Randomized phase II study of biweekly CHOP and dose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9505.

BACKGROUND: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for first-line chemotherapy in aggressive non-Hodgkin's lymphoma (NHL). However, the therapeutic efficacy of CHOP remains unsatisfactory, particularly in high-intermediate risk and high risk patients, and a new strategy is warranted in this patient population. The aim of the present study was to explore a suitable therapeutic-intensified regimen for the treatment of aggressive NHL. PATIENTS AND METHODS: Between May 1995 and July 1998, a total of 70 patients with high-intermediate risk or high risk aggressive NHL, according to the International Prognostic Index, were enrolled and randomly assigned to receive either eight cycles of standard CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide 1500 mg/m(2), doxorubicin 70 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose of 2 micro g/kg/day s.c., was administered daily from day 3 until day 13 with biweekly CHOP and until day 20 with the dose-escalated CHOP. The primary endpoint was complete response rate. RESULTS: The complete response rate was 60% [21 of 35; 95% confidence interval (CI) 42% to 76%] with biweekly CHOP and 51% (18 of 35; 95% CI 34% to 69%) with dose-escalated CHOP. The major toxicity was grade 4 neutropenia and was more frequent in the dose-escalated CHOP arm (86%) than in the biweekly CHOP arm (50%). Grade 4 thrombocytopenia was also more frequent in the dose-escalated CHOP arm (20%) than the biweekly CHOP arm (3%). Non-hematological toxicities were acceptable in both arms. One treatment-related death (due to cardiac arrhythmia) was observed in a dose-escalated CHOP patient. Progression-free survival at 3 years was 43% (95% CI 27% to 59%) in the biweekly CHOP arm and 31% (95% CI 16% to 47%) in the dose-escalated CHOP arm. Although seven patients were deemed ineligible by central review of the pathological diagnosis, the results for both eligible and all enrolled patients were similar. CONCLUSIONS: Similar complete response rates and progression-free survival rates, but lower toxicity, indicated that biweekly CHOP was superior to dose-escalated CHOP in the treatment of aggressive NHL. Based on these results, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting a randomized phase III study comparing biweekly CHOP with standard CHOP in newly diagnosed patients with advanced-stage aggressive NHL.     

Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients.

BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients, we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G-CSF) regimen which, in a national multicenter trial, induced good complete response (CR) and relapse-free survival rates with only moderate toxic effects. Here we report a prospective, multicenter, randomized trial comparing the efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS AND METHODS: From February 1996 to June 2001, 306 consecutive previously untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and 148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively. Hematological and non-hematological toxicities were similar in both treatment groups. CONCLUSIONS: Our data show that extending induction treatment with the VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or provide a more durable remission.     

耳蜗血管纹组织块的缘细胞培养

目的 :建立豚鼠耳蜗血管纹 (SV)组织块缘细胞 (MCs)的培养方法 ,为进一步研究药物耳毒性及其作用机制奠定基础。方法 :2 6只豚鼠按SV培养时间随机分成 4组 :2 4h组 (n =8) ;72h组 (n =8) ;>72h组 (n =8) ;对照组 (新鲜SV固定组 ,n =2 )。显微解剖数段连同螺旋韧带的SV组织块 ,置于 5 %CO2 / 95 %空气的二氧化碳恒温 (37℃ )培养箱中进行培养 ,分别进行形态学和组织学观察。结果 :培养 2 4hSV组织块保持良好活性 ,其组织学结构与新鲜固定的SV结构无明显差异 ;培养 72hSV组织块与新鲜固定的SV在组织学结构方面有显著性差异 ,不能观察到正常的SV结构 ,组织结构松散 ,缘细胞从组织块离心性生长出来 ;从SV组织块培养出的缘细胞能在培养皿内存活 13d。结论 :采用组织块培养技术 ,成功地建立了豚鼠耳蜗SV组织块的缘细胞培养方法 ;培养 2 4h的SV组织块光镜下保持了良好活性和正常组织学结构 ,可用来进一步研究药物耳毒性及其作用机制。     

Metastasis to the breast from extramammary malignancies: a report of four cases and a review of literature

Breast metastases from extramammary tumours are rare with few cases reported. Four cases of metastasis to the breast are presented and the diagnostic problems of this condition are reviewed. Correlation between the histology of primary tumour and the cytology of breast metastatic tumour can avoid the surgical breast biopsy and unnecessary mastectomy. Metastasis to the breast has poor prognosis.     

Characteristics of Cryopreserved Semen from Men with Lymphoma

Purpose: This study compared the pretreatment semen quality in patients with Hodgkin's disease and non-Hodgkin's lymphoma with a group of healthy donors. We also examined the differences in prefreeze and postthaw semen quality among the different stages of Hodgkin's disease. Methods: The study included 89 patients with Hodgkin's disease, 18 with non-Hodgkin's lymphoma, and 50 healthy sperm donors. Results: In patients with Hodgkin's disease, the prefreeze and postthaw semen characteristics were significantly lower than those of the healthy donors. Similar results also were seen in patients with non-Hodgkin's lymphoma. No significant differences in the prefreeze semen quality were seen in patients with different stages of cancer. Conclusions: Patients with Hodgkin's disease and non-Hodgkin's lymphoma in our study had poor semen quality when compared with healthy donors both before and after cryopreservation. As cancer therapy significantly impairs reproductive potential, sperm banking should be offered to these men before the start of their therapy.     

Primary laryngeal T/NK-cell lymphoma, nasal-type: an unusual location for an aggressive subtype of extranodal lymphoma

Primary haematopoietic neoplasms of the larynx constitute less than 1% of all laryngeal tumours. Most of them are extramedullary plasmocytomas, diffuse large B-cell lymphomas, or MALT-type marginal zone B-cell lymphomas. T- or NK-cell lymphomas have rarely been reported in this location. The diagnosis of laryngeal lymphomas is a challenge, due to the absence of clinical and gross differential criteria. A pathological study is required in all cases. We present hereby a primary laryngeal T/NK-cell lymphoma, nasal-type. The patient, of Mexican origin, presented with involvement of the epiglottis, both aryepiglottic folds, and cervical lymphadenopathies. Polychemotherapy was administrated with initial partial response, but rapid local progression and exitus followed six months after the diagnosis. The extranodal T/NK-cell lymphoma, nasal-type is a very aggressive subtype of extranodal lymphoma, usually located in the nasal cavity or in nearby sites. Primary involvement of the larynx is extremely unusual. The prognosis of extranasal cases of this type of lymphoma is poor, even when they are diagnosed in localized stages.     

Comparative Preclinical Study of Three Bone Marrow Purging Methods Using PCR Evaluation of Residual t(14;18) Lymphoma Cells

The t(14;18) chromosomal translocation occuring in most follicular lymphomas can be exploited by a Bcl2/JH polymerase chain reaction (PCR) to detect residual disease and to monitor the effectiveness of ex-vivo tumor cell immunological purging. We first demonstrated the 10^-5 Bcl2/JH PCR sensitivity with serial dilutions of OCY-LY8 lymphoma cell lines in normal mononuclear cells; and then the specificity and reproductibility of this technique by analysing follicular and non follicular lymphoma samples. With the Bcl2/JH PCR, we tested the efficiency of three marrow purging protocols with an experimentally contaminated bone marrow either treated by three anti-B cell monoclonal antibodies (mAb) followed by three rounds of rabbit complement or two rounds of immunomagnetics beads. Samples obtained after each purging were amplified by Bcl2/JH PCR and hybridized with PFL3 probe. We were able to produce a 2 to 3 log tumor cell reduction after three rounds of complement and a 4 to 5 log reduction after two rounds of beads.

This study showed that it is feasible to use the Bcl2/JH PCR technique for residual cell lymphoma detection in patients undergoing intensive chemotherapy or BM transplantation. These results indicate that ex-vivo immunomagnetic BM purging is probably superior to complement mediated lysis for the eradication of B lymphoma cells from the marrow of patients undergoing autologous transplantation.     

Castleman's disease as a uncommon cause of a neck mass

Castleman's disease is an uncommon cause of a neck mass; in only 6% of the cases reported in the literature was the disease located in the neck. We present the case of a 21-year-old woman who developed a swelling in the left side of her neck that was subsequently diagnosed as Castleman's disease. The different forms of the disease and its histopathology are discussed.     

Factors that influence the further survival of patients who survive for five years after the diagnosis of cancer in childhood or adolescence

To evaluate the further survival, and to identify disease and treatment factors which influence the further survival, of five-year survivors of cancer diagnosed during childhood or adolescence, we reviewed the courses of 591 previously untreated patients who were less than 20 years of age at diagnosis and survived for five years after diagnosis. Fifty-three of 143 patients who experienced disease recurrence during the first five years after diagnosis died during the period of observation, compared to 18 of 448 patients who did not experience disease recurrence during the first five years after diagnosis. The sex-specific standardized mortality ratios for the group of patients who never relapsed or relapsed more than five years after diagnosis were not significantly different from those of the New York State population. Cox proportional hazards modelling of the subgroup of patients who relapsed during the first five years after diagnosis demonstrated that disease which was treated surgically, a diagnosis of Hodgkin's disease or acute lymphoblastic leukemia, and older age at diagnosis were significantly associated with further survival in this group, whereas similar modelling of the patients who did not experience disease recurrence during the first five years after diagnosis failed to identify any variables which were associated with continued survival. The results of this study suggest that childhood and adolescent cancer patients who survive for five years without disease recurrence have a survival rate similar to that of the general population. Continued follow-up of this cohort is required to determine if the present findings can still be demonstrated as the majority of the cohort ages beyond 35 years of age. © 1994 Wiley-Liss, Inc.