scholarly journals Cepp in Previously Untreated Patients with Mature T Cell Lymphomas

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1371-1371
Author(s):  
Hian Li Esther Chan ◽  
Joanne Lee ◽  
Sanjay De Mel ◽  
Anand Devaprasath D. Jeyasekharan ◽  
Yen Lin Chee ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Clinical Stage ◽  
International Prognostic Index ◽  
Autologous Transplantation ◽  
Prognostic Index ◽  
Disease Stage ◽  
Control Group ◽  
Curative Intent ◽  
Salvage Regimen

Abstract Introduction There is currently no standard of care for the upfront management of patients with mature T cell non-Hodgkin lymphomas (T-NHL). The role of anthracyclines in the treatment of T-NHL remains unclear and is also associated with significant toxicity. CEPP (cyclophosphamide, etoposide, procarbazine, and prednisone), a non-anthracycline regimen, is an effective salvage regimen for relapsed/refractory NHL and has shown a favourable toxicity profile. Since 2005, CEPP has been used in Singapore in the upfront treatment of T-NHL patients either with a contraindication to anthracyclines or at physicians' discretion. Our study aimed to assess the efficacy of CEPP in the upfront treatment of T-NHL. Methods A retrospective study of all patients with newly diagnosed T-NHL treated with CEPP with curative intent from 2005-2021 was undertaken across 2 national cancer centers in Singapore. Outcomes of this population was also compared with a 1:1 control group treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) in the same time period, and matched for age, T-NHL subtype, clinical stage and international prognostic index (IPI). Patient demographics, disease characteristics and clinical outcomes (progression free survival, PFS and overall survival, OS) were evaluated. None of the patients had upfront autologous transplantation. Results We identified 34 patients treated with CEPP who met the inclusion criteria. Clinical characteristics were as follows: Median age was 71 (range 39-85), 24 (71%) were male, 26 (76%) had advanced disease (Stage III-IV) and 21 (62%) had a high intermediate or high risk IPI ( IPI 3, 14 (41%) and IPI 4-5, 21 (21%)). The most common T-NHL subtypes were peripheral T-NHL (PTCL-NOS) not otherwise specified, 11 (32%) as well as angioimmunoblastic T cell lymphoma (AITL), 16 (47%). At a median follow up of 20 months (range 2-197months), the median PFS and OS were 17.6mths and 37.2mths respectively for the CEPP group. 15/34 (44%) CEPP patients have died (8 with lymphoma, 2 from treatment toxicity and 5 from unrelated causes). In the matched control comparison, the 5yr PFS and OS were both similar for patients treated with CEPP compared to patients in the CHOP control group, PFS 30% vs 32%, p= 0.43 and OS 47% vs 52%, p = 0.32, respectively (Figure 1) Conclusion Our findings show that CEPP is a well-tolerated regimen which can cure a proportion of patients with T-NHL even without autologous transplantation consolidation. Outcome of these patients do not seem to be significantly different compared to a similar population treated with standard CHOP. This study supports CEPP as a tolerable treatment option for selected patients who cannot tolerate anthracyclines and as an alternative to CHOP regimen for older patients who are not planned for ASCT. Figure 1 Figure 1. Disclosures Jeyasekharan: Turbine Ltd: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Perkin Elmer: Other: travel funding ; MSD: Consultancy.

scholarly journals Immunohistochemical Evaluation and Prognostic Value of Monocarboxylate Transporter 1 (MCT1) and 4 (MCT4) in T-cell Non-Hodgkin Lymphoma

2021 ◽  
Author(s):  
Hu Zhao ◽  
Yuan Chen ◽  
You-Ping Liao ◽  
Hai-Mei Chen ◽  
Qiu-Hong Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Value ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Monocarboxylate Transporter ◽  
Disease Stage ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
Monocarboxylate Transporter 1

Abstract Tumor cells often exhibit the Warburg effect, wherein, they preferentially undergo glycolysis over oxidative phosphorylation for energy production. Monocarboxylate transporter 1 (MCT1) and 4 (MCT4) are critical symporters mediating lactate efflux and preventing intracellular acidification during tumor growth. Numerous studies have focused on inhibiting MCT1 or MCT4 in various cancers. However, its role in T-cell lymphoma (TCL) is not yet investigated owing to the low incidence of TCL. This study was designed to investigate the expression of MCT1/MCT4 in patients with TCL and determine their prognostic value in this cancer. We performed immunohistochemistry to evaluate the expression level of MCT1/MCT4 in 38 TCL tissue samples and then compared their expression among different TCL subgroups, which were formed based on different clinical characteristics. Survival analysis was performed to evaluate the relationship between MCT1/MCT4 expression and both overall survival (OS) and progression-free survival (PFS). Our results revealed that MCT1 and MCT4 expression was significantly increased in TCL tissues compared to the control group. In addition, increased MCT1 expression associated with the female sex, advanced disease stage, increased serum LDH, Ki-67 at ≥50%, and intermediate or high-risk groups as categorized by the International Prognostic Index (IPI) score. We also found that increased MCT1 expression may be associated with reduced OS and PFS. In conclusion, MCT1 and MCT4 are overexpressed in patients with TCL, and may predict poor prognosis. MCT1 inhibition might be a novel treatment strategy for TCL, and further preclinical trials are required.

scholarly journals Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines

2021 ◽  
Vol 5 (5) ◽  
pp. 1483-1489
Author(s):  
Alden A. Moccia ◽  
Kimberly Schaff ◽  
Ciara Freeman ◽  
Paul J. Hoskins ◽  
Richard J. Klasa ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Standard Dose ◽  
Clinical Stage ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Curative Intent ◽  
International Prognostic Index Score ◽  
The Impact

Abstract Doxorubicin plays an integral role in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) but can be associated with significant toxicity. Treatment guidelines of British Columbia (BC) Cancer recommend the substitution of etoposide for doxorubicin in standard-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (R-CEOP) for patients who have a contraindication to anthracyclines; however, it is unknown if this compromises treatment outcome. We identified all patients with newly diagnosed DLBCL who were treated in BC with curative intent with R-CEOP (n = 70) within the study period. Outcome in this population was compared with a 2:1 case-matched control group (n = 140) treated with R-CHOP and matched for age, clinical stage, and International Prognostic Index score. The 10-year time to progression and disease-specific survival were not significantly different for patients treated with R-CEOP compared with patients in the R-CHOP control group (53% vs 62% [P = .089] and 58% vs 67% [P = .251], respectively). The 10-year overall survival was lower in the R-CEOP group (30% vs 49%, P = .002), reflecting the impact of underlying comorbidities and frailty of this population. R-CEOP represents a useful treatment alternative for patients with DLBCL and an absolute contraindication to the use of anthracyclines, with curative potential.

scholarly journals The Relationship Between Hematological Neoplasms and Lipid Profile

2021 ◽  
Author(s):  
Erman Öztürk
Keyword(s):  
Lipid Profile ◽  
Total Cholesterol ◽  
Chronic Diseases ◽  
Hematological Malignancies ◽  
Hematologic Malignancy ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Density Lipoprotein ◽  
Group Method ◽  
Control Group

Objective: Hypocholesterolemia is a metabolism disorder that may be seen in chronic diseases and malignancies. Various dyslipidemia profiles have been shown in adult and pediatric hematological malignancies. We aimed to evaluate the lipid profile properties in patients diagnosed with a hematological malignancy compared to a healthy control group. Method: Out of 1213 patients diagnosed with hematologic malignancy, the data of 98 patients whose pretreatment lipid profiles had already been studied, were reviewed. Forty healthy individuals were selected as the control group. The levels of total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were compared. Results: Triglyceride values were significantly higher (p=0.02), and the total cholesterol, LDL and HDL levels were lower in the study group compared to the control group. Triglyceride values were higher (p=0.013), and HDL levels were lower (p=0.022) in parallel with increases in uric acid levels. There was a significant correlation between the International Prognostic Index (IPI) score and TG (p=0.003) in those diagnosed with non-Hodgkin lymphoma (NHL). Whereas no significant correlation was found between TG, total cholesterol, and LDL values in the limited (early) and advanced stage NHL, while a significant negative correlation was found with HDL (p=0.027). Conclusion: Hypertriglyceridemia, as well as low LDL and HDL values may be seen in hematological malignancies. It should be kept in mind that there may be chronic diseases and malignancies in the etiology of incidental hypocholesterolemia and hypertriglyceridemia. Further studies are needed on this subject to determine the effects of dyslipidemia on the pathogenesis and prognosis of the disease in hematological malignancies.

scholarly journals A Novel Prognostic Index for Patients with EBV-DLBCL NOS: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1436-1436
Author(s):  
Brady E Beltran ◽  
Denisse Castro ◽  
Luis Villela ◽  
Efreen Montaño Figueroa ◽  
Ana Florencia Ramirez-Ibarguen ◽  
...  
Keyword(s):  
Latin American ◽  
Research Funding ◽  
Cox Regression ◽  
International Prognostic Index ◽  
Eastern Cooperative Oncology Group ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
World Health ◽  
Serum Lactate Dehydrogenase ◽  
Latin American Countries

Abstract Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. Current prognostic models such as the Oyama and the International Prognostic Index (IPI) score have limited prognostic value in this patient population. Therefore, we aim to evaluate the ability of these models to risk stratify patients and propose a novel prognostic model in the largest cohort of Latin American patients with EBV+ DLBCL, NOS. Methods: This retrospective cohort study included patients ≥18 years from six Latin American countries diagnosed and treated at tertiary centers from 2010 to 2020. Hematopathologists at each institution reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL, NOS. We collected clinicopathological data by reviewing the medical records of the patients. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last visit. The secondary endpoint, progression-free survival (PFS), was defined as the time from diagnosis until death, progression, or last visit. Our novel model (Grupo de Estudio Latinomericano de Linfoproliferativos [GELL] Score) includes the Eastern Cooperative Oncology Group (ECOG) performance status ≥2, extranodal involvement >1, serum albumin <3.5 g/dL, serum lactate dehydrogenase (LDH) above the upper limit of normal, and platelet-to-lymphocyte ratio >455. We assigned a value of 1 to each of the abovementioned elements in the score and classified the patients as low (0 points), intermediate (1-2 points), and high (3-5) risk. OS and PFS probabilities were computed with the Kaplan-Meier method and compared with the log-rank test. We used Cox regression to evaluate the proportional hazard ratios (HR) of each score for our study outcomes. The C-index was employed to measure discrimination of each model. We used cross-validation to evaluate the model performance. Results: A total of 154 patients with EBV+ DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with a slight male predominance (53%). EBER was positive in all cases (range 1-100%). Clinically, 39% presented ECOG ≥2, 57% had B symptoms, 50% had an extranodal disease as a primary tumor, and 71% had Ann Arbor stage III/IV. Fifty-one percent of the patients had an elevated LDH level, and 43% had albumin <3.5 g/dL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was administered in 79% of individuals as first-line treatment. The overall response rate was 80% (62% complete response and 18% partial response). With a median follow-up of 61 months, the 5-year OS and PFS rates were 61% and 47%, respectively. The 5-year OS rates of patients with low, intermediate, and high-risk disease according to the GELL score was 90%, 59%, and 33%, respectively (Fig 1A). The 5-year PFS rates were 82%, 39%, and 23%, respectively (Fig 2A). Table 1 shows the Cox regression and the discrimination analysis for each of the scores. The GELL score has the highest discriminatory index for OS and PFS compared to the IPI, Revised-IPI, National Comprehensive Cancer Network-IPI, and the Oyama score (Figure 1 and 2). Conclusions: This study proposes a novel score for risk stratification of patients with EBV+ DLBCL, NOS. The GELL score appears to better discriminate OS and PFS than previous scores. Our results should be validated in an independent prospective cohort. Figure 1 Figure 1. Disclosures Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

scholarly journals Itolizumab As a Potential Therapeutic for the Prevention and Treatment of Graft Vs Host Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5603-5603 ◽  
Author(s):  
Cherie Tracy Ng ◽  
Jeanette Ampudia ◽  
Robert J. Soiffer ◽  
Jerome Ritz ◽  
Stephen Connelly
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Vehicle Control ◽  
Control Group ◽  
Employment Equity ◽  
Equity Ownership

Background: CD6 is a co-stimulatory receptor, predominantly expressed on T cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen presentation cells and various epithelial and endothelial tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation, proliferation, differentiation and trafficking and is central to inflammation. While effector T cell (Teff) are CD6hi and upregulate expression upon activation, regulatory T cells (Treg) remain CD6lo/-, making this an attractive target to modulate Teff activity while preserving Treg activity. Early studies by Soiffer and colleagues demonstrated using T12, an anti-CD6 monoclonal antibody (mAb) that ex-vivo depletion of CD6+ donor cells prior to transplantation decreased the incidence of both acute and chronic GVHD, highlighting the importance of CD6+ cells in GVHD pathogenesis and validating it as a therapeutic target. However, it remains to be shown whether modulating the CD6-ALCAM pathway in vivo can attenuate GVHD. We investigated the use of itolizumab, a humanized anti-CD6 mAb that has demonstrated clinical efficacy in other autoimmune diseases, as both a preventive and therapeutic treatment for GVHD, using a humanized xenograft mouse model. Methods: Humanized xenograft mice were generated by intravenous transfer of 2x10^7 human PBMCs into 6-8 weeks old NOD/SCID IL2rγ-null (NSG). To investigate the ability of itolizumab to prevent GVHD, mice were dosed with either 60μg or 300μg of itolizumab, 150μg of abatacept (CTLA4-Ig), or vehicle, starting one day prior to PBMC transplantation. To investigate the therapeutic effect of itolizumab, mice were dosed with either 150μg of itolizumab or vehicle, starting at Day 5 post-PBMC transfer, when transplanted T cells are already activated. All treatments were administered IP every other day. Weight and disease scores were monitored throughout the study. At Days 18 and 35, peripheral blood was evaluated by flow cytometry to examine T cell prevalence, and tissues were collected for histological examination of pathology and T cell infiltration. Results: When administered as prevention (Day -1), treatment with either 60μg or 300μg of itolizumab significantly decreased mortality compared to the vehicle control (100% vs. 10%); this decrease was similar to the positive control group treated with abatacept (Figure 1). At 60μg, itolizumab-treated mice demonstrated significant reductions in the prevalence of human T cells in peripheral blood vs. vehicle-treated mice at Day 18 (<0.2% vs. 74.5%; p < 0.001). The reduction in peripheral T cells was accompanied by reductions in tissue-infiltrating T cells in lung (85-fold) and gut (9.5-fold), as well as reductions in disease scores and weight loss. When administered therapeutically, treatment with itolizumab was associated with a survival rate of 50% compared to 10% in the control group (Figure 2). Similarly, peripheral T cell prevalence (34.3% vs. 65.1%; p < 0.001), weight loss, and disease scores were inhibited by itolizumab compared to vehicle control mice. Conclusions: These data suggest that systemic treatment with itolizumab can modulate pathogenic Teff cell activity, establishing this antibody as a potential therapeutic for patents with GvHD. A phase I/II study using itolizumab as first line treatment in combination with steroids for patients with aGVHD is currently ongoing (NCT03763318). Disclosures Ng: Equillium: Employment, Equity Ownership. Ampudia:Equillium: Employment. Soiffer:Mana therapeutic: Consultancy; Kiadis: Other: supervisory board; Gilead, Mana therapeutic, Cugene, Jazz: Consultancy; Juno, kiadis: Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Cugene: Consultancy; Jazz: Consultancy. Ritz:Equillium: Research Funding; Merck: Research Funding; Avrobio: Consultancy; TScan Therapeutics: Consultancy; Talaris Therapeutics: Consultancy; Draper Labs: Consultancy; LifeVault Bio: Consultancy; Celgene: Consultancy; Aleta Biotherapeutics: Consultancy; Kite Pharma: Research Funding. Connelly:Equillium: Employment, Equity Ownership.

A Multicenter Clinicopathologic Experience of HTLV-1 ATLL: A Retrospective 15 Year Review Reveals Little Progress.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3569-3569
Author(s):  
Adrienne A. Phillips ◽  
Iuliana Shapira ◽  
Robert D. Willim ◽  
Jasotha Sanmugarajah ◽  
William B. Solomon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Latin America ◽  
T Cell ◽  
Median Overall Survival ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Presenting Symptoms ◽  
The Us ◽  
The Caribbean

Abstract Adult T cell Leukemia/Lymphoma (ATLL) is a rare manifestation of Human T-Lymphotropic Virus type 1 (HTLV-1) which is endemic in Japan, the Caribbean, and regions of Africa and Latin America. Endemic regions have also been identified in the US, primarily where immigrants of endemic countries reside. The NYC metropolitan area has the greatest number of Caribbean-born immigrants to the US which has formed the basis for this retrospective review. A diagnosis of ATLL was made according to the following criteria: a clinical history consistent with ATLL; a positive HTLV-1 antibody by ELISA and Western Blot, or evidence of HTLV-1 proviral integration by PCR; and histological findings compatible with ATLL. A total of 89 patients were identified at 3 institutions in NYC from 8/92 to 5/07. There were 37 men and 52 women with a median age of 50y (range 22 to 82y). All but 6 patients had immigrated to the US from the Caribbean, Latin America or Africa, and the majority were from Jamaica (25.8%) and the Dominican Republic (19.1%). The acute subtype predominated (68.5%), followed by the lymphomatous (20.2%), chronic (6.8%) and smoldering (4.5%) subtypes. The most common presenting symptoms were lymphadenopathy (80.9%) and skin rash (39.3%) and the median ECOG performance status was 3. WBC counts ranged from 3.0 to 334.0 x 109/l (median of 12.5 X 109/l). Hypercalcemia was seen in 71.9% of patients (median calcium level of 13.5 mg/dl, range 9.8 to 27.0 mg/dl). Twenty-eight patients (31.5%) had CNS involvement during their course. The median International Prognostic Index (IPI) was 4. Most patients received a combination-alkylator based chemotherapy regimen in the frontline setting (ex: CHOP) (61.3%), with an overall response rate (ORR) to the frontline treatment of 58.2%. Twenty patients (20.2%) received AZT and IFN at sometime during their course with an ORR of 25%. Twelve patients (13.5%) received a biologically based therapy at sometime during their course, with only two patients achieving a partial response (to alemtuzamab and denileukin diftitox). Despite initial responses to therapy, the median overall survival for all subtypes was 6 mos (range 0.5 to 78.5 mos). Median survival for specific subtypes was noted to be: 4 mos for the acute subtype (range 0.5 to 78.5 mos); 9 mos for the lymphomatous subtype (range 1 to 63 mos), 17 months for the chronic subtype (range 5 to 22 mos) and 34 mos for the smoldering subtype (range 16 to 48 mos). Conclusion: This retrospective series represents one of the largest North American experiences to date among primarily Caribbean descendants. Interestingly, when placed into the context of other experiences published over the past 30 years, it is clear there has been little to no change in the outcome of patients diagnosed with this disease. In fact, this population, with a median overall survival of only 6 mos, represents one of the poorest outcomes reported for any sub-type of lymphoma. These data suggest that radically new ATLL directed therapies are needed. The recent development of several new T-cell active agents, in addition to other strategies (ex: transplantation) need to be specifically studied in this population.

Clinical Usefulness and Prognostic Value of Interim PET/CT for the Treatment of Peripheral T Cell Lymphomas.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2808-2808
Author(s):  
Deok-Hwan Yang ◽  
Jung-Joon Min ◽  
Ho-Chun Song ◽  
Yong Yeon Jeong ◽  
Soo-Young Bae ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Predictive Value ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Interim Pet ◽  
Pet Ct

Abstract Abstract 2808 Although interim 18F-fluoro-2-dexoy-D-glucose-positron emission tomography (FDG-PET)/computerized tomography (CT) scan has emerged as a powerful prognostic tool in predicting treatment outcome in Hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL), the positive predictive value (PPV) of interim PET/CT scanning has not been determined in patients with peripheral T cell lymphoma (PTCL). The sequential interim PET/CT was prospectively investigated to determine whether it provided additional prognostic information and could be a positive predictable value for the treatment of PTCL. Patients and Methods: Fifty-five newly diagnosed patients with PTCL were enrolled from Sep. 2005 to July 2009 at a single institution. The PET/CT analysis was performed at the time of diagnosis and mid-treatment of CHOP/CHOP-like or other chemotherapy (EPOCH and IMEP). The clinical stage and response of the patients were assessed according to revised response criteria for aggressive lymphomas (Cheson, J Clin Oncol, 2007). The positivity of interim PET/CT was determined based on the semi-quantitative assessment of the maximal standardized uptake value (Cut-off SUVmax value of 3.0). Results: Median age was 55 years (range: 23–77). 31 patients (56.4%) presented in advanced stages and 13 (23.6%) had bone marrow involvements. The histological subtypes were 40.0% PTCL-unspecified (n=22), 5.1% angioimmunoblastic T cell (n=5), 38.2% nodal or extranodal NK/T cell (n=21), and others. At diagnosis, 24 patients (43.6%) were classified as high-risk by the international prognostic index (IPI) and 22 (40%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). 47 patients could be assessed the interim response and 24 patients (43.6%) remained positive metabolic uptakes in interim PET/CT. The patients with positive interim PET/CT showed a significantly higher relapse rate (75.0%) than those with negative interim PET/CT (43.5%) (P =0.028). After following median 12.7 months, positivity of interim PET/CT was the prognostic factor for both OS and PFS, with a hazard ratio of 4.11 (1.30 – 13.01) and 3.26 (1.19 – 8.96), respectively. Six patients (10.9%) who determined to have positive interim PET/CT were revealed false-positive uptakes after locoregional biopsy (PPV of 0.75). Conclusions: Interim PET/CT has a significant predictive value for disease progression and survival of PTCL. The patients with positive interim PET/CT response should be considered an intensive therapeutic plan for overcoming their poor clinical outcome. Disclosures: No relevant conflicts of interest to declare.

Efficacy of a Dose-Intensified CHOP (Double-CHOP) Regimen for Peripheral T-Cell Lymphomas

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4855-4855
Author(s):  
Hiromichi Takahashi ◽  
Noriyoshi Iriyama ◽  
Yoshihiro Hatta ◽  
Katsuhiro Miura ◽  
Yujin Kobayashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
High Dose ◽  
Chop Regimen ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 4855 Background: Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of non-Hodgkin lymphomas, often resulting in poor prognoses. The CHOP chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, had been used previously to treat other types of lymphomas. Here, we examined the efficacy and safety of a dose-intensified CHOP regimen (Double-CHOP), which was followed by autologous stem-cell transplantation (ASCT) or high-dose methotrexate (HDMTX), in PTCL patients. Patients and Methods: Twenty-eight PTCL patients, who received 3 courses of Double-CHOP at our institution, were retrospectively studied from 1996 to 2012. Patients with anaplastic lymphoma-kinase-positive anaplastic large-cell lymphoma (ALK+–ALCL) were excluded from this study. The Double-CHOP regimen consisted of 3 courses of intravenous (iv) administration of cyclophosphamide (750 mg/m2, days 1–2, over 2 h), doxorubicin (50 mg/m2, days 1–2, over 30 min), vincristine (1.4 mg/m2, day 1, max 2 mg/Kg body weight), and per os (p.o.) prednisone (50 mg/m2, days 1–5). For patients aged >60, cyclophosphamide and doxorubicin doses were modified. The third cycle of Double-CHOP regimen was used for stem cell mobilization. Consolidating high-dose therapy (HDT) regimen consisted of cyclophosphamide (60 mg/kg, day 6 and 7, iv, over 3 h), etoposide (500 mg/m2; day 4, 5, and 6; iv; over 6–8 h), and ranimustine (250 mg/m2, day 2 and 3, iv, over 1 h). ASCT was performed on day 0 and G-CSF administered from day 1 until neutrophil engraftment. As an alternative to HDT/ASCT, HDMTX (8 g/m2, day 1, iv, over 4 h) was indicated for patients who could not yield a sufficient number of stem cells or were ineligible for HDT/ASCT. Results: Patients' median age was 58 years (range: 17–69). They had low-intermediate (n = 11), high-intermediate (n = 10), or high (n = 7) risk according to the International Prognostic Index (IPI). The overall complete remission (CR) rate following Double-CHOP treatment was 68%. Of all the CR patients, 10 could successfully tolerate a consolidated HDT followed by ASCT, and 7 received HDMTX. Only a single case of treatment-related mortality was recorded during the study. On a median 31-month follow-up, the estimated 3-year overall survival (OS) rate and 3-year relapse-free survival (RFS) rate after CR were 68% and 60%, respectively. Conclusion: Although this study included elderly and excluded low-risk IPI and ALK+–ALCL patients, both RFS and OS results were superiorly favorable, indicating the efficacy of this Double-CHOP regimen and Double-CHOP followed by ASCT/HDMTX consolidations is safe and may achieve prolonged EFS, especially in patients with poor prognostic factors. However, an effective treatment strategy for refractory or relapsing patients needs to be validated and established. Disclosures: No relevant conflicts of interest to declare.

Safety and Efficacy Of Bendamustine In Patients With Aggressive Non-Hodgkin Lymphomas (NHL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4371-4371 ◽  
Author(s):  
Jakob Hammersen ◽  
Michael Sommer ◽  
Christin Gössel ◽  
Ulf Teichgräber ◽  
Sabine Hahnfeld ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
Sustained Remission ◽  
Cox Regression Analysis ◽  
Line Therapy

Abstract Introduction Frail patients with aggressive NHL frequently do not qualify for CHOP-based chemotherapy. Alternatives are required urgently. Bendamustine has been well established as a standard treatment of indolent lymphomas. Its use in high grade lymphoma has been suggested as a promising option. However, which patients benefit most effectively requires further clarification. Methods We retrospectively characterized 51 unselected consecutive patients (39,2% female, 60,8% male, median age 70 years, range 32 - 92 years) with aggressive NHL treated with bendamustine +/- rituximab. They were analyzed for baseline characteristics (histological type, IPI, ABC/GCB-subtypes, age, ECOG, comorbidity (CIRS-G), outcome (ORR, PFS, OS), and toxicity (CTCAE)). Results 21 patients with aggressive NHL received Bendamustin as 1st-line therapy and 30 patients beyond 1st-line. Of the 1st line patients 14 suffered from diffuse large cell B cell lymphoma (DLCBL), 5 from mantle cell lymphoma (MCL), and 2 from other subtypes. In 1st line patients median age was 82 years, ECOG-status was ≥ 2 in 38%. Median international prognostic index (IPI) was 3 (range 1-4). Comorbidity assessment by CIRS-G revealed median 3 (range 1 to 5) severely or very severely affected organs. The overall response rate (ORR) in 1st line treatment was 91%, with a median progression free survival (PFS) of 6 months and a median overall survival (OS) of 15 month. In DLBCL 5 GCB- and 6 ABC-lymphomas were differentiated. GCB-patients showed an ORR of 80% (2 complete remission (CR), 2 partial remission PR)), a median PFS 8 month and OS of 15 months, respectively. ABC-patients had an ORR 67% (no CR, 4 PR, 2 SD), a median PFS of 6 month and OS of 8 months, respectively (n.s.). 7 patients achieved a long term-remission >5 years. Univariate analysis of prognostic variables showed significance for ECOG (p<0.0001) and CIRS-G (p=0.002) for OS, Cox-regression analysis showed significance for ECOG (p=0.016). No significance was shown for disease stage or LDH activities. The ORR in patients beyond 1st-line therapy (median age 64 years, ECOG-status ≥ 2 in 17%) was 66% with a median PFS of 8 month and OS of 24 month. Median cumulative dose was 540 mg/m2 in median 4 cycles. Toxicity in the 1st-line cohort was moderate, mainly grade 1 & 2. Three patients showed grade 3 leukocytopenia. Other side effects primarily were: inappetence, weight-loss, fever. Conclusion Bendamustine shows high efficacy in aggressive NHL, even sustained remission was achieved by a subgroup, which requires further definition. Toxicity was well manageable. Defining prognostic parameters we showed GCB-subtype of DLBCL might predict a better outcome in bendamustine treated patients. Remarkably, performance and comorbidity assessment is of crucial prognostic value with a greater impact on outcome compared to classic parameters. Currently, the BRENDA trial (NCT01686321) prospectively investigates the role of bendamustine in aggressive NHL. Disclosures: Off Label Use: Use of Bendamustine in aggressive NHL. Wedding:Roche: Speakers Bureau; Amgen: Speakers Bureau; Chugai: Speakers Bureau; Janssen-Cilag: Speakers Bureau; Novartis: Speakers Bureau; Cephalon: Speakers Bureau; Prostarkan: Speakers Bureau; Pfizer: Speakers Bureau. La Rosée:Mundi Pharma: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document