Treatment of high-grade,disseminated non-Hodgkin's lymphoma in elderly patients

PURPOSE: Treatment of non-Hodgkin's lymphoma (NHL) in the elderly is difficult because of an increased risk of toxicity and frequent chronic or debilitating diseases. The aim of this paper is to describe the main studies in this field. CURRENT KNOWLEDGE AND KEY POINTS: Most recent clinical trials deal with anthracyclin or assimilated drugs regimens. Potential interest of chemotherapy and associated immunotherapy is on study. Without any influence on survival duration, haematopoietic growth factors seem to improve the tolerance of the treatment. FUTURE PROSPECTS AND PROJECTS: For elderly patients with good performance status and without severe co morbidity, curative strategy with anthracyclin-containing regimen like CHOP is still the standard chemotherapy. Association with rituximab improves the prognosis. For patients with poor performance status and/or associated disease, optimal strategy remains to be defined with quality of life evaluation.     

COP-BLAM regimen combined with granulocyte colony-stimulating factor and high-grade non-Hodgkin's lymphoma

Abstract: The clinical efficacy of COP-BLAM chemotherapy combined with human recombinant granulocyte colony-stimulating factor (G-CSF) was evaluated in 104 previously untreated patients with non-Hodgkin's lymphoma (NHL). According to the method of Laurence et al., a modified COP-BLAM regimen was administered every 21 days. G-CSF was added when the granulocyte count fell below 1000 × 10⁹/l. Ninety-eight of 104 (94.2%) patients achieved a complete remission; the 4-year survival rate was 82.4% with a median duration of observation of 26 months. Survival was significantly longer in patients with low serum LDH levels, B-cell type or low CRP or in earlier clinical stages, than in patients with high serum LDH levels, T-cell type or higher CRP levels or in advanced clinical stages. The mean duration of administration of G-CSF was 5.4 days. Twelve patients developed infections during treatment. The adverse effects of G-CSF included interstitial pneumonia, bone pain and fever. Patients administered COP-BLAM combined with G-CSF achieved a high rate of remission and had a low incidence of infection. Nearly all the patients could be treated in 21-day cycles. The results suggest that G-CSF combined with COP-BLAM was effective in treating NHL, because the patients can tolerate a higher dose of the anticancer agents.     

Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma

The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eighty-two patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progression-free survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248.     

Myocardial infarction in patients aged 70 years and over

109 subjects aged 70 years (58 women, 51 men; average age 77 years) were hospitalized in the CICU (Cardiology Intensive Care Unit) over the period stretching from 1984 to 1986. The average length of stay in the CICU was 1 week, completed by an average stay of 5 days in the cardiology department. 100 per cent of the patients were followed up. Of the clinical parameters made evident by this study, the authors note that hypertension was the predominant risk factor (52.2 per cent); a history of coronary disease was noted in 60.5 per cent; 26.6 per cent of the patients were hospitalized before the 6th hour, chest pain being typical in 78 per cent versus painless in 11 per cent of patients; topographically, the infarction was anterior in 55 per cent, posterior in 40.4 per cent, and around the circumference in 4.6 per cent of cases; 80.8 per cent of the infarctions were transmural versus 19.2 per cent of infarctions without the Q wave--the latter accounted for a higher hospital mortality rate (38 per cent versus 27.3 per cent). The main complications were disturbances in rhythm (60.6 per cent) and LVI (56.9 per cent). Complications on the form of infections were noted in 15.6 per cent. Apart from the usual indicators of severity (cardiogenic shock, VF, LVI), infarction of the RV and AF had a serious effect on the prognosis. latrogenic disease accounted for 18.9 per cent. From the point of view of prognosis, hospital mortality was 30 per cent; mortality after one year was 44 per cent and 47.7 per cent after 2 years (in a group of 76 subjects).(ABSTRACT TRUNCATED AT 250 WORDS)     

Outcomes of auto-SCT for lymphoma in subjects aged 70 years and over

The safety and efficacy of auto-SCT for lymphoma in older patients is not well established, particularly in those ≥70 years old. We performed a retrospective analysis comparing 17 auto-SCT recipients ≥70 years old with 39 recipients aged 65-69 years. Hematopoietic cell transplantation comorbidity index (HCT-CI) scores were similar in both groups. Nonrelapse mortality (NRM) was increased in patients aged 70 years and older (hazard ratio (HR) 6.04, P=0.0029), and OS was decreased (HR 1.98, P=0.082). 1-year NRM was 35% in patients aged ≥70 years vs 8% in those aged 65-69 years (P=0.017). The incidence of in-hospital falls was higher in those aged ≥70 years (29 vs 8%, P=0.047). In a secondary exploratory analysis, we found that the occurrence of in-hospital falls was strongly associated with inferior OS (HR 3.36, P=0.0023) and NRM (HR 4.60, P=0.009) among all patients of aged 65 years and older. We conclude that auto-SCT is feasible in older patients but that mortality rates appear increased in those over age of 70 years. In-hospital falls were correlated with higher mortality, and prevention of falls may improve outcomes. Susceptibility to falls may indicate underlying frailty and should be explored prospectively as a means of selecting older patients for auto-SCT.     

Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an intensive epirubicin-containing regimen

An intensive chemotherapy regimen (EVDAC), including high-dose epirubicin, vincristine, and dexamethasone followed by cyclophosphamide and high-dose cytarabine, was administered to 54 untreated adults with intermediate or high-grade non-Hodgkin's lymphomas (NHL). The median age was 59, 61% were Ann Arbor Stage IV, 57% had "B" symptoms, 50% had serum lactate dehydrogenase greater than 250 U/L, and 48% had masses greater than 7 cm (33% > 10 cm) in diameter. Seventy-six percent of patients attained complete or probable complete remissions. The Kaplan- Meier actuarial failure-free survival at 7 years is 50%, and 59% (32 of 54) of all patients started on therapy remain alive and in first remission at a median of 62+ (range, 49+ to 76+) months from completion of therapy. Nearly all patients developed severe neutropenia. Febrile episodes requiring hospitalization during neutropenia occurred after 56% of courses of epirubicin, vincristine, and dexamethasone and after 9% of courses of cyclophosphamide and cytarabine; 80% of patients were hospitalized at least once. Platelet count nadirs of less than 20,000/microL occurred after only 1 of 146 evaluable courses of epirubicin and after none of the cyclophosphamide/cytarabine courses. Although 8 patients had decreases of at least 0.12 in their left ventricular ejection fractions (5 to below normal levels), none have developed clinically evident congestive heart failure. Clinically significant mucositis occurred after only 8% of courses of high-dose epirubicin. Three deaths from infections and one from hyperkalemia with cardiac arrest occurred during therapy. These results confirm that high remission and sustained, failure-free survival rates can be achieved in patients with aggressive NHL, using high-dose anthracycline-containing chemotherapy regimens. Epirubicin appears to have an advantage over doxorubicin at high doses because of decreased toxicity at a therapeutically equivalent dose. These phase II study results need to be validated in a randomized phase III trial, and growth factors should be used to attempt to reduce the neutropenia-associated complications.     

Treatment of elderly patients with intermediate- and high-grade non-Hodgkin's lymphoma: a retrospective population-based study

PURPOSE AND METHODS: Nowadays more people are becoming older. The median age of a patient with non-Hodgkin's lymphoma (NHL) at diagnosis is over 60 years. The incidence of NHL in elderly has increased in the last decades. Therefore, in the future, NHL will be diagnosed more often in the elderly. Data of all patients in the south-east of the Netherlands with newly diagnosed NHL between January 1991 and January 1995 were analysed in a retrospective multicentre population-based study to investigate if and how elderly patients (> 60 years) with advanced NHL (Ann Arbor Staging > or = IIB) of intermediate- and high-grade malignancy were treated. Treatment modalities applied, outcome, and causes of death were evaluated. Treatment was considered inadequate if it deviated from the standard anthracycline-containing chemotherapy (CNOP/CHOP) for a minimum of six cycles. RESULTS: The entry criteria were met by 68 patients. Of these patients, 57 (83.8%) were treated and 11 (16.2%) were not treated. The treatment consisted of CHOP (36 patients), CNOP (6 patients), chlorambucil (13 patients), or COP (2 patients). Forty-two of 68 patients had adequate treatment, but 14 of 42 (33.3%) patients had a suboptimal numbers of cycles (< 6). Of 28 patients with adequate chemotherapy, only 16 had the optimal number of cycles and dose; the result is that the treatment of 76.5% (52/68) of patients differed from that of their younger counterparts. The most important reason for treatment not being optimal was high age (23%) or poor performance (35%). In the appropriately treated patients, 62.5% (10/16) had a complete response. Survival in the CHOP/CNOP-treated group was better than in other groups. The main cause of death in the total study group was NHL. The results cannot be explained by the different international prognostic index. CONCLUSION: A significant subset (76.5%) of elderly people with intermediate/high-grade NHL received suboptimal therapy, mainly because of a suboptimal performance status. However, a significant part of the patients (23%) were not treated optimally because of high age, despite a good performance. For improving the overall survival in the elderly, it is not only the schedule that is important, but also the intention to treat the elderly patient.     

7O岁以上老年卵巢癌患者的化学治疗

目的观察70岁以上卵巢癌患者化疗的情况。方法选择1988年1月至2003年8月间我科初治的年龄≥70岁的卵巢癌化疗患者28例（老年组），年龄〈60岁卵巢癌化疗患者49例（非老年组），比较两组患者的临床资料、化疗的耐受性、生存期等。结果老年组和非老年组的化疗率分别为82．4％和98．0％，化疗的平均疗程数分别为5个和9个，两组比较差异有统计学意义（P〈0．05）。两组的化疗方案和按时化疗率比较，差异无统计学意义（P〉0．05）。老年组出现消化道反应的发生率（39．3％）明显低于非老年组（77．6％）。两组患者骨髓抑制需要治疗的比率分别为91．7％和52．0％，差异有统计学意义（P〈0．01）。随访期间，两组的生存时间差异无统计学意义（P〉0．05）。结论年龄大于70岁的卵巢癌患者能够耐受化疗；但化疗前应详细地评价全身状态，治疗方案个体化，严密监测和处理化疗的毒副反应。     

A dexamethasone,vinblastine, cyclophosphamide,etoposide, methotrexate and bleomycin (D-VICEMB) protocol as first-line treatment of patients aged 70 years or older affected by intermediate/high grade non-Hodgkin's lymphoma

We treated 30 consecutive untreated patients aged > 70 years with advanced aggressive non-Hodgkin's lymphoma with 6 courses of cyclophosphamide, mitoxantrone, etoposide, bleomycin, vinblastine and dexamethasone (D-VICEMB). The global response was 93%. The 6-year overall survival and progression-free survival were 50%, and disease-free survival was 63%.     

Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma

We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT. A total of 50 patients (94%) were consolidated in complete ( n=25) or partial ( n=25) remission, whereas 3 patients had chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%) had received prior radiotherapy (RT) excluding total body irradiation (TBI) as part of the conditioning regimen. The main nonhematological toxicities (grade II-IV according to the Bearman score) in 52 evaluable patients were mucositis (79%) and hepatic toxicity (15%). Severe veno-occlusive disease (VOD) occurred in three patients (5.8%) including one treatment-related death caused by VOD. Overall, treatment-related mortality was 3.8%. After a median follow-up for surviving patients of 21 months (range: 6-118), 20 patients (38%) are in continuous complete remission, 8 patients (15%) are alive in relapse, and 25 patients (47%) died. Probabilities of relapse, event-free survival, and overall survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31% (95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion, Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in patients with HD and NHL. Both toxicity and outcome were not significantly different in patients treated with 30 mg/kg and 45 mg/kg etoposide, respectively. The observed long-term results are even comparable to those published for other established high-dose protocols, including TBI-based regimens. However, further investigations are necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol for malignant lymphoma, especially in patients who have already received extensive RT.     

Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP

INTRODUCTION: During the last few years epirubicin (E) and mitoxantrone (M) (Novantrone) have been used in the treatment of non-Hodgkin's lymphoma (NHL), because of their favorable principal profile. In particular, M has less severe non-hematological toxicity. PATIENTS AND METHODS: A randomized multicenter phase III study was conducted in order to compare the efficacy and toxicity of CEOP and CNOP in intermediate- and high-grade NHL. CEOP (arm A) consisted of cyclophosphamide 1000mg m(-2), vincristine 2mg, E 70mg m(-2) on day 1 and prednisone 60mg on days 1-7. The CNOP regimen (arm B) was identical to CEOP except for replacement of E by M at a dose of 12mg m(-2). Randomization was stratified according to stages I-IV. From September 1993 to March 1999, 249 patients registered for the trial. Patient characteristics were equally distributed in the two arms, except for age and International Prognostic Index (IPI) groups. RESULTS: There were no significant differences between the two groups in the rates of complete (CR) and partial response (PR). The overall response rate was 78% in arm A (57% CR, 21% PR) and 82% in arm B (60% CR, 22% PR). With a median follow-up time of 47.3 months, the median survival was not reached in arm A, while it was 39.5 months in arm B (P=0.09). Three-year survival rates were 62.5% for CEOP and 51.5% for CNOP. There was no significant difference regarding the time to progression between the two groups (29.7 vs. 18.5 months); furthermore the median duration of CRs was 71.6 and 49 months for CEOP and CNOP, respectively (P=0.07). The therapeutic efficacies of both regimens were equivalent among the four IPI groups. More alopecia was observed in arm A. WHO grade >2 neutropenia was more frequent in arm B. Supportive treatment with G-CSF was given to 22 and 24 patients, respectively. CONCLUSION: There were no significant differences in terms of overall response rates, overall survival and time to progression between CEOP and CNOP in the treatment of intermediate- and high-grade NHL. Patients with low or low intermediate IPI risk treated with either CEOP or CNOP showed significantly better survival, response rates and time to progression than those with high intermediate or high IPI risk. Therefore, new improved therapeutic approaches should be developed for the treatment of high IPI risk patients.     

A novel preparative regimen for autologous transplant in non-Hodgkin's lymphoma: long-term experience with etoposide and thiotepa

The purpose of this study was to evaluate the efficacy and toxicity of the preparative regimen of thiotepa and etoposide in patients undergoing autologous transplantation for relapsed non-Hodgkin's lymphoma. The study involved 65 consecutive patients who underwent autologous transplantation using the thiotepa/etoposide regimen for relapsed intermediate-grade NHL at the University of Wisconsin Hospital and Clinics (UWHC) between 1987 and 2001. The regimen consisted of thiotepa 300 mg/m(2)/day and etoposide 700 mg/m(2)/day on days -6, -5, and -4. The median age at the time of transplant was 49 years. A total of 50 patients (76%) had diffuse large-cell lymphoma. A total of 50 (77%) patients had chemosensitive disease, and 15 (23%) were chemoresistant. With a median follow-up of 34 months (range, 3-163), 28 patients (43%) remain in CR and 33 (51%) have developed recurrent or progressive disease. The overall survival and event-free survival at 3 years are 40% (95% CI 26-53%) and 32% (95% CI 20-45%), respectively. There was one death attributed to regimen-related toxicity (RRT). Reversible gastrointestinal toxicity was the major RRT, and there was minimal pulmonary and cardiac toxicity. We conclude that the combination of thiotepa and etoposide is an effective preparative regimen with acceptable RRT.     

Mitral balloon valvuloplasty for patients aged over 70 years: an alternative to surgical treatment

We report the results and one-year follow-up of 20 elderly patients (age range 70-82 years) with severe rheumatic mitral stenosis treated by mitral balloon valvuloplasty (MBV). All 20 were breathless at rest despite treatment with diuretics and digoxin. At cardiac catheterization, successful dilatation was achieved in 17 patients: mean transvalvular mitral gradient fell by 45%, mean cardiac output rose by 24% and mean valve area increased by 76%. There was no procedure-related mortality. At one month, 15 patients had experienced an improvement in symptoms of at least one New York Heart Association class and, at one year, ten had maintained this improvement. Three patients proceeded to mitral valve replacement because of a suboptimal symptomatic result. Mitral balloon valvuloplasty can be successfully performed with significant symptomatic benefit in frail elderly patients unfit for surgery and may also be offered to other selected elderly patients as an alternative to surgical treatment.     

70岁及以上不可切除的胰腺癌患者生存因素分析

Objective To explore the effect of related factors on survival of patients with unresectable pancreatic cancer aged 70 years and over. Methods Fifty-seven patients with unresectable locally advanced or metastatic pancreatic cancer aged 70 years and over were enrolled.Their survival time were analyzed with SPSS 13.0 by taking account of gender, age, smoking history,alcohol history, pancreatic disease history, diabetes mellitus history, Eastern Collaborative Oncology Group (ECOG) scoring, chemotherapy, radiotherapy, CEA and CA199 levels. Results Gender,ECOG scoring, chemotherapy and radiotherapy had relationship with overall survival. The median survival time was 8.9 months and one-year survival rate was 28.1%. The median survival was (10.7±5.4) months in male group and (5.5±2.3) months in female group (P=0.000). The median survival was(10.1±5.8) months in patients with ECOG 0～1 group and(7.3±3.8)months in patients with ECOG 2 group (P=0.040). The median survival was(7.76±5.27) months in nochemotherapy group and(11.5±5.0)months in chemotherapy group (P=0.038). The median survival was(8.87±5.36)months in no radiotherapy group and (13.7±3.8) months in radiotherapy group (P=0.048). Conclusions The patients who have better ECOG performance status and receive chemotherapy or radiotherapy show better survival.     

70岁及以上不可切除的胰腺癌患者生存因素分析

Objective To explore the effect of related factors on survival of patients with unresectable pancreatic cancer aged 70 years and over. Methods Fifty-seven patients with unresectable locally advanced or metastatic pancreatic cancer aged 70 years and over were enrolled.Their survival time were analyzed with SPSS 13.0 by taking account of gender, age, smoking history,alcohol history, pancreatic disease history, diabetes mellitus history, Eastern Collaborative Oncology Group (ECOG) scoring, chemotherapy, radiotherapy, CEA and CA199 levels. Results Gender,ECOG scoring, chemotherapy and radiotherapy had relationship with overall survival. The median survival time was 8.9 months and one-year survival rate was 28.1%. The median survival was (10.7±5.4) months in male group and (5.5±2.3) months in female group (P=0.000). The median survival was(10.1±5.8) months in patients with ECOG 0～1 group and(7.3±3.8)months in patients with ECOG 2 group (P=0.040). The median survival was(7.76±5.27) months in nochemotherapy group and(11.5±5.0)months in chemotherapy group (P=0.038). The median survival was(8.87±5.36)months in no radiotherapy group and (13.7±3.8) months in radiotherapy group (P=0.048). Conclusions The patients who have better ECOG performance status and receive chemotherapy or radiotherapy show better survival.     

70岁及以上不可切除的胰腺癌患者生存因素分析

目的 探讨影响70岁及以上不可切除的胰腺癌患者生存的相关因素.方法 总结57例70岁及以上的晚期胰腺癌住院患者的临床资料,分析性别、年龄、既往糖尿病史、胆道疾病史、吸烟史、化疗、放疗、美国东部肿瘤协作组(Eastern Collaborative Oncology Group,ECOG)评分、肿瘤标志物癌胚抗原(carcinoembroynic antigen,CEA)和CA199升高情况等对总生存的影响.结果 性别、行为状态、化疗、放疗与生存密切相关.男性和女性比较,中位生存期分别为(10.7±5.4)个月和(5.5±2.3)个月,P=0.000;ECOG评分0～1分和≥2分比较,中位生存期分别为(10.1±5.8)个月和(7.3±3.8)个月,P=0.040;未接受化疗组和接受化疗组比较,中位生存期分别为(7.8±5.3)个月和(11.5±5.0)个月,P=0.038;未接受放疗组和接受放疗组比较,中位生存期分别为(8.9±5.4)个月和(13.7±3.8)个月,P=0.048;差异均有统计学意义.胰腺癌总的中位生存期为8.9个月,1年生存率为28.1%.结论 70岁及以上老年人胰腺癌的预后与性别、行为状态、化疗和放疗相关.对于不可切除但行为状态好的老年胰腺癌患可以考虑化疗,部分患者甚至可以考虑联合放疗.