Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood changes preceding therapy-related leukemia were studied in 105 patients who had received cytotoxic therapy, 53 for Hodgkin's disease and 52 for other cancers. Preleukemic anomalies were observed in 74.3% of the cases, appearing after a mean interval of 68.7 months after diagnosis of the initial cancer. This interval was only 57.5 months in patients aged 50 years or older and only 42.3 months in patients with Hodgkin's disease having received cytotoxic therapy for 6 months or less. The first changes most frequently observed were pancytopenia (24.8%) and isolated erythrocyte abnormalities such as anemia or macrocytosis (18.1%). Involvement of two cell lines, isolated thrombocytopenia or leukopenia, circulating immature cells, monocytosis, leukocytosis, or thrombocytosis were also observed. Therapy-related myelodysplastic syndrome was recognized in 19 patients and myelofibrosis in 3. Median duration of the preleukemic phase was 6 months; 9 months in cases of isolated erythrocyte involvement and 5 months in the other cases. Myelomonocytic or monoblastic leukemia appeared less frequently when the first sign involved erythrocytes only. Hematological surveillance thus appears necessary in all patients having received cytotoxic therapy. Bone marrow study with cytogenetic examination should be performed in cases of persistent peripheral blood abnormalities.
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PMID:Preleukemic changes in cases of nonlymphocytic leukemia secondary to cytotoxic therapy. Analysis of 105 cases. 373 Oct 20

Therapy-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (t-AML) has been reported after autologous bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT) for various malignancies. We retrospectively reviewed all adult ABMT/PBSCT cases performed at the University of Chicago Medical Center from 1985 to 1997 in order to determine the incidence of therapy-related leukemia. Among 649 patients, seven (1.1%) developed therapy-related acute lymphoblastic leukemia (one patient) or t-MDS/t-AML (six patients). Of these seven, primary malignancies included one case of breast carcinoma, five cases of Hodgkin's disease (HD) and one case of non-Hodgkin's lymphoma (NHL). Disease-specific incidences for therapy-related leukemia occurring after ABMT/PBSCT were one in 354 (0.3%) for breast carcinoma, five in 79 (6.3%) for HD and one in 103 (1%) for NHL. The median latency periods for the development of therapy-related leukemia from the time of initial diagnosis and of ABMT/PBSCT were 5.5 and 1.5 years, respectively, for the combined HD and NHL group of patients and 4.4 and 2.8 years, respectively, for the one breast carcinoma patient. All seven patients had clonal cytogenetic abnormalities, and five had recurring abnormalities typical of myeloid disorders. Given the similar latency period observed in patients treated with conventional chemotherapy alone, our findings support the hypothesis that therapy-related leukemia after ABMT/PBSCT likely results from pre-transplant therapy. Early detection of therapy-related leukemia is therefore critical to exclude these patients from undergoing ABMT/PBSCT.
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PMID:Myelodysplasia and acute leukemia following high-dose chemotherapy and autologous bone marrow or peripheral blood stem cell transplantation. 1038 56

Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is an increasingly recognized treatment complication in patients treated with radiotherapy or chemotherapy for previous hematologic malignancies or solid tumors. Distinct clinical entities have been described according to the primary treatment, corresponding to defined genetic lesions. Chromosome 7 and/or 5 losses or deletions are typical of alkylating agent-induced AML, while development of t-AML with balanced translocations involving chromosome bands 11q23 and 21q22 has been related to previous therapy with drugs targeting DNA-topoisomerase II. In addition, antimetabolites, and in particular the immunosuppressant azathioprine, have been shown to induce defective DNA-mismatch repair. This could promote survival of misrepaired cells giving rise to the leukemic clone. Individual predisposing factors, including polymorphisms in detoxification and DNA repair enzymes have been identified. Their combination may significantly increase the risk of t-MDS/AML. Among patients with hematologic malignancies, long-term survivors of Hodgkin's lymphoma are exposed to an increased risk of t-MDS/AML, particularly when receiving MOPP-based, and escalated BEACOPP regimens, and when alkylators are combined with radiotherapy. Patients with Hodgkin's and non-Hodgkin's lymphoma are at highest risk when total body irradiation followed by autologous stem cell transplantation is used as rescue or consolidation therapy. The addition of granulocyte-colony-stimulating factor and radiotherapy plays a significant role in t-AML following treatment of children with acute lymphoblastic leukemia. In non-hematologic malignancies, treatment for breast cancer and germ-cell tumors has been associated with a 1-5% lifetime risk of both lymphoid as well as myeloid leukemia. In all cases the risk of t-MDS/AML drops sharply by 10 years after treatment.
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PMID:Therapy-related leukemia and myelodysplasia: susceptibility and incidence. 1776 13

Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a long-term complication of pediatric cancer. We retrospectively studied pediatric t-MDS/AML patients treated at MD Anderson from 1975 to 2007. We also compared those patients to pediatric patients with de novo MDS/AML during this time interval. Among 2589 children with cancer treated at MD Anderson, we identified 22 patients with t-MDS/AML. Patients with t-MDS/AML had a median age of 14 years. There was a male and Hispanic predominance. The most common primary malignancies were osteosarcoma and Hodgkin lymphoma. The median latency period was 4.1 years. Three patients received supportive care only. Group 1 (n=5) underwent stem cell transplantation without induction chemotherapy. Group 2 (n=5) patients received AML-type chemotherapy and a stem cell transplant postremission (n=5). Group 3 (n=4) received a stem cell transplant as salvage therapy. The respective 2-year survival rates for groups 1, 2, and 3 were 20%, 40%, and 25% (P=0.85). Patients with de novo AML were younger (P=0.001) and higher rates of complete remission (P=0.03), and survival (P<0.0001). Independent factors predicting shorter survival were poor/intermediate-risk cytogenetics (P=0.01), lower hemoglobin level (P=0.0001), and t-MDS/AML (vs. de novo) (P=0.003). Childhood t-MDS/AML has a poor prognosis. Although patients benefited from AML-type induction chemotherapy followed by stem cell transplantation as postremission therapy, effective therapies, and prevention are needed.
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PMID:Pediatric therapy-related myelodysplastic syndrome/acute myeloid leukemia: the MD Anderson Cancer Center experience. 1980 47