Feasibility and results of a multimodality approach in elderly patients with localized intermediate to high-grade non-Hodgkin's lymphomas

AIMS AND BACKGROUND: A prospective clinical study to determine efficacy and feasibility of a brief course or standard course of anthracycline-based chemotherapy and consolidation radiation therapy in non-Hodgkin's lymphoma patients over 60 years of age. METHODS: Twenty-five consecutive patients with stage I-IE intermediate to high-grade non-Hodgkin's lymphoma aged 60 and older were treated in an outpatient setting in the Radiotherapy Oncology and Hematology units. All patients had a performance status of 0-1 according to WHO criteria. The survival end points, ie, overall survival, disease-free survival and event-free survival, were considered. Lactate dehydrogenase value, nodal versus extranodal localization and dose intensity were assessed as risk factors for disease-free and overall survival. A comparison using logrank analysis with a well-matched group of stage I-IE non-Hodgkin's lymphoma patients aged less than 60 years was performed. RESULTS: The 5-year overall and disease-free survival rates were 90% and 86%, respectively. There was no statistical difference with respect to the younger population regarding these survival end points. Finally, the 5-year event-free survival was 85% and 86% for elderly and younger patients, respectively, without statistical difference (P = 0.41). Neither acute nor late toxicity (G3-G4) was observed during chemotherapy and radiotherapy treatment and the follow-up in the elderly group. CONCLUSIONS: We confirm the efficacy and feasibility of a full-dose combined chemoradiotherapy in elderly patients with a good performance status with localized I-IE intermediate to high-grade non-Hodgkin's lymphoma.     

Pyothorax-associated lymphoma: a review of 106 cases.

PURPOSE: Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity after a long-standing history of pyothorax. Full details of PAL are provided here. PATIENTS AND METHODS: Clinical and pathologic findings were reviewed in 106 patients with PAL collected through a nationwide survey in Japan. RESULTS: Age of the patients with PAL was 46 to 82 years (median, 64 years), with a male/female ratio of 12.3:1. All patients had a 20- to 64-year (median, 37-year) history of pyothorax resulting from artificial pneumothorax for treatment of pulmonary tuberculosis (80%) or tuberculous pleuritis (17%). The most common symptoms on admission were chest and/or back pain (57%) and fever (43%). Laboratory data showed that the serum neuron-specific enolase level was occasionally elevated (3.55 to 168.7 ng/mL; median, 18.65 ng/mL), suggesting a possible diagnosis of small-cell lung cancer. Histologically, PAL usually showed a diffuse proliferation of large cells of B-cell type (88%). In situ hybridization study showed that PAL in 70% of the patients was Epstein-Barr virus (EBV)-positive. PAL was responsive to chemotherapy, but the overall prognosis was poor, with a 5-year survival of 21.6%. CONCLUSION: This study established the distinct nature of PAL as a disease entity. PAL is a non-Hodgkin's lymphoma of exclusively B-cell phenotype in the pleural cavity of patients with long-standing history of pyothorax, and is strongly associated with EBV infection. Development of PAL is closely related to antecedent chronic inflammatory condition; therefore, PAL should be defined as malignant lymphoma developing in chronic inflammation.     

Weekly alternating combination chemotherapy for good prognosis AIDS-related lymphoma

Early studies reported that the major adverse prognostic factors in AIDS-related non-Hodgkin's lymphoma (ARL) are low CD4 cell count, prior AIDS defining diagnosis and poor performance status. Since 1989 we have adopted a prognosis-stratified approach for ARL. In this study, we identified a group of good prognosis patients. These patients with one or no adverse prognostic factors were treated with alternating weekly chemotherapy using the bleomycin, etoposide, vincristine, methotrexate, prednisolone/cyclophosphamide, doxorubicin (BEMOP/CA) schedule (Bower M, Block C, Gulliford T, et al. Cancer Chemother Pharmacol 1995, 38, 106-109). Modifications to the regimen with the aim of reducing toxicity were a briefer duration (12 weeks) and the addition of prophylaxis against pneumocystis and mycobacteria. Intrathecal methotrexate was administrated fortnightly to patients with Burkitt's histology, meningeal involvement or base of skull disease. 30 patients were treated, including 5 with prior AIDS, 3 with ECOG status 3 and 1 with CD4 <100/microl. The mean age was 40 (range 22-60 years), the median CD4 cell count at ARL diagnosis was 262/microl (range 44-588/microl). The International non-Hodgkin's lymphoma (NHL) prognostic factors project classifications were low risk 8 (maximum 5.4 years) (27%), low-intermediate risk 6 (20%), high-intermediate risk 11 (37%) and high risk 5 (17%). The median follow-up was 2.1 years. 3 patients withdrew from treatment within 2 weeks due to toxicity, 2 patients died within 2 weeks of starting chemotherapy. The major toxicity was myelosuppression with 14 patients developing grade 4 neutropenia. The 2-year overall survival rate is 46% (95% confidence interval (CI)=27-65%), and lymphoma-specific survival at 2 years is 59% (95% CI: 40-78%). For selected patients with good prognosis ARL 12 weeks BEMOP/CA therapy produces good overall survival at 2 years.     

Combination chemotherapy of diffuse large-cell non-Hodgkin's lymphoma--superiority of the adriamycin combination

In patients with diffuse large-cell non-Hodgkin's lymphoma, the results of combination chemotherapy containing adriamycin (ADM) were compared with those of combination chemotherapy without ADM. None of the patients had had any prior therapy and there was no difference in any other background factors for these two treatment groups. Of 32 patients treated without ADM, 19 (59%) achieved complete response (CR) and 12 (38%) achieved partial response (PR). Of 20 patients treated with ADM. 14 (70%) achieved CR and 6 (30%) achieved PR. For patients treated without ADM, median duration of CR was 9 months, projected 5-year relapse-free rate was 27%, median survival time was 1 year 6 months and projected 5-year survival rate was 27%. For patients treated with ADM, median duration of CR was not reached, projected 5-year relapse-free rate was 85%, median survival time was 2 years 2 months and projected 5-year survival rate was 49%. Combination of ADM was superior and therefore should be used for the initial treatment of this type of non-Hodgkin's lymphoma.     

Effective salvage chemotherapy in relapsed or refractory non-Hodgkin's lymphoma

BACKGROUND: Over the last few years, high-dose chemotherapy has been extensivelyinvestigated in relapsing/refractory non-Hodgkin's lymphoma(NHL). However, this approach is reserved to a limited subsetof cases and new conventional-dose second-line chemotherapiesneed to be investigated. PATIENTS AND METHODS: Thirty consecutive out-patients with refractory or recurrentNHL were given polychemotherapy in a regimen consisting of ifosfamide,mitoxantrone and etoposide on day 1 and vindesine, cisplatinumand cytosine arabinoside on day 15: courses were repeated every29 days. Five patients had refractory disease following first-linechemotherapy and 25 were relapsing. RESULTS: The median number of administered cycles was 4 (range 2–8).We observed 16 complete (53%; 95% confidence interval, 34%–72%)and 3 partial remissions, for an overall remission rate of 63%(95% confidence interval, 44%–80%). Responses were seenonly among patients who achieved at least a partial responseduring first-line therapy. The median duration of complete remissionwas 15 months (range 5–47+), whereas median survival ofthe treated patients was 26 months (range 2–50+). Fivepatients were long-term responders after 34+, 35+, 46+, 46+and 47+ months. No-life threatening toxicity was observed. Themain side effects were myelosuppression, nausea/vomiting andalopecia. CONCLUSIONS: The proposed regimen is feasible and effective in terms of completeremission rate and disease-free survival, suggesting that thistreatment may be potentially curative in a subgroup of relapsedpatients with limited tumor burden and normal LDH values. Amore aggressive approach is needed in refractory patients. non-Hodgkin's lymphoma, salvage chemotherapy     

Radiotherapy for primary localized (stage I and II) non-Hodgkin's lymphoma of the oral cavity

PURPOSE: To assess the role of radiation therapy in the treatment of primary localized (Stage I: 24 cases and Stage II: 13 cases) non-Hodgkin's Lymphoma (NHL) of the oral cavity. METHODS AND MATERIALS: In total, 37 patients (27 male, 10 female) with primary localized NHL of the oral cavity have been treated with radiotherapy alone (23 cases) or radiation with chemotherapy (14 cases). The age range was 29 to 86 years (median: 65). Clinical and treatment variables with potential prognostic significance for survival were evaluated by univariate and multivariate analysis. Of the 37 patients, 31 (84%) had intermediate-grade lymphomas and six (14%) had high-grade lymphomas. Four patients showed necrotic ulcer in the central portion of the hard palate. RESULTS: The 5-year actuarial survival rate for all cases was 73%. The 5-year survival rates for intermediate-grade and high-grade lymphoma were 85% and 14%, respectively. Significant prognostic factors identified by the multivariate analysis were histologic grade of malignancy (p = 0.02) and central necrotic ulcer in the tumor (p = 0.02). Chemotherapy did not improve survival (p = 0.41). CONCLUSIONS: Our analysis suggests that radiotherapy alone may be approved as the treatment for localized oral NHL with no ulceration and intermediate histology. However, patients with high-grade lymphoma and/or necrotic ulcer are difficult to cure with radiation alone and aggressive treatment should be advocated to improve survival.     

Cyclophosphamide metabolism in children with non-Hodgkin's lymphoma.

PURPOSE: The purpose of our study was to determine whether variation in cyclophosphamide metabolism influences the incidence of recurrence among children receiving chemotherapy for B-cell non-Hodgkin's lymphoma. EXPERIMENTAL DESIGN: The pharmacokinetics and metabolism of cyclophosphamide were studied during a single course of treatment in 36 children receiving a uniform chemotherapy regimen for B-cell non-Hodgkin's lymphoma and were analyzed in terms of disease recurrence and hematological toxicity. RESULTS: At a median follow-up of 43 months (range, 17-98 months), six children had developed recurrent disease, giving an overall disease-free survival of 83%. The median clearance of cyclophosphamide in patients who remain free of B-cell non-Hodgkin's lymphoma was 3.7 liter/h/m(2) (range, 2.3-5.0 liter/h/m(2)), compared with 2.2 (range, 1.5-2.5 liter/h/m(2)) in those with disease recurrence. Likelihood of recurrence was higher in patients with low clearance (<3.5 liter/h/m(2)) of cyclophosphamide (P < 0.01) and positively related to detection of the inactive metabolites carboxyphosphamide and dechloroethylcyclophosphamide in plasma (P = 0.01). There was no correlation between cyclophosphamide metabolism and hematological toxicity. CONCLUSIONS: Inadequate clearance of cyclophosphamide to active metabolites is associated with increased risk of recurrence of B-cell non-Hodgkin's lymphoma in children. Modified chemotherapy strategies should be considered in patients who exhibit low rates of clearance of the parent drug and/or extensive production of inactive metabolites.     

Primary lymphoma of bone in children

Primary lymphoma of bone (PLB) occurs infrequently in children. Between January 1962 and November 1988, 395 children with non-Hodgkin's lymphoma (NHL) were treated at St. Jude Children's Research Hospital. Eleven of these patients (2.8%) presented with a bone primary, usually in the femur (eight of 11 patients). The median age of these seven boys and four girls at presentation was 13 years (range, 5.5 to 19 years). Seven patients had one or more additional bones involved. All patients had high-grade lymphomas based on the National Institutes of Health (NIH) Working Formulation. The histologic subtypes included six large-cell lymphomas, three lymphoblastic lymphomas, one small-noncleaved, non-Burkitt's lymphoma, and one unclassifiable lymphoma. Treatment consisted of multiagent chemotherapy combined with local radiation therapy in seven of 11 patients. Six of 10 children who received chemotherapy as a component of their initial therapy, including all who presented with localized tumor, are alive with no evidence of disease 2+ to 85+ months (median, 42.5 months) after cessation of treatment; one patient has just completed chemotherapy. Each of the four patients who died showed leukemic conversion 5 to 11 months after diagnosis, and three died of progressive disease. One patient died of sepsis during chemotherapy-induced neutropenia with no evidence of disease at necropsy. We conclude that optimal therapy for PLB, as with all other forms of NHL, should focus on the histologic subtype and stage of disease.     

37例原发骨恶性淋巴瘤的临床特点及预后因素分析

探讨原发骨恶性淋巴瘤（primary bone lymphoma,PBL）的临床特点及其与预后的相关性。方法:回顾性分析1995年6月至2009年5月本院收治的37例PTL患者的临床资料,以Kaplan-Meier法绘制生存曲线,用Log-rank检验进行单因素分析,多因素分析采用Cox回归模型以评估独立的预后因素。结果:37例患者的中位发病年龄为61（18～85）岁,首发症状主要表现为骨痛,局部软组织肿胀、肿块形成和病理性骨折。78%患者的病理类型为弥漫大B细胞淋巴瘤。经化疗和/或放疗,18例完全缓解（complete response,CR）,13例部分缓解（partial response,PR）,3例稳定（stable disease,SD）,2例进展（progressive disease,PD）。中位随访时间32（7～171）个月,5年和10年总生存率分别为59.5%和43.2%。患者接受4周期以上化疗,B细胞淋巴瘤加用利妥昔单抗者疗效较好。多因素分析显示:Ann Arbor分期、B症状、年龄和结外受侵数是PBL的独立预后因素。结论:PBL应采取综合治疗,同时给予蒽环类药物为主的全身化疗,B细胞淋巴瘤首选利妥昔单抗联合化疗,给予帕米膦酸盐治疗骨病变。Ann Arbor分期、B症状、年龄和结外受侵数为PBL预后的独立影响因素。      

Primary intracerebral lymphoma: A clinicopathological study of 28 patients

Primary intracerebral lymphoma is an uncommon presenting site for non-Hodgkin's lymphoma. The authors review 28 histopathologically confirmed, consecutive cases, presenting over a 15-year period. The cohort included 20 males and 8 females with a mean age at diagnosis of 54 years (range 27-75 years). Subtotal resection was performed in 8 patients. Radical whole brain irradiation was given to 27 patients. One patient was too unwell to receive treatment and quickly died. Three patients also had chemotherapy. Clinical remission was achieved in 19 patients. Of these, 9 relapsed after a median interval of 18 months. Nine patients (32% total cohort) are still alive and in remission after a median follow-up of 2 years and 10 months (range 11 months to 11 years and 5 months). Cause of death was intracerebral lymphoma in 13 of the 19 patients who died. Median survival was 12 months in this group (range 1 week to 4 years and 9 months). Actuarial 5-year survival for all patients was 19%. The prognosis for patients with primary intracerebral lymphoma treated with radiotherapy alone is poor.     

儿童恶性淋巴瘤化疗后胸腺反应性增生的临床分析

背景与目的：恶性肿瘤患者化疗后胸腺反应性增生不易与肿瘤残留或复发鉴别。常被误诊为肿瘤残留或复发而过度治疗。本研究通过分析儿童恶性淋巴瘤化疗后胸腺反应性增生的病例．探讨化疗后胸腺反应性增生的临床特征,以加深对此种病征的认识。方法：收集1999年3月至2004年3月初治淋巴瘤患者经化疗后胸腺反应性增生者共13例。其中霍奇金淋巴瘤5例。非霍奇金淋巴瘤8例。确诊后均予化疗。常规行CT检查评价疗效或追踪观察。纵隔出现新增肿块后,部分患者行正电子发射计算机断层扫描（positive electron tomography computed tomography,PET／CT）检查,明确肿块性质,再决定进一步的治疗;因经济条件所限而不能做PET／CT检查者,予密切追踪观察。结果：10例患者起病时肿瘤即侵犯纵隔,3例患者起病时纵隔无肿瘤侵犯。9例在化疗结束后随诊期间出现胸腺增生,4例在维持治疗期间出现（均为淋巴母细胞性非霍奇金淋巴瘤患者）。CT显示纵隔新增肿块影最大横径为2．2～6．0cm。平均3．7cm。胸腺增生距离上次化疗结束时间2～12个月,平均4个月。5例患者行PET／CT检查,均显示纵隔肿块无肿瘤活性。3例胸腺增生患者被误诊为肿瘤进展或复发,予二线治疗。所有患者随访1-6年（中位时间4年）,无肿瘤复发征象。结论：儿童淋巴瘤患者在强烈化疗后胸腺可出现反应性增生．临床上须避免误诊为胸腺恶性肿瘤而过度治疗。     

Therapeutic results in 22 cases of childhood non-Hodgkin's lymphoma treated by ACOP combination chemotherapy

Twenty-two cases of childhood non-Hodgkin's lymphoma were treated during the past 8 years from 1979 to 1986. Median age was 7 years 4 months and the age range was from 2 years 4 months to 14 years 9 months, the male to female ratio being 18 : 4. Primary sites were common in the mediastinum (n = 7) and abdomen (n = 6) followed by submandibular lymph nodes (n = 3). According to Murphy's staging system, 7 were in stage I/II and 15 in stage III/IV. Histological studies of lymphoma tissues and blasts in the cerebrospinal fluid, pleural effusion or ascites revealed that 9 cases were lymphoblastic lymphoma while only 3 were defined as Burkitt's lymphoma. With our protocol of systemic combination chemotherapy (i.e. ACOP), intrathecal methotrexate and/or involved field irradiation, twenty-one out of the 22 cases (93%) attained complete remission and 14 patients are currently alive in continuous complete remission, with a median survival of 28+ months (range 6+ approximately 76+ months).     

自体造血干细胞移植治疗中、高度恶性淋巴瘤

背景与目的:自体造血干细胞移植(autologoushemotopoieticstemcelltransplantation,ASCT)支持下的大剂量化疗目前已成为治疗对化疗敏感的淋巴瘤最有效的手段之一。本研究评价自体造血干细胞移植支持下的大剂量化疗加放疗治疗预后差的中、高度恶性淋巴瘤的疗效。方法:1995年11月～2001年5月收集到的13例病例中,非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)11例,复发霍奇金淋巴瘤(Hodgkinsdisease,HD)2例。移植前首次完全缓解(firstcompleteremission,CR1)8例,第二次完全缓解(secondcompleteremission,CR2)4例,第二次部分缓解(secondpartialremission,PR2)1例。预处理方案:单纯化疗4例;化疗加受累区放疗6例;全身放疗加化疗3例。2例采用自体骨髓移植,11例行自体外周血干细胞移植。结果:本组病例回输单核细胞(mono-nuclearcell,MNC)和粒-巨细胞系祖细胞(granulocyte-macrophagecolony-formingcells,CFU-GM)的均数(范围)分别为2.55(2.07～3.31)×109/L和1.43(0.6～2.36)×109/L。随访到2001年10月,所有患者造血功能都获得重建。白细胞恢复到≥1.0×109/L和血小板>50×109/L的中位时间(范围)分别为6(7～35)天和8(6～32)天。CR持续时间为4～57个月,中位时间为16个月,1年生存率76.9%,3年生存率46.2%。结论:自体造     

2-Chlorodeoxyadenosine treatment of low-grade lymphomas.

PURPOSE: Because of the need to identify effective new agents in the treatment of non-Hodgkin's lymphoma and because of the high activity of the purine analog 2-chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade lymphocytic lymphomas. PATIENTS AND METHODS: Forty patients with low-grade lymphocytic lymphomas including diffuse small lymphocytic, follicular small-cleaved, and follicular mixed histologies were enrolled onto the study. Conventional therapies had failed in all patients, and six patients had lymph node biopsies showing evidence of histologic evolution to a higher-grade lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had received a median of three prior therapies (range, one to six therapies). RESULTS: An overall response rate of 43% was achieved, with eight patients experiencing complete responses (CRs) and nine patients experiencing partial responses (PRs). The duration of responses ranged from 1 to greater than 33 months without maintenance therapy (median duration of response, 5 months). Histology and prior therapy history did not seem to correlate with responses. Significant toxicity was limited to bone marrow suppression; 18% of patients developed neutropenia, and 30% developed thrombocytopenia. CONCLUSIONS: This phase II trial demonstrates that 2-CdA is an effective antilymphocyte, antineoplastic agent with significant activity as a single agent in patients with recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved with an acceptable toxicity profile. Further trials of this agent in previously untreated patients and in combination regimens are indicated and will be developed.     

Gonadal function after MACOP-B or VACOP-B with or without dose intensification and ABMT in young patients with aggressive non-Hodgkin's lymphoma

BACKGROUND:: The late effects of chemotherapy of aggressive non-Hodgkin'slymphoma on gonadal function are largely unknown. PATIENTS AND METHODS:: In a retrospective study the gonadal function after chemotherapywith MACOP-B or VACOP-B with or without dose intensificationand ABMT in first remission was examined in patients with aggressivenon-Hodgkin's lymphoma by patient history and determinationof hormonal function. Thirty adult patients of age 40 or lessat diagnosis who were alive and free of relapse for at least1 year after completion of chemotherapy were included in thestudy. RESULTS:: With a median time of 28 months (range 11 to 62 months) aftercompletion of therapy, gonadal dysfunction was found in 1 of7 female and none of 15 male patients, or a total of 5% of patientstreated with chemotherapy alone. Of patients receiving doseintensification and ABMT in first remission, gonadal dysfunctionwas present in 2/6 (33%) treated with cyclophosphamide, BCNUand etoposide in 3/4 treated with cyclophosphamide and TBI. CONCLUSIONS:: Our data suggest that therapy of aggressive non-Hodgkin's lymphomaswith MACOP-B or VACOP-B has little impact on future fertilityand that fertility may be preserved in the majority of patientsreceiving dose-intensification with CBV in first remission.     

Pegylated liposomal doxorubicin as single-agent treatment of low-grade non-Hodgkin's lymphoma: a phase II multicenter study

The purpose of this study was to determine the objective response rate, median duration of response, time to disease progression, and survival time and to evaluate the safety of pegylated liposomal doxorubicin in previously treated patients with low-grade non-Hodgkin's lymphoma. Thirty-two patients with low-grade non-Hodgkin's lymphoma were treated and analyzed. Pegylated liposomal doxorubicin 30 mg/m2 was administered intravenously as a single dose on day 1 of each 3-week cycle. Patients had an Eastern Cooperative Oncology Group performance status of 0-1 and had stage II-IV disease. The median baseline left ventricular ejection fraction was 60%, and the median age was 68 years. In 29 evaluable patients, there were 3 (10%) complete responses, 6 (21%) partial responses, 11 (38%) patients with stable disease, and 9 (31%) with progressive disease. The median number of cycles was 4 (range, 1-22 cycles). The median duration of response (complete response plus partial response) was 11.0 months (range, 2.3-37.0 months). The estimated median time to progression was 5.6 months (range, 1.1-40.5 months) and the estimated median survival was 29.6 months (range, 3.9-41.6 months). Treatment-related toxicities grade = 3 included neutropenia (25%) and palmoplantar erythrodysesthesia (9%). Only 1 clinically significant cardiac toxicity was observed. There were 17 deaths; none were treatment related. Single-agent pegylated liposomal doxorubicin 30 mg/m2 every 3 weeks, is associated with antitumor activity in the treatment of low-grade non-Hodgkin's lymphoma, as shown by an objective response of 31%, and produced no significant cardiac or hematologic toxicity. Based on these results, pegylated liposomal doxorubicin should be further evaluated in combination with other agents in low-grade non-Hodgkin's lymphoma.     

Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy

For cancer patients with chronic hepatitis B virus (HBV) infection, who receive cytotoxic chemotherapy, HBV reactivation is a well-described complication, which may result in varying degrees of liver damage. Several clinical features and the pre-chemotherapy HBV viral load have been suggested to be associated with an increased risk of developing the condition: (1). to assess the clinical and virological factors in a comprehensive manner and thereby identify those that are associated with the development of HBV reactivation; (2). to develop a predictive model to quantify the risk of HBV reactivation. In all, 138 consecutive cancer patients who were HBV carriers and undergoing chemotherapy were studied, of which 128 patients had sera available for real-time PCR HBV DNA measurement. They were followed up throughout their course of chemotherapy and the HBV reactivation rate was determined. The clinical and virological features between those who did and did not develop viral reactivation were compared. These included age, sex, baseline liver function tests, HBeAg status and viral load (HBV DNA) prior to the chemotherapy, and the use of specific cytotoxic agents. In all, 36 (26%) developed HBV reactivation. Multivariate analysis revealed pre-chemotherapy HBV DNA level, the use of steroids and a diagnosis of lymphoma or breast cancer to be significant factors. Based on real-time HBV DNA PCR assay, detectable baseline HBV DNA prior to the administration of cytotoxic chemotherapy, the use of steroids and a diagnosis of lymphoma or breast cancer are predictive factors for the development of HBV reactivation. A predictive model was developed from the current data, based on a logistic regression method.     

Allogeneic bone marrow transplantation for relapsed and refractory lymphoma using genotypically HLA-identical and alternative donors

Twenty-two patients, ages 16.6 to 43.9 years (median age, 30 years), with relapsed or refractory lymphoma were treated by allogeneic bone marrow transplantation after high-dose chemotherapy with or without total body irradiation (TBI). Seven patients had Hodgkin's disease, four had low-grade histology non-Hodgkin's lymphoma (NHL), seven had intermediate-grade NHL, and four had high-grade NHL. Of the 22 patients, 17 received T-cell (CD-3)-depleted marrow after intensive pretransplant chemoradiotherapy, and five received T-cell-replete grafts after chemotherapy-based preparative regimens. Five patients were transplanted from donors other than genotypically HLA-identical siblings: four from partially HLA-matched relatives, and one from a phenotypically HLA-identical unrelated donor. Acute graft-versus-host disease (GVHD) was less than or equal to grade II in all patients, and chronic GVHD was limited or absent in all but one patient. Of the 21 assessable patients, 17 (80.9%) achieved complete remissions. Death due to transplant-associated complications occurred in five patients, and five patients have relapsed. Thirteen patients are alive, and 12 are continuously relapse-free at a median follow-up of longer than 28 months (range, greater than 10 to greater than 58 months) from transplant. The cumulative probability of treatment failure from relapse or progression of lymphoma was 29% (95% confidence interval [CI], 12% to 51%), while the actuarial lymphoma-free (ie, event-free) survival plateau is 54.6% (95% CI, 34% to 76%). For young patients with advanced malignant lymphoma, allogeneic bone marrow transplantation appears superior to salvage chemotherapy for achievement of long-term, lymphoma-free survival and may be preferable to autologous bone marrow transplantation for selected patients.     

Final analysis of the ECOG I-COPA trial (E6484) in patients with non-Hodgkin's lymphoma treated with interferon alfa (IFN-alpha2a) plus an anthracycline-based induction regimen.

The Eastern Cooperative Oncology Group (ECOG) performed a prospectively randomized study (E6484) evaluating the use of interferon alfa 2a (IFN-alpha2a) in patients with aggressive low-grade or with intermediate-grade non-Hodgkin's lymphoma (NHL) accruing close to 300 patients between 1985 and 1988. Patients were eligible for study if they had bulky or symptomatic low-grade lymphoma or defined intermediate-grade subtypes. Of 291 patients enrolled, 249 were eligible for analysis. All patients were randomized to receive a four-drug cytotoxic chemotherapy regimen including cyclophosphamide, doxorubicin, vincristine and prednisone in 4-week cycles with or without IFN-alpha2a in addition (COPA vs I-COPA). Treatment was given for up to 8-10 months. This report, at a time when the median follow-up among survivors has reached 12 years, updates the analysis of time to treatment failure (TTF), duration of disease-free survival (DFS), and overall survival. Patients randomized to receive IFN-alpha2a had a prolonged TTF (P= 0.008; median 2.4 vs 1.6 years). DFS for those patients who had complete responses was also longer if IFN-alpha2a had been given (P = 0.035; median 2.7 vs 1.8 years). There was a clinically but not a statistically significant prolongation of overall survival by IFN-alpha2a (P= 0.107; median 7.8 vs 5.7 years). There were fewer deaths over time due to lymphoma in patients receiving IFN-alpha2a (67 vs 80 deaths). A subset analysis, based on disease histology (low-grade, follicular, intermediate-grade), revealed a significant prolongation of TTF in patients receiving IFN-alpha2a with either low-grade (P = 0.002; median 2.4 vs 1.6 years) or follicular (P= 0.01; median 2.5 vs 1.7 years) NHL but not intermediate grade (P = 0.622; median 2.3 vs 1.6 years) NHL. This analysis, performed approximately 12 years after closure of the study to accrual, supports the addition of interferon alfa to an induction cytotoxic chemotherapy regimen including cyclophosphamide and doxorubicin in the treatment of follicular NHL.     

Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults.

PURPOSE: To assess the cardiac status of the long-term survivors and to estimate the incidence and the features of subclinical cardiotoxicity induced after conventional treatment with doxorubicin for non-Hodgkin's lymphoma or Hodgkin's lymphoma. PATIENTS AND METHODS: We analyzed a group of patients who previously received doxorubicin-based chemotherapy for lymphoma. Echocardiograms were performed at least 5 years after therapy with anthracyclines. Clinical cardiomyopathy was defined by the presence of clinical signs of congestive heart failure (CHF). Subclinical cardiomyopathy was defined by decrease of left ventricular fractional shortening (FS) without clinical signs of CHF. Cumulative dose of doxorubicin, male sex, older age, relapse, radiotherapy (mediastinal or total-body irradiation), autologous stem-cell transplantation, high-dose cyclophosphamide, and cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, familial history of cardiac disease, being overweight, and smoking history) were evaluated as potential risk factors for the development of cardiac dysfunction. RESULTS: Of 141 assessable patients (median age, 54 years; median cumulative dose of doxorubicin, 300 mg/m(2)), only one developed CHF. Criteria of subclinical cardiomyopathy were found in 39 patients. In multivariate analysis, factors that contributed to decreased FS were male sex (P <.01), older age (P <.01), higher cumulative dose of doxorubicin or association with another anthracycline (P =.04), radiotherapy (P =.04), and being overweight (P =.04). CONCLUSION: Cardiac abnormalities can occur in patients treated with doxorubicin for lymphoma in the absence of CHF, even in patients who received moderate anthracycline doses. Male sex, older age, higher dose of doxorubicin, radiotherapy, and being overweight were risk factors for the development of cardiomyopathy.