Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis

Trastuzumab has shown activity in early breast cancer patients that overexpress HER2. Significant resources have to be allocated to finance this therapy, underlining the need for cost-effectiveness analysis. A model was set up, societal costs were calculated and the discount rate was 3%. Life expectancy data were based on the literature and prolonged according to qualified guess (10% and 20% absolute improvement in overall survival (OS)). The comparator was the FEC₁₀₀ regimen. The median additional health care cost per patient treated was €33 597. The yielding cost per life year gained (LYG) was €15 341 with a 20% improved OS and €35 947 with 10% improved OS. The corresponding net health care cost per quality adjusted life year (QALY) was €19 176 and €44 934. Including all resource use the figures were €8148 and €30 290 per LYG. Sensitivity analyses documented survival gain, price of trastuzumab, production gain and discount rate to be the major factors influencing cost-effectiveness ratio. Trastuzumab is indicated cost effective in Norway.     

Medical costs associated with non-Hodgkin's lymphoma in the United States during the first two years of treatment

OBJECTIVES: To determine the direct costs of medical care associated with aggressive and indolent non-Hodgkin's lymphoma (NHL) in the United States; to show how costs for aggressive NHL change over time by examining costs related to initial, secondary and palliative treatment phases; and to evaluate the economic consequences of treatment failure in aggressive NHL. PATIENTS AND METHODS: A retrospective cohort analysis of 1999 - 2000 direct costs in newly diagnosed NHL patients and controls (subjects without any cancer) was conducted using the MarketScan medical and drug claims database of large employers across the United States. Treatment failure analysis was conducted for aggressive NHL patients, and was defined by the need for secondary treatment or palliative care after initial therapy. Cost of treatment failure was calculated as difference in regression-adjusted costs between patients with initial therapy only and patients experiencing initial treatment failure. RESULTS: Patients with aggressive (n = 356) and indolent (n = 698) NHL had significantly greater health service utilization and associated costs (all P < 05) than controls (n = 1068 for aggressive, n = 2094 for indolent). Mean monthly costs were 5871 dollars for aggressive NHL vs. 355 dollars for controls (P < 0001) and 3833 dollars for indolent NHL vs. 289 dollars for controls (P < 0001). The primary cost drivers were hospitalization (aggressive NHL = 44% of total costs, indolent NHL = 50%) and outpatient office visits (aggressive NHL = 39%, indolent NHL = 34%). For aggressive NHL, mean monthly initial treatment phase costs (10,970 dollars) and palliative care costs (9836 dollars) were higher than costs incurred during secondary phase (3302 dollars). The mean cost of treatment failure in aggressive NHL was 14,174 dollars per month, and 85,934 dollars over the study period. CONCLUSION: The treatment of NHL was associated with substantial health care costs. Patients with aggressive lymphomas tended to accrue higher costs, compared with those with indolent lymphomas. These costs varied over time, with the highest costs occurring during the initial treatment and palliative care phases. Treatment failure was the most expensive treatment pattern. New strategies to prevent or delay treatment failure in aggressive NHL could help reduce the economic burden of NHL.     

Cost Analysis of Autologous Peripheral Stem Cell Transplantation Versus Autologous Bone Marrow Transplantation for Patients with Non Hodgkin's Lymphoma and Acute Lymphoblastic Leukaemia

We evaluated the costs of unpurged autologous stem cell transplantation in a non-randomised study of 54 consecutive patients with lymphoproliferative malignancies who have been transplanted at the Nijmegen University Hospital between July 1992 and March 1998. Thirty-five patients were transplanted with autologous peripheral stem cells (APSCT): 30 had non Hodgkin's lymphoma (NHL) and 5 acute lymphoblastic leukaemia (ALL). Nineteen patients were transplanted with autologous bone marrow stem cells (ABMT): 17 had NHL and 2 ALL. The number of progenitor cells (CFU-GM, BFU-E) and nucleated cells was significantly higher in peripheral blood transplants. The duration of cytopenia was shorter after APSCT. The leucocyte recovery to 0.5 × 10⁹ /L was 13 days for recipients of peripheral stem cells compared to 20 days for bone marrow recipients (P 4.001). The platelet recoveries to 20 × 10⁹L were 13 and 29 days, respectively (P = 0.001). This resulted in significantly shorter admission duration 24 days after APSCT versus 30 days (P = 0.003) after ABMT.

Furthermore, a statistically significant difference between both groups was observed for antimicrobial costs (mean: fl 2,939 vs fl 4,888; P = 0.008), platelet transfusions (median: 3 vs 7 units; P = 0.01) and erythrocyte transfusions (median: 6 vs 10 units; P = 0.03). The mean overall costs were lower in patients transplanted with stem cells from' peripheral blood: fl 34, 178 versus fl 43, 469 (P = 0.007). This study suggests that the APSCT results in significant cost savings due to shorter hospital stay and less costs of supportive care, despite higher mobilisation costs. The costs of blood transfusions and antimicrobials for patients with ALL were significantly higher when compared to patients with NHL.     

Cost analysis of autologous peripheral stem cell transplantation versus autologous bone marrow transplantation for patients with non Hodgkin's lymphoma and acute lymphoblastic leukaemia

We evaluated the costs of unpurged autologous stem cell transplantation in a non-randomised study of 54 consecutive patients with lymphoproliferative malignancies who have been transplanted at the Nijmegen University Hospital between July 1992 and March 1998. Thirty-five patients were transplanted with autologous peripheral stem cells (APSCT): 30 had non Hodgkin's lymphoma (NHL) and 5 acute lymphoblastic leukaemia (ALL). Nineteen patients were transplanted with autologous bone marrow stem cells (ABMT): 17 had NHL and 2 ALL. The number of progenitor cells (CFU-GM, BFU-E) and nucleated cells was significantly higher in peripheral blood transplants. The duration of cytopenia was shorter after APSCT. The leucocyte recovery to 0.5 x 10(9)/L was 13 days for recipients of peripheral stem cells compared to 20 days for bone marrow recipients (P <0.001). The platelet recoveries to 20 x 10(9)/L were 13 and 29 days, respectively (P = 0.001). This resulted in significantly shorter admission duration 24 days after APSCT versus 30 days (P = 0.003) after ABMT. Furthermore, a statistically significant difference between both groups was observed for antimicrobial costs (mean: fl 2,939 vs fl 4,888; P = 0.008), platelet transfusions (median: 3 vs 7 units; P = 0.01) and erythrocyte transfusions (median: 6 vs 10 units; P = 0.03). The mean overall costs were lower in patients transplanted with stem cells from peripheral blood: fl 34,178 versus fl 43,469 (P = 0.007). This study suggests that the APSCT results in significant cost savings due to shorter hospital stay and less costs of supportive care, despite higher mobilisation costs. The costs of blood transfusions and antimicrobials for patients with ALL were significantly higher when compared to patients with NHL.     

Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador

Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4±6.4%) than those with ALL (12.5±1.7%; P<0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P=0.98). Among children with ALL, low monthly income (P=0.04) and low parental education (P=0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL.     

Proton therapy of cancer: potential clinical advantages and cost-effectiveness

Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about €10 130. If the value of a QALY was set to €55 000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about €20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used.     

Prophylactic bilateral salpingo-oophorectomy (PBSO) with or without prophylactic bilateral mastectomy (PBM) or no intervention in BRCA1 mutation carriers: a cost-effectiveness analysis

Women with germline BRCA1 mutation have a significant risk of breast and/or ovarian cancer. Prophylactic bilateral mastectomy (PBM) and prophylactic bilateral salpingo-oophorectomy (PBSO) prevent cancer in mutation carriers.The cost-effectiveness of PBSO (age of 35 years) with or without PBM five years earlier was compared to a no intervention setting employing a marginal cost analysis. National data on cancer incidence, mortality rates and costs were implemented together with observed Norwegian BRCA1 data in a Markov model and PBSO was assumed to reduce the risk of ovarian cancer by 90%. A 3% discount rate was used.The additional health care cost per mutation carrier undergoing PBSO and PBM was €15,784, and 6.4 discounted life years gained (LYG) was indicated (PBSO alone with 100% acceptance 3.1 LYG). The additional cost per LYG was €1973 (PBSO alone €1749/LYG). Including all resource use, the figure was a cost of €496 and €1284 per LYG, respectively.PBSO with or without PBM in BRCA1 mutation carriers is cost-effective. A testing of all incident breast cancers to identify mutation carrying families should be explored.     

Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: bevacizumab in combination with interferon-��2a compared with sunitinib

Background:

Bevacizumab plus interferon-α2a (IFN) prolongs progression-free survival to >10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing adverse events may be an important factor in selecting therapy.

Methods:

Costs of managing adverse events affecting patients with metastatic RCC eligible for treatment with bevacizumab plus IFN or sunitinib were evaluated using a linear decision analytical model. Management costs were calculated from the published incidence of adverse events and health-care costs for treating adverse events in the United Kingdom, Germany, France and Italy.

Results:

Adverse event management costs were higher for sunitinib than for bevacizumab plus IFN. The average cost per patient for the management of grade 3–4 adverse events was markedly lower with bevacizumab plus IFN compared with sunitinib in the United Kingdom (€1475 vs €804), Germany (€1785 vs €1367), France (€2590 vs €1618) and Italy (€891 vs €402). The main cost drivers were lymphopaenia, neutropaenia, thrombocytopaenia, leucopaenia and fatigue/asthaenia for sunitinib; and proteinuria, fatigue/asthaenia, bleeding, anaemia and gastrointestinal perforation for bevacizumab plus IFN.

Conclusion:

The costs of managing adverse events are lower for bevacizumab plus IFN than for sunitinib. The potential for cost savings should be considered when selecting treatments for RCC.     

Leukemias and lymphomas: time trends in the UK, 1984–93

Objective: To investigate recent time trends of some selected and common neoplasms of the blood and lymphatic tissues.Methods: A specialist population-based register of hematological and related neoplasms was set up in parts of the UK in 1984. Secular changes over the first 10 years were investigated using log-linear Poisson modeling. The results are presented in tabular and graphical form.Results: The analyses of 26,899 cases revealed a decline in incidence of acute myeloid leukaemia (AML), the myeloproliferative disorders (MPD) including chronic myeloid leukaemia (CML) and, in males only, Hodgkin's disease (HD). No secular trends for acute lymphoblastic leukaemia (ALL) were observed at any age. A marked increase in incidence in non-Hodgkin's disease (NHL) and the pre- leukemia group of myeloid dysplasias (MDS) was found.Conclusions: The rise in MDS and decline in AML and related conditions are most likely to reflect diagnostic changes. Changes in NHL may reflect, in part, a similar phenomena, but an underlying upward trend cannot be excluded. The decline in HD is in one gender only and the significance of this remains to be investigated.     

Social inequality and incidence of and survival from Hodgkin lymphoma, non-Hodgkin lymphoma and leukaemia in a population-based study in Denmark, 1994-2003

We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from haematological cancers diagnosed in 1994-2003 with follow-up through 2006 in Denmark using information from nationwide registers. The analyses were based on data on 636 patients with Hodgkin lymphoma (HL), 4516 with non-Hodgkin lymphoma (NHL) and 3486 with leukaemia in a cohort of 3.22 million people born between 1925 and 1973 and aged >or=30 years. No consistent differences in incidence were seen by socioeconomic position, but an association with comorbidity was found. Patients in the lowest socioeconomic groups and those with other serious illnesses, especially men, had a worse survival of NHL. Survival results for leukaemia tended to be similar to those for NHL, although associations were generally weaker and insignificant. Thus, there were no strong associations between socioeconomic position and the incidence of these cancers; survival after NHL might be affected.     

Survival in France after childhood acute leukaemia and non-Hodgkin's lymphoma (1990-2000)

This article describes the survival after childhood acute leukaemia (AL) and non-Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and 1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML and NHL, respectively. Survival after AL increased from 77% (95% CI 75-80) in 1990-1992 to 85% (95% CI 83-87) in 1997-2000 for ALL and from 47% (95% CI 41-54) to 61% (95% CI 55-67) for AML. Among AL cases, children aged 1-4 years had the most favourable prognosis. Down's syndrome was associated with poor survival after ALL. No gender-related variations in survival were in evidence. The results reported herein are similar to those reported by other European registries and clinical trials.     

Examination of temporal trends in the incidence of childhood leukaemias and lymphomas provides aetiological clues.

The age-sex distributions and temporal trends in incidence of leukaemia and lymphoma from the Manchester Children's Tumour Registry (MCTR), 1954-1998, are reported. This 45-year study includes 1795 children, all of whom had a histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses all the children were under 15 years of age and were resident in a geographically defined area of northwest England covered by the MCTR. Log-linear modelling identified significant linear increases in acute lymphoblastic leukaemia (ALL) (average annual increase 0.7%; P= 0.005) and in Hodgkin's disease (HD) (1.2%, P=0.04), but not in acute myeloid leukaemia (AML), nor in non-Hodgkin's lymphoma (NHL). The increase in ALL was most pronounced amongst males, aged 1-4 years, and is likely to be due to precursor B-cell leukaemias. The increases in ALL and HD are discussed in relation to current hypotheses suggesting a role for infection. Additionally, a non-linear cohort effect was identified for NHL (P= 0.008), which may indicate the involvement of environmental factors other than infection.     

Longer breast-feeding and protection against childhood leukaemia and lymphomas

The role of breast-feeding in protecting against childhood acute leukaemia and lymphomas is uncertain. We investigated this issue in a case-control study comprising 117 patients, aged 2-14 years, with acute lymphocytic leukaemia (ALL), Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL), as well as 117 controls matched for age, sex and ethnicity. Information was collected via a telephone interview of the mothers. The median duration of breast-feeding among patients was significantly shorter than among controls, 7 (range 0-23) and 10 (range 0-20) months, respectively (P<0.0001). Breast-feeding of 0-6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for ALL (OR=2.47, 95% confidence interval (CI) 1.17-5.25), HL (OR=3.75, 95% CI 0.80-18.69), NHL (OR=4.06, 95% CI 0.82-22.59), and overall (OR=2.79, 95% CI 1.54-5.05). In the patient group, there were a significantly higher number of children and people per family, and patients were of a higher birth order than controls. In multivariate analysis, breast-feeding duration continues to be an independent predictor of lymphoid malignancies (P=0.015). In conclusion, breast-feeding lasting longer than 6 months may protect against childhood acute leukaemia and lymphomas.     

Adjuvant fluorouracil, epirubicin and cyclophosphamide in early breast cancer: is it cost-effective?

Adjuvant chemotherapy (ACT) in breast cancer exposes patients to morbidity, but improves survival. The FEC (fluorouracil, epirubicin, cyclophosphamide) regimen has taken over the prior role of CMF (cyclophosphamide, methotrexate, fluorouracil). In this model, efficacy, tolerability and quality of life (QoL) data from the literature were incorporated with Norwegian practice and cost data in a cost-effectiveness approach. The FEC efficacy was calculated 3-7% superior CMF. There was no difference in quality of life. An 80-100% dose intensity range was employed, one Euro (€ 1) was calculated NOK 8.78 and a 3% discount rate was used. The total cost of FEC employing the friction cost method on production loss, including amount spent on drugs, administration and travelling ranged between € 3 278-3 850 (human capital approach € 12 143-12 715). Money spent on drugs alone constituted 15-48%, depending on method chosen. A cost-effectiveness analysis revealed a cost per life year (LY) saved replacing FEC by CMF of € 3 575-15 125. Adjuvant FEC is cost effective in Norway.     

The monetary costs of childhood cancer to the families of patients

The medical costs of cancer treatment are well described, but there are few reports of expenses incurred by families of children with malignant disease. The objective of this study was to describe the monetary costs borne by families of patients with childhood cancer and to determine whether these costs represent an important component of the burden of illness. Families completed a prospective diary survey about daily expenses incurred during each sample week of therapy. We also undertook a retrospective, cross-sectional questionnaire survey about expenses, incurred during the entire duration of treatment, associated with major or one-time cost items. Seventy families of children treated for high risk acute lymphoblastic leukemia, 19 families of children treated for Wilms' tumor stages 2-5, and 16 families of children treated for neuroblastoma stages 3 and 4 completed diaries or questionnaires detailing the costs resulting from the diseases and their treatment. The mean total expenses (in 1986 Canadian dollars) incurred by families of childhood cancer patients over the entire course of therapy are $26,070 for acute lymphoblastic leukemia? $20,074 for Wilms' tumour, and $10,376 for neuroblastoma. On-going weekly costs rather than major one-time purchases account for the largest share of expenses. Overall, in spite of universal first dollar coverage for medical care in Canada, family-borne costs during the course of these illnesses are at least one-third of the average family's after-tax income.     

Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958-1996: a search for common mechanisms

The Swedish Family-Cancer Database was used to analyse site-specific risk of second primary malignancies following 53 159 haematolymphoproliferative disorders (HLPD) diagnosed between 1958 and 1996. Standardized incidence ratio (SIR) of a second malignancy was calculated as the ratio of observed to expected numbers of second malignancies by applying site-, sex-, age-, period-, residence- and occupation-specific rates in the corresponding population in the Database to the appropriate person-years at risk. Among 18 960 patients with non-Hodgkin's lymphoma (NHL), there was over a 3-fold significant increase in cancer of the tongue, small intestine, nose, kidney and nervous system, squamous cell carcinoma (SCC) of the skin, NHL, Hodgkin's disease (HD) and lymphoid and myeloid leukaemia. Among 5353 patients with HD, there was over a 4-fold significant increase in cancer of the salivary glands, nasopharynx and thyroid, NHL and myeloid leukaemia, and over a 1.6-fold increase in cancer of the stomach, colon, lung, breast, skin (melanoma and SCC), nervous system and soft tissues and lymphoid leukaemia. Among 28 846 patients with myeloma and leukaemia, there was a significant increase in cancer of the skin, nervous system and non-thyroid endocrine glands and all HLPD except for myeloma. Our findings showed some clustering between first and second primaries among Epstein-Barr virus-, ultraviolet radiation- and immunosuppression-related cancers.     

Cost-Effectiveness Analysis of Granisetron-Based versus Standard Antiemetic Regimens in Low-Emetogenic Chemotherapy: A Hospital-based Perspective from Malaysia

Background: In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primaryprophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysisof two antiemetic regimens from the payer perspective. Materials and Methods: This cost evaluation refers to2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drugacquisition, materials and time spent for clinical activities from prescribing to dispensing of home medicationswere evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1%vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfullytreated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness.Results: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimenthan for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities wereincluded, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47).Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-basedregimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change ofantiemetic effects of granisetron-based regimen. Conclusions: While providing a better efficacy in acute emesiscontrol, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis inLEC controversial.     

The impact of healthcare costs in the last year of life and in all life years gained on the cost-effectiveness of cancer screening

It is under debate whether healthcare costs related to death and in life years gained (LysG) due to life saving interventions should be included in economic evaluations. We estimated the impact of including these costs on cost-effectiveness of cancer screening. We obtained health insurance, home care, nursing homes, and mortality data for 2.1 million inhabitants in the Netherlands in 1998–1999. Costs related to death were approximated by the healthcare costs in the last year of life (LastYL), by cause and age of death. Costs in LYsG were estimated by calculating the healthcare costs in any life year. We calculated the change in cost-effectiveness ratios (CERs) if unrelated healthcare costs in the LastYL or in LYsG would be included. Costs in the LastYL were on average 33% higher for persons dying from cancer than from any cause. Including costs in LysG increased the CER by €4040 in women, and by €4100 in men. Of these, €660 in women, and €890 in men, were costs in the LastYL. Including unrelated healthcare costs in the LastYL or in LYsG will change the comparative cost-effectiveness of healthcare programmes. The CERs of cancer screening programmes will clearly increase, with approximately €4000. However, because of the favourable CER''s, including unrelated healthcare costs will in general have limited policy implications.     

Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma

An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary NHL were included in a pooled analysis of 13 cancer registries. The observed numbers of second cancers were compared to the expected numbers derived from the age-, sex-, calendar period- and registry-specific incidence rates. We also calculated the standardised incidence ratios for NHL as a second primary after other cancers. There was a 47% (95% confidence interval 43-51%) overall increase in the risk of a primary cancer after NHL. A strongly significant (P<0.001) increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*, nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was increased after cancers marked with an asterisk. Patterns of risk indicate a treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid leukaemia. Common risk factors may be involved for cancers of the lung, bladder, nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for several cancer sites of potential viral origin argue strongly for a role for immune suppression in NHL.     

Incidence of childhood leukaemia and non-Hodgkin's lymphoma in France: National Registry of Childhood Leukaemia and Lymphoma, 1990-1999.

The French National Registry of Childhood Leukaemia and Lymphoma (NRCL) covers the whole French mainland population aged less than 15 years (approximately 11 million children) for all childhood haematopoietic tumours since 1 January 1990, except Hodgkin's disease, which has been registered since 1 January 1999. During the period from 1990 to 1999, 5757 cases of leukaemia, lymphoma and myelodysplastic syndrome were registered in the NRCL, with an average of 2.5 sources per case. The age-standardized incidence rates per million per year were 43.1 for leukaemia (34.3 for acute lymphoblastic leukaemia, 7.1 for acute myeloblastic leukaemia, 0.6 for chronic myeloid leukaemia and 0.5 for chronic myelomonocytic leukaemia), 8.9 for non-Hodgkin's lymphomas and 6.7 for Hodgkin's disease. Down's syndrome was present in 110 cases of acute leukaemia (2.5%) and three cases of non-Hodgkin's lymphoma (0.3%). The incidence of acute lymphoblastic leukaemia showed a typical peak at age 2 years for girls and 3 years for boys. The incidence rates of leukaemia and non-Hodgkin's lymphoma did not show any temporal trends over the 10 year period.