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)

The National Cancer Registry of the German Democratic Republic identified 105 leukaemias which had developed during 1968-1980 as second primary malignancies in women previously registered with a tumour of the breast or ovary. Matched controls were selected who had been diagnosed with the same first tumour, but had survived without further malignancy as long as the corresponding case. Treatment records were abstracted for leukaemia cases and controls, and a comparison made of the therapy received. There was a ten-fold increase in the risk of leukaemia following ovarian cancer among those treated with chemotherapy, which was almost exclusively cyclophosphamide. Among the breast cancer survivors, the relative risk of acute leukaemia associated with cyclophosphamide was 2.7.
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PMID:A case-control study of leukaemia as a second primary malignancy following ovarian and breast neoplasms. 358 91

The risk of second primary malignancy was assessed in a population-based cohort study of all persons registered with Hodgkin's disease (n = 2,970), ovarian cancer (n = 11,802) and testicular cancer (n = 2,013) in the South Thames Cancer Registry during the period 1961-80, to identify for further study those second malignancies which might be treatment-related. A total of 244 second malignancies was observed. After adjustment for age, sex and calendar period, the relative risk of any second malignancy was 1.4 (90% confidence interval (CI) 1.1-1.7) after Hodgkin's disease, 1.1 (90% CI 1.0-1.2) after ovarian cancer and 0.7 (90% CI 0.5-1.0) after testicular cancer. In particular, the relative risk for leukaemia was 11.9 after Hodgkin's disease, 3.7 after ovarian cancer and 2.5 after testicular cancer. Excess risks were also observed for cancers of the cervix and lung after Hodgkin's disease, for cancers of the breast, lung and rectum after ovarian cancer, and for contralateral testicular cancer. Confounding by social class or smoking does not explain these observations. The excess risks of leukaemia and of second cancer were higher in patients first diagnosed with Hodgkin's disease and ovarian cancer in the 1970s than for those first diagnosed in the 1960s. Increased use of multiple-agent chemotherapy regimes for these tumours in the 1970s may have contributed to these increases in excess risk.
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PMID:Second primary malignancy after Hodgkin's disease, ovarian cancer and cancer of the testis: a population-based cohort study. 366 81

Second malignancies were observed in 181 cases after treatment of antecedent breast cancer, among 5,302 primary breast cancer cases. The accumulated incidence of double cancer was as follows: 2.8% for 5 years, 5.2% for 10 years, 7.6% for 15 years, and 10.0% for 20 years. The observed incidence of second malignancy for all sites was 1.58 times as frequent as in the normal group. Statistically significant increased risks were observed for opposite breast cancer (O/E ratio 5.92), ovarian cancer (O/E ratio 4.47), corpus uterine cancer (O/E ratio 5.97) and thyroid cancer (O/E ratio 5.07). Among 5,302 cases, 2,431 (45.9%) underwent adjuvant chemotherapy. In chemotherapy groups, significantly increased risk of stomach cancer, thyroid cancer, leukemia and hepatoma was observed, but there were no remarkable differences between the MMC group and the CPA group. However, in the MMC + CPA combination treatment group, the risk of stomach cancer and leukemia was higher than in the single drug treatment groups. When multiple drugs were administered in large doses as long-term adjuvants, the risk of second malignancy seemed to become greater.
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PMID:[Effects of surgery and adjuvant chemotherapy of breast cancer on the incidence of a second malignancy]. 372 65

We examined the activity reported in phase II trials for all cytotoxic drugs introduced into clinical trial by the National Cancer Institute (NCI) since 1970. For each drug in each tested tumor type we derived a response rate from the pooled data of all trials reported either in the literature or to the NCI. We rated a drug active if the lower 80% confidence bound of the response rate was greater than 10%. Of the 83 drugs developed and introduced by the NCI, there are 47 which we considered evaluable. Of these drugs, 24 were rated active in at least one cancer type, of which ten were analogs of drugs in wide clinical use. Diseases most commonly responsive include lymphoma (74% of the tested drugs rated active), leukemia (35%), urothelial cancer (29%), small cell lung cancer (29%), ovarian cancer (22%), cervical cancer (22%), and breast cancer (18%). For colon cancer and melanoma, only one of 42 and two of 30 tested drugs rated active, respectively. We also examined the completeness of clinical testing: among the 47 drugs there were 20 tested in greater than or equal to 14 patients with leukemia, 23 tested in patients with lymphoma, and 18 tested in patients with small cell lung cancer; whereas 34 drugs for breast cancer, 42 for colon cancer, and 33 for non-small cell lung cancer were more completely evaluated. Considering the "clinical panel" of seven cancer types (breast, non-small cell lung, small cell lung, colon, melanoma, leukemia, and lymphoma), drugs were tested in greater than or equal to 30 patients in a median of four tumor types. Testing in this panel failed to detect activity in only one drug found active in another tumor, although testing in diseases other than this clinical panel was even less complete. Phase II testing should emphasize completion of minimum accrual goals, testing in patient populations with minimum prior therapy, and evaluation in a minimum set of tumor types.
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PMID:Clinical drug development: an analysis of phase II trials, 1970-1985. 379 Dec 70

Marrow transplantation is effective treatment for a number of hematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is successful in the treatment of aplastic anemia with 70-85% long-term survival. It offers 10-30% apparent cures for patients with acute leukemia who have relapsed at least once, and for those with chronic myelocytic leukemia in blast crisis. Although still somewhat controversial, it appears to be the treatment of choice for patients with acute nonlymphoblastic leukemia in first chemotherapy induced remission, and for those with chronic myelogenous leukemia in the chronic phase since approximately 50-60% of these patients experience long-term, disease-free survival. Patients with acute lymphoblastic leukemia grafted in second or subsequent remission may expect a 30% "cure" of their disease. Marrow grafting is the only effective treatment for many patients with inherited immunologic deficiencies and certain genetic storage diseases. Cures of congenital Fanconi's anemia, Blackfan-Diamond anemia, osteopetrosis, paroxysmal nocturnal hemoglobinuria and thalassemia major have been achieved. Marrow transplantation is being explored for the therapy of patients with lymphoma, Hodgkin's disease, preleukemia, multiple myeloma, hairy cell leukemia, small cell lung cancer, testicular cancer, ovarian cancer and neuroblastoma. Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. More recently, marrow transplants from HLA-nonidentical family members and even from unrelated donors have been successfully explored.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marrow transplantation: the Seattle experience. 391 47

In human tumor cells freshly obtained from patients with breast cancer, ovarian cancer, or adenocarcinoma of unknown etiology and in normal human bone marrow cells, the cell-to-medium ratio (intracellular/extracellular concentration) in vitro of 5.42 microM melphalan rose rapidly to levels of 6-17 after 35 min at 37 degrees C in Dulbecco's phosphate-buffered saline containing bovine serum albumin and glucose. Only patient C (breast cancer) had received chemotherapy. In all cells studied, L amino acids (1 mM) such as leucine, glutamine, tyrosine, and methionine reduced the cell-to-medium ratio of melphalan at 3 and 35 min. There was a good correlation between the reduction of melphalan transport at 35 min in the heterogeneous nucleated bone marrow cell population by amino acids and their effect on melphalan cytotoxicity in the CFU-C system. Aminoisobutyric acid (A1B), a specific substrate of the A system of amino acid transport, at a concentration between 1 and 50 mM had no significant effect on melphalan uptake at 3 min in any of the human cells studied except those of patient C. At 35 min A1B (10 or 50 mM) significantly reduced the intracellular melphalan concentration in normal bone marrow cells and tumor cells from patients B and C. At 2 mM, 2-aminobicyclo-(2, 2,1)-heptane-2-carboxylic acid (BCH), a specific substrate of the L system of amino acid transport, reduced the cell-to-medium ratio to 70% of control at 3 and 35 min in human bone marrow cells. In tumor cells from patients A, B, D, and F, 2 mM BCH had no significant effect on melphalan uptake at 3 min; it slightly decreased uptake in tumor cells from patient C. At 35 min, 2 mM BCH significantly reduced melphalan transport in tumor cells from patients C and F only. The lack of a BCH-suppressible component to melphalan uptake into human tumor cells freshly obtained from previously untreated patients contrasts with the presence of this component in murine L1210 leukemia cells, murine P388 leukemia cells, and human tumor cell lines. This suggests that minor differences in melphalan transport may exist amongst species and also between human tumor cells which are freshly obtained and cell lines maintained in culture.
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PMID:Effects of amino acids on the transport and cytotoxicity of melphalan by human bone marrow cells and human tumor cells. 401 61

Erythrocyte mean corpuscular volume (MCV) evolution during cytotoxic therapy of Hodgkin's disease, lymphoma, multiple myeloma, ovarian cancer, and breast cancer was studied. The fastest and the highest MCV increases were observed in the diseases and with the therapies the most frequently involved in secondary leukemia: Hodgkin's disease treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone), and multiple myeloma and ovarian cancer treated with melphalan. On the contrary, with cytotoxic regimens not linked to a high frequency of secondary leukemia such as CMF (cyclophosphamide, methotrexate, 5-fluorouracil) used in ovarian or breast cancer, MCV increase was moderate. As the MCV increase reflects the bone marrow reaction to cytotoxic therapy, an unusually high increase could indicate bone marrow damages which could lead to secondary leukemia.
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PMID:Erythrocyte mean corpuscular volume during cytotoxic therapy and the risk of secondary leukemia. 403 78

A prospective study of 1572 women treated with radiotherapy for cervical (1478 women) and ovarian cancer (94 women) was done. Patients had been followed clinically and especially by blood tests between 1961 and 1981, comprising 8990 woman-years (WY). Following radiotherapy, 5 patients developed non-lymphocytic leukemia [2 acute myeloblastic leukemia (AML), 1 acute monocytic leukemia (AMoL), and 2 chronic myeloid leukemia (CML)]. Based on rates for the general population, 0.45 case would be expected and, therefore, the relative risk was 11.2. The average mean marrow dose for all our subjects was calculated to be 1177 rad, the risk of radiation-induced leukemia was 0.43 excess case per year per one million women exposed to 1 rad of radiation to the bone marrow. Four patients with cervical cancer who developed leukemia were in a high-dose-rate group treated with both a linear accelerator (Linac) and remote afterloading system (RALS), and 1 patient with ovarian cancer who developed leukemia was treated with a Linac alone. This is the first report of a statistically significant increased risk of leukemia for patients treated with large doses of radiation for malignant neoplasms in the pelvic region.
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PMID:Leukemia in patients following radiotherapy for malignant neoplasms in the pelvic region. 406 51

The risk of second primary cancer was evaluated in more than 25,000 women with cancer of the genital organs diagnosed between 1935 and 1982 in Connecticut. Significant excesses of subsequent cancers were observed following cancers of the cervix (35%, n = 656), uterine corpus (16%, n = 1,060), and ovary (58%, n = 366). When observed and expected second cancers of the female genital tract were excluded, these excesses became 40%, 30%, and 59% after cervix, uterine corpus, and ovary, respectively. Among women with either cancer of the cervix or uterine corpus, the risk of developing a second cancer rose with increasing duration of follow-up, reaching an excess of 61 and 34%, respectively, after 20 years. In contrast, among patients with ovarian cancer, the second cancer risk decreased over time to 41% after 10 years. Cancers related to smoking, i.e., oral cavity and pharynx, esophagus, and respiratory system, were notably increased among cervical cancer patients. The twofold to threefold risks observed for these second cancers are consistent with recent evidence linking cervical cancer to cigarette smoking and seem too large to be artifacts of confounding by low socioeconomic status. An increased incidence of second cancer of the abdominal organs (colon, rectum, kidney, bladder, ovaries) was generally observed for each gynecologic site. However, only rectal cancer was consistently linked with radiation treatment for the first primary cancer. Leukemia occurred in excess after cancers of the uterine corpus and ovary, but not after cervical cancer. The predominant cell type was acute nonlymphocytic leukemia, and the excess was associated with radiotherapy for uterine corpus cancer and with chemotherapy for ovarian cancer. Cancers of the breast and colon were increased following uterine corpus and ovarian cancer and vice versa, which supports the notion that these sites share a common etiology, perhaps related to dietary or hormonal factors. Cervical cancer patients experienced a deficit of subsequent breast cancer, possibly due to ovarian removal or ablation by radiation. Investigators need to explore further the association between the smoking-related cancer sites and cervical cancer, to clarify the role of radiotherapy and chemotherapy in relation to excess cancers, and to define more fully the etiologic factors that link cancers of the breast, colon, uterine corpus, and ovary.
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PMID:Second cancer following cancer of the female genital system in Connecticut, 1935-82. 408 93

Changes in mean corpuscular volume (MCV) were studied in cancer patients. Vitamin B12 or erythrocyte folate deficiencies were observed in only 9% of macrocytic patients (MCV greater than or equal to 100 fl). Bone marrow study in seven macrocytic patients with normal hemograms and normal levels of vitamin B12 and folic acid, on per os daily cyclophosphamide single agent therapy, showed myelodysplastic features. The highest MCV and MCV increases during therapy among 203 patients were observed in those cancers and cytotoxic therapies most commonly followed by secondary leukemia: Hodgkin's disease treated with MOPP and radiotherapy, and multiple myeloma and ovarian cancer treated with Melphalan. 21 patients who developed secondary leukemia had a higher MCV and a greater MCV increment than the control patients. Differences were significant in Hodgkin's disease. This preliminary report strongly supports monitoring MCV changes during cytotoxic therapy to attempt identification of patients at high risk of secondary leukemia.
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PMID:[Changes in the mean corpuscular volume during the cytotoxic treatment of cancer and risk of secondary leukemia. Preliminary results]. 632 84


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