pirarubicin and Lymphoma--Large-B-Cell--Diffuse

A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; CD5 Antigens; Cyclophosphamide; Doxorubicin; Female; Herpesvirus 4, Human; Humans; Iatrogenic Disease; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Mixed Connective Tissue Disease; Prednisolone; Rituximab; Sjogren's Syndrome; Tacrolimus; Vincristine

Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2 months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P = .82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP.

Topics: Adult; Age Factors; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisolone; Prednisone; Prospective Studies; Rituximab; Survival Rate; Vincristine

We previously described the effectiveness of the THP-COP regimen comprising cyclophosphamide, pirarubicin (tetrahydropyranyl adriamycin; THP), vincristine and prednisolone in patients with diffuse large B-cell lymphoma (DLBCL). The anthracycline drug THP was apparently less cardiotoxic than doxorubicin. However, that study was completed before rituximab was introduced into clinical practice. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) against DLBCL.. Six to 8 courses of the regimen were administered every 2 weeks in 48 patients who were younger than 70 years.. The complete remission rate was 92%, the 3-year overall survival rate was 83% and 3-year progression free survival rate was 74%. No deaths were associated with the treatment regimen.. We conclude that R-THP-COP regimen is very effective against DLBCL. The results of our study urge randomized trials of R-CHOP and R-THP-COP among patients with CD20+ DLBCL.

Topics: Aged; Anemia; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Nausea; Neutropenia; Prednisolone; Rituximab; Survival Analysis; Treatment Outcome; Vincristine

In the NHL960 non-LB study, we treated diffuse large B-cell lymphoma (DLBCL) using a short-term ALL-like protocol. Thirty children up to 16 years of age with DLBCL were stratified into group 1 with stage I/II disease, or group 2 with stage III/IV disease. Their ages ranged from 9 months to 16 years of age, with a median of 9 years of age. The Murphy's stages were stage I in 7, stage II in 10, stage III in 6, and stage IV in 7 subjects. They received an ALL-like treatment without prophylactic cranial irradiation for 6 or 9 months. All children achieved a complete remission. Two patients with stage 3 disease experienced recurrences at 18 and 37 months after the start of chemotherapy. They responded to a short intensive regimen with Rituximab, followed by stem cell transplantation, and are alive without disease. The follow-up time ranged from 41 to 124 months with a median of 80 months. For all patients analyzed in this study, their overall survival and event-free survival (EFS) at 7-years was 100% and 93% +/- 4%, respectively. The 7-year EFS according to the treatment group was 100% for group 1, and 83% +/- 11% for group 2, respectively.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Follow-Up Studies; Humans; Infant; Japan; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisolone; Remission Induction; Survival Analysis; Treatment Outcome; Vincristine

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Alanine Transaminase; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Case-Control Studies; Cyclophosphamide; DNA, Viral; Doxorubicin; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Incidence; Induction Chemotherapy; Japan; Liver Function Tests; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Retrospective Studies; Rituximab; Survival Analysis; Vincristine; Virus Activation

The proportion of elderly patients with diffuse large B cell lymphoma (DLBCL) appears to be increasing, with outcomes varying widely because of the patients' heterogeneity. Geriatric assessment is used to predict prognosis in elderly patients with DLBCL, but the utility of two simple screening tools for patients with DLBCL, the Flemish version of the Triage Risk Screening Tool (fTRST) and G8, has remained to be elucidated. We retrospectively assessed patients using fTRST and G8, and evaluated the impacts of the scores on survival outcomes in older patients with newly diagnosed DLBCL. A total of 59 patients aged 65 years or older and who were diagnosed with DLBCL were included. The median age was 77 years (range, 65-91 years), and the initial treatments were R-CHOP (63%) and R-THPCOP (31%). The estimated 2-year overall survival (OS) rate was significantly lower in patients with abnormal fTRST scores (≥ 2; N = 17) than in those with normal fTRST scores (< 2; N = 42): (50.5% (95% CI, 22.7-73.0%) vs. 82.2% (95% CI, 63.8-91.8%), P = 0.007). The estimated 2-year OS rate was significantly lower also in patients with abnormal G8 scores (≤ 14; N = 38) than in those with normal G8 scores (> 14; N = 21): (66.1% (95% CI, 46.7-79.5%) vs. 86.8% (95% CI, 55.7-96.7%), P = 0.03, respectively). These associations were independently significant after adjusting for other significant factors by multivariate analysis. These results suggest that the easy-to-use geriatric screening tools, fTRST and G8, have strong prognostic value for OS in older patients with DLBCL.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Geriatric Assessment; Humans; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse; Male; Mass Screening; Prednisolone; Prognosis; Retrospective Studies; Rituximab; Treatment Outcome; Vincristine

Topics: Abdominal Neoplasms; Aged; Antineoplastic Combined Chemotherapy Protocols; Antirheumatic Agents; Arthritis, Rheumatoid; Cyclophosphamide; Doxorubicin; Female; Heart Failure; Heart Neoplasms; Heart Ventricles; Humans; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Methotrexate; Prednisolone; Tomography, X-Ray Computed; Vincristine

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Cyclophosphamide; Doxorubicin; Elder Nutritional Physiological Phenomena; Female; Geriatric Assessment; Hospitals, Urban; Humans; Japan; Lymphoma, Large B-Cell, Diffuse; Male; Malnutrition; Middle Aged; Neoplasm Staging; Nutrition Assessment; Prednisone; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk; Rituximab; Survival Analysis; Tumor Burden; Vincristine

The treatment of patients with diffuse large B cell lymphoma (DLBCL) would be greatly facilitated with a rapid method for determining prognosis that can be performed more easily and earlier than cytological or specific pathological examinations. It has been suggested that newly diagnosed patients with DLBCL who have low maximum standard uptake value (SUV(max)) on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) are more likely to be successfully treated and remain in remission compared with patients with high SUV(max), but this concept has been poorly studied. We retrospectively analyzed 50 patients with de novo DLBCL to evaluate the relationship between the SUV(max) and disease progression. For patients with low SUV(max) (n = 10) and high SUV(max) (n = 40) (P = 0.255), respectively, the 3-year overall survival rates were 90 and 72 %, and the progression-free survival (PFS) rates were 90 and 39 % (P = 0.012). By multivariate analysis, the revised International Prognostics Index (R-IPI) and SUV(max) at diagnosis were shown to predict longer PFS. The 3-year PFS for patients with low SUV(max) classified into the good prognosis group by R-IPI was 100 vs. 62 % for those with high SUV(max) (P = 0.161), and patients with low SUV(max) classified into the poor prognosis group by R-IPI was 80 vs. 18 % for those with high SUV(max) (P = 0.050). We conclude that the SUV(max) on FDG-PET for newly diagnosed patients with DLBCL is an important predictor of disease progression, especially for patients with poor prognosis by R-IPI.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Patient Selection; Positron-Emission Tomography; Prednisolone; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Retrospective Studies; Rituximab; Treatment Outcome; Vincristine

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Cyclophosphamide; Doxorubicin; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenine; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Osmolar Concentration; Prednisolone; Prednisone; Prognosis; Retrospective Studies; Rituximab; Vincristine; Young Adult

We describe a 14-year-old boy who exhibited left palatine tonsillar enlargement after 6 cycles of aggressive chemotherapy for diffuse large B-cell lymphoma of the right palatine tonsil. The cervical computed tomography scan at 4 months after completion of chemotherapy revealed enlargement of the left palatine tonsil in addition to the thymus without any clinical symptoms. The F-fluorodeoxyglucose positron emission tomography indicated focal areas of strong F-fluorodeoxyglucose uptake in the left palatine tonsil. Histologic examination confirmed tonsillar hyperplasia with no evidence of recurrence. Reactive tonsillar hyperplasia after chemotherapy is rarely reported.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Fluorodeoxyglucose F18; Humans; Hyperplasia; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Neoplasm Staging; Palatine Tonsil; Positron-Emission Tomography; Prednisolone; Radiopharmaceuticals; Tonsillar Neoplasms; Vincristine

A 76-year-old man presented with fever of unknown origin and renal dysfunction. Laboratory examination revealed anemia, thrombocytopenia, hypoalbuminemia, proteinuria, and elevations of C-reactive protein, lactic dehydrogenase, creatinine and ferritin. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging showed FDG accumulation in the renal cortex and spleen. Based on the imaging study, renal biopsy was performed and histological diagnosis of intravascular large B-cell lymphoma (IVLBCL) was made. Renal impairment due to IVLBCL is uncommon and is often difficult to diagnose early. FDG-PET/CT may be a useful tool for the early diagnosis of IVLBCL.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Fever of Unknown Origin; Fluorodeoxyglucose F18; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Positron-Emission Tomography; Prednisolone; Radiopharmaceuticals; Renal Insufficiency; Rituximab; Tomography, X-Ray Computed; Treatment Outcome; Vascular Neoplasms; Vindesine

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Drug Evaluation; Female; Genes, bcl-2; Humans; Immunotherapy; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; NF-kappa B; Prednisolone; Retrospective Studies; Rituximab; Survival Analysis; Treatment Outcome; Vincristine

A 76-year-old woman was admitted with a one-month history of low grade fever and dizziness. She had a palpable right supraclavicular lymph node. Abdominal ultrasonography showed swollen lymph nodes around the abdominal aorta. A specimen from the right supraclavicular lymph node showed malignant lymphoma (diffuse large B cell type). We started chemotherapy according to the low-dose THP-COP protocol (pirarubicin, cyclophosphamide, vincristine and prednisolone) on the 31st hospital day. Since no adverse effects were detected after two low-dose cycles, the patient received a third course with standard doses on the 87th hospital day. The total dose of pirarubicin was 72 mg/m2. Two days after the third course started, she suffered from dyspnea caused by congestive heart failure. A chest X-ray showed advanced cardiomegaly, severe congestion and bilateral pleural effusion. These conditions improved with transvenous administration of diuretics, a vasodilator and phosphodiesterase inhibitor. In this case, congestive heart failure developed even though the total dose of pirarubicin was lower than in previous reports of this complication. When the THP-COP protocol is indicated in elderly patients, cardiotoxicity should be monitored even if the total dose of pirarubicin is very low.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Heart Failure; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Prednisolone; Vincristine

A 33-year-old house wife with malignant lymphoma in the lesser omentum was treated with a combination of surgery and VEP-THP chemotherapy (consisting of pirarubicin, cyclophosphamide, fildesin and predonine). Complete remission has been observed by reduction surgery and subsequent chemotherapy of VEP-THP. Although mild bone marrow suppression was seen during the chemotherapy, gastrointestinal toxicity and alopecia were minimal, which led to 10 complete courses of VEP-THP regimen. The patient has been in good health 5 years after the operation with no sign of recurrence. This case indicates that even advanced malignant lymphoma may be successfully treated with a combination of surgery and proper chemotherapy.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Omentum; Peritoneal Neoplasms; Remission Induction; Vindesine