Therapeutic effects of proanthocyanidin and coenzyme Q10 on nitrogen mustard-induced ocular injury / Efeitos terapêuticos da proantocianidina e da coenzima q10 em lesão ocular induzida por mostarda de nitrogênio

ABSTRACT Purpose: Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury. Methods: Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/μL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology. Results: The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement. Conclusions: Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.

RESUMO Objetivo: A mostarda de nitrogênio (MN) é um agente de guerra química devastador. Não existe um antídoto eficaz para tratar lesões oculares induzidas por MN. Nosso objetivo foi avaliar os efeitos da proantocianidina (PAC) e da coenzima Q10 (CoQ10) na lesão ocular induzida por MN. Métodos: Dezoito ratos machos foram divididos em 4 grupos: MN, MN + PAC, MN + CoQ10 e Controle. Três grupos receberam uma dose única de MN (0,02 mg/μL) destilada no olho direito para gerar lesão ocular. Os animais do grupo controle receberam apenas solução salina. Trinta minutos após a aplicação de MN nos animais, o grupo MN + PAC recebeu PAC (100 mg/kg) por gavagem gástrica, enquanto a CoQ10 (10 mg/kg) foi administrada ao grupo MN + CoQ10 por meio de injeção intraperitoneal. A administração de PAC e de CoQ10 foi realizada uma vez por dia, durante 5 dias consecutivos. Os ratos foram, então, sacrificados. Imagens macroscópicas dos olhos foram examinadas e tecidos oculares foram coletados para histologia. Resultados: Os grupos de tratamento foram comparados ao grupo de controle quanto à opacidade da córnea e quanto aos escores de lesão da cobertura da córnea. Os resultados foram insignificantes para ambos os grupos. Ambos, o grupo MN+PAC e o grupo MN+CoQ10, apresentaram melhoras das alterações histológicas observadas no grupo MN. Conclusões: Nossos resultados indicam que os tratamentos com PAC e com CoQ10 têm efeitos terapêuticos sobre lesões oculares induzidas por MN em um modelo em ratos. A proantocianidina e a CoQ10 podem ser uma nova opção nesses casos.

A Case of Woringer-Kolopp Disease of the Hand / 대한피부과학회지

Woringer-Kolopp disease, also known as localized pagetoid reticulosis, is a rare variant of mycosis fungoides that presents as a solitary localized hyperkeratotic patch or plaque on the extremities and follows a benign course. Effective treatments for Woringer-Kolopp disease include skin-directed therapies such as topical nitrogen mustard, high-potency topical steroids, and phototherapy. Surgical excision has been pursued in cases of small, localized lesions. A 39-year-old man presented with a 3-month history of an asymptomatic plaque on his hand. Physical examination showed a 10-mm-diameter solitary round erythematous hyperkeratotic plaque with a slightly raised edge on the dorsum of his left hand. A skin biopsy revealed that numerous atypical lymphocytes had infiltrated the upper dermis and expanded into the epidermis with a pagetoid pattern. These atypical pagetoid cells were strongly positive for CD3, CD8, and T-cell intracellular antigen-1; focally positive for CD4; and negative for CD20, CD30, and CD56. A subsequent general examination revealed no evidence of systemic involvement and the lesion was treated with surgical excision. Here we report a rare case of Woringer-Kolopp disease.

Effect of brentuximab vedotin combined with chlormethine hydrochloride on the treatment of 6 patients with relapsed and refractory Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and side effects of brentuximab vedotin (BV) plus chlormethine hydrochloride (CH) in patients with relapsed and refractory Hodgkin lymphoma (HL) after failure with BV alone.</p><p><b>METHODS</b>From March, 2014 to December, 2014, 6 patients who failed with BV monotherapy were enrolled in this study. The chemotherapy regimen consisted of BV (1.2-1.8 mg/kg, iv. gtt, d1) and CH (6 mg/m2, iv. gtt, d1) was given for 3 weeks as one course, and all patients received about 3-8 courses of chemotherapy, with an median of 4 courses. Clinical efficacy and adverse events were assessed and observed by radiographic examination and serological detection.</p><p><b>RESULTS</b>Among 6 patients, the overall response rate was 100% with 2 complete remission and 4 partial remission. The main adverse events were grade I (2 patients) and IV (2 patients) bone marrow depression, grade II (2 patients)gastrointestinal reaction, grade I (1 patient) increase of transaminase and myocardial enzyme and grade I (1 patient) mouth ulcers.</p><p><b>CONCLUSION</b>The combination of BV and CH in the treatment of relapsed and refractory HL after failure with BV alone was high effective and the toxicities were well tolerable.</p>

Chronic Lymphocytic Leukemia-Era of Targeted Therapy / 대한내과학회지

Chronic lymphocytic leukemia (CLL) is a unique indolent B-cell leukemia which is rare in Korea. Many patients with early stage CLL do not require immediate treatment, while those with advanced stage or symptoms need systemic chemotherapy. As our understanding about the pathophysiology of CLL increases, significant advances have been achieved in the treatment of this disease. Modern molecular genetics have been revealing remarkable heterogeneity of various genetic alterations and the corresponding prognostic stratification in CLL. The treatment of CLL had been developed from nitrogen mustard alkylating agent like chlorambucil to combination therapy including purine analogues like pentostatin and fludarabine until early 2000s. Since the introduction of targeted agent like anti-CD20 and anti-CD52 monoclonal antibodies in the treatment of CLL, the treatment outcome of CLL has leaped further. In conclusion, one of the current standard regimens in patients with untreated CLL is the combination of rituximab, cyclophosphamide and fludarabine. We recently passed the entrance for the era of targeted therapy, and are exploring various new agents and their combinations.

Clinical analysis of childhood and adolescent Hodgkin's lymphoma: a report of 88 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the clinicopathological characteristics, effective treatment and prognosis in childhood and adolescent Hodgkin's lymphoma.</p><p><b>METHODS</b>A total of 88 patients with childhood and adolescent Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005. The clinicopathological and follow-up data of the patients were retrospectively reviewed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. COX multivariate prognosis analysis was performed.</p><p><b>RESULTS</b>The 2-year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free survival rate was 61.4%, and the 5-year overall survival rate was 95.5%. Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P = 0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033), chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall survival rate. Multivariate analysis showed that chemotherapy regimen (P = 0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation (P = 0.046) were independent prognostic factors of 5-year overall survival rate.</p><p><b>CONCLUSIONS</b>The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation, associated with "B" symptoms and bulky disease are independent prognostic factors of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy regimen are independent prognostic factors of 5-year overall survival rate.</p>

Treatment of Advanced Hodgkin Lymphoma / 대한내과학회지

The major portion of Hodgkin lymphoma (HL) patients, even at an advanced stage can be cured with optimal initial treatment. ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is the standard treatment regimen for the advanced stage HL, while Stanford V (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) and escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) can be reasonable alternatives for selected patients. Although radiotherapy is the key component in Stanford V regimen, radiotherapy should be applied only at the residual lymphoma in patients who received ABVD and BEACOPP therapy. These three representative treatments for advanced HL have individual advantages and disadvantages, so that the choice of the initial treatment should be dependent on patients' relapse risk, comorbidity, and age.

The Three Dimensional Conformal Radiotherapy for Hyperkeratotic Plantar Mycosis Fungoides

The localized early-stage of Mycosis fungoides (MF) (stage IA-IIA) is usually treated with topical agents, such as nitrogen mustard, steroids, and phototherapy (UVB/PUVA) as first line therapy; response to these initial treatments is usually good. However, hyperkeratotic plantar lesions are clinically rare and have decreased responsiveness to topical agents. For such cases, physicians may consider local radiotherapy. Here, a case of an 18-year-old Korean woman who was treated with three-dimensional conformal radiotherapy (3D-CRT) for hyperkeratotic plantar lesions that were refractory to UVA-1, methotrexate, and topical steroids is reported. Complete remission was attained after radiotherapy. During the one-year follow-up period, there has been no evidence of disease recurrence and no chronic complications have been observed.

Combined-modality therapy for 150 cases of early-stage Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the efficacy of chemotherapy alone, radiotherapy alone and combined-modality therapy in the treatment for early-stage Hodgkin's lymphoma (HL).</p><p><b>METHODS</b>From 1999 to 2002, totally 150 patients with stage I or II HL were treated in our hospital. They were stratified into several groups based on initial treatment strategy: chemotherapy alone (CT group, n = 22), radiotherapy alone (RT group, n = 18), combined-modality therapy (CMT group, n = 109) and surgical resection (SR group, n = 1). Chemotherapy regimens were mainly ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) and MOPP (mechlorethamine, vincristine, procarbazine and prednisone). Radiotherapy modes included involved field radiotherapy (IFRT), extended field radiotherapy (EFRT) and sub-total nodal irradiation (STNI).</p><p><b>RESULTS</b>The pathological types included nodular sclerosis (NS, n = 84), mixed-cellularity (MC, n = 39), lymphocyte-predominant (LP, n = 23), lymphocyte-depleted (LD, n = 3) and nodular lymphocyte predominant Hodgkin's disease (NLPHD, n = 1). Of those, 72 were evaluble in terms of prognostic factors. No poor prognostic factor was found in 36.1% or 29.2% of the patients according to EORTC or GHSG criteria, respectively. There were 33 patients with complete response (CR), 109 with partial response (PR), 5 with stable disease (SD) and 3 with progressive disease (PD) after initial therapy. The median follow-up period was 71.5 months. The overall 7-yr survival rate was 89.3%, and treatment failure rate at 6 years was 18.8%. The response rate of CMT group was superior to that of CT group, and the patients with nodular sclerosis or mixed-cellularity type had significantly lower risk of treatment failure (P = 0.009 and 0.019, respectively). The multivariate analysis revealed that the treatment strategies affected the prognosis significantly. The risk of failure of chemotherapy alone was 2.52 times higher than that of combined-modality therapy (P = 0.004). No predictive factor affecting OS was identified by either univariate or multivariate analysis. The patients in CMT group suffered more adverse effects than those in either CT or RT groups, which mainly consisted of leucopenia, alopecia and gastrointestinal symptoms.</p><p><b>CONCLUSION</b>Combined-modality therapy is more effective than chemotherapy alone or radiotherapy alone in the treatment for early stage Hodgkin's lymphoma. Though its acute adverse effects are more severe than that of chemotherapy or radiotherapy alone, it may reduce the risk of treatment failure.</p>

Phyllanthus urinaria extract promotes N-cadherin expression in nitrogen mustard-disrupted testicular tissues in vivo / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the protective effect of the Phyllanthus Urinaria (PU) extract on the N-cadherin expression in the testicular tissues disrupted by nitrogen mustard (HN2) in vivo.</p><p><b>METHODS</b>HN2 was intraperitoneally injected into male KM mice at the dose of 5 mg/kg to make reproductive toxicity models, and at the same time PU was administered for intervention at the dose of 125 mg/kg, 250 mg/kg and 500 mg/kg. N-cadherin distribution, mRNA and protein expression in the testicular tissues were detected by immunohistochemistry, RT-PCR and Western blotting.</p><p><b>RESULTS</b>N-cadherin was mainly distributed in the membrane and cytoplasm of Sertoli cells at the basement of seminiferous epithelia, Leydig cells and peritubular cells, scarcely expressed in the basement of seminiferous epithelia and peritubular cells after HN2 administration. The expressions of mRNA and proteins of N-cadherin were significantly elevated with the increased dose of PU (P < 0.01). Compared with the normal control, the distribution and expression of N-cadherin showed no significant differences in either the high-dose PU group or the HN2 with high-dose PU intervention group (P > 0.05).</p><p><b>CONCLUSION</b>The PU extract can effectively promote the N-cadherin expression in the testis tissues disrupted by HN2.</p>

Comparison of preliminary results of involved-field with extended field radiotherapy combined with chemotherapy for early stage Hodgkin's disease / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate whether involved-field (IF) radiotherapy is equally effective and less toxic in comparison with extended-field (EF) radiotherapy for patients with early-stage Hodgkin's disease (HD) who received combined modality therapy.</p><p><b>METHODS</b>The data of 88 early-stage HD patients treated with combined modality therapy were retrospectively reviewed. According to Ann Arbor classification, 12 patients (13.7%) had stage IA disease, 56 stage IIA (63.6%), and 20 IIB (22.7%). Forty-two (47.7%) patients underwent involved field radiotherapy (IF group), whereas the other 46 (52.3%) received extended field radiotherapy (EF group).</p><p><b>RESULTS</b>Of 6 patients who developed recurrence, 3 (7.1%) were in IF group and the other 3 (6.5%) in EF group. Only one patient's recurrence developed inside the radiation field in EF group. Three patients (7.2%) in IF group and 9 (19.5%) in EF group had WHO grade 1 and 2 leukopenia (P = 0.089). Overall survival rate at 1-, 2- and 3-year was 100.0%, 97.1%, and 97.1% in IF group versus 100.0%, 100%, and 95.8% in EF group (P = 0.86), respectively. Freedom from progression survival rate at 1-, 2- and 3-year was 97.6%, 94.8%, and 91.7% in IF group versus 97.8%, 93.2%, and 93.2% in EF group (P = 0.65), respectively.</p><p><b>CONCLUSION</b>Compared with extended-field radiotherapy, involved-field radiotherapy is equally effective and less toxic for patient with early-stage Hodgkin's disease treated with combined modality therapy.</p>

Two Cases of Early Stage Mycosis Fungoides Treated with Acitretin and Narrow Band UVB Phototherapy / 대한피부과학회지

Early stage mycosis fungoides (MF) has been treated with skin directed therapies including topical steroids, phototherapy (UVB), photochemotherapy (PUVA), topical nitrogen mustard, or total skin electron beam therapy. Recently, several studies have been reported that treat early-stage MF with narrow band UVB (NBUVB), which is an effective and convenient modality compared to other alternatives. Herein, we describe two cases of early stage MF treated with NBUVB. During the remission induction therapy, oral acitretin combined with NBUVB was used for several weeks to clear the MF, followed by treatment with only NBUVB for maintenance.

A Case of Bladder Cancer in a Patient with Systemic Lupus Erythematosus Treated with Oral Cyclophosphamide / 대한류마티스학회지

Cyclophosphamide, a cytotoxic alkylating agent, is widely used in various benign diseases like systemic lupus erythematosus (SLE), Wegener's granulomatosis, rheumatoid arthritis, nephrotic syndrome as well as in malignancies and organ transplantation. Cyclophosphamide is metabolized in the liver to various chlormethine metabolites and acrolein, which mediates the toxic effect to the urothelium and can cause hemorrhagic cystitis, bladder fibrosis, and has also been associated with urothelial malignancies including bladder cancer. It is known that SLE is not associated with an increased risk for the development of most of the solid tumors. But it has been suggested that the risk of the bladder cancer increases in patients with benign diseases such as SLE treated by cyclophosphamide. There are only very few reports of cyclophosphamide-induced bladder cancer in SLE so far. We report a case of a patient who developed bladder cancer 13 years after cyclophosphamide was given as therapy for SLE. This case shows that careful observation and urologic evaluation is undoubtedly important for patients treated with cyclophosphamide.

Pleurodese: perspectivas futuras / Pleurodesis: future prospects

Apesar de estarmos completando praticamente um século desde a realização da primeira pleurodese, a metodologia não está consensualmente definida. A tendência atual de executarmos procedimentos minimamente invasivos estimulou novas pesquisas com o objetivo de reduzir a agressão, incluindo o uso de novas substâncias, a colocação de drenos mais finos e a redução ou abolição da necessidade de internação hospitalar. Dentre as drogas esclerosantes, o talco tem a preferência mundial. Entretanto, o possível desenvolvimento da síndrome da angústia respiratória, por vezes fatal, fez renascer o interesse por outras drogas. Os quimioterápicos não têm evidente efeito esclerosante e originam importantes efeitos colaterais. Os agentes irritantes hidróxido de sódio e nitrato de prata produzem pleurodese efetiva. Ambos podem ser utilizados em seres humanos

Clinical Significance of bcl-2 and p53 protein Expression in Patients with Malignant Lymphoma / 대한혈액학회지

BACKGROUND: Overexpression of bcl-2 protein is observed both in follicular lymphoma, in which bcl-2 has usually undergone a translocation t (14;18). The experimental findings that transfection of bcl-2 in to murine lymphoid cells confers resistance to nitrogen mustard and camptothecin by inhibiting apoptosis suggests that bcl-2 overexpression may confer clinical drug resistance in lymphomas. In contrast to bcl-2, p53 arrests cells exposed to DNA-damaging agents in G1 to allow DNA repair or if essential repairs are not possible, promotes apoptosis. Experimentally, loss of p53 function produces cellular resistance to alkylating and topoisomerase-II drug classes, suggesting that loss of p53 function in lymphomas may cause drug resistance. These observations led to the hypothesis that bcl-2 and p53 play a role in the development of drug resistance in lymphoma. Although several studies assessed the association between bcl-2 expression and disease-free survival, they reached conflicting conclusions. METHODS: We analyzed tumor tissue from 42 patients with advanced NHL for p53 and bcl-2 expression and correlation with multiple clinical characteristics, response to therapy and overall survival. Among 42 tumors, 8 (19.0%) tumors had bcl-2 expression and 19 (45.2%) had a p53 overexpression. RESULTS: A significant correlation was found between bcl-2 expression and poor performance, advanced stage (stage III and IV) at diagnosis, and bone marrow involvement in a univariate analysis (P50%) were more likely to be poor prognosis than tumors with negative or week expression (<50%) and to have a shorter long-term survival (28.6% vs 75.5%; P<0.05). However, the expression of p53 did not correlate with any clinical characteristics and overall survival was not influenced by p53 protein expression. CONCLUSION: These results suggest that bcl-2 protein expression in patients with malignant lymphoma appears to be predictive of shorter long-term survival and it might be considered as a strong independent prognostic factor.

Survival improvement with combined radio-chemotherapy in the primary central nervous system lymphomas

The benefits of radio-chemotherapy in HIV-negative primary central nervous system (CNS) lymphomas were analyzed in 40 patients, who received radiotherapy to the brain or craniospinal axis with the total dose of 4460-5940 cGy to the primary tumor. Radiotherapy was followed by systemic chemotherapy, mainly with the cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen, in 16 of the patients. Follow-up ranged from four to 95 months with a median of 15 months. The relapse rate was 72.5%, and 83% of the relapses occurred within the radiation field. Median survival was 19 months and the two-year survival rate was 41%. Survival was significantly influenced by treatment method and radiation dose when measured by univariate analysis; median survival and the two-year survival rate was 29 months and 63% after radio-chemotherapy, while 13.5 month and 29% after radiotherapy alone (p= 0.027), and 22 months and 49% with doses of 50 Gy or more, but 12.5 months and 13% with doses less than 50 Gy (p=0.009). However, statistical significance was lost in multivariate analysis. These results might suggest the short-term efficacy of radio-chemotherapy, however, cautious observation is needed to confirm long-term effects.

Ineficacia de la mostaza nitrogenada en el tratamiento del síndrome nefrótico corticorresistente / Inefficacy of nitrogen mustard in the treatment of corticoresistant nephrotic syndrome

Introducción. En los niños con síndrome nefrótico idiopático corticorresistente (SNCR) se han utilizado diversos tratamientos en base a antimetabolitos como la ciclofosfamida y la mostaza nitrogenada. Este último tratamiento se ha recomendado particularmente en niños con infecciones recurrentes que impiden la indicación de tratamientos prolongados. Material y métodos. Se revisó la respuesta al tratamiento en 10 niños con SNCR que recibieron mostaza nitrogenada durante el período comprendido entre 1988 y 1996. Resultados. Sólo 2 pacientes presentaron remisión del síndrome nefrótico: uno remisión parcial y el otro completa. Dos pacientes presentaron cuadros infecciosos graves (neumonía), en uno de ellos asociado a leucopenia grave. Conclusiones. El tratamiento con mostaza nitrogenada en niños con SNCR no ofrece ventajas aparentes en relación a otros esquemas terapéuticos

Efeitos tardios do tratamento da Doença de Hodgkin em crianças abaixo de 12 anos de idade / Late effects of treatment for Hodgkin's disease in children below 12 years of age

A doença de Hodgkin é um tipo de neoplasia maligna que apresenta aspectos epidemiológicos particularmente interessantes, tornando-a mais frequente em crianças nos paises em desenvolvimento. Sua cura no últimos 30 anos tem sido elevada a patamares muito altos com o emprego de radioterapia e quimioterapia. Com o objetivo de avaliar os efeitos indesejáveis tardios do tratamento, 24 crianças com idades inferiores a 12 anos ao diagnóstico (20 meninos e 4 meninas), tratadas em uma única instituição (Hospital dos Servidores do Estado - RJ), entre maio de 1979 e fecereiro de 1994, foram avaliadas...Concluímos que o emprego de radioterapia nesta faixa etária deve se limitar às grandes massas tumorais e em doses inferiores a 25 Gy. Radioterapia abdominal somente deverá ser substituída devido ao seu elevado potencial carcinogênico. É também objetivo deste trabalho alertar os serviços que tratam deste tipo de patologia no nosso país par falhas que podem ser cometidas e que poderão trazer graves consequências para p futuros destas crianças

COPP/ABV Hybrid Chemotherapy in Pateints with Hodgkin's Disease / 대한암학회지

PURPOSE: MOPP/ABV hybrid regimen incorporates MOPP and ABVD into a single regimen on the tenets of the Goldie-Coldman hypothesis. This study was performed to determine the efficacy of COPP/ABV hybrid regimen, in which cyclophosphamide was substituted for mechlorethamine, in patients with advanced Hodgkin's disease. MATERIALS AND METHODS: Patients with advanced Hodgkin's disease were treated with cyclophosphamide(600 mg/m2 iv, Dl), vincristine(1.4 mg/m2 iv, D1), procarbazine(100 mg/m2/d po, D1-7), prednisolone(40 mg/m2/d po D1-14), doxorubicin(35 mg/m2 iv, D8), bleomycin(10 mg/m2 iv, D8) and vinblastine(6 mg/m2 iv, D8). The treatment was repeated every 4 weeks. RESULTS: Between Aug. 1989 and Aug. 1996, 28 patients were enrolled. The median age was 33 years. Twenty one(75%) were previously untreated, newly diagnosed patients and 7(25%) were those who had relapsed after previous radiotherapy(RT). The common histologic types were nodular sclerosis(46%) and mixed cellularity(36%). Twenty three (82%) patients achieved complete remission(CR), three(11%) with the assistance of involved-field RT. Only one patient was primary treatment failure. The median follow-up duration was 56 months. Of the 23 patients achieving CR, three(13%) relapsed. Five-year relapse-free survival was 84.4%. Eight patients died. Five-year overall survival rate was 66.6% and 5-year failure-free survival rate was 66.3%. The survival rate of those who had relapsed after previous RT was significantly lower than that of newly diagnosed patients(P=0.03). The hematologic toxicities were common, but nonhernatologic toxicities were uncommon. Five patients died of treatment-related pneumonia or sepsis. Among them, four were those who had relapsed after previous RT. CONCLUSION: COPP/ABV hybrid regimen could cure significant proportion of patients with advanced Hodgkin's disease but the treatment-related mortality was high, especially in those who had relapsed after previous RT. Another regimen should be considered for those who received previous RT.