Non-Hodgkin’s Lymphoma Refractory to First Line Therapy: Incidence, Associated Clinical and Histological Factors, and Outcome among 503 Newly Diagnosed Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1373-1373
Author(s):  
Angela Gueli ◽  
Daniele Caracciolo ◽  
Manuela Zanni ◽  
Luciana Bergui ◽  
Paolo Gavarotti ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Disease Progression ◽  
Refractory Disease ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Histological Factors

Abstract Introduction: Non-Hodgkin’s lymphoma (NHL) are malignancies usually sensitive to chemotherapy; this results in prolonged survival and often disease eradication in a large proportion of patients. Despite general improvements in treatment options, a variable number of NHL patients still shows refractoriness, i.e. poor or absent response to induction therapy. This study was undertaken to evaluate the actual rate of refractory patients, to identify possible factors predictive of refractory disease and to compare long-term outcome of refractory vs. responsive patients. Patients and Methods: Data have been collected on 503 NHL patients referred and treated at our Hematology Division between 1990 and 2005. The series included 461 B-cell and 42 T-cell NHL, main histologic subtypes included: 305 high-grade, 183 low-grade and 15 mantle-cell lymphoma. Patient median age was 53 yrs, 55% were male; 359 (73%) patients presented with advanced stage disease. Refractory patients were identified for stable/progressive disease or transient response with disease progression within 6 months, following first-line therapy. Overall, 298 (59%) patients received conventional chemo-radiotherapy, 205 (41%), with either high-risk presentation or unfavorable histology, had high-dose sequential therapy (HDS) with autograft front-line; rituximab was employed in 158 (31%) patients. Results: Overall, 126 (25%) patients were refractory (39% with no response at all, 61% with short-lasting response soon followed by disease progression). The rate of refractoriness was as high as 40% in the small T-cell NHL subgroup, while the overall incidence was 24% for B-cell NHL. There was no significant difference in the distribution of refractory patients among the histological subtypes of B-NHL, in other words none of the B-cell NHL subtypes was specifically associated with poorer response. Among several parameters evaluated for their potential predictive value, in multivariate logistic regression analysis, two factors only were associated with a higher risk of refractory disease: high serum level of lactate dehydrogenase (LDH) and stages IIB-IV, with an Odds Ratio (OR) of 3.52 and 3.75, respectively; the use of HDS program was associated with reduced risk of refractory disease (OR=0.30). Overall, refractory patients had a definitely short life expectancy, with a median survival of 21 months and a 14-yr survival projection of 10%, which is markedly worse compared to 88%, 76% and 65% survival projections at respectively 5, 10 and 15 yrs., of responsive patients, as shown in Figure 1. Conclusions. i. patients with refractory disease represent approximately one fourth of NHL undergoing induction therapy; ii. besides advanced stage and high LDH levels, no other clinical and histological factors are specifically associated to refractoriness; iii. further studies are needed to identify markers predictive of refractoriness, in order to design induction therapies adapted for refractory patients, given their dismal outcome with currently available treatment strategies. Figure 1. Overall survival of 126 refractory and 377 responsive NHL ptients Figure 1. Overall survival of 126 refractory and 377 responsive NHL ptients

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Fludarabine Monophosphate as First Line Therapy for Chronic Lymphocytic Leukemia (CLL) - 11 Years Clinical Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4970-4970
Author(s):  
J.E. Novoa ◽  
A.L. Rojo ◽  
B. Beñaran ◽  
R. Draper ◽  
H. Calvo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Intravenous Formulation

Abstract Background: fludarabine (F) has become the standard first line therapy for chronic lymphocytic leukemia (CLL) in younger patients. Treatment of early stage patients with chlorambucil without risk stratification has not been shown to prolong survival. In recent years effective and potentially curative approaches such as nucleosides analogues, stem cell transplantation or monoclonal antibodies have been developed. The attraction of monoclonal antibodies is based on selective targeting of tumor - relevant surface markers and a distinct mechanism of action (antibody-dependent cellular cytotoxicity). Aims: to assess the efficacy, safety and quality of life of F in previously untreated B-cell CLL patients in a group of medical institutions in Uruguay during 11 years (1995–2006). Methods: 168 patients between the period 1995 – 2006 were evaluated.120 of them received F intravenous formulation (1995–2006) and 48 the oral one (2002–2006). Age: 48 – 85 years old, media 67 years old. Gender: male 90, female 78. Inclusion criteria for B-cell CLL was Binet stages B, C and A progressive (Ap), 18 to 85 years old, non multiorganic failure, performance status 0 – 2 (WHO), written informed consent. First condition was non previous treatment. Staging: Binet A 12/168, B 116/168 & C 40/168. Treatment: as first line therapy all the patients received (minimum): 6 cycles of i.v. Fludarabine (Fludara®, Schering) 25 mg/m2/daily (5 days) e/30 days or Oral Fludarabine, 40 mg/m2/daily (5 days), 6 cycles. Results: on this B-cell CLL cohort the overall response rate (ORR) was 78% (CR+PR), 80% of them have immunophenotypic response. Safety: on the 1100 cycles in 168 patients, the toxicity was: 1 AIHA, 2 pancytopenia, 3 plaquetopenia. Grade 3–4 infection rate was 1,3%. No alopecia was observed in any patient. Kaposi sarcoma (0,7%). Mortality rate: 1,7% (3/168 patients). Other adverse factors to overall survival were, age over 65 (p=0,0001) and hepatic impairment (p=0,0001). Toxicity: (WHO>2): granulocytopenia 28%, thrombocytopenia 8%, infection 2%. Although fludarabine-treated patients experienced more significant myelosuppression, no difference in the treatment group was demonstrated. Causes of death: Richter 12%, sepsis 5%, associated disease 34%, second malignancy 17% and others 30%. Comparing oral with intravenous formulation in overall survival the results were: CLL 34% vs 36% (p= NS). Conclusions: fludarabine monofosfate (Fludara®) looks like an effective and safe treatment for B-cell CLL. The oral and intravenous formulations have a similar response rate in elderly and young patients. The challenge remains to integrate new information to apply novel therapies in a disease-specific and risk-adapted maner. A longer follow up and a larger trial, might be needed to confirm these results.

Primary Refractory Disease in Non-Hodgkin's Lymphoma: A Retrospective Study On 3,952 Newly Diagnosed Patients Undergoing First-Line Chemotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 305-305
Author(s):  
Corrado Tarella ◽  
Angela Gueli ◽  
Federica Delaini ◽  
Andrea Rossi ◽  
Anna Maria Barbui ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Disease Progression ◽  
Median Survival ◽  
Cell Lymphoma ◽  
Female Gender ◽  
Refractory Disease ◽  
First Line ◽  
Early Relapse ◽  
Line Chemotherapy

Abstract Abstract 305 Introduction: Non-Hodgkin's lymphoma (NHL) are malignant tumors usually sensitive to chemotherapy; this results in prolonged survival and possibly disease eradication in a large proportion of patients. However, despite the general improvement in treatment options, a variable number of patients still shows a refractory disease, i.e. poor or absent response to induction therapy. Prediction and management of refractory disease is a major issue in the biological and clinical research programs for NHL. The present study was undertaken to evaluate on a large series of NHL patients, managed at two Italian centers over the last three decades: i. the actual rate of refractory patients; ii. the main factors associated with refractory disease; iii. the long-term outcome of refractory vs. responsive patients. Patients and Methods: Data have been collected on a series of 3,952 NHL patients, referred and treated at the University Hematology of Torino (S. Giovanni B. and Mauriziano Hospitals) (864 cases) and at the Hematology Division of Ospedali Riuniti di Bergamo (3,088 cases), between 1984 and 2012. There were 1,819 (46%) female patients, 2,056 (52%) were aged less than 60 yrs, B-cell NHL were 3,633 (92%), with 318 (8%) patients diagnosed as T-NHL; main histological subtypes included: 1,809 (45.8%) Diffuse Large Cell Lymphoma (DLCL), 758 (19.2%) follicular lymphoma (FL), 210 (5.3%) mantle-cell lymphoma, the remaining 1,175 (29.7) had other histologies. According to Ann Arbor staging, 2,369 (62%) patients presented with advanced stage disease and 914 out of 2,174 evaluable patients (42%) had an intermediate-high IPI score. Overall, 1,430 out of 3,187 (44.9%) received conventional chemo-radiotherapy supplemented with rituximab. The criteria to identify refractory patients were: stable or progressive disease (fully refractory) or transient response with disease progression within 6 months (early relapse), following first-line chemotherapy. Results: Among 2,543 broadly analysed patients, treated during the last 28 yrs, 649 (25.5%) were classified as refractory, including 14% fully refractory and 11.5% with early relapse or disease progression. The overall incidence of refractory disease was similar in the two Centers, 24.1% in Torino and 26.3% in Bergamo. The rate of refractoriness was as high as 46.9% in the small T-cell subgroup, while the overall incidence was 23.6% for B-cell NHL (p<0.001), with refractory patients more frequently observed among DLCL (26.0%) than in FL (15.1%) (p<0.001). Besides T-cell histology, the following factors had the highest association (p<0.001) with treatment response: i. intermediate-high risk IPI presentation, with 38.5% refractory patients, compared to 16.7% for 0–2 IPI scores; ii. female gender, with a markedly lower incidence (22%) of refractoriness compared to males (28.4%); iii. rituximab addition, that cut the incidence of refractoriness to 19.2% compared to 28.8% for patients treated without rituximab. These factors maintained their independent predictive values in multivariate regression analysis. At a median follow-up of 5.4 yrs., 1,607 (61%) out of 2,543 patients are alive, 11.8% of them were refractory to their first line treatment. Indeed, among 649 refractory patients, 189 (29%) are presently alive, compared to 1,418 alive (75%) among 1,894 responsive patients. Lastly, the overall survival (OS) was significantly poorer for fully refractory (median survival: 1.1 yrs) compared to early relapse patients (2.09 yrs) (p<0.001); both these refractory subgroups had a definitely poorer OS compared to responsive patients, whose median survival was 22.2 yrs (see Figure 1). Conclusions: i. Overall, in this large series of NHL patients who received induction therapy both in the pre- and post-Rituximab era, approximately one fourth displays full refractoriness or early relapse/progression; ii. the introduction of rituximab has markedly reduced the risk of refractory disease, whose incidence is now around 19%; iii. a markedly higher rate of refractory disease is observed with T-subtypes compared to B-cell NHL; iv. intermediate-high IPI score is associated to refractoriness, while female gender significantly reduces the risk of refractory disease; iv. patients responsive to first-line therapy have a very prolonged life expectancy, with a median survival around 22 yrs, whereas the median survival for refractory patients does not exceed 2 yrs. Disclosures: Tarella: Hoffmann-La Roche: Consultancy, Honoraria. Rambaldi:Hoffmann-La Roche: Consultancy, Honoraria.

Differences in Cell of Origin (COO) Affect Outcomes in Caucasian(C) but Not in African American(AA) Patients with Diffuse Large B-Cell Lymphoma(DLBCL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1460-1460 ◽  
Author(s):  
Uma Borate ◽  
Deniz Peker ◽  
James M. Foran ◽  
Luciano J Costa
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
Rank Test ◽  
Advanced Stage ◽  
Cell Of Origin ◽  
First Line ◽  
First Line Therapy ◽  
Log Rank Test ◽  
Line Therapy

Abstract Introduction: DLBCL is an aggressive mature B-cell neoplasm with a low incidence in African Americans and other minority groups. The differences in outcomes based on DLBCL Cell of Origin(COO) immunophenotypic subtypes as defined by the Hans algorithm using CD10, Bcl-6, and MUM1 namely germinal center B-cell (GCB) and non-GCB have been based on predominantly Caucasian patients (pts) and their impact on outcomes in AA patients have not been well studied. Material and Methods: A retrospective review of clinicopathologic data from patients diagnosed and treated for DLBCL at UAB between 2002-2011 was conducted following IRB approval .The data collected included patient demographics (age, sex, self identified race), DLBCL subtype (GCB vs. non-GCB based on the Hans algorithm), disease stage, first line therapy regimens and patient outcomes. We analyzed group differences in both C and AA pts with GCB and non-GCB subtypes of DLBCL in all the parameters mentioned above using the chi square test for categorical variables,. In addition, OS was examined using Kaplan Meier curves and the log rank test. We performed univariate and multivariate analyses to examine the effects of variables of interest on OS. All results were considered statistically significant at α=0.05 level. Results: We included a total of 259 pts in our analysis after excluding patients with missing demographics, disease related data, primary mediastianal DLBCL, missing first line therapy data and outcomes data as well as race identified as other than C or AA. 45 patients (17.4%) of patients self identified as AA and 214 (82.6%) self identified as Caucasian. The mean age of presentation for AA pts was 52 yrs compared to 58 years for C patients (p=0.045) and 28 (62.2%) AA patients presented with advanced Stage III and IV disease compared to 89 (44.6%) of C patients (P=0.04) both being statistically significant. Based on COO characterization using immunophenotype by Hans algorithm, 27 AA pts (60%) and 145(67%) of C pts were GCB by immunophenotype(p=0.317). 95% of all patients received R-CHOP as first line therapy , 3.5% received R-CVP and the remaining received a combination of Rituximab alone, FCR or radiation therapy .On analyzing OS based on COO, AA patients did not demonstrate a significant difference in OS based on COO with both GCB and non-GCB groups having a median OS of 84 months ( p=0.74)( 95% CI 72-121 months). However, the median OS for C pts with GCB phenotype was 104 months compared to 25 months for the non-GCB phenotype and the median OS was 55 months +/-12.6 months for the C pt group as a whole( p<0.001 by log rank test )which was highly statistically significant.Multivariate analyses of different factors affecting OS showed only COO (p<0.001), age(p=0.07) and stage of DLBCL at presentation(p=0.027) to affect OS significantly.Race,Gender and IPI score did not appear to impact OS significantly. Conclusion: Our study aimed to study the impact of COO and Race on OS in DLBCL especially in AA pts where this has not been well characterized. Our results show that as expected the incidence of DLBCL is lower in AA patients compared to C pts. However, DLBCL presents at younger age and with more advanced stage in AA than in C patients. Although distribution of COO is similar in AA and C patients, our findings suggest that COO may not have the same effect on prognosis among AA pts as it does among the C pt population where we see non-GCB patients do significantly worse than their GCB counterparts. This may reflect a different disease biology in AA patients that has yet to be understood. Our study limitations include not taking into account disease relapse, second line therapy and effect of autologous bone marrow transplantation on overall survival. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

Lymphoma Patients Secondary to Congenital and Acquired Immunodeficiency Syndroms in a Turkish Pediatric Oncology Center

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5445-5445
Author(s):  
Nurdan Tacyildiz ◽  
Gulsah Tanyildiz ◽  
Gulsan Yavuz ◽  
Emel Unal ◽  
Handan Dincaslan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Lymphoproliferative Syndrome

Abstract PURPOSE An increased incidence of lymphoma is seen in various types of immune deficiency syndromes,including congenital immune deficiency diseases, organ transplantation with iatrogenic immunosuppression and autoimmune disorders. Prognosis of the lymphomas secondary to immunodeficiencies is stil poor. We aimed to analyse clinical features and treatment results of our patients that diagnosed as lymphoma and have immundeficiency syndrom. PATIENTS Between 2002-2014, we have seen 12 (7male, 5 female) childhood lymphoma that related immunodeficiencies. Ages of patients were between 4-15 years (median 8 years).The follow up period is 1-140 months (median: 38.5 months) and survival rate is %58. Five of patients died because of the progressive disease. The characteristics of patients are summarized in the table. TABLE- Clinical characteristics of patients Patient Age (year) Gender Diagnosis Follow up (months) Survival 1. G.C 10 Male T-NHL + AT 6 Alive (lost to follow up) 2. İ.D 4 Male T-NHL + ALPS 9 Eksitus 3. M.K 12 Female T cell rich B cell lymphoma+ CVID 2 Eksitus 4. S.K 9 Female B cell lymphoblastic lymphoma+AT 54 Alive 5. B.C 5 Male BL + Renal transplantation 1 Eksitus 6. S.K 7 Female BL + AT 6 Eksitus 7. C.G 12 Male BL + WAS 48 Eksitus 8. K.B 11 Female BL+EBV associated lymphoproliferative syndrome 29 Alive 9. M.Y 15 Female HL + CVID 140 Alive 10. B.Ç 4 Male HL + selective IgA deficiency 132 Alive 11. S.S 7 Male HL + AT 70 Alive 12. B.K 5 Male HL + AT 48 Alive TOTAL n = 12 4-15 years Median : 8 4 female 8 male 8 NHL (survival % 37.5) 4 HL (survival% 100) 1-140 months Median : 38.5 Survival %58 RESULTS Two of 5 Ataxia Telangiectasia (AT) patients diagnosed as Hodgkin's lymphoma (HL) while other three diagnosed as non-Hodgkin's lymphoma (NHL) (1 Burkitt's lymphoma-BL,1 B cell lymphoblastic lymphoma-BCLL,1 T-cell NHL). One of 2 common variable immunodeficiency (CVID) patient diagnosed as HL and the other one diagnosed T-cell rich B-cell lymphoma (TCRBCL). Wiscott-Aldrich syndome (WAS), autoimmune lymphoproliferative syndrome (ALPS ) and selective immunoglobulin A deficiency patients diagnosed as large B-cell lymphoma (LBCL), T-cell NHL and HL, respectively. In one patient, EBV associated BL developed secondary to renal transplantation. Another EBV associated BL patient has been diagnosed recently who has DNA instability defect. Follow-up period of patients were between 1-140 months (median 38.5 months). Almost half of the patients ( 42%) were diagnosed as BL,BCLL or TCRBCL. Although, survival of our patients for median 38.5 months is 58% (5 patients died with progressive disease) ,four of the 5 BL&TCRBCL patients have been died. Two patients who are living after BL and BCLL diagnosis in that group are treated with Rituximab as first line therapy. CONCLUSİON BL is most common lymphoma type in immundeficient lymphoma patients which may be subject for future research . Although special attention has been given to these patients, especially survival of BL lymphoma secondary to immunodeficiencies are poor. Special treatment modalities, like targeted terapies may be necessary as first line therapy to improve survival of these patients. Disclosures No relevant conflicts of interest to declare.

High Dose Chemotherapy with Autograft in First Relapse May Overcome the Poor Prognosis of Diffuse Large B-Cell Lymphoma Patients with MYC/BCL2 Co-Expression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1976-1976
Author(s):  
Francesco Maura ◽  
Anna Dodero ◽  
Alessio Pellegrinelli ◽  
Martina Pennisi ◽  
Liliana Franca Devizzi ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Refractory Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Extranodal Disease ◽  
First Relapse

Abstract The immunohistochemical (ICH) co-expression of MYC and BCL2 (double expressors, DE) has been emerging as a strong and reproducible risk factor in diffuse large B cell lymphoma (DLBCL) patients (pts) treated with R-CHOP. Our aim was to analyze the prognostic value of the co-expression in DLBCL pts treated with high-dose chemotherapy followed by autologous stem cell transplantation at first relapse. In this retrospective study, we analyzed a cohort of 64 young [median age 53, (range18-70)] and/or fit DLBCL pts treated between 2003 and 2015 at the Istituto Nazionale dei Tumori Milano. All pts relapsed at median time of 4.9 months after a Rituximab-based chemotherapy (48 R-CHOP-like and 16 other intensive regimens). All pts were considered fit and eligible for high-dose chemotherapy salvage treatment. Tumor samples were analyzed by ICH for MYC and BCL2 (40%/70% threshold). Germinal B-Cell (GBC) and Activated B-Cell (ABC) DLBCL classification was done with ICH as established by the Hans algorithm. Pts characteristics at relapse were: refractory: 37/64 (58%), Ann Arbor stage≥3: 42/64 (65%), IPI score≥2: 26/60 (43%); Extranodal disease: 37/64 (58%); Bulky (defined as max diameter ≥5 cm): 29/64 (45%); CNS involvement: 8/64 (12.5%). Twenty-nine of 64 (45%) pts responded to salvage high-dose therapy (CR,PR) and 25 of them underwent autologous stem cell transplantation (ASCT). Among 39 (61%) refractory pts to first salvage intensive chemotherapy approaches, 11 (28%) responded after third or fourth chemo-immunotherapy salvage lines and underwent ASCT as well. Overall the reasons for not receiving ASCT were: refractory disease (n=20), poor mobilization (n=3), the occurrence of significant infection or toxic complications during the salvage therapy (n=4) or patient decision (n=1). ICH MYC and BCL2 positive expression was observed in 31 (48%) and 39 (61%) pts respectively. Among them, 17 (26%) were characterized by BCL2 and MYC co-expression. According with Hans algorithm, 23 (56%) and 18 (44%) DLBCL pts were classified as GBC and ABC-DLBCL. DE pts did not show any significant differences compared to others in terms of age, IPI score, presence of extranodal disease, BM infiltration, CNS involvement at relapse, refractory disease or relapse occurrence less than 1 year after first line therapy, and proportion of ABC-DLBCL subtype. Considering the whole pts cohort 5-years progression free survival (PFS) and overall survival (OS) were 27.3% (95% CI, 21.1%-33,4%) and 40.6% (95% CI, 33.2%-48%) respectively. In univariate analysis, pts with disease relapsed less than 1 year after first line therapy were characterized by a significant worse outcome in terms of 5-years PFS [11.5% (95% IC 6.1%-16.9%) vs 72.2% (95% IC 60%-84.4%] and OS [24.5% (95% IC 16.9%-32.1%) vs 84.4% (95% IC 74%-94.8%)] (p=0.0001 and p=0.0009 respectively). Similar results were observed comparing pts with refractory disease to first line therapy with others [5-years PFS 11.7% (95% IC, 5.9%-17.5%) vs 48.2% (95% IC, 37.1%-59.3%)] and 5-years OS [19.9% (95% IC, 11.8%-28%) vs 67.9% (95% IC, 57.6%-78.2%)] (p=0.0003 and p=0.001 respectively). Other variables at first relapse associated with worse outcome in terms of PFS and OS were IPI score ≥2 and presence of bulky disease. In contrast, DE patients did not shown any significant differences compared to other patents in term of 5-years PFS [39.7 (95% IC, 27.5-51.9) vs 25.1 (95% IC, 18.4-31.8), p=0.5] and 5-years OS [40.8 (95% IC, 32.3-49.3) vs 22.2 (95% IC, 5-39.4), p=0.8]. Furthermore singularly ICH MYC or BCL2 expression did not influence neither PFS nor OS. These data suggest that salvage programs with high dose chemotherapy with autograft in first relapse may overcome the previously reported poor prognosis associated with ICH MYC/BCL2 co-expression. The most significant and robust prognostic factor among DLBCL pts in first relapse is still represented by refractoriness and the time of relapse. Disclosures No relevant conflicts of interest to declare.

scholarly journals Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma

2011 ◽  
Vol 29 (35) ◽  
pp. 4696-4701 ◽  
Author(s):  
Andrew Hodson ◽  
Siobhan Crichton ◽  
Silvia Montoto ◽  
Naheed Mir ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Interferon Alfa ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
Adult T Cell Leukemia ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

Purpose Adult T-cell leukemia/lymphoma (ATLL) is a mature (post-thymic) T-cell lymphoma associated with human T-lymphotropic virus type 1 infection. Survival in aggressive subtypes remains poor, and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon alfa (IFN-α) has been associated with improved response rates in small studies and prolonged overall survival in leukemic ATLL subtypes in a recent meta-analysis. Patients and Methods We report the clinicopathologic characteristics, treatment, and outcome of 73 patients with aggressive ATLL (acute ATLL, 29; lymphoma ATLL, 44) diagnosed and treated in England between 1999 and 2009. The impact of ZDV/IFN-α on treatment response and survival was assessed. Results The overall response rate ranged from 49% with chemotherapy alone to 81% with combined first-line therapy (chemotherapy with concurrent/sequential ZDV/IFN-α). Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFN-α at any time prolonged survival in acute (P < .001) and lymphoma ATLL (P < .001) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio, 0.23; 95% CI, 0.09 to 0.60; P = .002). Combined first-line therapy prolonged median OS in acute (P = .0081) and lymphoma ATLL (P = .001) compared with chemotherapy alone. Conclusion These data support the use of low-dose ZDV/IFN-α with chemotherapy in first-line treatment of acute and lymphoma ATLL.

Outcomes After Multiple Lines of Chemotherapy for Platinum-Resistant Epithelial Cancers of the Ovary, Peritoneum, and Fallopian Tube

2011 ◽  
Vol 21 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Richard Wyn Griffiths ◽  
Ying-Kiat Zee ◽  
Saran Evans ◽  
Claire L. Mitchell ◽  
Gireesh C. Kumaran ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Progression ◽  
Fallopian Tube ◽  
Poor Prognosis ◽  
Platinum Resistance ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Platinum Resistant ◽  
Cytotoxic Treatment

Background:Platinum-resistant and refractory cancers of the ovary, fallopian tube, and peritoneum have a poor prognosis, yet in some cases, they can respond to multiple lines of chemotherapy. Uncertainty remains over optimal drug choice and when therapeutic focus should be switched from active therapy to supportive care.Methods:A retrospective case note review was performed on 274 women treated for platinum-resistant/refractory ovarian, fallopian tube, or peritoneal carcinoma at the Christie Hospital between 2004 and 2008. Baseline data at onset of platinum resistance and outcomes from subsequent lines of therapy were recorded.Results:A total of 689 lines of therapy were administered with a median overall survival from initiation of first-line therapy for platinum-resistant disease of 61 weeks. Twenty-eight percent of women commenced cytotoxic therapy in the last 3 months of life. Treatment efficacy declined rapidly with successive lines of therapy particularly if disease progression occurred during first-line therapy. Factors independently associated with worse overall survival at recognition of platinum resistance were performance status, presence of stage IV disease, elevated cancer antigen 125, and platinum-refractory disease.Conclusions:A significant proportion of women who were treated received therapy within the last few months of life with little clinical benefit. Disease progression on 2 consecutive lines of therapy should be used as a guide to discontinue cytotoxic treatment. A subset of patients with poor prognosis at the onset of platinum resistance, who may have little gain from anticancer treatment, can be identified.

scholarly journals Outcomes in Advanced-Stage Plasmablastic Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2519-2519
Author(s):  
Sophia Lee ◽  
Christen Dillard ◽  
Raphael E Steiner ◽  
Babak Soltanalizadeh ◽  
Lei Feng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Progression Free Survival ◽  
Plasmablastic Lymphoma ◽  
Advanced Stage ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin B-cell lymphoma (NHL), often characterized by immunoblastic morphology and plasmacytic immunophenotype. PBL was initially described in HIV-positive patients (pts) and is now often diagnosed in post-transplant and HIV-negative pts with other immunodeficiency. Pts with limited stage disease treated with induction chemotherapy and consolidative radiotherapy have a good prognosis; however, pts with advanced stage have poor outcome. Previously studied treatment regimens vary and include CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone), HyperCVAD (cyclophosphamide, vincristine, Adriamycin, dexamethasone alternating with methotrexate and cytarabine), and DA-EPOCH (etoposide, vincristine, cyclophosphamide, Adriamycin, prednisone) with or without radiation and autologous stem cell transplant, with no current standard therapy, largely due to the rarity of PBL. Methods: We conducted a retrospective analysis of pts diagnosed with PBL between April 2003 and August 2020 to describe outcomes for pts treated at our center over the past 2 decades. We hope to use this to improve outcomes with novel therapies in the future. We evaluated the baseline demographics, stage, therapy, response rate, progression-free survival (PFS) and overall survival (OS). We used descriptive statistics including mean, standard deviation, median, and range for continuous variables, and frequency counts and percentages for categorical variables. Best response and its 95% exact confidence interval were calculated. Kaplan-Meier method was used to estimate the time-to-event endpoints including progression free survival, and overall survival. Results: 39 pts with PBL were identified, with a median age of 51 years (range 27-91). 16 were HIV+, and 5 were on immunosuppression for autoimmune disease (2), infectious hepatitis (2), or liver transplant (1); the other 18 had no apparent immunosuppression other than advanced age (defined as 70 years and older) in 13. Among those with HIV, 14 were on antiretroviral therapy at time of diagnosis of PBL. The median CD4 count was 140 (range 15-391) and 5 patients had an active viral load. 24 pts were EBV/EBER positive. 6 pts had stage III disease and 33 had stage IV disease. The primary sites of disease included head and neck (13), lymph node (7), gastrointestinal tract (6), other soft tissue (3), abdomen (3), breast (2), gynecologic (2), skin (2), and bone (1). The median LDH was 629 IU/L (313-618). A serum protein electrophoresis was checked in 21 pts and the median was 1.4 g/dL (range 0.2-2.6 g/dL, normal = 0). A beta 2 microglobulin was checked in 28 pts and the median was 3.95 (range 2.55-10.4, normal =0.8 to 2.3 mg/L). The median Ki-67 proliferation index was 85%, and the PBL cells were invariably CD20 negative. 12 cases showed MYC overexpression; 2 had MYC rearrangement by FISH. 32 pts received systemic therapy and were evaluable with 2 median lines of treatment (range 1-6). First line therapy included Hyper-CVAD (n=7), CHOP (n=3), EPOCH (n=19), and other (n=3). The antimyeloma therapy, bortezomib, a proteasome inhibitor, was added to EPOCH for 4 patients or used with dexamethasone in one pt, while the CD38 antibody daratumumab was added to hypercytoxan for the first cycle of an elderly pt with poor performance status (PS). He responded well with improvement in his PS, and subsequently completed 5 cycles of DA-EPOCH and remains in CR. After first line therapy, 59% pts achieved complete response, 13% partial response, and 9% stable disease. 20 pts received intrathecal chemotherapy, 9 pts received radiation, and 8 pts underwent autologous stem cell transplantation (7 as consolidation and 1 at relapse). Please see figure for PFS and OS based on different treatment modalities. Median PFS and OS were 21 and 35.2 months, respectively. Median follow up time was 25.85 months. Conclusions: The majority of our pts (87%) with advanced stage PBL were immunocompromised with HIV (16), requiring immunosuppression (5), or elderly (13). Despite a 56% CR rate with induction, 69% of patients relapsed. Median PFS was less than 2 years and OS was less than 3 years. The dismal outcomes of pts with PBL suggests that this rare and aggressive subtype of NHL with plasmacytic differentiation requires further evaluation with therapies against plasma cell directed antigens such as CD38, BCMA or SLAMF7. *S Lee & C Dillard contributed equally. Figure 1 Figure 1. Disclosures Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Loghavi: Abbvie: Current equity holder in publicly-traded company; Curio Sciences: Honoraria; Gerson Lehrman Group: Consultancy; Guidepoint: Consultancy; Peerview: Honoraria; Qualworld: Consultancy. Ahmed: Seagen: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Xencor: Research Funding. Patel: Pfizer: Consultancy; Janssen: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Oncopeptides: Consultancy.

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