Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapeutic success has focused attention on late effects in patients with testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, and acute leukaemia. Since most patients with testicular cancer are young, the impact of cytotoxic chemotherapy on fertility and hormone deficiency has become particularly important. It has been shown that pulsatile secretion of luteinizing hormone releasing hormone (LHRH) is a prerequisite for normal gonadal function. In contrast, non-pulsatile, chronic treatment with supraphysiological doses of LHRH-analogues (LHRHA) results in suppression of the pituitary-gonadal axis. It has been suggested that inhibition of spermatogenesis during exposure to cytotoxic drugs might reduce gonadal toxicity. The protective effects of LHRHA during chemotherapy or irradiation has been examined in 11 preclinical studies. In only 6 out of 11 models could protection be demonstrated. Four clinical trials have been performed using LHRHA as a gonadal protector. In none of these trials could LHRHA significantly influence severity and duration of germ cell impairment. New approaches are needed to minimize or even prevent gonadal toxicity during chemotherapy or irradiation, such as reduction of courses, alternative schedules, or new drugs.
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PMID:The role of LHRH-analogues in protecting gonadal functions during chemotherapy and irradiation. 847 75

Now that a substantial group of cancer patients has such a favourable prognosis, it has become increasingly important to evaluate the long-term complications of treatment. Of all late effects of treatment, secondary leukaemia is one of the most serious. Increased risk of AML has been observed both after RT and after CT; however, several types of CT have much stronger leukaemogenic properties than RT. Limited field radiation in the therapeutic dose range is associated with very little or no increased risk of leukaemia, which has been attributed to cell killing at the higher radiation doses. With respect to CT, two different syndromes of treatment-related AML have been recognized. Risk of alkylating agent-related AML is highest in the 5-10 year follow-up period and seems to decrease afterwards. This type of leukaemia is often preceded by MDS, and is characterized by deletions of chromosomes 5 and 7. Leukaemias related to treatment with the topoisomerase II inhibitors are characterized by a short induction period, presentation as myelomonocytic or monocytic leukaemia (rather than MDS) and balanced chromosomal translocations involving bands 11q23 and 21q22. This review addresses the risk of secondary AML and MDS following treatment of HD, NHL, testicular cancer, ovarian cancer, breast cancer and paediatric malignancies. In patients with HD, the risk of AML is higher with an increasing number of mechlorethamine-procarbazine-containing cycles, a greater number of CT episodes, and after splenectomy. The majority of data shows that RT does not add to the leukaemia risk from CT, but this issue is still surrounded by some controversy. ABV(D)-treated patients have a very low risk of AML. Generally, patients with NHL, testicular cancer and breast cancer experience much lower risk of AML than patients with HD. NHL and breast cancer treatment regimens with cumulative cyclophosphamide doses of 20 g or less do not confer an appreciable increase of AML. Recently, strongly increased AML risk has been observed following autologous bone marrow transplantation and other dose intensification strategies. Risk factors for this excess remain to be defined. PVB treatment for testicular cancer is not followed by increased leukaemia risk, but modern etoposide-containing regimens do confer excess risk, of which the magnitude at conventional drug doses is not yet well known. High risk of leukaemia has been reported in children treated with epipodophyllotoxins. The leukaemogenic hazards of cancer treatment should be weighed against their therapeutic benefits.
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PMID:Risk of acute myelogenous leukaemia and myelodysplasia following cancer treatment. 873 May 51

One thousand and sixty-three twins with cancer whose co-twin was born alive were identified among patients born since September 1939 with cancers incident in England and Wales during 1971-1984 at childhood and young adult ages. Site-specific risks of cancer were analysed in relation to birth order within the twinship and sexes of the twin pair, using adjusted national birth data to give control distributions of these variables. Risk of leukaemia was increased in first-born twins, risk of testicular cancer was increased in second-born twins with female co-twins but decreased in second-born twins with male co-twins and lung cancer risk was increased in first-born twins with same-sex co-twins. Cutaneous melanoma risk was increased in persons with opposite-sex co-twins, nervous system cancer risk was increased in females with opposite-sex co-twins and Hodgkin's disease risk was increased in persons with same-sex co-twins. For most of the findings, no previous comparable analyses are available, so interpretation of the results must be provisional until the analyses can be repeated on other data. The result for leukaemia would accord with previous suggestions that leukaemia may be of prenatal origin and may sometimes lead to intrauterine death. The Hodgkin's disease result would fit with theories of an infectious aetiology, and this view is strengthened by reanalysis of previous data on paralytic poliomyelitis in twins, which show a pattern similar to that for the Hodgkin's disease patients. Cancer risk in relation to birth order and sex of twins can give novel, objective data relating to prenatal and infectious disease aetiology of cancers.
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PMID:A population-based study of cancer risk in twins: relationships to birth order and sexes of the twin pair. 875 3

High-dose chemotherapy with haematopoietic stem cell rescue has proven to be an effective treatment in relapsed lymphoma and neuroblastoma. This treatment approach should be considered also in selected patients with leukaemia, multiple myeloma, breast cancer, ovarian cancer and testicular cancer. Relative contraindications include progression of the disease on appropriate conventional treatment, poor performance status, active infection as well as serious renal, pulmonary, liver and cardiac dysfunction. Increasing age should also be taken into consideration when autologous stem cell transplantation is planned. Every effort should be made to eliminate malignant cells that can be present in the stem cell containing population, which will be infused to the patient following myeloablative treatment.
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PMID:Autologous stem cell transplantation in the treatment of cancer. 893 7

Primary mediastinal non-seminomatous germ-cell tumors (PMNSGCTs) are rare neoplasms that occur in young male adults. Incidence is evaluated about half that of extra-gonadal GCT. Their treatment is generally based on protocols used for testicular cancer, but with poorer results. Based on our experience of 40 patients with PMNSGCTs and data from the literature, we review here the clinical and biological data of these neoplasms. PMNSGCTs seem to constitute a specific entity, distinct from other GCT by the following criteria: true extra-gonadal origin, high incidence in patients with the Klinefelter's syndrome, over-representation of the yolk-sac component, poorer chemosensitivity and survival compared to other GCT, frequent occurrence of non-treatment related hematological neoplasia. The finding of an isochromosome of the short arm of the chromosome 12 in the leukemic karyotype is one of the strongest argument for a common origin in the yolk-sac component of the PMNSGCTs and their associated leukemia. Treatment of PMNSGCTs is still a challenge and should be conducted by a well-trained medical team.
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PMID:[Primary mediastinal non-seminomatous germ-cell tumors: from clinics to biology]. 920 79

The National Institute for Occupational Safety and Health (NIOSH) published a report in 1995 suggesting the possibility of increased incidence of testicular cancer, leukemia, and cancers of the brain, eye, and skin among police officers working with traffic radar. NIOSH recommended epidemiologic study of the issue. This report presents the results of a retrospective cohort cancer incidence study among 22,197 officers employed by 83 Ontario police departments. The standardized incidence ration (SIR) for all tumors sites was 0.9% (95% confidence interval [CI] = 0.83-0.98). There was an increased incidence of testicular cancer (SIR = 1.3, 90% CI = 0.9-1.8) and melanoma skin cancer (SIR = 1.45, 90% CI = 1.1-1.9). These anatomical sites might absorb energy from radar units, but at this time the author has no information about individual exposures to radar emissions, and it is not possible to draw etiologic conclusions. Nested case-control studies are planned to assess individual radar exposures.
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PMID:Cancer incidence among Ontario police officers. 965 25

High-dose chemotherapy--in conjunction with the transplantation of either mononuclear cells harvested from the marrow or CD 34+ cells harvested from the peripheral blood--has proved effective in curing certain patients with leukemia, lymphoma, and, to a lesser extent, multiple myeloma. Though the CD 34+ therapy is a relatively new treatment and the mononuclear cell therapy is more standard, both have been successfully used to reconstitute lethally damaged hematopoietic stem cells. Allogeneic transplants have been more effective than autologous transplants against tumors, but they also pose a greater hazard of death from complications, graft-versus-host disease, and infections. More currently, this approach has been used in patients with certain solid tumors, either in a metastatic or recurrent disease setting or as an adjuvant to surgery and/or standard doses of chemotherapy in patients with a known high risk of recurrence. Unfortunately, the majority of the studies about the impact of this therapy have been small and nonrandomized against standard therapy, and they have encompassed diverse populations of patients. This makes comparisons with contemporary standard--dose approaches--already problematic from a statistical point of view--even more dangerous because of the dissimilarity of the groups being compared. Particularly in the high-risk adjuvant setting, data suggest that those patients that meet the eligibility criteria for high-dose therapy and transplantation exhibit the prognostic factors for a positive outcome. When one compares these results with those of a more heterogeneous group of patients treated with conventional therapy, the conclusion might be drawn that high-dose therapy is superior to standard therapy, when a longer follow-up of the patients in the study will show this to be untrue. Thus there is a plea from clinicians and physicians conducting trials for prospective, randomized trials that would allow a fair comparison between high-dose therapy in combination with transplant procedures and a more conventional, standard chemotherapy, which is often less toxic and definitely less expensive. This article reviews the data for transplantation in four tumors: breast cancer, ovarian cancer, small-cell lung cancer, and germ cell testis cancer. There is such a small number of randomized trials that an attempt must be made to compare these small high-dose therapy studies with similar, though not identical, large studies of conventional therapy. This article attempts to make those comparisons, and several conclusions are drawn, which are detailed below. First, few data support the use of high-dose chemotherapy in any patient with recurrent and drug-resistant breast cancer or ovarian cancer. Similarly, few data support the use of high-dose approaches for patients with extensive small-cell lung cancer. For patients with metastatic breast cancer that has responded completely to conventional chemotherapy, no data suggest a survival advantage for the immediate consolidation of that response with high-dose chemotherapy. The only trial addressing this issue found that immediate transplantation led to a better disease-free survival rate, but overall survival, as compared with that of patients who received transplants at relapse, was not affected, and the study did not address the issue of the relative merits of conventional chemotherapy in either case. The only study of high-dose versus conventional chemotherapy was statistically underpowered, and it showed poorer-than-anticipated outcomes in the patients who received conventional therapy. Ongoing or recently completed trials will, it is hoped, address the many unanswered questions in this area. For patients with high-risk, non-metastatic breast cancer, no completed and analyzed phase III randomized studies address the relative merits of conventional versus high-dose therapy. (ABSTRACT TRUNCATED)
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PMID:High-dose chemotherapy and autologous bone marrow or stem cell reconstitution for solid tumors. 965 70

Secular and cohort trends in mortality from cancer in Scotland during 1953-93, and incidence during 1960-90, were analysed using individual records from the national mortality and registration files. For certain cancer sites, the secular analyses of mortality were extended back to 1911 by use of published data. Mortality from cancer at older ages in Scotland has increased over the last 40 years. In each sex, this trend has been dominated by the effects of smoking: all-cancer rates and rates of lung cancer, now the most common fatal cancer in men and in women in Scotland, reached a peak in the cohort of men born at the turn of the century and the cohort of women born in the 1920s. For much of the period, the Scottish all-age rates of lung cancer were the highest reported in the world; they are now decreasing on a secular basis in men, but are still increasing in women. There have also been large increases at older ages in the incidence and mortality rates for cancer of the prostate in recent years. bladder cancer, nervous system cancer, non-Hodgkin's lymphoma, myeloma and leukaemia; for each there is likely to be a considerable artefactual element to the increase, with differing degrees of possibility that there may in addition be an element of real increase. Substantial decreases in mortality at all ages have occurred for stomach and colorectal cancers and substantial increases at all ages for pleural cancer and melanoma. Rates of mortality from breast cancer, the most common cancer in women in Scotland, have generally increased over the past 80 years; a temporary cessation in this upward trend occurred in the years during and after the Second World War, and recently rates have turned downward, probably at least in part because of better treatment. Mortality from ovarian cancer, the second most common reproductive-related female tumour in Scotland, has also increased at older ages. At younger ages, mortality from cancer in Scotland has decreased, especially in men, whereas incidence has not. This divergence, which has been a consequence of better treatment, has occurred especially for cancers of the testis and ovary, Hodgkin's disease and leukaemia. There have been increases at young adult ages, however, in both mortality from and incidence of oral and pharyngeal, oesophageal and laryngeal cancers in men, and melanoma and non-Hodgkin's lymphoma in each sex. Cervical cancer rates at young ages also increased, but this trend has reversed for incidence in the most recent birth cohorts. Incidence rates have also increased for testicular cancer in young adults and leukaemia in children. With the possible exceptions of non-Hodgkin's lymphoma and childhood leukaemia, the increasing rates are likely largely to reflect real rises in incidence, and they highlight the need for investigation of the causes of these cancers, and, when causes are known, for preventive action.
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PMID:Trends in cancer incidence and mortality in Scotland: description and possible explanations. 966 78

California, the leading agricultural state in the United States, has maintained a population-based cancer registry since 1988, and it also maintains a comprehensive, state-wide pesticide reporting system. Data on cancer incidence and pesticide use reporting are available, by county, for all 58 counties in California. Average annual age-adjusted cancer incidence rates (1988-1992), on a county-, sex-, and race/ethnicity-specific basis, were obtained from the California Cancer Registry (CCR), which maintains the population-based cancer registry throughout California. Pesticide use data (i.e., pounds of active ingredient applied annually in each county) were obtained from the California Department of Pesticide Regulation for 1993. Investigators used Pearson product-moment correlation coefficients (r) to correlate age-adjusted incidence rates for selected cancers with the use data for selected pesticides. For most sex- and race/ethnicity-specific groups, the correlation coefficients were very close to zero or negative in sign, indicating no correlation between pesticide use and cancer incidence. There were, however, several exceptions, particularly in Hispanic males for whom the following correlations were observed: leukemia and atrazine (r=.40), leukemia and 2,4-dichlorophenoxyacetic acid (r=.41), leukemia and captan (r=.46), atrazine and brain cancer (r=.54), and atrazine and testicular cancer (r=.41). For black males, we observed the following: atrazine and prostate cancer (r=.67) and Captan and prostate cancer (r=.49). In females, only a few of the correlations were elevated. Although most of the correlations examined in this analysis were not elevated, several of those in the Hispanic and black male populations were. These segments of the population have traditionally been employed as farm workers in California and have had the greatest potential for exposure to pesticides. This was an ecological study for which no data about exposure to pesticides at the individual level were available for analysis. In addition, no latency period was allowed between potential exposure and diagnosis with cancer. However, the results obtained in two minority groups who represented the majority of farm workers in the fields suggested that additional research studies, in which more rigorous study designs are used, should be conducted in those groups.
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PMID:Correlation analysis of pesticide use data and cancer incidence rates in California counties. 988 60

Improved survival in testicular cancer has been accompanied by concern about long-term side effects of chemotherapy or radiotherapy. Secondary malignant neoplasia represents one of the worst possible long-term complications, leading to death in patients cured of their primary malignancy. Patients with testicular germ cell tumors appear to have a 2-fold increased risk of developing any second cancer 25-30 years after the diagnosis, resulting in a cumulative incidence of 16-23% at that time. The risk for secondary solid tumors can be mainly attributed to radiotherapy. There is strong evidence of an increasing risk for secondary solid tumors with time since treatment. Tumor-specific analysis of the risk for second cancers revealed statistically significant excesses for stomach, pancreas, bladder, rectum, prostate, and kidney cancer, as well as for cancer of the thyroid, melanoma, sarcomas, and non-Hodgkin's lymphoma. No significantly elevated risk for secondary solid tumors was observed after treatment with chemotherapy alone. The risk of secondary leukemia was associated with both radiotherapy and in particular with chemotherapy. In recent clinical surveys of patients with testicular cancer, estimates of the risk of leukemia after chemotherapy have ranged from 10- to 300-fold. An elevated risk was observed within the first two decades after diagnosis, later the risk was as expected in the normal population. Etoposide seems to be leukemogenic, especially at cumulative doses higher than 2 g/m2, although the effects of dose and schedule as well as the effects of other cytotoxic agents and radiotherapy remain to be finally clarified. Based on currently available data in patients with testicular cancer, it can be concluded that a significant elevated risk for the development of secondary leukemia exits after chemotherapy. However this risk does by far not outweigh the therapeutic benefit of etoposid-based therapy in patients with germ cell tumors. Secondary Raynaud's phenomenon is the main late vascular toxicity affecting about one third of patients after curative chemotherapy for testicular cancer. Hypertension will occur in one fifths of the patients. The incidence of vascular toxicity appears to be lower following PEB-therapy compared to PVB-therapy and major vascular events seem to be rare. Other frequent symptomatic toxicities are ototoxicity and peripheral neuropathy. A major risk factor for the development of toxicity is the cumulative dose of cisplatin given. Alterations of gonadotropin levels and Leydig cell insufficiency persist in more than half of young patients cured from testicular cancer by cisplatin-based combination chemotherapy. Approximately one fourth of patients have low serum magnesium or phosphat levels, or elevated creatinine levels. These toxicities seldomly result in clinical symptoms. We conclude that 3-4 courses with bleomycin, cisplatin and etoposide in testicular cancer patients will only rarely lead to symptomatic impairment of organ functions and a decrease of quality of life. Germ cell cancers have served as a valuable model for the development of new treatment strategies contributing largely to defining the role of cisplatinum, etoposide and recently ifosfamide in medical oncology. However, germ cell cancer may also be a useful model for investigating the long term side effects of the oncological therapies. Thus, germ cell cancer is not only a "model for a curable neoplasm" (L.H. Einhorn) but can also be seen as a "model for the study of late sequelae of modern oncological therapies".
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PMID:[Late toxicity after chemotherapy of malignant testicular tumors]. 988 93


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