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)

One of the most serious possible consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can be distinguished currently. These include classic therapy-related myeloid leukemia, leukemia that follows treatment with agents that inhibit topoisomerase II, acute lymphoblastic leukemia, and leukemias with 21q22 rearrangements or inv(16) or t(15;17). These types of leukemia are discussed in detail in this article.
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PMID:Therapy-related myeloid leukemia. 870 57

The last decade has seen a dramatic improvement in prognosis of hairy cell leukaemia (HCL) but concern has emerged with regard to the incidence of second malignancy. A recent report found an 18.8% incidence of second cancers and suggested a possible role for alpha-interferon (IFN) in their pathogenesis. We reviewed our larger series of 200 patients with HCL. We found second malignancies in 8 cases (4.0%), all but one of whom had received IFN. However, when compared to age- and sex- matched population data this represents no increase in relative risk of second cancer in patients with HCL and provides no evidence of a role for IFN in the pathogenesis of these second malignancies.
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PMID:Second malignancy in hairy cell leukaemia: no evidence of increased incidence after treatment with interferon alpha. 872 35

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).
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PMID:Leukaemias and cancers following iodine-131 administration for thyroid cancer. 904 33

One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogenic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase II, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11q23 or 21q22. The MLL gene at 11q23 or the AML1 gene at 21q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 11q23 rearrangements. Therapy-related leukemias with 11q23 or 21q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts.
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PMID:Myeloid leukemia after hematotoxins. 911 10

Poland's syndrome, a rare congenital disorder with pectoralis muscular girdle defect, have been reported in association with lymphoreticular malignancies in the past. Childhood solid tumors in association with this congenital anomaly have not been reported so far. We describe this rare association of Poland's syndrome and Wilms tumor. Due to the possibility of increased risk of leukemogenesis in patients with Poland's syndrome, chemo-radiation therapy of Wilms tumor in our patient may increase the risk of secondary leukemia. Therapeutic modification of primary cancer in these patients may be necessary with careful long-term follow-up for early detection and treatment of secondary cancer.
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PMID:Poland's syndrome and Wilms tumor: an unusual association. 937 93

In Caucasians, Hodgkin's disease demonstrates constant incidence rates, with a first peak occurring in adolescents and in young adults, and a second peak in the elderly. Age is an important risk factor for overall survival of patients; staging strategies and treatment expose elderly patients to an even higher risk arising from surgical complications, death from secondary cancer and leukemia or lethal cardiac complications. In contrast to non-Hodgkin's lymphoma, optimal staging and treatment procedures have not yet been defined for this disease in elderly patients. However, due to the very poor prognosis of inadequately treated patients, treatment recommendations at present must be based on those for younger patients while keeping the individual risk profile in mind. If staging laparotomy is omitted, most patients will require a combined modality treatment. While in low-risk patients a reduced number of cycles with full-dose chemotherapy like ABVD (Adriblastina, bleomycin, vinblastine, dacarbazine) or of six cycles with less toxic drugs like VBM (vinblastine, bleomycin, methotrexate) followed by limited field radiotherapy may suffice, patients with well-defined risk factors will require a more prolonged chemotherapy. Currently, there is no evidence that C(M)OPP [cyclophosphamide (mustargen), vincristine, procarbazine, prednisone]/ABVD or ABVD may successfully be replaced by less toxic regimens. Therefore, further studies are required on the specific definition of biological age, the cost/benefit ratio of staging procedures and treatment and the influence of these strategies on the quality of life in the elderly.
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PMID:Prognosis and management strategies of lymphatic neoplasias in the elderly. II. Hodgkin's disease. 966 14

Epipodophyllotoxins are associated with leukemias characterized by translocations of the MLL gene at chromosome band 11q23 and other translocations. Cytochrome P450 (CYP) 3A metabolizes epipodophyllotoxins and other chemotherapeutic agents. CYP3A metabolism generates epipodophyllotoxin catechol and quinone metabolites, which could damage DNA. There is a polymorphism in the 5' promoter region of the CYP3A4 gene (CYP3A4-V) that might alter the metabolism of anticancer drugs. We examined 99 de novo and 30 treatment-related leukemias with a conformation-sensitive gel electrophoresis assay for the presence of the CYP3A4-V. In all treatment-related cases, there was prior exposure to one or more anticancer drugs metabolized by CYP3A. Nineteen of 99 de novo (19%) and 1 of 30 treatment-related (3%) leukemias carried the CYP3A4-V (P = 0.026; Fisher's Exact Test, FET). Nine of 42 de novo leukemias with MLL gene translocations (21%), and 0 of 22 treatment-related leukemias with MLL gene translocations carried the CYP3A4-V (P = 0. 016, FET). This relationship remained significant when 19 treatment-related leukemias with MLL gene translocations that followed epipodophyllotoxin exposure were compared with the same 42 de novo cases (P = 0.026, FET). These data suggest that individuals with CYP3A4-W genotype may be at increased risk for treatment-related leukemia and that epipodophyllotoxin metabolism by CYP3A4 may contribute to the secondary cancer risk. The CYP3A4-W genotype may increase production of potentially DNA-damaging reactive intermediates. The variant may decrease production of the epipodophyllotoxin catechol metabolite, which is the precursor of the potentially DNA-damaging quinone.
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PMID:Association of CYP3A4 genotype with treatment-related leukemia. 978 61

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

Since the advent of cisplatin-based chemotherapy in the 1970s, the majority of metastatic testicular cancer patients can be cured with chemotherapy followed by surgery. The high-curability of testicular cancer, along with young age of afflicted patients, can result in patients living for many years after the initial treatment. The development of second cancer represents one of the most severe long-term complications in these patients. Patients who have achieved a long-term disease-free status have an increased risk of developing germ-cell tumor in the contralateral testis. Late relapse (occurring more than 2 years after initial treatment) of germ-cell tumor at any site has also been found in approximately 3% of all patients. Patients receiving radiotherapy or chemotherapy for testicular cancer a have small, but clearly identifiable, risk of developing second malignancies. Radiotherapy is associated with a two- to threefold increased risk for second solid cancer. Chemotherapy, especially high-dose etoposide regimens, is associated with increased risk for second leukemia. Although the incidence of second malignancies is rather low, it is important to monitor the carcinogenic potential of therapy, and to develop a preventive approach for second cancer.
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PMID:[Treatment of testicular and second cancer]. 1058 66

In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell-sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation-associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data.
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PMID:Relative risks of radiation-associated cancer: comparison of second cancer in therapeutically irradiated populations with the Japanese atomic bomb survivors. 1065 48


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