pirarubicin and Lymphoma--Non-Hodgkin

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CD2 Antigens; CD4 Antigens; CD56 Antigen; Cyclophosphamide; Doxorubicin; Female; Humans; Immunophenotyping; Karyotyping; Lymphoma, Non-Hodgkin; Male; Middle Aged; Nasopharyngeal Neoplasms; Prednisone; Skin; Skin Neoplasms; Spinal Cord Neoplasms; Vincristine

We studied the remission rate and adverse effects in THP-COPBLM therapy consisting of pirarubicin (THP), which is said to be less cardiotoxic than doxorubicin. Subjects were 21 non-Hodgkin's lymphoma (NHL) patients older than 70 years of age. Of 21 patients, complete remission (CR) was achieved in 16 patients (76.2%) and partial remission in 2 patients (9.5%). Classified by stages, CR was achieved in 5 out of 6 patients in stage II, 7 out of 8 in stage III and 4 out of 7 in stage IV. Two-year survival rate was 61.5%. Adverse effects were observed in 7 patients (33.3%) with grade 3 or above leukocytopenia, 2 (9.5%) with thrombocytopenia and 1 (4.8%) with gastrointestinal symptoms. However, no abnormality in EKG was found, and the left ventricular ejection fraction in echocardiography did not differ before and after therapy. One patient each developed pneumonia and sepsis when they had granulocytopenia. THP-COPBLM therapy seemed useful in treatment of elderly patients with NHL. There were few adverse effects such as gastrointestinal symptoms or cardiotoxicity. However, leukocytopenia was observed in many patients despite combined use of G-CSF, suggesting the dose and administration method of THP should be studied further.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leukopenia; Lymphoma, Non-Hodgkin; Male; Prednisolone; Procarbazine; Remission Induction; Vincristine

Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2"R)-4'-O-tetrahydropyranyladriamycin (THP). THP (10-55 mg/m2) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3-4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m2 THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR + PR) was noted in 10 (40%) of 25 patients treated every 3-4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Clinical Trials as Topic; Doxorubicin; Drug Administration Schedule; Electrocardiography; Female; Heart; Hodgkin Disease; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Naphthacenes

Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography-tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1-500 ng/mL for THP, 2-1000 ng/mL for DOX, 2.5-1250 ng/mL for CTX, and 3-1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from -0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromatography, High Pressure Liquid; Cyclophosphamide; Doxorubicin; Humans; Indicator Dilution Techniques; Lymphoma, Non-Hodgkin; Tandem Mass Spectrometry; Vincristine

Pirarubicin is an analog of doxorubicin. Few studies have compared the long-term outcomes of patients receiving pirarubicin-based THP-COP and doxorubicin-based CHOP in the treatment of non-Hodgkin's lymphoma (NHL). We retrospectively compared the efficacy and safety of these two regimens in 459 previously untreated aggressive NHL patients admitted to Sun Yat-Sen University Cancer Center from 1987 to 2003. For initial treatment, 205 patients received the THP-COP regimen, and 254 patients received the CHOP regimen. The patients' characteristics were well balanced. The groups did not differ in the complete remission rate (THP-COP, 57.1% vs. CHOP, 57.0%; P = 0.998) or response rate (THP-COP, 82.9% vs. CHOP, 81.5%; P = 0.691). At a median follow-up of 95.7 months, the 8-year survival rates were also similar (overall survival: THP-COP, 55.8% vs. CHOP, 56.7%; progression-free survival: THP-COP, 47.3% vs. CHOP, 43.5%; lymphoma-specific survival: THP-COP, 51.2% vs. CHOP, 48.5%). The THP-COP group had fewer cases of alopecia (P < 0.001) and gastrointestinal toxicities (P = 0.015). A tendency toward decreased arrhythmia (P = 0.075), especially in elderly patients (P = 0.030), was found. In combination chemotherapy for aggressive NHL, pirarubicin has comparable efficacy to doxorubicin and has a lower incidence of alopecia, gastrointestinal toxicities, and arrhythmia. Further studies are warranted to confirm these results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Remission Induction; Retrospective Studies; Survival Analysis; Treatment Outcome; Vincristine; Young Adult

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Doxorubicin; Female; Humans; Infusions, Intravenous; Lymphoma, Non-Hodgkin; Male; Middle Aged; Pain; Risk Factors; Veins

We report a case of primary leptomenigeal lymphoma (PLML) in an 11-year-old boy presenting with headache, vomiting, and diplopia. The patient was treated on an advanced non-Hodgkin lymphoma protocol with systemic/intrathecal chemotherapy without cranial radiotherapy. He remains in complete remission 33 months after treatment.

Topics: Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Child; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 8; Cyclophosphamide; Cytarabine; Dexamethasone; Diplopia; Doxorubicin; Facial Paralysis; Headache; Humans; Hydrocortisone; Lymphoma, Non-Hodgkin; Male; Meningeal Neoplasms; Methotrexate; Prednisolone; Remission Induction; Translocation, Genetic; Vincristine

To analyse the effectiveness and toxicity of combined chemotherapy regimen containing pirarubicin (THP) in the treatment of non-Hodgkin's lymphoma (NHL).. Three hundred and ninety two patients with NHL were treated by THP containing regimen with or without involved field radiotherapy. The clinical characteristics, response, toxicity and long-term survival rates were analysed.. The median age of the patients was 47 (5 - 87) years and 26.0% aged more than 60 years. 61.0% of the patients were males and 39.0% females. B-cell and T/NK cell NHL accounted for 68.4% and 23.2% respectively with 56.9% of diffuse large B cell lymphoma and 12.5% of peripheral T cell lymphoma. 92.6% of the patients were ECOG < 1, 63.2% in stage I + II, 84.7% with IPI score 0 - 2 and 25% with B symptoms, 93.9% (368/392) of the patients received CTOP (containing THP) regimen chemotherapy and among them 28.5% (112/392) plus involved field radiotherapy. Altogether 1598 courses were administered on 368 patients. The overall response rate was 88.5% (341/385) with a complete remission (CR) rate of 63.6%, major toxicity was myelosuppression with 12.8%, 1.0% and 1.5% of grade III - IV neutropenia, thrombocytopenia and anemia, respectively. G-CSF support was given for 553 courses (34.6%). Alopecia account for 19.8%. The incidence of mild cardiotoxicity was 5.8%. Treatment-related mortality was 1.6% (6/368). Median follow-up was 24 months. The 1, 3 and 5 year actuarial survival rates were 86.4% , 66.5% and 59.2%, respectively. Median survival time has not been achieved.. The efficacy of THP based regimen CTOP for the treatment of aggressive NHL is promising. Further clinical trial is warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Doxorubicin; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Survival Rate; Treatment Outcome

To address the issue of salvageability in relapsed children with NHL who had all received the same frontline therapy, we retrospectively studied the treatment response and the outcome of 27 children who relapsed following the CCLSG-NHL890 protocol. The reinduction rates and 3-year survival rates (mean +/- SD) were as follows: lymphoblastic lymphoma (LB, n = 9), 44% & 17 +/- 14%; leukemia lymphoma syndrome (LLS, n = 8), 25% & 0%; large cell lymphoma (LC, n = 3) 100% & 67 +/- 27%; Burkitt's lymphoma (B, n = 7) 0% & 0%. Thus, the salvageability of LC lymphoma was good, but the outcome of Burkitt's lymphoma was very poor. CCLSG-NHL960 protocol for LB lymphomas and intensive multiagent regimens for LC lymphomas produced favorable response rates, but the effect of the high-dose Ara-C regimen for Burkitt's lymphoma was not determined. The initial stages of the disease seemed to be associated with the patient outcome: the outcome of the patients in stage IV was inferior to that of patients in stages II or III. Other clinical variables, such as relapse sites, relapse time and BM rescue did not affect the patients' outcome.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Lymphoma, Non-Hodgkin; Male; Methotrexate; Prednisolone; Prognosis; Recurrence; Retrospective Studies; Salvage Therapy; Survival Rate; Vincristine

123I-metaiodobenzylguanidine (MIBG) myocardial single photon emission computed tomography (SPECT), 123I-beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial SPECT, and holter ECG recording were performed in patients with non-Hodgkin's lymphoma who underwent chemotherapy including pirarubicin (THP), in an attempt at early detection of cardiac toxicity from THP. Twenty-six patients with untreated non-Hodgkin's lymphoma who received THP-COPBLM therapy were studied. For THP-COPBLM therapy. THP was administered at a dose of 40 mg/m2 every 21 days and the total dose was 250 mg/m2 on average (40 approximately 400 mg/m2). 1) The washout rate (WR) correlated with the total THP dose, and was considered to be a useful index of cardiac sympathetic nervous dysfunction. 2) The left ventricular ejection fraction (LVEF) correlated negatively with the total dose of THP. 3) The total dose of THP showed a correlated positively with the extent score and severity score determined by BMIPP. 4) The WR correlated with the frequency of premature ventricular contraction. Animal studies have indicated that THP has less cardiac toxicity than doxorubicin, but the present study showed that cardiac toxicity occurred at a total THP dose of about 360 mg/m2 in elderly patients. Accordingly, when THP is used to treat elderly patients, multimodal evaluation of cardiac is necessary to detect cardiotoxicity and to determine the optimal dosage.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Electrocardiography, Ambulatory; Fatty Acids; Granulocyte Colony-Stimulating Factor; Heart; Humans; Iodine Radioisotopes; Iodobenzenes; Lymphoma, Non-Hodgkin; Prednisone; Procarbazine; Tomography, Emission-Computed, Single-Photon; Vincristine

THP-COPBLM including pirarubicin (THP), which is thought to be less toxic than doxorubicin, was used to treat non-Hodgkin's lymphoma (NHL) and the remission rate and adverse effects were studied in 26 patients older than 70 years. Complete remission (CR) was achieved in 19 patients (73.1%) and partial remission in three (11.5%). Classified by stages, CR was achieved in seven out of nine stage II patients and 12 out of 17 stage III, IV patients. The 2-year survival rate was 60.3%. Grade 3 or higher adverse effects included leukopenia in eight patients (30.8%), anemia in three (11.5%), thrombocytopenia in two (7.7%) and nausea/vomiting in 1 (3.8%). The THP-COPBLM regimen appears useful for the treatment of NHL in elderly patients. The regimen was seldom associated with gastrointestinal symptoms and cardiotoxicity. Despite the administration of granulocyte colony-stimulating factor (G-CSF), however, the white blood cell count decreased in many patients, suggesting the necessity for further study of this regimen to modify the dose of THP.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Non-Hodgkin; Male; Prednisone; Procarbazine; Prospective Studies; Survival Analysis; Treatment Outcome; Vincristine

Non-Hodgkin's lymphoma (NHL) of the thyroid gland is a rare disease. In the present study, the survival rate and characteristics were retrospectively analyzed in 22 patients with stage IE and IIE thyroid NHL treated with radiotherapy with or without combination chemotherapy. Seventeen NHL had histological evidence of lymphoma of mucosa-associated lymphoid tissue (MALT) type. The 5-year survival rate was 85% in all patients, with 100% and 63% respectively, for stage IE and stage IIE patients. The highly significant factor correlated with decreased determinate survival was concomitant stridor.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Follow-Up Studies; Humans; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neoplasm Staging; Prednisolone; Respiratory Sounds; Retrospective Studies; Survival Rate; Thyroid Neoplasms; Vincristine

Twenty-eight patients with non-Hodgkin's lymphoma (NHL) were treated with a combination of (2''-R)-4'-o-tetrahydropyranyladriamycin (pirarubicin, THP), cyclophosphamide, vincristine, and prednisolone (VEP-THP therapy). Eleven (45.8%) of twenty-four evaluable patients achieved complete response (CR). CR rate (52.8%) was higher in the intermediate-grade histology group than in high- or low-grade group. Toxicity was generally acceptable although leukopenia less than 2,000/microliters was observed in 17 (60.7%) of 28 patients. Clinical signs of cardiotoxicity were not observed and alopecia was mild. Therefore, VEP-THP therapy is useful as a first-line chemotherapy in the treatment of NHL, particularly for the patients with intermediate-grade histology. Higher CR rate and longer relapse-free survival can be expected by administering a greater dose of THP or employing a schedule of fractionated low doses.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisolone; Vincristine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisolone; Prednisone; Remission Induction; Vincristine

Thirty-eight patients with adult acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) were treated intravenously with (2"-R)-4'-o-Tetrahydropyranyladriamycin (THP) at a dose of 10 mg/m2 for 5 consecutive days. Seven complete and 15 partial responses were observed in 35 evaluable patients (overall response rate, 62.8%). Both antitumor activity and antitumor spectrum were similar to those for doxorubicin. Since the patients who had had chemotherapy previously, including other kinds of anthracycline, responded rather poorly to THP, cross-resistance between THP and other anthracyclines may be present. Leukopenia and thrombocytopenia were dose-limiting factors. Nausea and vomiting episodes were mild, and epilation was also minimal. Although the observation period was short and a cumulative dose was not large enough to evaluate cardiotoxicity, there were no abnormal EKG changes or clinical signs of cardiotoxicity in this study. THP is a potent antitumor agent in the treatment of lymphoid malignancies.

Topics: Adult; Aged; Doxorubicin; Female; Humans; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Retrospective Studies