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[Humoral antiviral immunity in children with hematologic neoplasms].

Antiviral humoral immunity was studied in patients with Hodgkin's disease, idiopathic thrombocytopenic purpura (ITP), and aplastic anemia (AA). Insufficiency of antiviral humoral immunity as regards antigenically unrelated viruses and Mycoplasma pneumoniae was characteristic of all these conditions. A remission of Hodgkin's disease and ITP was associated with a reliable increase of the studied parameters in comparison with the acute period of the disease. After splenectomy humoral immunity parameters were virtually unchanged in patients with ITP, whereas in patients with Hodgkin's disease and AA the deficiency of antibody production is 40% increased after the operation.

Adolescent↗

Genetic instability of microsatellites in hematological neoplasms.

Genetic instability has been recently related to point mutations on genes involved in DNA repair pathway of errors produced during replication. These molecular alterations have been described in hereditary and sporadic colon carcinomas and related tumors. To examine genetic instability on lympho- and myeloproliferative processes, we analyzed the behaviour of 10 microsatellite markers and one VNTR on different chromosomes in 10 patients with non-Hodgkin lymphomas (NHL), one patient with acute lymphoblastic leukemia (ALL) and 10 patients with acute myeloid leukemia (AML). Mobility shifts were found in three of those cases. One of them showed genetic instability for several markers--microsatellites and VNTR- and the other two showed differences for only one marker. As a correlation between point mutations in MSH2 gene and the presence of genetic instability in hereditary non-polyposis colon cancer (HNPCC) and related tumors has been found, we analyzed the sequence of a conversed region of this gene in the cases showing this phenomenon. We only found a polymorphism, previously described, in 669 codon from cDNA.

Burkitt Lymphoma↗

[Hematological neoplasm--how to treat low-grade lymphomas].

Low-grade lymphomas are rare in Japan, comprising about 10% of non-Hodgkin's lymphomas. They are indolent in natural history with median survival of 7-10 years. Despite a good initial response to radiotherapy or chemotherapy, most patients (Pts), being incurable, ultimately die of their disease. Pts with clinical stage (CS) I/II disease are generally treated with locoreginal radiotherapy. Long-term survival of 60% to 70% and disease-free survival (DFS) of 50% to 55% have been reported. The more precise the staging procedures, the better the results. Chemotherapy used as a primary therapy or as an adjuvant to radiotherapy may improve DFS of pts with CS II with many sites of lymph node involvement or bulky disease. For CS III/IV disease there is no accepted standard therapy. There is no survival advantage for any of the different first-line treatment methods ranging from initial deferral of treatment albeit in highly selected pts, an alkylating agent +/- steroid hormone, to combination chemotherapy (C-MOPP, CHOP, ProMace-MOPP etc) +/- irradiation. The international index for prognostication of aggressive lymphoma has also been shown to be applicable to stratification of low-grade lymphomas. In future studies effectiveness of treatment strategies should be investigated with long-term DFS and improved quality of life being set as primary endpoints.

Female↗

[Systemic fungal infections in hematologic neoplasms. An autopsy study of 1,053 patients].

BACKGROUND: Mycoses are common complications of haematological neoplasias. For successful antimycotic treatment, a knowledge of preferential underlying disease, frequency, species and site of the mycosis is of importance. PATIENTS AND METHODS: Postmortem material comprising clinical data, autopsy protocols and histological sections obtained between 1976 and 1990 from 1,053 patients with leukaemia and malignant lymphomas following antineoplastic therapy was analysed retrospectively. RESULTS: Autopsy revealed systemic mycoses in 184 patients (17.5%). Between 1976 and 1990, the incidence of fungal infections increased from 12% to 30%, most being found in acute leukaemia (24%). Myeloproliferative syndrome (18%), non-Hodgkin's lymphomas (16%), Hodgkin's disease (10%) and plasmocytoma (2.5%) were less frequently associated with mycoses. With no preference for any particular malignancy in evidence, aspergillosis predominated at histology (85 cases), while candidosis occurred in 75 cases. A combination of two mycoses (aspergillosis and candidosis) (14 patients), zygomycosis (eight patients) and cryptococcosis (two patients) were much less common. While aspergillosis caused mostly pulmonary (81 cases) and cerebral (18 cases) infections, candidosis most frequently affected the GI tract (83 cases). The fungal infection was regarded as the main cause of death in some 76% of the cases. An analysis of bone marrow of patients with mycosis (184 cases) revealed a predominance of hypoplasia (54%) over tumour infiltration (34%) and normal bone marrow (12%). In malignancies with no mycoses (869 cases) in contrast, hypoplasia was significantly less common (19%) than infiltration (59%) or normal bone marrow (22%) (p < 0.001). CONCLUSION: The incidence of mycoses in haematological neoplasias in our post mortem series has continued to increase. Bone marrow hypoplasia in particular predisposes to fungal infection. The lungs are the organs of predilection, and aspergillosis is likely to be the infection presenting.

Autopsy↗

[The effect of chemotherapy on energy and nitrogen balance in patients with hematologic neoplasms].

Energy balance and nitrogen balance were evaluated within the opening week of standard induction chemotherapy in 26 haematooncological patients. The patients were uncomplicated in good nutritional status and nutritional requirements were covered by oral diet under the daily assistance of specially trained dietary nurse. Resting energy expenditure (REE) measured by indirect calorimetry under standard circumstances was elevated to 113.1% of predicted value by Harris-Benedict equation. We found a significant decrease in REE to 106.1% of predicted value (p < 0.01) on day 7 after the beginning of induction chemotherapy. Total energy requirements calculated on the basis of measured REE were not elevated during chemotherapy and mean energy balance was balanced. On the other hand mean nitrogen balance was markedly negative during chemotherapy even on the second day of treatment (-6.9 gN/day, cumulative nitrogen balance -28.0 gN/5 days). The negativity correlated will with markedly elevated urinary nitrogen output but worse with nitrogen intake in the diet. Significant correlation was found between the negativity of cumulative nitrogen balance for the whole period of follow up and the magnitude of decrease in REE after chemotherapy (r = 0.74, p < 0.01). This dependence may give evidence of the decay of tumor mass as the main factor of changes shown. Findings described here may support the assumption that energy requirements of haematooncological patients in good nutrition status during chemotherapy may be covered by oral diet even though this usually does not prevent the negativity of nitrogen balance.

Antineoplastic Agents↗

[Evaluation of phenazone oxidation and sulfadimidine acetylation in patients with hematologic neoplasms].

The aim of our study was to estimate of phenazone oxidation and sulfadimidine acetylation in patients with Hodgkins disease, non Hodgkins lymphoma and acute leukemia. We observed increase in liver microsomal enzyme activity and predominance of the rapid acetylator phenotype in these pathological states. It should be taken into account when dosing drugs which are metabolized as markers of the liver metabolic efficiency like phenazone and sulphadimidine. One can also expect these patients to have a genetic predisposition to the development of cancer disease.

Acetylation↗

Industries and cancer.

Epidemiologic evidence on the relationship between selected industries and cancer is reviewed. This article will focus on several industries which have not been covered elsewhere in this volume, briefly describe current research on cancer in the agricultural and construction industries, and discuss surveillance data on cancer mortality in relation to industry listed on US death certificates. Employment in the rubber industry has been associated with bladder cancer, leukemia, stomach, and lung cancer and is considered by the International Agency for Research on Cancer (IARC) to have 'sufficient evidence of carcinogenicity in humans.' Studies of workers exposed to polychlorinated biphenyls (PCBs) have reported excess mortality from gastrointestinal neoplasms, hematologic neoplasms, and skin cancer (specifically malignant melanoma); IARC considers that the evidence for carcinogenicity in humans is 'limited.' Employment in the boot and shoe industry has been associated with nasal adenocarcinomas in England and Italy ('sufficient'). Hairdressers and barbers have been found to have excess bladder cancer and less consistent evidence for several other sites ('limited'). Workers exposed to wood dust have excess mortality from cancer of the nasal sinuses and paranasal cavities; there is less consistent evidence for excess laryngeal cancer ('sufficient'). Workers employed in the petroleum industry have limited evidence for excess leukemia and other lymphatic and hematopoietic neoplasms, and skin cancer (particularly malignant melanoma) ('limited').

Adenocarcinoma↗

Thoracic tuberculosis, mycobacteriosis, MERosis, and BCGosis in a cancer treatment center.

Radiographs and clinical records of 100 patients with tuberculosis or mycobacteriosis and six patients infected with Bacillus Calmette-Guerin (BCG) or methanol extraction residue of BCG (MER) were reviewed. Radiographic presentations were categorized. Tuberculosis or mycobacteriosis simulated pulmonary neoplasm in 64 patients. Tuberculosis or mycobacteriosis complicated pulmonary neoplasm, hematological neoplasm, or acquired immune deficiency syndrome in 27. Coincident tuberculosis or mycobacteriosis and bronchogenic carcinoma were encountered in seven. Bronchogenic carcinoma developed in an area of chronic stable tuberculosis in three. Miliary granulomatous lesions developed in four following MER immunotherapy and in two following BCG immunotherapy. Differentiating tuberculosis or mycobacteriosis from bronchogenic carcinoma, metastasis, or pneumonia was difficult and biopsy was often necessary.

BCG Vaccine↗

Anorectal and perianal complications of hematologic malignant neoplasms.

Among 17 adults with hematologic malignant neoplasms in whom anorectal complications developed, the overall mortality was 53%; for those in whom the disease was not in remission the mortality was 69%, compared with zero for patients who were in remission. All but one of the deaths were directly attributable to septicemia secondary to the anorectal lesion. Over half of the patients had a history of previous anorectal problems or disordered bowel pattern preceding the anorectal complication. The anorectal lesions affecting these 17 patients included prolapsed hemorrhoids (in 5); discrete ulcers in the anal canal and surrounding cellulitis (8); necrosis of the anus and perianal area (2); and perirectal abscesses (2). Only the abscesses responded to surgical drainage. Treatment of the other lesions was conservative: bowel function was maintained as normal as possible, good perineal hygiene was practised and stool softeners were used, while efforts were directed towards achieving remission of the hematologic neoplastic disease.

Adult↗

Immunotoxin therapy of hematologic malignancies.

Patients with chemotherapy relapsed or refractory hematologic malignancies may be effectively treated with allogeneic or autologous stem cell transplants. However, many patients cannot be transplanted due to age, comorbidities, or lack of suitable donors. Further, a fraction of patients relapse post-transplant. Novel therapeutic agents that can kill multidrug-resistant malignant stem cells and are not myelosuppressive are needed. One class of such agents is immunotoxins. Immunotoxins consist of cell-selective ligands covalently linked to peptide toxins. The ligand delivers the molecule to specific cell surface receptors on malignant cells. The toxin triggers cell death either by reaching the cytosol and catalytically inactivating vital cell processes or by modifying the tumor cell surface membrane. We have synthesized immunotoxins for therapy of chemoresistant hematologic diseases. In this review, we will detail the synthesis of a number of these drugs and describe their preclinical and clinical activity. Several of these agents have shown dramatic antitumor effects in patients with hematologic neoplasms, and one immunotoxin has been approved for use by the US Food and Drug Administration (FDA). Over the next several decades, a growing number of these agents should reach the clinic.

Antineoplastic Agents↗

Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident".

Dioxin (2,3,7,8-tetrachlorodibenzo-para-dioxin, or TCDD) is a powerful carcinogen in experimental animals, whereas the evidence in humans is limited. We examined cancer mortality from 1976 to 1991 among residents of Seveso, Italy, which was highly contaminated after an industrial accident. The area was divided into zones with decreasing exposure to dioxin (A = highest, B = lower, R = lowest). The population of a surrounding noncontaminated area was used as a reference group. Zone A was small (11,516 person-years); in that zone, we saw a moderate increase in mortality from digestive cancer among women [relative risk (RR) = 1.5; 95% confidence interval (CI) = 0.5-3.5]. In zone B, we also saw excesses at digestive sites (83,610 person-years), 10 years after the accident. Women had an increased mortality from stomach cancer (RR = 2.4; 95% CI = 0.8-5.7), and men had increased mortality from rectal cancer (RR = 6.2; 95% CI = 1.7-15.9). Hematologic neoplasms were increased. The highest risks were seen in zone B for leukemia in men (RR = 3.1; 95% CI = 1.3-6.4), multiple myeloma in women (RR = 6.6; 95% CI = 1.8-16.8), and Hodgkin's disease in both genders (RR = 3.3; 95% CI = 0.4-11.9 in men; and RR = 6.5; 95% CI = 0.7-23.5 in women). Soft tissue sarcoma was elevated only among zone R males (256,408 person-years; RR = 2.1; 95% CI = 0.6-5.4). We found no increase for all-cancer mortality or major specific sites (for example, respiratory among males, breast among females). The specific excesses that we observed were not explained by bias or confounding, and their association with dioxin exposure is plausible. The follow-up is continuing.

Accidents↗

Serum ferritin levels in hematologic malignant neoplasms.

Data from 90 patients with a variety of hematologic malignant neoplasms were studied to determine the relation between changes in serum ferritin concentration and the clinical status of the patients. Patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, blastic crisis of chronic myelocytic leukemia, acute myeloblastic leukemia and acute lymphoblastic leukemia were found to have significantly elevated serum ferritin levels. Further study of serum ferritin concentration in certain hematologic malignant neoplasms might provide a valuable insight into the role of serum ferritin determination in the diagnosis and follow-up of patients with malignant diseases.

Female↗

Chromosomal aberrations in Bloom syndrome patients with myeloid malignancies.

Bloom syndrome (BS) predisposes affected individuals to a wide variety of neoplasms including hematological malignancies. Thus far, cytogenetic findings in hematological neoplasms have been reported in only a few BS patients. We present the karyotypic findings in a BS patient diagnosed with acute myeloid leukemia (AML), FAB subtype M1, and a review of the literature, showing the preferential occurrence of total or partial loss of chromosome 7 in BS patients with AML or myelodysplastic syndromes (MDS).

Acute Disease↗

Clinically significant cardiac infiltration in acute leukemia, lymphocytic lymphoma, and plasma cell myeloma.

Cardiac infiltration by hematologic neoplasms leading to clinically significant cardiovascular disease is rare. Three such cases are described in this report, and it is suggested that rare manifestations of hematologic neoplasms may become more common in the future since these diseases are more amenable to therapy than heretofore. Cardiac involvement with hematologic neoplasms is of more than academic interest since this complication is likely to respond to radiotherapy.

Adult↗