Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry.
Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.
BACKGROUND: The long-term survival of patients with advanced stage aggressive lymphoma has not improved significantly during the last twenty years. In a randomised trial, the efficacy of MACOP-B, a six-drug weekly chemotherapy regimen, was compared to CHOP, the current standard regimen, in terms of overall and failure-free survival, toxicity and health related quality of life. PATIENTS AND METHODS: Four hundred five patients with aggressive lymphoma, stage II-IV, age 18-67, were randomised to receive either 12 weeks of MACOP-B or 8 courses of CHOP over 24 weeks. Special emphasis was put in the definition of Ann Arbor stage in extranodal disease. A subset of 95 patients also entered a quality of life study, based on the EORTC QLQ-C30. RESULTS: Thirty-one patients were ineligible. Among the remaining 374 patients, the median age was 52 years. According to the age-adjusted International Prognostic Index, 37% were 'high-intermediate' or 'high-risk' patients. No difference could be demonstrated, either in overall survival (60% at five years in the MACOP-B group and 59% in the CHOP group) or in failure-free survival (47% at five years with MACOP-B and 44% with CHOP). In terms of quality of life, physical function and global quality of life were more impaired in patients receiving MACOP-B, who also exhibited more non-haematological toxicity. CONCLUSION: No superiority of MACOP-B compared to CHOP could be demonstrated. CHOP remains the treatment of choice in low-risk patients. At present, intensified or experimental treatment should be reserved for high-risk disease.
Department of Medicine, University of Toronto, Toronto Sunnybrook Regional Cancer Centre, 2075 Bayview Avenue, Toronto, Ont., Canada. rena.buckstein@tsrcc.on.ca
Practices regarding central nervous system (CNS) prophylaxis and treatment for non-"high-grade" lymphomas are not standardized. We designed a survey to address the CNS surveillance, prophylaxis and treatment (S + P + T) habits of Ontario oncologists, to compare tertiary with community care and gauge interest in a randomized controlled trial (RCT). We mailed 145 questionnaires to oncologists/hematologists registered at the Royal College of Physicians and Surgeons of Ontario between 1980 and 1999. The questionnaire posed questions of S + P + T for a variety of histologies, locations and risk factors. Results showed that 49/77 respondents treated adult NHL, (19 community, 30 tertiary care). Surveillance LP's were commonly done in testicular, orbital, sinus and epidural sites of presentation (76, 69, 71, 80%, respectively), but these were less commonly prophylaxed (45, 33, 29 and 41%). HIV associated NHL received surveillance and prophylaxis by 51 and 33% of respondents. Stage IV disease, increased LDH and extranodal-sites warranted infrequent S + P. IT chemotherapy via LP was the most commonly used form of prophylaxis (74%) or treatment (84%). Twenty percent used systemic agents that cross the blood brain barrier for prophylaxis, and 45% for treatment. A vast heterogeneity of practice within and between tertiary care and community physicians' practices was documented. Ninety percent of physicians indicated willingness to participate in a RCT. In conclusion, CNS surveillance and prophylaxis in non-"high-grade" NHL is highly variable, probably because there are poorly defined risk factors, inconclusive prophylaxis efficacy and the inconvenience/toxicity of therapy. Patients at high risk by International prognostic index criteria are at an increased risk for CNS relapse. A RCT comparing standard chemotherapy with or without CNS prophylaxis in selected patients is needed.
The purpose of this analysis was to assess the real-life direct costs of drug delivery for frequently used chemotherapeutic regimens in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL).
This was a retrospective analysis of direct costs of drug delivery (acquisition plus administration) of relapsed low-grade NHL in 424 patients in Canada, Germany, and Italy. Results were expressed as an average treatment cost per patient for six cycles of chemotherapy. Exchange rates used were $1 (Canada)= currency 0.672, 1 DM (Germany)= currency 0.511, and 1 Lit (Italy)= currency 0.000517.
Direct costs of drug delivery were greater for inpatients receiving fludarabine (Canada currency 12,669; Italy currency 13,027) than for CHOP (Canada currency 7856; Germany currency 7218; Italy currency 4251) or COP/CVP (Canada currency 7360; Germany currency 8449). Treatment administration setting was a major cost driver with inpatient treatment up to 9-fold more expensive than the same regimen given to outpatients. Drug administration costs comprised the largest proportion of the total for each regimen in the inpatient setting (69-98%). Costs of drug delivery in the outpatient setting were 10% to 65% of those in the inpatient setting. Again, fludarabine was more expensive (Italy currency 8493; Canada currency 7269) than CHOP (Canada currency 4403; Germany currency 2150; Italy currency 1264) and COP/CVP (Canada currency 3009; Germany currency 867). Administration costs were 2.5- to 15-fold higher for inpatients compared to outpatients.
Costs of drug administration are a major driver for total direct treatment costs in the treatment of relapsed low-grade NHL and are at least as important as drug acquisition costs. Drug administration practices, in terms of inpatient or outpatient treatment, are a major factor in determining overall direct costs. Therapeutic strategies, which offer shortened treatment duration and/or a simple mode of administration, are likely to be economically attractive.
Cost-utility analysis of primary prophylaxis versus secondary prophylaxis with granulocyte colony-stimulating factor in elderly patients with diffuse aggressive lymphoma receiving curative-intent chemotherapy.
The 2006 American Society of Clinical Oncology (ASCO) guideline recommended primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) instead of secondary prophylaxis (SP) for elderly patients with diffuse aggressive lymphoma receiving chemotherapy. We examined the cost-effectiveness of PP when compared with SP.
We conducted a cost-utility analysis to compare PP to SP for diffuse aggressive lymphoma. We used a Markov model with an eight-cycle chemotherapy time horizon with a government-payer perspective and Ontario health, economic, and cost data. Data for efficacies of G-CSF, probabilities, and utilities were obtained from published literature. Probabilistic sensitivity analysis (PSA) was conducted.
The incremental cost-effectiveness ratio of PP to SP was $700,500 per quality-adjusted life-year (QALY). One-way sensitivity analyses (willingness-to-pay threshold = $100,000/QALY) showed that if PP were to be cost-effective, the cost of hospitalization for febrile neutropenia (FN) had to be more than $31,138 (2.5 × > base case), the cost of G-CSF per cycle less than $960 (base case = $1,960), the risk of first-cycle FN more than 47% (base case = 24%), or the relative risk reduction of FN with G-CSF more than 91% (base case = 41%). Our result was robust to all variables. PSA revealed a 10% probability of PP being cost-effective over SP at a willingness-to-pay threshold of $100,000/QALY.
PP is not cost-effective when compared with SP in this population. PP becomes attractive only if the cost of hospitalization for FN is significantly higher or the cost of G-CSF is significantly lower.
The high incidence of EB virus infections (and possibly of other viruses) in patients with African lymphoma and, to a lesser extent, in patients with lymphosarcoma in the temperate zones, is thought to be due to its being a passenger virus which persists in the human body and, since it is lymphotropic, presents an opportunistic infection of proliferating lymphoid cells. The thesis is put forward that by entering the cell nucleus, the virus renders malignant lymphoid cells more vulnerable to cytotoxic drugs. Hence a deliberate policy of EB virus inoculation before starting chemotherapy might achieve a more rapid response and longer remissions in indigenous lymphomas of the temperate zones, and might possibly render drug-resistant cases once more drug-sensitive.
Notes
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In an unselected group of patients with high-grade non-Hodgkin's lymphoma (HG-NHL) treated at our institution during a 10-year period (1986-1995), we studied treatment outcome and influence of possible prognostic factors. 187 HG-NHL patients were analysed retrospectively with regard to personal, treatment and disease-specific characteristics. Median age was 65 years and the male:female ratio was 1.2:1. Over a median follow-up of 57 months the overall response rate was 87% (complete response 72%, partial response 15%). The 2- and 5-year cumulative disease-specific survival rates were 64+/-4% (mean +/- SEM) and 48+/-5%, respectively. In a univariate analysis, the following variables were associated with prognosis in terms of survival: Patient age, clinical stage, performance status, bone-marrow infiltration, haemoglobin, erythrocyte sedimentation rate, lactate dehydrogenase (LDH), and serum albumin. In multivariate analyses, patient age, performance status, LDH, and haemoglobin came out as independent prognostic factors for survival.
