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PubMed1983

[Acute leukemia and breast cancer : apropos of 12 cases observed in the Department of Oncology at the Henri Mondor Hospital].

The authors report 12 cases of acute leukemia observed after breast cancer. 4 patients received only adjuvant radiotherapy, whereas the other eight received both chemotherapy and radiotherapy. Acute leukemia appeared with a mean time of 5.5 years after the detection of breast cancer and was preceded in 7 cases by isolated pancytopenia during 4 months. Acute leukemias were always non lymphoblastic and myelofibrosis was very frequent. A complete remission was obtained at three patients out of the seven treated. The mean survival time was 5.6 months. The existence of acute leukemia after chemo-and/or radiotherapy poses several problems. The detection of patients with a high risk of leukemia by different methods such as cytogenetic, studies of dysmyelopoietic symptoms, is actually often too late occurring during preleukemia states of bad prognosis. We also need to know the exact incidence of secondary leukemia after treatment of breast carcinoma and the real benefit of such treatment.

Acute Disease↗
PubMed1982

Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia.

Structural abnormalities of the X chromosome are rarely found in neoplastic disorders. We describe three patients with a history of idiopathic acquired sideroblastic anemia (IASA); each one had an abnormal clone of cells in the bone marrow, characterized by a structurally abnormal X chromosome. In two of these patients, the predominant karyotype was 47,X,2idic(X)(q13); in the other patient, it was 46,X,t(X;11)(q13;p15). Inasmuch as all three of these cases involved chromosome band Xq13, as did two previously published cases, we suggest that band Xq13 may be more prone to structural rearrangement than other X chromosome bands in hematologic disorders. The common Xq13 chromosome breakpoint and clinical presentation (IASA) among these three patients and the occurrence of an X-linked type of sideroblastic anemia may suggest that an association exists between X chromosome abnormalities and IASA. Perhaps alteration of a gene or chromosome structure in or near band Xq13 predisposes to development of IASA. The fact that two of these patients had preleukemia and the third had overt acute leukemia may imply that patients with IASA and X chromosome abnormalities have a poor prognosis. Cases of IASA without associated X chromosome abnormalities are known; thus, if an association between IASA and an abnormal X chromosome does exist, most likely it involves only some patients with IASA.

Adult↗
PubMed1981

[Risk factor benzene (author's transl)].

Nearly one hundred years ago clinical and epidemiological studies have already assigned benzene as a markedly haematotoxic substance. Nowadays benzene is known as an important professional noxa, which is straight off directed against the haematopoietic system, essentially to a dose-time-effect. By this it can be taken as a model also for other noxious substances. Similar solvents often contain so-called "hidden benzene", that means not declared benzene, so that the consumer don't know what dangerous substance are available for his personal use. Impairment caused by benzene mostly are manifested earliest after months, years or for tens of years, and the point is, that these haematopoietic disorders are irreversible disturbances of the haematopoietic stem cell compartment. The consequence of this fact is a deep involvement of the proliferation of the erythro-, mono-, granulo- and thrombopoietic cell lines, mostly with the predominance of one of these myeloproliferative cell systems. In the further progression of the impairments due to benzene three different clinical pictures can be observed: the aplastic bone marrow syndrome (i.e. aplastic anemia), the haematopoietic dysplasia (i.e. preleukemia) and the acute leukemias (with the subtypes erythroleukosis, myeloblastic-promyelocytic or myelomonocytic from respectively). Also the transition from one clinical picture to another is possible.

Anemia, Aplastic↗
PubMed1980

The preleukemic syndrome. I. Clinical and hematological findings.

A long-term prospective study including 151 patients with preleukemia was performed in 1958--79. The series comprised 78 women and 73 men with a mean age of 79 and 72 years, respectively. Acute leukemia was the cause of death in 35 patients, 61 died of infections and/or hemorrhage or of unrelated causes. The mean interval between the initial diagnosis and death from acute non-lymphocytic leukemia was 36 months (range 2--121). Pitfalls in diagnosis are extensively discussed. The most striking was the advanced age of the patients. The presence of pancytopenia at the time of diagnosis was not predictive for subsequent blastic transformation.

Adult↗
PubMed1994

Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras.

Children with neurofibromatosis, type 1 (NF-1) are at increased risk of developing malignant myeloid disorders and their bone marrows frequently show loss of the normal allele of the NF1 tumor-suppressor gene. NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. We used a genetic approach to test the hypothesis that NF1 negatively regulates myeloid cell growth through its effect on Ras. This model predicts that, if RAS mutations and loss of NF1 function deregulate myeloid growth by the same biomechanical mechanism, then activating RAS mutations will be restricted to children with malignant myeloid disorders who do not have NF-1. We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS. The incidence of RAS mutations was 21% (12 of 55) in patients without NF-1 and 0% (zero of 16) in children with NF-1 (P = .04). Among the 55 patients who did not have NF-1, we found RAS mutations in four of 27 with Mo 7, in five of 24 with JCML, in two of 3 with AML, and in a patient with myeloproliferative syndrome (MPS). These data from primary human cancer cells provide strong genetic evidence that NF1 limits the growth of myeloid cells by regulating Ras.

Alleles↗
PubMedDate not supplied

Epidemiology of acute promyelocytic leukemia.

BACKGROUND: The estimated incidence of acute promyelocytic leukemia (APL) is approximately 6 cases per 10 million people per year with no apparent differences between sexes. The age of APL cases is younger than that of other acute myeloid leukemias (AML). Spatial and temporal clusters of APL have been reported. These observations suggest a possible selective role for environmental and/or occupational factors in APL development. METHODS: A multicenter case-control study was carried out on risk factors for acute leukemias and preleukemias. In this report data related to APL are selectively analyzed from the larger study to identify specific risk factors. RESULTS: The case-control study on 38 cases of APL showed a strong association with shoemaking (odds ration 6.3, 95% confidence interval 1.3-31.1). A moderate leukemogenic effect from living in houses built with tuff, a polous building material containing gamma-emitting radionuclides and having a high radon concentration, and from using hair dyes was also suggested. CONCLUSIONS: These data, together with the reported spatial and temporal clustering of APL, support the hypothesis of specific environmental and/or occupational risk factors for APL among other AML subtypes and indicate the need for additional ad hoc multicenter studies.

Adolescent↗
PubMed1983

Smoldering acute granulocytic leukemia. Observations on its natural history and morphologic characteristics.

In this prospective study, 24 patients with smoldering acute granulocytic leukemia received no specific treatment. Median survival duration from diagnosis was 9.29 months. Fourteen patients died of infection, four died of hemorrhage, two (8%) progressed to aggressive acute leukemia, and three remain alive at 36, 32, and 10 months. No survival predictions could be made from the severity of leukopenia, thrombocytopenia, or both. Neither sepsis nor hemorrhage, as causes of death, segregated into short- or long-term survivors (9.0 and 8.75 months' median survival, respectively). Thirteen patients (59%) had French, American, and British M2 subclassification of acute granulocytic leukemia. The following marrow findings distinguished this entity from preleukemia and other dysplastic states: clustering of stem cells; percentage usually between 20% and 40%; and Auer rods. The use of aggressive chemotherapy v only supportive measures in this condition remains unsolved.

Adult↗
PubMed1981

Ultrastructural characteristics of therapy-related acute nonlymphocytic leukemia: evidence for a panmyelosis.

Leukemic cells from 13 patients with therapy-related acute nonlymphocytic leukemia (ANLL) were studied by electron microscopy. All of the patients had radiotherapy, and/or alkylating agent chemotherapy for other neoplastic disease 25 to 182 months prior to the diagnosis of ANLL. All cases manifested ultrastructural evidence of a panmyelopathy. All marrow cell lines exhibited nuclear--cytoplasmic asynchrony and abnormalities of cell size. Developing granulocytes exhibited decreased primary and/or secondary granule formation and abnormal granules characterized by irregular shape, large size and internal membranous lamellae. Monocytes showed perinuclear bundles of microfilaments. In some cases, the predominant leukemic blasts showed evidence of early basophil granule development which was not appreciated in light microscopy. Abnormalities in erythroid cells included abundant intracristal mitochondrial iron, large vacuoles, infoldings of redundant membrane and membrane-bound nuclear blebs and intranuclear clefts. Megakaryocytes manifested decreased numbers of granules and demarcation membranes. Excessively large platelets with decreased or abnormal granules were identified; giant compound granules with irregular contour and variable electron density were present. Several of the changes in the developing hematopoietic cells were similar to those described in preleukemia and in certain nonneoplastic disorders. The consistent panmyelosis in therapy-related ANLL together with several uniform clinical features defines a specific clinicopathologic entity.

Adult↗
PubMed1982

Erythroleukemia and other hematologic complications of intensive therapy in long-term survivors of small cell lung cancer.

Eight patients with small cell bronchogenic carcinoma treated with intensive combination chemotherapy, with and without radiotherapy, have been followed for a minimum of two and a half years without relapse. One patient, after a prodrome of macrocytic sideroblastic anemia, leukopenia, and thrombocytopenia, experienced erythroleukemia 34 months after starting chemotherapy, and cytogenetic studies revealed extensive chromosomal abnormalities. Another patient had persistent macrocytic anemia and pancytopenia two years after cessation of therapy. The remaining six patients had normal peripheral blood smears and cell counts. A significant incidence of preleukemia syndromes and acute leukemia appearing as late complications in intensively treated small cell lung cancer patients requires confirmation in larger series of long-term survivors. Prospective determination of marrow karyotype abnormalities may help to identify patients at greatest risk for developing secondary leukemia.

Aged↗
PubMed1983

Acute febrile neutrophilic dermatosis (Sweet's syndrome) and myeloproliferative disorders.

Acute febrile neutrophilic dermatosis (ND) consists of the abrupt onset of red, tender, cutaneous plaques on the face, extremities, and upper trunk, accompanied by fever, malaise, and neutrophilic leukocytosis. Histologically, there are distinctive, dense, dermal infiltrates of neutrophils. Response to systemic steroids is dramatic. This report describes four patients with leukemia or preleukemia and ND (LND), reviews reports of 12 similar patients, and compares LND with ND in otherwise healthy individuals (idiopathic ND, IND). Although lesions of LND more frequently had vesiculobullous appearances or location on mucous membranes, this study showed no consistent difference between LND and IND with regard to cutaneous signs, symptoms, histologic findings, and response to therapy. The first episode of LND either preceded or followed documentation of the myeloproliferative disorder, and the most common associated hematologic conditions were acute myeloid or myelomonocytic leukemia. Moderate to severe anemia was present in nine of ten patients whose first episode of LND preceded the discovery of the hematologic condition by eight months or less. The presence of anemia is the most obvious and readily detectable difference between LND and IND. The possibility of an underlying myeloproliferative disorder should be considered in all patients with ND, and LND should not be confused with infectious complications in patients known to have myeloproliferative disorders.

Acute Disease↗
PubMed1985

Treatment of acute leukemia in adults with chemoradiotherapy and bone marrow transplantation.

The use of supralethal chemoradiotherapy followed by marrow transplantation has progressed from being an experimental approach applied only to a limited number of end-stage patients to an important therapeutic option appropriate for many adults with a variety of hematologic malignancies. With the use of transplantation, 10% to 30% of patients with relapsed leukemia and approximately 50% of patients with acute nonlymphoblastic leukemia in first remission can be cured. Cures have also been seen in a variety of other hematologic malignancies, including chronic granulocytic leukemia, preleukemia, hairy cell leukemia, and malignant lymphoma. Transplantation is currently limited by the need for a suitable marrow donor; by the complications of the transplant procedure, including infection, graft-versus-host disease, and the toxicities of intensive chemoradiotherapy; and by the risk of recurrent disease. Some of these limitations will likely be overcome as a result of current research. The use of partially matched family members and matched unrelated donors will make transplantation available to more patients. Some forms of posttransplant infection, including those associated with herpes simplex and cytomegalovirus, can now be prevented or treated. Improved methods of controlling graft-versus-host disease including T-cell depletion of marrow and the use of more effective immunosuppressive agents, as well as a better understanding of the toxicities of the preparative regimens, are making the transplant procedure safer and more tolerable. Finally, the development of better preparative regimens and transplantation earlier in the patient's disease course will likely allow for a larger percentage of patients to be cured.

Acute Disease↗
PubMed1987

Treatment-related cancers after gynecologic malignancy.

Second malignancies are one of the known complications of cancer treatment. Several recent studies which have quantified the risk of treatment-induced cancers following gynecologic malignancies are reviewed. After cervical cancer, there is a 9% excess risk of second cancers, of which only 5% could be attributed to radiation therapy. Most of the treatment-related malignancies after cervical or endometrial cancer are solid tumors occurring within the radiation field. Following both cervical and endometrial cancer, there is a small increased risk of leukemia associated with radiation therapy. In contrast, after ovarian cancer, there is significantly increased risk of leukemia related to treatment with alkylating agents, which varies by drug type and total dose. The cumulative risk of leukemia and preleukemia following single agent melphalan is 11.2% +/- 2.6% at ten years; the risk after cyclophosphamide is 5.4% +/- 3.2%. Overall, the risk of second malignancies following treatment of gynecologic cancers is small.

Antineoplastic Agents↗
PubMed1985

Malignancies due to occupational exposure to benzene.

There is no doubt about the leukemogenic effect of benzene in man. The evidence is as follows: (1) The incidence of leukemia in shoeworkers exposed to benzene in a period of 8 years in Istanbul was 13.6/100,000, which is significantly higher than that for leukemia in the general population. (2) Following the phase-out of benzene in Istanbul, the number of leukemic workers decreased and none were reported in the subsequent 3 years. (3) The development of leukemia in pancytopenic patients with benzene exposure was observed in 13 out of 51 patients. (4) The differences in the distribution of the types of leukemia in individuals exposed and in nonexposed groups were as follows: acute leukemia 96.1% in the former group, and 46% in the latter group. The high percentages of acute erythroleukemia and preleukemia were other interesting findings in the exposed group. (5) Two cases of leukemia were observed in a 6-year period at a tire cord manufacturing plant with 550 workers. At one location in the plant the concentration of benzene measured by gas chromatography was nearly 110 ppm. Additionally, we have studied 12 cases of malignant lymphoma, four cases of multiple myeloma, and six cases of lung cancer, all of whom were chronically exposed to benzene. The possible role of benzene in the etiology of these malignancies is discussed.

Adult↗
PubMed1985

Acute megakaryoblastic leukemia in Down's syndrome: report of a case and review of cytogenetic findings.

A case of a child with trisomy 21 and acute megakaryoblastic leukemia (AMBL) is reported. Histological examination of the bone marrow showed progressive fibrosis and replacement with megakaryoblasts. The diagnosis was confirmed by platelet peroxidase reaction and immunofluorescent staining with anti-factor VIII. Serial cytogenetic studies using banding techniques at various stages during the course of the disease (preleukemia, leukemia, remission, and relapse) showed several chromosomal abnormalities (unbalanced translocation between chromosomes 1 and 4 leading to trisomy 1q, trisomy 7q, monosomy 7p, and a reciprocal translocation between chromosomes 10 and 16). AMBL in childhood is probably more common than previously reported. Any association between AMBL and a particular cytogenetic abnormality must await further cytogenetic studies, specifically those employing banding techniques.

Acid Phosphatase↗
PubMed1988

Hematologic and clinical features of patients with chromosome 5 monosomy or deletion (5q).

This paper analyzes the hematologic features and outcome of 13 patients with chromosome 5 abnormalities (monosomy 5 or deletion of 5q), either isolated or with additional anomalies. Among four patients with isolated del (5q), two had a stable refractory macrocytic anemia with thrombocytosis (5q-syndrome). All nine patients with complex karyotypes had acute leukemia or refractory anemia with excess of blasts in acute transformation; two cases were TdT-positive, with a lymphoid or a mixed phenotype. In seven patients, preleukemia preceded overt leukemia, and in six, a prior therapeutic, or occupational exposure to mutagens/carcinogens had occurred. Additional chromosome 7 abnormalities were seen in four cases. The median survival of patients with complex karyotypes was 19 months from the time of diagnosis of the hematologic disorder and 5 months from the time of identification of the chromosome 5 abnormality. Pathogenetic implications of the chromosome 5 monosomy or del (5q) through a proto-oncogene activation and the putative hemopoietic stem cell involvement in a clonal disease are discussed.

Adult↗
PubMed1994

Evaluation of radiation injury by 1H and 31P NMR of human urine.

1H and 31P NMR techniques were applied to study the changes in metabolite profiles in human urine resulting from radiation exposure following the Chernobyl reactor accident. In cases of acute leukemia and different accumulated doses of external radiation (from 0.20 to 4.00 Sv), the proton spectra were classified on the basis of the peaks due to N-trimethyl groups, creatinine, citrate, glycine, and hippurate. Unidentified resonances were observed between 15.9 and 21.4 ppm in six phosphorus spectra of patients with preleukemia and acute leukemia. Characteristic spectral changes were similar for external radiation and incorporation-induced internal irradiation. The spectral patterns described may serve as a criterion of radiation injury.

Accidents↗
PubMed2001

Genetic imbalances in preleukemic thymuses.

To understand the molecular mechanisms involved in preleukemia, the suppression subtractive hybridization method was used in a murine radiation-induced thymic lymphoma model. Seventeen mRNAs overexpressed in preleukemic thymuses were identified: mouse laminin binding protein (p40/37LBP), E25 protein, Rattus norvegicus clone BB.1.4.1, profilin, poly(A) binding protein (PABP), mouse high mobility group protein 1, topoisomerase I, clusterin, proteasome RC1 subunit, rat prostatein C3 and C1 subunits; two ESTs and four unknown genes. The overexpression of PABP, clusterin, profilin, and the p40/37LBP mRNAs was confirmed in preleukemic thymuses and can be related to some cellular events observed during the preleukemic period, i.e., alterations of cell cycle and apoptosis properties. The p40/37LBP and 67-kDa laminin receptor proteins were upregulated during the preleukemic period. The data suggest that additional studies on p40/37LBP and 67-kDa laminin receptor regulation are required to evaluate their potential role in the lymphoma prevention by TNF-alpha and IFN-gamma.

Animals↗
PubMed1976

The use of the Robinson in vitro agar culture assay in adult acute leukemia.

Previous in vitro classification of adult acute leukemia incorporating morphology has been complex and difficult to understand. We have devised a simplified classification based solely on leukemic proliferation in vitro. Forty-four patients with adult acute leukemia previously untreated were included in this study and received identical chemotherapy. Three in vitro groups were recognized. The complete remission rate (CR) was 77% in the 13 patients with no leukemic growth in vitro (Group 1), 81% in 16 patients with leukemic cell growth but aggregated of 20 cells or less (Group 2) and only 27% in the 15 patients with aggregates of greater than 20 (Group 3). There was a highly significant difference in complete remission rates between Group 3 and the other 2 groups (p less than 0.01). Linear logistic regression analysis demonstrated the independence of the in vitro growth from other prognostic variables. The cause of death in failures suggested that this system detects resistance to the chemotherapy. Similar multifactorial analysis including in vitro agar culture may help to predict for chemotherapy response in preleukemia and leukemia with a low blast cell infiltrate when cytotoxic therapy is clinically indicated.

Acute Disease↗