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The article offers information on the incidence and inheritance of hyperphosphorylated paratarg-7 in patients with Waldenstrom's macroglobulinaemia. It mentions that genetic factors might play an important role in the development of Waldenstrom's macroglobulinaemia (WM) and multiple myeloma (MM); and also mentions the incidence of the pP-7 carrier state is variable in patients with monoclonal gammopathy of undetermined significance (MGUS) of IgG and Ig A type and MM.

Background: Waldenstrom’s macroglobulinemia (WM) is a rare lymphoprolipherative disorder with geographic and ethnic disparities in incidence. The cause of WM remains mostly unknown although a role for genetic, immune-related, and environmental factors has been suggested. Most cases of WM are sporadic although familial cases occur. Aim: This study estimated the incidence of WM in northern Sweden and identified and described patients with familial WM in this area. Patients and methods: The Swedish and Northern Lymphoma Registry, the Swedish Cancer Registry (1997–2011), and medical records were used to identify patients with WM in two counties (Norrbotten and Västerbotten) in northern Sweden and to calculate the overall age-adjusted incidence (2000–2012). We identified 12 families with a family history of WM, IgM monoclonal gammophathy (MGUS), and/or multiple myeloma (MM). Results: In Norrbotten and Västerbotten, the age-adjusted incidence of WM/LPL is 1.75 and 1.48 per 100 000 persons per year, respectively (2000–2012), rates that are higher than the overall incidence of WM/LPL in Sweden (1.05 per 100 000 persons per year; 2000–2012). Autoimmune diseases and other haematological malignancies in the medical history (their own or in relatives) were reported in 9/12 and 5/12 families, respectively. A high proportion of abnormal serum protein electrophoresis was found in the relatives; 12/56 (21%) had a MGUS and 13/56 (25%) showed abnormalities in the immunoglobulin levels (i.e. subnormal levels and poly/oligoclonality). Conclusion: The incidence of WM in Norrbotten and Västerbotten counties was higher than expected. We found a strong correlation between autoimmune/inflammatory diseases, other haematological malignancies, and familial WM and a high frequency of serum immunoglobulin abnormalities in the relatives of the WM patients, findings that strengthen the hypothesis that the aetiology of WM depends on both immune-related and genetic factors. [ABSTRACT FROM PUBLISHER]

Introduction. Rituximab has significantly improved the prognosis for patients with both indolent and aggressive non-Hodgkin's lymphoma. An economic evaluation was carried out to assess the cost-effectiveness in Sweden of rituximab as maintenance therapy for patients with follicular lymphoma in remission after second line therapy. Materials and methods. The incremental cost and effectiveness of rituximab maintenance therapy versus observation were evaluated in a health-state transition model. Primary effect measures were quality-adjusted life-years (QALY) and life-years gained (LYG). Model state transitions were calculated based on progression-free and overall survival data from the EORTC20981 trial. The analysis was made from the perspective of the healthcare provider, including direct medical costs presented in €, 2007 value. Effects and costs were discounted at a 3% annual rate. The stability of the base case results were tested in one-way and probabilistic sensitivity analyses. Results. The evaluation assessed rituximab maintenance therapy to be associated with an incremental cost per QALY gained of €12 600 and an incremental cost per LYG of €11 200. The average discounted life expectancy for patients on rituximab maintenance was 1.0 year longer than for patients on observation (5.96 vs. 4.94 years). Rituximab maintenance was associated with an additional 0.9 QALY, and total costs per patient were €11 500 higher in the treatment arm, compared to observation. Discussion. The results indicate that rituximab maintenance treatment after successful induction therapy for patients with relapsed/refractory follicular lymphoma in Sweden is cost-effective compared to observation. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for Hodgkin's disease (HD) is based on 113 scientific reports including four meta-analyses, 44 randomised studies, 18 prospective studies and 40 retrospective studies. These studies involve 69 196 patients. The conclusions reached can be summarised into the following points: •Chemotherapy is of utmost importance for the cure of HD. •At early stages, extended field radiotherapy cures most patients. For the majority of patients with relapse after radiotherapy, chemotherapy is curative and the total proportion of cured early stage patients is 75-90%. Chemotherapy in addition to extended field radiotherapy reduces recurrences but does not improve long-term survival. •In early stage HD with a large mediastinal mass and/or with systemic symptoms, combined treatment with chemotherapy and radiotherapy is recommended. •It is likely that chemotherapy will play a greater role in the future in the treatment also of early stage patients in order to reduce late consequences from extended field radiotherapy. However, this conclusion remains to be better documented in the literature. •At advanced stages, chemotherapy or a combination of chemotherapy and limited field radiotherapy are effective treatment options and, using the regimens available 10-20 years ago, 40-50% of the patients are cured. Based upon more favourable short-term (three to eight years) results of more recently developed regimens, it can be expected that today a higher proportion of the patients will become long-term survivors. •Several chemotherapy regimens containing four to eight drugs are effective in HD. The best regimen considering both antitumour activity and acute and late side-effects is not known. The choice of regimen is probably best done after considering various pre-treatment factors such as the number of poor prognostic signs, concomitant diseases and individual preferences. •The results of chemotherapy are more favourable in young than in elderly patients. The development of less toxic but still effective treatment programmes is therefore particularly important for the elderly. •High dose chemotherapy with stem cell support is presently often used in patients who are chemotherapy induction failures, who relapse after a short initial remission or after a longer initial remission and treated initially with seven or eight drugs, or who have had multiple relapses. However, this use is based on data from uncontrolled or small controlled studies, not being fully convincing with respect to effect on survival. •Persistent side-effects of treatment are common among long-term survivors, although most patients have an apparently normal life. The relative contributions of chemotherapy and radiotherapy to the persistent effects are not well documented. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on aggressive, high grade non-Hodgkin's lymphoma (NHL), chiefly diffuse large B-cell lymphomas, is based on 111 scientific articles, including 35 randomised trials, 44 prospective studies and 11 retrospective studies, including totally 21 830 treated patients. The conclusions reached can be summarised into the following points: •For patients with localised aggressive NHL (stage I and non-bulky II) a combination of chemo- and radiotherapy will result in cure for a large proportion of patients. For a subgroup of patients with stage I non-bulky disease and without risk factors, local radiotherapy alone is also adequate treatment. •For patients with disseminated aggressive NHL, including the elderly, the CHOP-regimen remains the standard primary chemotherapy. In an unselected population, this treatment cures about one third of the patients. •For most patients with poor prognostic factors, CHOP provides insufficient results. The results of therapy with dose-intensive combinations of cytotoxic drugs have been conflicting. Most randomised studies, using intensive regimens as first line therapy, have failed to show any benefit in comparison to CHOP. However, it is possible that regimens other than CHOP might be more beneficial in subgroups with 'high risk' disease. This remains to be investigated in prospective studies. •In young, poor prognosis, patients a further intensified induction therapy requiring haematopetic stem cell support, i.e. high dose therapy, has been suggested to be beneficial. The best results have been reported from studies with full course standard induction followed by high-dose therapy. However, the study data are conflicting, which is why additional controlled studies are recommended. •In patients refractory to or relapsing after initial therapy, different chemotherapy combinations may induce a new response. The responses are, however, rather short-lived and long-term survival is rarely seen. •In patients not attaining complete remission after initial standard therapy, high-dose therapy with stem cell support may improve the response, but the impact on survival is not established. •In patients refractory to initial standard therapy there is no evidence for a survival prolongation from high-dose therapy with stem cell support, although a subset of patients might benefit. •For patients with chemosensitive relapse, salvage therapy followed by high-dose therapy with stem cell support is recommended, since this may result in prolonged survival. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for indolent non-Hodgkin's lymphoma (NHL), predominantly follicular lymphoma, is based on 108 scientific reports including 31 randomised studies, 38 prospective studies and 18 retrospective studies. These studies involve 8 699 patients. The conclusions reached can be summarized into the following points: In initially localized disease •The addition of chemotherapy to radiotherapy as primary treatment has not convincingly prolonged remission duration or survival. In initially advanced disease •Alkylating agents are useful palliative treatment options which can result in improved well-being for most patients, often for long periods. Combinations of chemotherapy have not convincingly resulted in more or longer remissions. •There is no proof that initial combination chemotherapy will prolong survival in comparison with single drugs. •The addition of interferon to initial combination chemotherapy may increase the response rate, significantly prolong remission duration, but prolonged survival has not been unequivocally proven. •In the absence of disease-related symptoms, treatment can safely be deferred. For patients with relapsed lymphoma •Patients may repeatedly respond to alkylating agents or combinations containing an alkylating agent, although the proportion responding decreases with each relapse. •Patients relapsing after or who are refractory to treatment with alkylating agents often respond to treatment with combinations containing an anthracycline. Responses are also often seen in patients treated with purine analogues alone or in combination with other drugs. •High dose chemotherapy followed by autologous or allogeneic reestablishment of bone marrow function can induce long-term remissions but it is not proven whether they are more frequent or of longer duration than with conventionally dosed therapy. •The impact of the novel treatment strategies including high-dose therapy on overall survival is still uncertain. •A monoclonal antibody, rituximab, is a new active substance for patients with relapsed lymphoma. It can induce remissions also in chemoresistant patients. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for B-cell chronic lymphocytic leukaemia (B-CLL) is based on data from 20 randomised controlled trials and one meta-analysis. Moreover, data from 19 prospective studies, one retrospective study and four other articles were used. Totally 44 scientific articles are included, involving 11 289 patients. The conclusions reached can be summarized into the following points: •Primary treatment of patients with symptomatic B-CLL is recommended to be an oral alkylating agent such as chlorambucil. This drug induces tumour remission and symptomatic relief in a majority of patients with progressive disease. Response may be long-lasting, but cure is not obtained. Optimum dose and schedule of administration of chlorambucil or other alkylating agents have not been defined. •It is recommended to defer initial therapy until required by disease progression. Large randomised trials have demonstrated that early treatment with chlorambucil in a continuous or an intermittent schedule does not prolong survival in B-CLL patients with low tumour burden (Binet stage A). •The addition of corticosteroids to alkylator regimens has not been proven to give any benefit. •Combination chemotherapy as primary treatment has not shown any advantage compared with single drugs. Early inclusion of anthracyclines to the therapy does not convincingly add to the activity of alkylating agents. •The purine analogues fludarabine and 2-chlorodeoxyadenosine are active in B-CLL. However, like other drugs, they do not appear to be curative. In randomised multicentre trials a benefit from fludarabine as primary therapy compared with polychemotherapy (CHOP or CAP) has been observed in terms of tolerance and treatment response but not yet in survival. No randomised studies have been performed to show whether one of the purine analogues should be preferred. •At relapse after single drug treatment, retreatment with the same drug often induces new remissions. However, the proportion of patients responding declines each time chlorambucil or any other single agent is readministered. •At progression on single alkylating agents, the purine analogues or various combinations, mostly CHOP, frequently induce tumour remissions. •For patients with advanced B-CLL failing to respond to fludarabine or CHOP, the prognosis is poor. None of the salvage regimens reported has produced durable remissions. •High-dose chemo-radiotherapy with stem cell transplantation has been evaluated for young patients with B-CLL. A long survival has been shown in some patients following allogeneic and autologous transplantation. However, the risk of transplantation-related mortality is still high with allo-transplants and relapse is common after auto-transplantation. A benefit of purging autologous stem cells has been proposed but evidence is lacking. Thus, transplantation remains experimental; more patients and a longer follow-up are needed to assess if cure can be achieved. •In the future an individual risk-adapted therapy will be required. The clinical heterogeneity of the disease has pointed to the necessity of new predictors for prognosis evaluated in prospective trials. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy in patients with acute myeloid leukaemia (AML) is based on 129 scientific articles; one meta-analysis, 51 randomised trials, 39 prospective and 18 retrospective studies, and 20 other articles. Altogether, 39 557 patients were included in these studies. The conclusions reached can be summarized into the following points: •Standard induction therapy for patients with AML, consisting of daunorubicin and ara-C in conventional doses, results in a complete remission (CR) rate of 50-60% in an unselected population and a long-term survival of about 10-20%. The total doses of both ara-C and daunorubicin are of importance for remission duration and in some studies also for survival. •High-dose ara-C in the induction therapy prolongs remission duration in randomised trials, but has not been proven to affect long-term survival. It also increases toxicity and is not generally recommended. •Idarubicin, another anthracyclin, has been compared with daunorubicin in conjunction with ara-C, resulting in a higher CR rate, especially in younger patients. In a meta-analysis of the five-randomised trials performed, a slight survival advantage was also seen with idarubicin. Yet, there is inconclusive evidence to conclude that idarubicin is superior to daunorubicin, and further trials are needed. •Mitoxantrone improves the outcome of induction therapy in comparison with daunorubicin in some randomised studies, but conclusive evidence is still lacking. •The addition of etoposide to daunorubicin or mitoxantrone and ara-C has improved CR rates, but has not convincingly improved survival and secondary leukaemias may be induced. •New induction treatment strategies are defined by identification of prognostic subgroups. A risk stratification of AML patients as to chromosomal aberrations might be of importance for the choice of therapy. Moreover, the speed and the morphological response to the first induction course are predictive for relapse. However, no prospective randomised studies are as yet published regarding risk-adapted induction therapy. •Post-remission dose-intensive chemotherapy prolongs the duration of remission, seemingly most in patients <60 years. However, the data in support of these conclusions are sparse. A convincing effect on survival has not been shown. •Limited data indicate that post-remission maintenance therapy with long-term attenuated chemotherapy prolongs time to recurrence, without evidence for prolongation of survival. •Allogeneic bone marrow transplantation is an established practice for consolidation in first remission for young patients with an HLA-matched sibling. It is however not known which patients will really benefit from transplantation as no truly randomised comparison of allogeneic vs autologous transplantation or conventionally-dosed chemotherapy has been performed. Patients with and without an HLA-identical sibling have been compared on the basis of intention-to-treat principles ('genetic randomisation'). The disease-free survival seems to be prolonged in the donor group, due to a lower relapse rate with allogeneic transplantation. A higher procedure-related mortality makes the effects on total survival uncertain. Randomised trials with autologous transplantation vs conventional consolidation show a lower relapse rate and a trend for an improved disease-free survival. In one study, in which an autograft was added to four courses of intensive therapy, there was also a late survival advantage. Thus, the role for intensified post-remission treatment in first complete remission with high-dose chemotherapy followed by allogeneic or autologous marrow or stem cell transplantation requires further studies. Moreover, studies with stratification of therapy according to predictors for prognosis in the individual patient are needed. •Allogeneic stem cell transplantation after minimal or reduced myeloablative conditioning ('mini-transplantation' or non-myeloablative stem cell transplantation) induces a host-vs-graft tolerance and an immune graft-vs-leukaemia effect. This new concept of cellular immunotherapy seems to have a low procedure-related mortality, but long-term effects are unknown and evaluation in controlled clinical studies is required. •Patients with relapsed AML can only infrequently achieve long-term remissions with chemotherapy in conventional doses. Uncontrolled data indicate that allogeneic transplantation can be a curative treatment for these patients as well as for those refractory to initial conventional chemotherapy. No studies have compared the effect of allogeneic transplantation in first compared with second remission. •Treatment of elderly patients is controversial. In selected elderly patients with good performance status and absence of concomitant diseases, a combination of ara-C with an anthracycline, both in conventional doses, is the treatment of choice to prolong survival. Oral cytotoxic drugs, e.g. hydroxyurea and 6-thioguanine, or low dose ara-C subcutaneously are other treatment options that will lead to remission in a few patients, seemingly with a good quality of life and with few days spent in hospital. •The use of haematopoietic growth factors in patients with AML is doubtful. Most controlled studies show a shortened time for neutropenia and less infectious complications, but no better effect with reference to remission or survival. [ABSTRACT FROM AUTHOR]

This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75% of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1496 studies involving 558743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1590 patients. The working group's general conclusions are summarised in the following points •The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. •In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. •The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. •Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these studies have also documented palliative effects in a comparably limited proportion of the patients. It is of great importance to initiate a discussion whether such treatment should be recommended cancer patients in routine health care in Sweden. •The survey shows that in the instances where the literature shows small but convincing treatment effects, the use of chemotherapy is restrictive in Sweden. It is likely that this reflects the doctors' priorities of what treatments should be offered patients in routine care. It might, however, also represent an appropriate adaptation to the fact that the favourable effects have mostly been observed in selected patients with good prognosis. The patients' decisions after open information on treatment benefit and side-effects may also contribute to a limited use. Whether the same treatment benefit would be obtained in the 'whole' group of patients is not known. If such treatment should be offered all patients without medical contraindications, according to what has been demonstrated in prospective randomised trials, the number of treatments and the cost for chemotherapy would increase substantially. •Clinical trial protocols or written guidelines should preferably be widely applied as a basis for treatment decisions and for assessment of the clinical benefit from new treatments. A greater need exists for controlled clinical trials, which, when appropriate, should also include an assessment of impact on patients' quality of life (QoL) and economic consequences in conjunction with cancer treatment. This knowledge is, particularly in the palliative situation, essential for determining future recommendations, and choosing among alternative forms of treatment. Such studies usually require international collaboration. Assessment of QoL is clearly in need of further methodological development to be able to report reliable data. •The total drug cost for chemotherapy in Sweden is estimated at approximately 280 million Swedish kronor (SEK) in 1998. This represents 4% of the costs for cancer care and 1.7% of the costs for all medicinal products in Sweden. •The cost-effectiveness of chemotherapy has been studied, but these studies are mostly of low quality. They suggest, however, that chemotherapy is cost-effective, in terms of cost per life year saved, in comparison with other well-established routine treatments in a number of other diseases. •Since the treatment of cancer is far from successful, there is a need for further research. The survey showed that only about 10% of the treatments were given within clinical trial protocols aimed at further elucidating treatment effects. This figure should be considerably higher. [ABSTRACT FROM AUTHOR]