each). Thirty-nine (45.3%) patients had B-symptoms and 48 (54.7%) had no B-symptoms at diagnosis. Sixty-three (73.2%) patients presented at diagnosis with tumors of III or IV Ann Arbor stage, and 30 (34.8%) had bone marrow infiltration. Follicular Lymphoma International Prognostic Index (FLIPI) was assessed and patients were classified as follows: low-risk FLIPI (≤ 1 point) was seen in 34 cases (39.5%), medium-risk FLIPI (2 points) in 28 cases (32.5%), and high-risk FLIPI ( ≥ 3 points) was seen in 24 patients (27.9%). The VEGF 2578CC genotype was more common in patients with B-symptoms at diagnosis than in those without B-symptoms (51.2% versus 29.7%, p=0.04). The frequency of VEGF 2578CC genotype was also higher in patients with high-risk FLIPI than in those with medium and low-risk FLIPI (58.3% versus 32.2%, p=0.03). We found no association between genotypes and bone marrow infiltration at diagnosis. Considering clinical course of the patients, Kaplan Meier curves of OS showed that at 60 months of follow up, B-symptoms at diagnosis (65.2% of OS versus 87.1%, p=0.02), high-risk FLIPI (52.5% of OS versus 90%, p=0.002), and 2578CC genotype (62.1% of OS in 2578CC patients versus 89.4% in 2578CA plus 2578AA patients, p=0.01) had negative impacts on outcome. In univariate Cox analysis, presence of B-symptoms (p=0.03, HR=3.2, 95% CI: 1.09-9.38), high-risk FLIPI (p=0.01, HR= 3.91, 95% CI: 1.38-11.03) and 2578CC genotype (p=0.02, HR=3.70, 95% CI: 1.16-11.82) were also associated with a worse outcome. The prognostic role of the abovementioned polymorphism was still present after adjustment for age (p=0.04, HR=3.23, 95% CI:1.01-10.36) and Ann Arbor stage (p=0.02, HR=3.58, 95% CI:1.1-11.6) in univariate regression. After adjustment for FLIPI status as a whole, only a trend of association of 2578CC genotype with a worse outcome was found in the study (p=0.05, HR=3.24, 95% CI: 0.95-13.05). Conclusion: Our results present, for the first time, preliminary evidence that FL patients with the VEGF 2578CC genotype, related to higher production of VEGF, are more likely to develop aggressive form of the disease at diagnosis, and to succumb earlier to death. We recognize, however, that our study is based on a small sample size and that more numerous cohorts should be analyzed in order to assess additional associations. Also, further studies, such as correlations between relevant AG genes and tumor vascularization, should be done in order to clarify this issue in the context of FL. Disclosures No relevant conflicts of interest to declare.

Long-Term Follow-Up of Autologous Bone Marrow Transplantation in Patients With Relapsed Follicular Lymphoma

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3325-3333 ◽  
Author(s):  
Arnold S. Freedman ◽  
Donna Neuberg ◽  
Peter Mauch ◽  
Robert J. Soiffer ◽  
Kenneth C. Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplantation ◽  
Complete Remission ◽  
Follicular Lymphoma ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Autologous Bone

We report the results of high-dose chemoradiotherapy and anti–B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) in patients with relapsed indolent follicular lymphoma. Between March 1985 and May 1995, 153 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total body irradiation and bone marrow (BM) purging. All patients received multiple chemotherapy regimens before ABMT. At BM harvest, only 30% of patients were in complete remission, and overt BM infiltration was present in 47%. The disease-free survival (DFS) and overall survival (OS) are estimated to be 42% and 66% at 8 years, respectively. Patients whose BM was negative by polymerase chain reaction (PCR) for bcl2/IgH rearrangement after purging experienced longer freedom from recurrence than those whose BM remained PCR positive (P < .0001). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued complete remission (CR). The 12-year survival from diagnosis for these 153 patients is 69%. Considering that the median survival from diagnosis and first recurrence of patients with advanced follicular lymphoma are 8 and 5 years, respectively, our results provide evidence that myeloablative therapy and ABMT may prolong overall survival.

Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4004-4013 ◽  
Author(s):  
Marco Ladetto ◽  
Federica De Marco ◽  
Fabio Benedetti ◽  
Umberto Vitolo ◽  
Caterina Patti ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Disease Control ◽  
High Dose ◽  
Event Free Survival ◽  
Outcome Predictor ◽  
Free Survival ◽  
Intention To Treat

Abstract In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS–like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.

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