scholarly journals Retrospective Analysis of Prognostic Factors for Waldenström Macroglobulinemia: A Multicenter Cooperative Study in Japan

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5028-5028
Author(s):  
Akio Saito ◽  
Atsushi Isoda ◽  
Akihiko Yokohama ◽  
Hiroshi Handa ◽  
Norifumi Tsukamoto ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Pleural Effusion ◽  
Initial Treatment ◽  
Response Rate ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Japanese Patients ◽  
Western Countries ◽  
Significant Difference

Abstract Background: Analysis of prognostic factors and clinical trials of novel agents for Waldenstrӧm macroglobulinemia (WM) are ongoing in Western countries, but few studies of WM have been performed in Japan. As a step toward future investigations, we retrospectively analyzed clinical features and prognostic factors in Japanese patients with WM. Methods: We retrospectively analyzed clinical and laboratory characteristics, treatment and outcomes of 110 patients with WM, IgM-MGUS or lymphoplasmacytic lymphoma (LPL) diagnosed from January 2001 to March 2013 at 12 institutes. Overall survival (OS) was analyzed using Kaplan-Meier methods and survival was compared using log-rank testing. Several clinical characteristics at diagnosis were assessed by Cox regression for uni- and multivariate analysis for OS. Results: Median age at diagnosis was 69 (range, 41-96) years, 73.6% were male, 12.0% had an ECOG performance status 2-4 and 6.4% presented with B-symptoms. Hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia and cold agglutinin disease were shown in 9.1%, 4.5%, 1.8%, 4.5% and 2.7%, respectively. In 94 patients with available CT findings at diagnosis, lymphadenopathy, hepatosplenomegaly, pleural effusion, lung involvement, bone involvement and skin involvement were shown in 41.5%, 14.9%, 8.5%, 4.3%, 4.3% and 6.4%, respectively. Median serum monoclonal protein level was 2.62 g/dl (range, 0.70-9.35 g/dl). Symptomatic WM was present in 76 patients, asymptomatic WM in 23 and IgM-MGUS in 2 according to criteria of the Second International Workshop on WM. Seven patients showed IgG- or IgA-secreting LPL and 2 showed LPL without bone marrow infiltration. In patients with symptomatic WM, international prognostic scoring system for WM (ISSWM) was low in 9.2%, intermediate in 34.2%, high in 39.5% and unknown in 17.1%. Among patients with asymptomatic and symptomatic WM, watchful waiting was performed in 91.3% and 40.0%, respectively, with 61.9% and 36.7% remaining untreated, respectively. Median time to treatment from diagnosis of asymptomatic or symptomatic WM was 240 days (range, 3-1238 days) and 31 days (range, 0-2011 days), respectively. Oral alkylating agents were administered to 34.7% of patients with WM, 19.4% were treated with CHOP or CHOP-like regimen with or without rituximab, 8.2% received fludarabine mono- or combination therapy and 6.1% received rituximab monotherapy. Rituximab-containing therapy was administered as the initial treatment in 33.8% of patients who received treatment. Overall response rate (ORR) (complete + partial response rate) was 48.6%, and patients treated with rituximab-containing therapy displayed higher ORR (64.0%) compared to those with non-rituximab therapy (40.8%). Plasmapheresis was performed in 3.7% of patients. Three patients (2.7%) showed transformation to diffuse large B-cell lymphoma, and 7 (6.4%) developed second primary malignancies. Median follow-up was 38 months, 5-year OS rate for all patients was 74.9% (95% confidence interval (CI) 62.5-83.7) and rates for those with symptomatic WM, asymptomatic WM and other LPL were 66.0% (95%CI 50.6-77.6), 100% and 88.9% (95%CI 43.3-98.4), respectively. Significant differences in survival between risk groups of ISSWM in patients with symptomatic WM were not seen (5-year OS: high, 62.4%; intermediate, 64.3%; low, 75.0%; p=0.86). Although no significant difference in OS was observed compared to initial treatment (p=0.265), patients treated with rituximab during the observation period showed significantly prolonged OS compared to those treated without rituximab (5-year OS rates: 78.9% vs. 45.6%, p=0.036). In univariate analysis, age, pleural effusion, serum albumin, C-reactive protein and serum IgM levels were poor prognostic factors for OS. In multivariate analysis, age >65 years (hazard ratio (HR)=3.294; 95%CI 1.097-9.888, p=0.0336) and pleural effusion (HR=4.55; 95%CI 1.602-12.930, p=0.0045) were identified as significant prognostic factors for OS. Conclusion: Prognostic factors for WM in Western countries may not be applicable to Japanese patients. This study suggested presence of pleural effusion at diagnosis is associated with poor clinical outcomes. Further investigations including histopathological examinations and molecular analyses are required to elucidate prognostic factors in Japan. Disclosures No relevant conflicts of interest to declare.

ABCA3 Expression Predicts Response to Gemtuzumab Ozogamicin in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3946-3946 ◽  
Author(s):  
Antony Ceraulo ◽  
Aminetou Mint-Mohamed ◽  
Delphine Maucort-Boulch ◽  
Etienne Paubelle ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Relapse Rate ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Gemtuzumab Ozogamicin ◽  
Small Sample ◽  
Control Group ◽  
Prognostic Impact ◽  
Significant Difference

Abstract Background. The ATP binding cassette transporter 3 (ABCA3) has been recently found to induce a significant reduction in cytotoxicity following exposure to anthracyclines, mitoxantrone, etoposide, Ara-C, vincristine, and rituximab. ABCA3 acts through the modulation of multivesicular bodies (MVB) and contributes to drug sequestration in late endosomal organelles, i.e. MVB and lysosomes. Studies having investigated the prognostic impact of ABCA3 expression in AML have yielded conflicting results as ABCA3 expression has both been reported to exert unfavorable or neutral effects on patient outcomes. In addition, the small sample size of these studies precluded the use of multivariate analyses. Methods. Our goal was to investigate the prognostic impact of ABCA3 expression in adult patients with AML treated with IC with or without gemtuzumab ozogamicin (GO). To this end we investigated the relationship between ABCA3 expression and EFS in a representative series of 221 AML homogeneously treated in the ALFA-0701 trial. qRTPCR amplification of conserved ABCA3 mRNA sequences, as identified with FasterDB database, was performed with GUS and ABL as reference genes. Primer sets were complementary to conserved ABCA3 exons 6-7 and exon 19-20 junctions. Patients were given a 3+7 induction course without (control group, n=110) or with fractionated intravenous GO (n=111) (Castaigne S, Lancet 2012; 379:1508-1516). Results. Among the 278 randomized patients, 221 had available bone-marrow diagnostic samples with high-quality RNA. The same benefits associated with GO were observed in the 221 patients from the present study as in the entire trial population. Overall, median age, CR rate, relapse rate, median follow-up, 3-years EFS were 62.1 years, 76.5%, 66%, 47.45 months, 28±3%, respectively. There was no significant difference in the level of ABCA3 expression between responders and non-responders. In the 169 responders, ABCA3 expression at diagnosis was more than 3-fold higher in the 111 remitters who subsequently relapsed than in the 58 patients who remained in persistent CR (p=0.033). The level of ABCA3 expression was significantly lower in ELN favorable group than in intermediate and adverse risk AML (p= 0.004) and negatively correlated with CD33 expression (R=-0.272, p<10-4). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±3 vs 45±7 % p=0.002). Multivariate analysis identified age, treatment arm, and ELN risk group as independent prognostic factors for EFS. In the control group, there was no significant association between ABCA3 expression and CR rate, relapse rate, and EFS. In the 111 patients within the GO arm, there was no significant difference in the level of ABCA3 expression between responders and non-responder whereas in the 89 responders, ABCA3 expression at diagnosis was more than 7-fold higher in the 53 remitters who subsequently relapsed than in the 36 patients who remained in persistent CR (p=0.006). Through univariate analysis, higher ABCA3 expression was associated with shorter EFS (3-years: 22±5 vs 64±9 % p=0.0002). Multivariate analysis identified ABCA3 expression, cytogenetics, CD33 expression, and ECOG as independent prognostic factors for EFS (Figure 1). Conclusion. WhileABCB1 has been previously found to attenuate GO-induced cytotoxicity in AML cells (Walter RB, Blood 2003; 102:1466-1473), present results indicate that higher ABCA3 expression independently predicts poor outcome in AML patients treated with fractionated GO and intensive chemotherapy (IC). GO is an anti-CD33 antibody carrying a toxic calicheamicin derivative that, after hydrolytic release within lysosomal vesicles, induces DNA strand breaks, apoptosis, and cell death. Whether the clinical effect of ABCA3 expression relies on the modulation of CD33 internalization, calicheamicin release or combination thereof is under investigation. Finally our results encourage inhibiting ABCA3, such as with indomethacin, in order to overcome drug resistance in AML treated with GO-IC. Figure 1 Figure 1. Disclosures Thomas: Pfizer: Consultancy.

Prevalence and Prognostic Factors of EBV-Positive DLBCL of the Elderly In Peru

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4166-4166
Author(s):  
Brady Beltran ◽  
Domingo Morales ◽  
Pilar Quinones ◽  
Aly Gallo ◽  
Marco Lopez-Ilasaca ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Survival Analysis ◽  
Prognostic Factors ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Female Ratio ◽  
Immunohistochemical Profile

Abstract Abstract 4166 Background: EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is an entity recently described and included in the WHO classification of lymphomas. It usually affects patients older than 50 years with poor responses to chemotherapy and short survival. However, the majority of the cases are from Asian origin. In fact, in Western countries the incidence of EBV in patients with DLBCL is reported as <5%. The primary objective of this study is to establish the prevalence of EBV in patients with DLBCL and identify prognostic factors in these patients. Patients and methods: We investigated the EBV status by detection of EBV-encoded RNA (EBER) using a chromogenic in situ hybridization (CISH) technique in newly diagnosed patients with primarily nodal DLBCL, identified between January 2002 and December 2009. Clinical data were reviewed retrospectively and biopsies were analyzed for the presence of EBER by CISH and the immunohistochemical expression of BCL6, CD10 and MUM-1/IRF4 using standard procedures. Chi-square was used to compare the characteristics between EBER-positive and EBER-negative cases and to evaluate the association between complete response (CR) to chemotherapy and other clinical variables. Univariate survival estimates in patients who received chemotherapy were obtained using the Kaplan-Meier method. The multivariate survival analysis was performed using the Cox proportional-hazard regression test. Results: A total of 134 consecutive patients were eligible and were included in the comparative clinical analysis. In this cohort, the median age was 71 years (range 23–84) with a male-to-female ratio of 1.1 (71 male and 65 female cases) and a median overall survival (OS) of 47 months. 75% of the cases were 60 years or older, 62% had advanced clinical stage (III or IV), 63% has elevated LDH levels, 13% had involvement of 2 or more extranodal sites, 48% had an ECOG performance status of 2 or higher and 71% had a non-germinal center (NGC) immunohistochemical profile. Nineteen patients were positive for EBER but only 17 patients were included in the analysis because 2 patients were older than 50 years. When comparing EBER-positive and EBER-negative cases, there was an association between EBER expression and a worse outcome (p=0.003). EBER expression was not associated with gender, age, performance status, LDH levels, clinical stage, number of extranodal sites, B symptoms, immunohistochemical profile, overall response rate (ORR), CR rate, exposure to chemotherapy or IPI score. The only factors associated with CR were IPI score (p=0.047) and B symptoms (p=0.0004). Ninety nine patients received chemotherapy and were included in our survival analysis. In the univariate analysis, age over 60, performance status, LDH levels, number of extranodal sites, clinical stage, immunohistochemical profile and EBER expression were associated with OS. EBER-positive patients had a median OS of 12 months vs. 47 months in EBER-negative patients (p=0.045; Figure). In the multivariate analysis, performance status, LDH levels and EBER expression were independent factors for OS (p=0.02, 0.01 and 0.006, respectively). When evaluating EBER expression against the IPI score, both were independent prognostic factors for OS (p=0.002 and 0.03, respectively). Conclusions: The prevalence of EBV-positive DLBCL of the elderly in Peru is the highest reported in the world (13%). DLBCL patients expressing EBER had a worse outcome in comparison to EBER-negative DLBCL patients. In the multivariate analysis, EBER expression in the tumoral cells was an independent prognostic factor for OS along with the IPI score. Disclosures: No relevant conflicts of interest to declare.

What Is the Appropriate Dose Attenuation System of RCHOP for Elderly DLBCL Patients? - A Single Institutional Analysis in 115 Cosecutive Patients From Japan -

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3639-3639
Author(s):  
Akira Tanimura ◽  
Risen Hirai ◽  
Atsushi Sato ◽  
Miki Nakamura ◽  
Masataka Takeshita ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Elderly Patients ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Age Related

Abstract Abstract 3639 Background: The combination therapy of RCHOP [rituximab (R), cyclophosphamide (CY), doxorubicin (DOX), vincristine (VCR), and prednisone (PSL)] is a standardized treatment for diffuse large B-cell lymphoma (DLBCL). However, its clinical outcome is worse in elderly patients because of comorbidities, age-related decrease in organ function, and impaired drug metabolism. If possible, the dose of RCHOP in elderly patients and patients with comorbidities should be adjusted appropriately. Since 2005, we have used a unified dose attenuation system for RCHOP according to the age and comorbidities of patients. This study retrospectively verified this system. Patients/Methods: We analyzed 115 consecutive DLBCL patients treated at our institute from September 2001, when rituximab was approved in Japan, to December 2010. From September 2001 to August 2005, 33 patients received dose adjustment of RCHOP according to the physician's discretion (PHY group). From September 2005, 82 patients received RCHOP according to the unified dose attenuation system (UNI group). In the UNI group, patients younger than 60 years received the standard RCHOP dose [R, 375 mg/m2; CY, 750 mg/m2; DOX, 50 mg/m2; VCR, 1.4 mg/m2 (max 2.0 mg/body); PSL, 100 mg/m2]. In patients older than 60 years, the doses of CY, DOX, VCR, PSL, and R were attenuated as shown in Table 1. In addition to age, the doses of CY, DOX, and VCR were adjusted according to organ functions (Table 2). The two groups were compared statistically. Results: The median age of patients was 70 years (range, 38–91), with 70.4% of patients classified as stage III or IV DLBCL, 40.4% with an international prognostic index (IPI) score of 0–2, and 70.2% with a ECOG performance status (PS) of 0 or 1. Low serum albumin levels (under normal range) were observed in 50.5% patients, and a high Charlson comorbidity index (CCI) score of >1 was found in 58.3%. The characteristics of the patients in the two groups were almost similar. The UNI system was completed in 94% of patients. The complete response (CR) rate was 63% in all patients (UNI group, 73%; PHY group, 39%; P = 0.0006). Univariate analysis revealed that better prognostic factors for CR were a low IPI score, better PS, and the UNI group. In the multivariate analysis, only the UNI group was a significantly better prognostic factor for CR. With a median follow-up of 26 months, the 5-year event-free survival (EFS) and overall survival (OS) were 39.3% and 68% in all patients, 43% and 72% in the UNI group, and 27% and 59% (5-year EFS; P = 0.0083, 5-year OS; P = 0.16) in the PHY group, respectively. Multivariate analysis showed that better prognostic factors for EFS were a low IPI score, a low CCI score, and the UNI group, and that for OS were low IPI and low CCI scores. In elderly patients aged >70 years (N = 59), the CR rates were 81% and 13% in the UNI and PHY groups, respectively (P = 0.0004), with OS in the UNI group being longer than that in the PHY group (72% vs. 59%; P = 0.02; Fig.1). In the UNI group, patient age did not affect the CR rate (<70, 71% vs. 70–79, 83% vs. >79, 79%; P = 0.56) or 5-year OS (<70, 76% vs. 70–79, 70% vs. >79, 66%; P = 0.58). The actual dose of CY, DOX, and VCR compared with the standard RCHOP dose was 64% and 26%, 63% and 16%, and 63% and 21% in the UNI and PHY groups, respectively. Disease progression during treatment, discontinuation of therapy, and death during treatment were observed in 10% and 15%, 5% and 24%, and 5% and 3% in the UNI and PHY groups, respectively. Nineteen patients (23%) from the UNI group died over a median follow-up of 15 months, while 15 patients (45%) of the PHY group died over a median follow-up period of 29 months. Lymphoma-related deaths were 12 (14%) in the UNI group and 8 (24%) in the PHY group. Five secondary primary malignancies (SPM) were observed (1 colon cancer and 1 breast cancer in the PHY group, and 1 lung cancer and 2 myelodysplastic syndrome in the UNI group). Four deaths were related to SPM. Conclusion: The unified dose attenuation system determined by the patients' age and comorbidities may achieve an effective dose level and better prognosis in elderly DLBCL patients. Disclosures: No relevant conflicts of interest to declare.

Prognostic Factors Of Response and Survival To Azacitidine (AZA) +/- EPO In RBC Transfusion Dependent (TD) IPSS Low and Int-1 (LR) MDS Resistant To EPO, With Particular Emphasis Of Genetic Lesions: A Study By The GFM

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 658-658 ◽  
Author(s):  
Sylvain Thepot ◽  
Raouf Ben Abdelali ◽  
Sylvie Chevret ◽  
Aline Renneville ◽  
Odile Beyne Rauzy ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Genetic Markers ◽  
Research Funding ◽  
Prognostic Value ◽  
Response Rate ◽  
Univariate Analysis ◽  
Snp Array ◽  
Erythroid Response ◽  
Rbc Transfusion

Abstract Background Although anemia of LR MDS initially responds to erythroid stimulating agents (ESA) in 40-50% of patients, response is generally transient. AZA may lead to RBC transfusion independence (RBC-TI) in 30-40% of LR-MDS patients but it has not been studied prospectively in those resistant to ESA. While prognostic factors of response and survival to AZA have been largely analysed in high risk MDS, including by our group (Itzykson, Blood, 2011), they remain uncertain in LR-MDS, especially regarding new genetic factors. We previously reported (J Clin Oncol 30, 2012 # 6523) in a randomized phase II trial comparing AZA and AZA+EPO in 93 LR-MDS that were RBC-TD and resistant to ESA, a similar erythroid response rate in the 2 treatment arms (NCT01015352). Here, we report prognostic factors of response and overall survival in this trial, including genetic markers (SNP array-based karyotype and somatic mutations). Methods Patients included in the trial received AZA 75mg/m2/d for 5 days every 28 days for 6 cycles (AZA arm) or with added EPO 60000U/week (AZA+EPO arm). Erythroid response was evaluated after 4 and 6 cycles of AZA, according to the IWG 2000 criteria. Responders were then eligible for 12 AZA+/-EPO maintenance cycles. Affymetrix SNP array 6.0 (SNPa) analysis was performed at baseline on marrow mononuclear cells, and mutations of SF3B1, TET2, DNMT3A, ASXL1, JAK2 and 19 other genes were screened by next generation sequencing and validated by Sanger sequencing. The following factors were analysed for their prognostic value on erythroid response (IWG 2000) and survival: age, gender, IPSS, IPSS cytogenetics, WHO diagnosis, time since MDS diagnosis, SNPa karyotype, SF3B1, TET2, DNMT3A, ASXL1 and JAK2 mutations. Results In the 93 patients, M/F was 65/28; median age 72 y (IQR: 65-78); WHO diagnosis: RA 5.3%, RARS 40.9%, RCMD 15.1%, RCMD-RS 17.2%, RAEB-1 12.9%, CMML 7.5%, MDS-U 1%. Median MDS duration prior to inclusion was 37.2 months. IPSS was low in 35 and int-1 in 57 patients (NA in 1). IPSS cytogenetics was fav in 65, int in 9, defav in 2 patients, and failed or not done at study entry in 17 (but cytogenetics at MDS diagnosis was available in 16 of them). An abnormal SNPa karyotype was present in 33/79 patients analysed, including 9 with normal conventional cytogenetics. SF3B1, TET2, DNMT3A, ASXL1 and JAK2 mutations were detected in 59/86, 29/87, 12/87, 5/89 and 3/87 patients. Of the 19 other genes analysed, 12 showed no mutation and 7 (UA2F1, CBL, EZH2, RUNX1, ETV6, KIT, IDH2) were mutated in ≤3 patients and were not further considered in this analysis. In ITT analysis (N=93), erythroid response was 34% after 4 courses (37.5 % vs. 31% in the AZA and AZA+EPO arms, respectively, p=0.82) and 30% after 6 courses (35% vs. 24%, p=1.00). In univariate analysis, none of the factors listed above, including genetic markers, significantly predicted treatment response after 4 or 6 courses, while a trend was observed for a higher response rate after 6 cycles for SF3B1 mutated versus wt. patients (35.6 vs. 14.8 % respectively, P=0.07). Median follow-up of the 93 patients was 30 months (IQR: 23-34). Five patients developed AML (1 in AZA arm and 4 in AZA+EPO arm, P=0.19), all 5 in non-responders after 6 cycles. Median OS was 42.2 months and 2.5 years-OS 79.2% (95%CI: 71.2-88.1), with no difference between randomization arms (P=0.69). In univariate analysis, a shorter time since MDS diagnosis (HR=0.97, 95%CI: 0.95-0.99,P=0.011), IPSS int-1 (HR=2.83, 95%CI: 1.05-7.63, P=0.04), an abnormal SNPa karyotype (HR=3.01, 95%CI: 1.26-7.22, P=0.013) and presence of ASXL1 mutation (HR=5.08, 95%CI: 1.48-17.48, P=0.010) were associated with worse survival. In multivariate analysis, however, only time since MDS diagnosis (HR=0.97, 95%CI: 0.95-0.99) and abnormal SNPa karyotype (HR=2.92, 95%CI: 1.07-8.01) remained of prognostic value. Conclusions In this prospective AZA trial in LR-MDS resistant to ESA, no significant prognostic factor for response to AZA+/- EPO was identified, but a trend for better response (p=0.07) was seen in SF3B1 mutated patients, i.e 2/3 of patients. Among mutations analysed, only ASXL1 mutation predicted survival in univariate analysis, while abnormal SNPa karyotype predicted survival both in univariate and multivariate analysis (together with MDS duration). Thus, SNP array-based karyotyping and ASXL1 gene mutation analysis may become important tools to predict the long-term outcome of ESA resistant LR-MDS treated by AZA Disclosures: Guerci-Bresler: Novartis: Honoraria; BMS: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Fenaux:Celgene, Inc: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Gardin:Celgene, inc: Research Funding.

Extranodal-NHL: Outcomeand Comparison with Nodal NHL. Single Institution Experience Year: 1988–2004.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4755-4755
Author(s):  
Amar Lal ◽  
Nehal Masood ◽  
Salman Adil
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Early Stage ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Primary Site ◽  
Stage I ◽  
Significant Difference

Abstract Background & Objective: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of Diffuse large B-cell lymphoma (DLBCL) patients according to the primary site (extra nodal vs nodal) with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 711 cases of NHL were diagnosed at our Institute. Out of these 145 (20%) patients were excluded as they were other than DLBCL hitopathology. Five hundreds fifty-seven (80%) patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Ann Arbor staging system was used for staging with bone marrow biopsy, chest and abdominal radiography/CT. Results: Median age was 48.7 ± 15.3 years; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I; and EN sites, 235 (42%), including gastro-intestinal tract (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and unusual sites less than 3% each as breast, CNS, testis, lungs and skin. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I -II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI.

Prognostic Factors and Response Duration in 419 MDS Treated with Erythropoietin±GCSF: The GFM Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 522-522 ◽  
Author(s):  
S. Park ◽  
C. Kelaidi ◽  
S. Grabar ◽  
O. Beyne-Rauzy ◽  
S. Cheze ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Predictive Factors ◽  
Response Rate ◽  
Response Duration ◽  
Response Rates ◽  
Multilineage Dysplasia ◽  
Major Response ◽  
Significant Difference ◽  
The Impact

Abstract Background: EPO and its derivative darbepoietin alfa (DAR) are important treatments of anemia in lower risk MDS. Prognostic factors of response and of its duration have been recently updated (Blood, 2005, 106, 803–11) and we reanalyzed them in a large series of patients (pts) treated in France and Belgium. Patients: 419 MDS pts were treated with EPO (≥30000UI/wk for at least 12 wks) or DAR (300μg/wk)± GCSF in 25 GFM centers between 1998 and 2006 (160 prospectively analyzed in 3 consecutive trials, and 259 retrospectively analyzed). Median follow-up was 54 months, median age: 73.5 years. WHO classification: RA (14%), RCMD (16%), 5q- syndrome (4%), RARS (21%) RCMD-RS (13%), RAEB-1 (22%), RAEB-2 (6%), and also 4%CMML (FAB); karyotype: 64% FAV, 16% INT, and 4% UNFAV (16% failure or not done). IPSS: 34% LOW, 40% INT-1, 8% INT-2, 2% HIGH (16% unavailable). 185, 126, 80 and 28 pts received EPO alone (alfa or beta), DAR, EPO+G and DAR+G respectively. Median pre-treatment EPO level was 76 UI/l (only 7% pts>500 UI/l). All pts had Hb<10g/dl and 54% required RBC transfusions (including 36% with >2 RBC units/month). Results: 63% pts responded (IWG criteria: 43%HI-E major and 20% HI-E minor), including 57%, 63%, 57%, 66%, 63% with EPO alfa alone, beta alone, EPO+G, DAR alone, DAR+G response (p=ns). Median response duration was 20 mos (range 3–74 mos), 25 and 14 mos for major and minor responses (p= 0.001). Relapse was associated with treatment discontinuation (45%), progression to higher grade MDS (12%) or AML (13%), but without evident cause in 30% cases. In univariate analysis, significantly higher response rates were observed in pts with <10% blasts (p= 0.002), low and INT-1 IPSS score (p=0.001), transfusion <2 RBC units/month (p<0.0001), EPO level<200UI/l (p<0.0001) whereas no significant difference in response rate were seen between RA (69%,) RCMD (72%), RARS (59%), RCMD-RS (71%), RAEB-1 (60%) and 5q- syndrome (52%), and between cytogenetic groups. The response rate in RARS and RCMD-RS was similar with EPO or DAR alone (62.5%), and EPO or DAR+G (60%). In multivariate analysis, EPO <200UI/l (p=0.008), transfusion requirement (p<0.0001) and IPSS (p=0.047) remained predictive factors of response. Longer response duration was significantly associated with blasts<10% (20 mos vs 8 mos for blasts>10%, p=0.007), major response (vs minor), IPSS low-INT-1 (median 22 mos vs 8 mos for INT-2/HIGH, p=0.001) and in pts with absence of multilineage dysplasia (24 mos vs 16 mos, p=0.01). In multivariate analysis, blasts <10% and major response remained predictive factors of longer response. Conclusions: EPO level <200UI/l, RBC transfusions <2 units/month were confirmed as major prognostic factors of response to EPO±G. Good response rates were seen in RAEB-1, and with EPO alone, in RARS and RCMD-RS. Multilineage dysplasia was not associated with lower response rates, but with shorter response duration. Other prognostic factors of shorter response duration were minor response (vs major), and blasts >10%. A case control study with pts of the International MDS risk Analysis Workshop, who received RBC transfusion alone, is in progress to evaluate the impact of EPO treatment on leukemia-free survival and overall survival, and its results will be presented.

scholarly journals Clinicopathological and Prognostic Features of Hepatitis B Virus-associated Diffuse Large B-cell Lymphoma: A Single-Center Retrospective Study in China

2021 ◽  
Author(s):  
Dao-guang Chen ◽  
Gang Chen ◽  
Chang Wang ◽  
Long-feng Ke ◽  
Hui Wu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Advanced Disease ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Clinicopathological Characteristics ◽  
Hbv Infection ◽  
Disease Stage ◽  
Prognostic Features ◽  
Positive Hbsag ◽  
Significant Difference

Abstract The main aim of our study was to retrospectively investigate the clinicopathological characteristics and prognosis factors of DLBCL patients with HBV infection in China. We collected 420 patients with DLBCL who were originally diagnosed and treated at Fujian Cancer Hospital, China. In our study, 127 (30.2%) patients were HBsAg-positive. HBsAg-positive DLBCL displayed a younger median onset age (50 vs. 54 years, P=0.002), more frequent involvement of the spleen (19.7% vs. 6.1% , P<0.001), less frequent involvement of the small and large intestine (2.3% vs 11.2%, P=0.003), more advanced disease (stage III/IV: 56.7% vs. 45.1%, P=0.028), and lower expression rate of MYC (49.1% vs. 66.7%, P=0.026). The median follow-up time was 61.9 months. Univariate analysis showed that there was no significant difference in overall survival (OS) between HBsAg-negative and -positive DLBCL (P=0.577). In the HBsAg-positive DLBCL subgroup, age older than 60 years, advanced disease, elevated lactate dehydrogenase (LDH), spleen involvement, B symptoms (fever, night sweats, weight loss), and double expressers of MYC and BCL2 had a significantly worse outcome, and patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) had a better prognosis. Multivariate analysis further confirmed that spleen involvement and rituximab use were independent prognostic factors in HBsAg-positive DLBCL patients. Our study indicates that HBsAg-positive DLBCL has unique clinicopathological features and independent prognostic factors. Moreover, HBV infection does not appear to affect the prognosis of DLBCL patients, and the use of rituximab significantly improves OS in HBsAg-positive DLBCL patients.

Clinical Prognostic Factors in Chemosensitive Multiple Myeloma (MM) Patients Intensified with High Dose Therapy/Stem Cell Support (HDT/SCS): Results of the Spanish Trial (PETHEMA/GEM2000).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 937-937
Author(s):  
María-Victoria Mateos ◽  
Juán-José Lahuerta ◽  
Anna Sureda ◽  
Javier de la Rubia ◽  
Ramón García-Sanz ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
Response Rate ◽  
Univariate Analysis ◽  
Young Patients ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Abstract Autologous stem cell transplantation (ASCT) has become the standard of care for young MM pts. The analysis of prognostic factors will contribute to identify which pts benefit more from this procedure. However, in this type of analysis it is important that all pts receive uniform treatment, and since primary refractory pts have a different prognosis from pts sensitive to initial chemotherapy, our policy was to use up-front a more intensive treatment approach for the refractory pts. In this report we will focus on the analysis of clinical prognostic factors in sensitive MM pts to induction chemotherapy. The Spanish PETHEMA/GEM2000 trial included untreated MM pts younger than 70 years and consisted on six alternating cycles of chemotherapy VBMCP/VBAD followed by high dose therapy (BuMel or Mel200) supported with ASCT. Pts achieving CR IF- or CR IF+ after the first transplant received maintenance treatment with interferon/prednisone, while pts with a remaining visible M-spike (partial or minimal response) received a second HDT/SCS with CBV (cyclophosphamide, etoposide and BCNU) or a dose-reduced intensity allogeneic transplant if donor is available. Between January 2000 and December 2004, 803 pts were considered to have chemosensitive disease and were transplanted as above described. Median age at time of diagnosis was 59 y (range: 31–70). Baseline characteristics were similar to those previously reported in other series in which young patients were included. Following initial chemotherapy, the response rate was: 13.6% CRIF-, 14% CRIF+ and 60% PR. Response rate increased after HDT/SCS: CRIF-, CRIF+ and PR rates were 38%, 20% and 35%, respectively. Early death rate, occurring during the first two months after ASCT was 3,5% (28 pts). 207 out of 803 pts received a second HDT/SCS. 531 pts (66%) started maintenance therapy after transplant with interpheron and prednisone in most of them (77%). After a median follow-up of 45 months (range: 6–91), the median EFS time for the 803 pts was 45 months (95% CI: 40,5–49,1), defining event as relapse/progression or death; median OS time has not been reached and the estimated 8-year EFS and OS were 30 and 53%, respectively. Univariate analysis identified the following adverse prognostic factors for EFS: age ≥ 59 y, advanced Durie and Salmon stage, advanced ISS stage, Monoclonal component ≥ 30g/l, Hemoglobin (Hb) level < 11 g/dl, creatinine > 1,5 mg/dl, Bone Marrow Plasma cells infiltration ≥ 45%, performance status according to EGOG 3–4, and failure to achieve CR IF- after induction chemotherapy or after the first transplant. The same prognostic factors were identified in the univariate analysis for OS. On multivariate analysis only five variables retained an independent prognostic influence on EFS and OS: age ≥ 59 y (p:0,04), Hb < 11 g/dl p:0,000), advanced ISS stage (p:0,03) and lack of CRIF- after transplant (p:0,000). The three ISS stages could be subdivided into two subgroups using the variables selected in the multivariate analysis. Thus pts who didn’t achieve CR IF- after transplantation and had an additional adverse factor (either age or anemia) showed a significant different outcome within the ISS stage I, II and III.

Clinicopathologic characterization and prognostic factor in extraintestinal neuroendocrine tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15131-e15131
Author(s):  
Eucario Leon Rodriguez ◽  
Sandra Ileana Perez Alvarez ◽  
Omar Macedo ◽  
Elizabeth Escobar
Keyword(s):  
Palliative Care ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Initial Treatment ◽  
Univariate Analysis ◽  
Objective Response ◽  
Locally Advanced ◽  
Term Survival

e15131 Background: The frequency, prognostic factors and long-term survival of E-NET are poorly known. Methods: A retrospective analysis of clinical, histological characteristics and survival of patients with E-NET were done. Survival analyses were assessed by the Kaplan-Meier method and prognostic factors of overall survival were tested by uni/multivariate analysis. Results: Between 1997-2010, 241 patients were identified with NET. 31 Patients were E-NET (12.8%): median age was 55 years (16-79) and 55% were females. Primary location was lung, 58%, prostate 13%, breast 10%, urinary bladder 7%, and others 12%. At diagnosis 87% patients had symptoms and 52% were localized. A functioning tumor was in 7 patients (6 ACTH). Initial treatment was surgery 61%, chemotherapy 26% (23% had objective response) and palliative care 13%. After complete resection 4/14 patients recurred. With follow-up of 15months, the cancer-specific mortality was 55%. Overall 1- and 5-year survival were 72% and 35% respectively, which were lower than survival for GEP-NET (p=0.001, Figure 1). 5 year survival differed significantly according to age at diagnosis (47% ≤50 vs 27% >50 years); location (60% lung vs 10% non-lung); extension (58% localized vs 15% metastatic/locally advanced); stage at diagnosis (59% stage I-II vs 13% III-IV); histology (52% NET/carcinoid vs 14% NEC); degree of differentiation (44% well/moderately vs 0% poorly differentiated); initial treatment (55% surgery, 25% palliative care and 0% chemotherapy); and recurrence (100% absent vs 25% present). In univariate analysis, the negative prognostic factors were age >50 years, no lung site, symptomatic, metastatic/locally advanced disease, extrahepatic metastases, NEC, poor differentiation and recurrence. In multivariate analysis, only age >50 years was an independent predictor of survival (p=0.027). Conclusions: In our experience, E-NET represent 13% of all the NET. Present symptoms with a fewer frequency, are less functional, have more frequently metastases, and a worst prognosis (5-year survival 34 vs 72%). The most important prognostic factor for overall survival was age >50 years.

scholarly journals Prognostic Significance of Metabolic Parameters by 18F-FDG PET/CT in Thymic Epithelial Tumors

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 712
Author(s):  
Joohee Lee ◽  
Young Seok Cho ◽  
Jhingook Kim ◽  
Young Mog Shim ◽  
Kyung-Han Lee ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Fdg Pet ◽  
Univariate Analysis ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
Masaoka Stage ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. Conclusion: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors.

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