Intensive chemotherapy for peripheral T-cell lymphomas.

Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.     

Management of advanced stage intermediate grade non-Hodgkin's lymphomas.

The treatment result of 271 cases of advanced stage intermediate grade lymphoma were reviewed. Ninety-four patients received CHOP chemotherapy, 45 BACOP and 17 m-BACOD. The clinical characteristics of the three groups of patients were comparable. Patients receiving CHOP had a complete response (CR) rate of 60 per cent, the disease-free survival of CR patients was 31 per cent at 5 years. The overall survival following CHOP chemotherapy was 38 per cent at 5 years. The use of the BACOP or m-BACOD regime did not appear to improve significantly the prognosis of these patients. Clinical staging, B symptoms, age and serum lactate dehydrogenase level were the most important independent prognostic factors.     

The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen.

One hundred thirty-four assessable patients with stage II-IV large-cell lymphoma (LCL) were treated with the combination chemotherapy regimen methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) between July 1981 and May 1986. The m-BACOD regimen substituted moderate-dose methotrexate (200 mg/m2 x 2) for the high-dose methotrexate used in the preceding M-BACOD regimen; all other drugs were administered as with m-BACOD. Eighty-two patients (61%) in the completed m-BACOD trial achieved a complete response (CR). With a median follow-up of 3.6 years, 62 patients (76%) continue in CR. Predicted survivals of 1, 3, and 5 years for the entire m-BACOD group are 80%, 63%, and 60%, respectively, with a 5-year disease-free survival (DFS) of 74% for the patients who achieve CR. The results obtained with m-BACOD are comparable with those obtained in the preceding M-BACOD trial, which now has a median follow-up of 8.0 years. The reduction in methotrexate dosage in m-BACOD patients was not associated with an increased incidence of CNS relapse. Long-term follow-up of the 215 M/m-BACOD patients indicates that the regimens are not associated with an increased incidence of secondary malignancy. Prolonged follow-up also indicates that advanced-stage patients have a persistent rate of late relapse of about 7.0% per year for years 2 to 5 of their follow-up and that stage II patients have an approximate 2.1% per year rate of late relapse. Application of the previously described prognostic factor model to the 215 M/m-BACOD patients from the completed trials identifies a high-risk group of patients with a CR rate and predicted 5-year survival (38% and 24%, respectively) that are significantly worse than those of the group as a whole (65% and 57%, respectively).     

改良BFM-90方案治疗20例儿童青少年淋巴母细胞型淋巴瘤

背景与目的：儿童青少年淋巴母细胞型淋巴瘤属于高度恶性淋巴瘤．进展快,死亡牢高。德国BFM-90淋巴母方案是目前治疗儿童青少年淋巴母细胞型淋巴瘤疗效最好的方案之一。本研究采用改良BFM-90淋巴母方案治疗中国儿童青少年淋巴母细胞型淋巴瘤,观察其疗效、毒性和可行性。方法：20例3～18岁初治的T淋巴母细胞淋巴瘤患者,Ⅲ期7例,Ⅳ期13例。18例(90％)患者有纵隔肿块伴上腔静脉阻塞综合征,10例(50％)有骨髓侵犯。所有患者均接受改良BFM-90方案化疗．方案包括诱导缓解、巩固治疗和中枢神经系统预防、再诱导缓解和维持治疗。总疗程2年。用Kaplan-Meier法统计全组生存率。结果：诱导缓解结束后18例(90％)患者获得完全缓解(complete response,CR),1例(5％)部分缓解(partial response,PR),1例(5％)肿瘤进展(progressive disease,PD),总有效率95％。PR和PD的2例患者最后肿瘤进展死亡。CR的18例患者中有2例在再诱导结束后CR1时行外周血自体造血干细胞移植。移植后有1例复发,经再次化疗后CR存活;另1例一直存活。其他CR的患者中有5例复发,其中1例行异基因移植后存活,1例自体造血干细胞移植后存活,3例复发后单纯化疗的患者肿瘤进展死亡。全组患者3年总生存率74％。所有患者在诱导和再诱导阶段均发生Ⅲ／Ⅳ骨髓抑制,积极对症处理后可恢复。结论：改良德国BFM-90淋巴母方案适用于中国儿童青少年淋巴母细胞型淋巴瘤患者,可明显改善生存率;主要不良反应是血液毒性,应在有经验的血液／肿瘤中心中应用。     

m-BACOD chemotherapy for intermediate- and high-grade non-Hodgkin's lymphoma

Summary A total of 92 patients with previously untreated intermediate- or high-grade non-Hodgkin's lymphoma attending the University Department of Medicine, Queen Mary Hospital, Hong Kong, were treated with the m-BACOD chemotherapy regimen (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine and dexamethasone). Additional involved-field radiotherapy was given to 32 (35%) patients. Myelosuppression was the major toxicity, and 5 (5%) treatment-related deaths occurred due to pneumonia, bleomycin sensitivity, doxorubicin cardiotoxicity and reactivation of hepatitis B infection. The overall complete response (CR) rate was 65/92 (71%) and the relapse rate was 22/65 (34%). The disease-free survival of the 65 CR patients at 2 years was 52% and the overall survival of all 92 patients at 3 years was 56%. The CR rate of stage I and II patients was significantly better than that of those with stage III and IV disease (87% vs 59%;P=0.01), and the CR rate of stage III patients was superior to that of those with stage IV disease (86% vs 50%;P=0.05). The overall survival of stage III and IV patients was significantly worse than that of subjects with stage I and II disease (31% vs 73%;P=0.02). Multivariate analysis revealed that the independent prognostic variables significantly determining the CR rate and survival included the clinical stage and the serum lactate dehydrogenase level. From this study, the results of treatment with the m-BACOD regimen in patients with advance disease appeared to be similar to those obtained using the conventional CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone).     

Copp chemotherapy for elderly patients with intermediate and high grade non-Hodgkin's lymphoma

One hundred and forty-one consecutive patients above and 231 below the age of 60 years with previously untreated intermediate or high grade non-Hodgkin's lymphoma were included in this study. Patients above the age of 60 years were treated with the COPP chemotherapy regimen. The younger patients, at or below the age of 60, received a doxorubicin-containing regimen (119 had CHOP, 65 had BACOP and 47 had m-BACOD). For stage I patients, the clinical results were similar but for stage II, III or IV disease, those receiving COPP had significantly worse CR rate and survival than those who had a doxorubicin-containing regimen. Multivariate analysis on patients receiving the COPP chemotherapy revealed that the independent prognostic variables significantly determining CR rate and survival included clinical stage (p =0·04) and serum lactate dehydrogenase level (p =0·001). Myelosuppression was the major toxicity following COPP chemotherapy in this group of patients. There were 10 (7 per cent) treatment-related deaths. Compared to the reported results using doxorubicin-containing regimens to treat elderly patients with aggressive NHL in the literature, the more aggressive treatment does not appear to improve significantly the clinical outcome of this group of patients and seems to produce treatment results very much similar to COPP. However, accurate comparison is difficult because of the variation in the patient characteristics. Further prospective controlled randomized trials will be necessary to determine the optimal therapy for these patients.     

Bleomycin,epidoxorubicin, cyclophosphamide,vincristine and prednisone (BACOP) in patients with follicular non-Hodgkin's lymphoma: results of a prospective,multicenter study of the Gruppo Italiano Per Lo Studio Dei Linfomi (GISL)

At present we report the results of a prospective, non-randomized open trial, conducted on follicular lymphoma (FL) patients by the Gruppo Italiano per lo Studio dei Linfomi (GISL), after a median follow-up of 62.6 months. Seventy-three patients with FL were registered to the study and treated with combination chemotherapy consisting of cyclophosphamide, epidoxorubicin, vincristine, bleomycin and prednisone, weekly administered every 4 weeks. After chemotherapy, involved-field radiotherapy was delivered in case of either localized, bulky and extranodal disease at presentation or limited residual disease at the end of chemotherapy. Patient received four or eight chemotherapy courses in case of localized or advanced disease, respectively. The overall response rate at the end of the treatment program was 97.3%, with 78.1% CR and 19.2% PR. CR rate was 94.3 and 63.1% in stage I-II and III-IV, respectively ( p =0.006). Beside the stage, response rate was significantly influenced by bone marrow involvement, and the number of extranodal sites. Relapse free survival was 60.8% at 5 years in the whole series; in localized disease it was 70.3 vs. 44.8% in advanced disease ( p =0.044) . Relapse free survival was significantly influenced by stage, bone marrow involvement, number of extranodal sites and International Prognostic Index (IPI) score. The overall 5-year survival rate was 90.2%; being 95.6% for patients with stage I-II and 85.1% for those III-IV ( p =0,0133). In addition, both IPI and Italian Lymphoma Intergroup (ILI) score had a significant impact on survival. The toxicity profile of the treatment was acceptable. From the results of this prospective study it is possible to conclude that this regimen and the whole treatment program is effective as first line therapy for the general population of FL. In particular the BACOP schedule is a valid anthracycline-containing regimen, and in this respect suitable to be considered as a treatment option.     

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study.

This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.     

COP-BLAM Multidrug Infusion Chemotherapies for Lymphoma: Results in a Community Hospital Setting

Twenty-two patients with malignant lymphoma were treated with three different COP-BLAM infusional chemotherapy protocols at the Jersey Shore Medical Center. The treatment group included 18 patients with large-cell lymphoma, 3 patients with Hodgkin's disease, and I patient with composite lymphoma (large-cell lymphoma and Hodgkin's disease). Three patients were treated with COP-BLAM III, 9 with COP-BLAM IV, and 10 with COP-BLAM V. The age of the patients at diagnosis ranged from 18 to 74 years, with a median age of 64 years. One patient had stage 1 bulky disease, 4 had stage II bulky disease, 3 had stage III disease, and 14 had stage IV disease. Twenty patients were evaluable for response; 2 were too early to evaluate. Complete response (CR) was seen in 18 of the 20 evaluable patients (90%). Potential cure (excludes non-lymphoma-related deaths) at 24 months is projected at 78%. Eleven patients are presently without disease and off therapy (55%). Projected failure-free survival at 2 years is 71% (a failure being death from any cause). Eleven of 22 patients developed 15 febrile episodes. Vin-cristine neuropathy was seen in 6 patients. Subclinical pulmonary fibrosis was seen in 1 patient. There was one cardiotoxic death. The COP-BLAM infusional protocols are highly effective, tolerable regiments that are applicable in community hospitals and can yield good response rates, with a high percentage of disease-free survivors in all age groups. The treatment can be completed in a short period with acceptable toxicity.     

MACOP-B Regimen Followed by Involved-Field Radiation Therapy in Early-Stage Aggressive Non-Hodgkin's Lymphoma Patients: 14-Year Update Results

A single-center, retrospective study was conducted to evaluate therapeutic results of the MACOP-B third-generation chemotherapy regimen followed by involved-field radiation therapy in a stage I-II aggressive non-Hodgkin's lymphoma (NHL) patients. From 1986 to 1995, 118 consecutive patients with the diagnosis of aggressive NHL, stage I-IE or II-IIE, with or without bulky disease were treated with MACOP-B regimen followed, when appropriate, by 30-36 Gy involved-field radiation therapy The complete response (CR) rate was 95% after the combined modality treatment (97% for stage I-IE and 93% for stage II-IIE). Patients with bulky disease had a CR rate of 92%. Treatment was well tolerated and no deaths occurred from acute toxicity. After a median follow-up of 68 months, 24 (21%) patients relapsed. The 14-year projected relapse-free and overall survival rates were 78% and d 69%, respectively. MACOP-B regimen with/without involved-field radiation therapy provides a safe and effective combined modality treatment for early-stage aggressive NHL, with the possibility to definitively cure two thirds of the patients     

Anthracycline‐fludarabine‐containing regimens with or without rituximab in the treatment of patients with advanced follicular lymphoma

BACKGROUND:

Recent experience has suggested that there has been a stepwise improvement in the survival outcomes of patients who have follicular lymphoma with the introduction of new treatment options. In the current study, the authors report the results of 2 subsequent phase 2 trials of 238 previously untreated patients.

METHODS:

In a trial of bleomycin, epidoxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP) plus fludarabine, mitoxantrone, and dexamethasone (FND), 144 patients received 2 BACOP treatments followed by 4 FND treatments. In a trial of BACOP plus fludarabine and rituximab (FR), 94 patients received 3 BACOP treatments followed by 4 FR treatments.

RESULTS:

The complete remission (CR) rate for BACOP/FND was 62%. After a median follow‐up of 60 months, the failure‐free survival (FFS) and overall survival (OS) rates at 4 years were 53% and 77%, respectively. The CR rate for BACOP/FR was 79%. After a median follow‐up of 36 months, the FFS and OS rates at 4 years were 56% and 97%, respectively, which were significant compared with the CR and OS rates achieved with BACOP/FND. Twenty‐five of 42 bcl‐2‐positive patients attained a molecularly negative CR and had improved FFS. No significant differences were observed between the 2 trials in the percentage of infections or neutropenia.

CONCLUSIONS:

The CR and OS rates achieved with BACOP/FR were better, and overall toxicity did not increase. Furthermore, patients who received rituximab had a better FFS compared with patients who received chemotherapy alone. Finally, although conclusions between nonrandomized groups may depend on differences in observed and unobserved prognostic features, the current results suggested that the addition of rituximab to anthracycline‐fludarabine–containing regimens have a favorable effect on the prognosis of patients with advanced follicular lymphoma. Cancer 2009. © 2009 American Cancer Society.     

改良标准型BEACOPP方案治疗进展期霍奇金淋巴瘤的疗效和安全性

目的:探讨改良标准型BEACOPP方案(博来霉素+依托泊苷+多柔比星+环磷酰胺+长春新碱+甲基苄肼+强的松)治疗进展期霍奇金淋巴瘤的疗效和安全性.方法:22例初治的进展期霍奇金淋巴瘤患者接受改良标准型BEACOPP方案化疗,同时对于初始肿瘤最大径≥5 cm及化疗后有肿瘤病灶残留的患者给予放疗.结果: 22例患者中有16例获得完全缓解,5例获得部分缓解,总有效率为95.5%.在各项临床因素中,国际预后评分对能否获得完全缓解有显著影响(P = 0.011).所有患者的1、2和3年总生存率均为95.5%,1、2和3年无进展生存率分别为72.7%、53.1%和53.1%,1、2和3年的无病生存率分别为85.9%、76.4%和76.4%.单因素分析发现,性别、国际预后评分以及能否获得完全缓解对无进展生存的影响有统计学意义(P<0.05).主要不良反应为骨髓抑制和肝功能损害,其中3例(13.6%)患者出现Ⅲ度药物性肺损伤.治疗期间未观察到治疗相关性死亡.结论:改良标准型BEACOPP方案治疗初治的进展期霍奇金淋巴瘤是有效而安全的.     

CVDLP与CHOP方案治疗Ⅲ/Ⅳ期淋巴母细胞性淋巴瘤诱导缓解期疗效比较

目的：探讨早期强烈诱导缓解方案提高晚期淋巴母细胞性淋巴瘤的完全缓解（complete remission,CR)率。方法：11例Ⅲ/Ⅳ期初治淋巴母细胞性淋巴瘤,诱导缓解期接受CVDLP方案化疗：环磷酰胺1000mg/m^2d1,长春新碱1．5mg/m^2d1、d8、d15、d21,阿霉素40mg/md1、d2、d21,门冬酰胺酶10000U/m^2d15-24,强的松60mg/m^2d1-28,第15天逐步减量。氨甲喋呤加阿糖胞苷鞘内注射每周一次,共4次,28-33每天 评价疗效。同时回顾性比较9例初治Ⅲ/Ⅳ期淋巴母细胞性淋巴瘤,采用标准CHOP方案治疗两疗程后的疗效（第35天）。结果：CVDLP方案组10例初治病人获得完全缓解,1例病人获得部分缓解,完全缓解率达90．9％;10例病人出现Ⅳ级血液毒性,1例病人出血Ⅲ级血液毒性（WHO标准）。CHOP组3例完全缓解,5例部分缓解,1例微效,完全缓解率达33％;3例病人出现Ⅲ级血液毒性,6例病人出现Ⅱ级血液毒性。结论：对于晚期淋巴细胞瘤,诱导缓解采用CVDLP方案获得的早期完全缓解率明显高于CHOP方案,血液毒性也比CHOP大小,但加强支持疗法,此诱导缓解方案安全可行。     

Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. Groupe d'Etudes des Lymphomes de l'Adulte.

PURPOSE: To compare a short intensified regimen followed by sequential consolidation therapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone [ACVBP]) to the standard regimen of methotrexate, bleomycin, cyclophosphamide, and etoposide (m-BACOD) in patients with low-risk aggressive lymphoma. PATIENTS AND METHODS: A total of 752 patients with intermediate- or high-grade lymphoma and no adverse prognostic factors (Eastern Cooperative Oncology Group performance status of 2 to 4, >/= two extranodal sites of disease, tumor burden >/= 10 cm in largest dimension, bone marrow or CNS involvement, Burkitt's or lymphoblastic subtypes) were registered. Of 673 eligible patients, 332 received ACVBP and 341 received m-BACOD. RESULTS: The complete remission rate was identical (86%) in the two groups. With a median follow-up duration of 7 years, the 5-year failure-free survival (FFS) rate was 65% in the ACVBP group and 61% in the m-BACOD group (P =.16). The 5-year overall survival rate was 75% in the ACVBP group and 73% in the m-BACOD group (P =.47). ACVBP was responsible for more severe and life-threatening infections (P <.01), but m-BACOD caused more pulmonary toxicity (P <.001). The number of treatment-related deaths did not differ between the two regimens. A multivariate analysis indicated that ACVBP was associated with a longer FFS in patients with two or three risk factors of the International Prognostic Index. CONCLUSION: In this population of patients with low-risk aggressive lymphoma, toxicities of the regimens are different, but the rates of response and survival are identical. The survival advantage of ACVBP over standard regimen in patients with advanced disease is suggested by this analysis but remains to be assessed in prospective studies specifically designed for this purpose.     

弥漫大B细胞性淋巴瘤临床病理特点与利妥昔单抗疗效的关系

目的 探讨弥漫大B细胞性淋巴瘤(DLBCL) 临床病理特点与利妥昔单抗疗效之间的关系.方法 回顾性分析69例采用利妥昔单抗联合化疗治疗DLBCL患者的临床资料,探讨DLBCL临床病理特征对疗效的影响.应用免疫组化SP法检测Bcl-2、survivin及bax蛋白的表达,分析其表达与利妥昔单抗疗效之间的关系.结果 采用利妥昔单抗联合化疗治疗初治DLBCL患者,有效率为90.7%,完全缓解(CR)率为69.8%;难治或复发患者的有效率为80.8%,CR率为30.8%.分期晚(P=0.046)、血清乳酸脱氢酶(LDH)水平较高(P=0.024)、难治或复发(P=0.009)以及合并大肿块(P=0.013)的患者疗效明显差.Bcl-2表达阳性者的疗效明显好于阴性者(P=0.04);bax和survivin的表达则与疗效无关(P>0.05).结论 利妥昔单抗联合化疗治疗DLBCL患者,有效率和CR率较高,且患者耐受性良好.但分期较晚、LDH水平较高、难治或复发、合并大肿块以及Bcl-2表达阴性患者的疗效较差.     

MACOP-B Chemotherapy for the Treatment of Aggressive Non Hodgkin's Lymphoma

From September 1986 to September 1990, 26 patients with aggressive non Hodgkin's lymphoma were treated with the MACOP-B regimen (21 patients as first treatment, 5 relapsed or refractory to an anthracycline derivative containing regimen). 17 patients (65%) achieved a complete response, 4 (15%) had a partial response and 5 (20%) were treatment failures. After complementary radiotherapy 2 patients with PR achieved CR achieving a subsequent CR rate of 73%. CR rate was adversely affected by stage of the disease (IV = 40% vs I + II + III = 80%) and B symptoms (B = 58% vs A = 85%). Relapses occurred in 7 patients (7/19). For complete responders, the Disease-Free-Survival was 55% Over a median follow-up of 20 months, the overall probability of survival was 51%.

Toxicity was moderate with no treatment-related toxic deaths but 3 Pneumocystis carinii infections occurring before the introduction of systematic prophylaxis with sulfamethoxazol-trimethoprim. This study confirms the efficiency of the MACOP-B regimen for the treatment of patients with standard aggressive NHL. However, there is a subset of patients with poor prognosis factors (like stage IV disease) who might benefit from other therapeutic modalities like dose-intensification based regimens with hematopoietic growth factors support or intensive consolidation with autologous bone marrow transplantation.     

Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy

This paper reports the 5-year results of a prospective randomized study beginning in 1976 on 177 evaluable patients with pathologic Stage I-IE and II-IIE non-Hodgkin's lymphomas with diffuse histology according to the Rappaport classification. Treatment consisted of either CVP or BACOP chemotherapy (3 cycles) followed by regional radiotherapy (40 to 50 Gy) and further cycles of either combination. In both arms, complete remission at the end of combined treatment was high (CVP 93%, BACOP 98%) regardless of age, stage or bulky disease. At 5 years, the comparative freedom from first progression was 62% for CVP vs 78% for BACOP (p = 0.02), respectively. Clinically relevant differences favoring BACOP chemotherapy were essentially documented in patients with large cell lymphomas (International Working Formulation), those with Stage II having more than three involved anatomical sites, bulky disease and age over 60 years. Recurrence within radiation fields was documented in only 5% of complete responders. Combined treatment was, in general, well tolerated particularly when BACOP was used. In only 2 patients given CVP post radiation cutaneous fibrosis was documented. Second solid tumors were detected in 4 patients. One patient started on CVP died because of brain stem necrosis after 45 Gy. We conclude that in Stage I-II patients with nodal and extranodal diffuse non-Hodgkin's lymphomas, particularly large cell lymphomas, combined modality approach with primary Adriamycin and bleomycin containing regimen, such as BACOP, followed by adjuvant radiotherapy offers high chances of cure with minimal toxicity.     

改良BFM-90方案明显改善儿童青少年淋巴母细胞型淋巴瘤的疗效

目的探讨改良BFM-90方案治疗儿童青少年淋巴母细胞型淋巴瘤的疗效,分析其不良反应和生存率。方法收集36例3～18岁初治的淋巴母细胞型淋巴瘤患者入组,Ⅱ期1例,Ⅲ期9例,Ⅳ期26例。28例(77.7%)为T细胞表型,26例(72.2%)患者有纵隔肿块,21例(58.3%)有骨髓侵犯。全部患者采用改良的BFM-90方案化疗,其方案包括诱导缓解、中枢神经系统预防、再诱导缓解和维持治疗,总疗程2年。此方案与标准的BFM-90方案不同之处是不做头颅预防照射,但维持治疗期间定期大剂量甲氨蝶呤(HD-MTX)静脉输注和鞘内注射。结果32例(88。8%)患者获得完全缓解(CR),1例(2.7%)部分缓解(PR),总有效率90.7%。1例进展(PD)。2例患者在第1次完全缓解后(CR1)行自体造血干细胞移植(APBSCT),2例患者行纵隔放疗。复发5例,其中2例挽救治疗后存活,另3例肿瘤进展死亡;诱导期死亡2例,1例死于真菌败血症,另1例死于脑出血。PR和PD2例患者均死于肿瘤进展;共7例患者死亡。中位随访时间28个月,3年总生存率为78.3%。主要的毒性反应是骨髓抑制、感染和出血等,需要积极处理。结论改良BFM-90方案可明显改善儿童青少年淋巴母细胞型淋巴瘤的疗效和生存率,主要不良反应为骨髓抑制,应在有经验的肿瘤中心或血液科中应用。     

Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin''s lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern.     

单纯CHOP样方案与CHOP样方案联合造血干细胞移植巩固治疗淋巴母细胞淋巴瘤的疗效分析

目的 探讨单纯CHOP样方案与CHOP样方案+高剂量治疗联合造血干细胞移植(HDT-HSCT)一线巩固治疗淋巴母细胞淋巴瘤(LBL)的疗效.方法 63例有完整治疗及随访记录的LBL患者,初治均采用标准CHOP样方案,42例获得完全缓解(CR)或不确定CR(CRu).其中26例接受HDT-HSCT巩固治疗,16例单纯进行6～8个周期CHOP样方案治疗.结果 63例患者中,初治总缓解率为82.5%.中位随访24个月时,5年生存率为31.2%,5年无病生存率为29.3%.接受HDT-HSCT巩固治疗的26例患者,5年生存率为59.8%;单纯CHOP样方案治疗的16例患者,5年生存率为14.6%,差异有统计学意义(P=0.004).单因素预后分析结果显示,年龄、骨髓侵犯、初治缓解情况与预后有关(均P<0.05).18例骨髓受侵的患者中,3例接受异基因造血干细胞移植(allo-HSCT)的患者在随访22、32和37个月时仍生存,而4例接受自体造血干细胞移植(auto-HSCT)的患者,均在14个月内死亡.结论 单纯应用CHOP样方案治疗LBL疗效欠佳.HDT-HSCT作为一线巩固治疗有可能提高LBL患者的总生存率和无病生存率.骨髓受侵的LBL患者,allo-HSCT的效果优于auto-HSCT.