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Biomedical subjects

R V Pierre

Publications and source records attributed to R V Pierre.

At least 19 recordsLinked to original sources

Refractory thrombocytopenia. A myelodysplastic syndrome that may mimic immune thrombocytopenic purpura.

The French-American-British classification scheme of myelodysplastic syndromes includes a category of refractory cytopenia that includes refractory thrombocytopenia (RTC). Because dysmegakaryopoiesis manifesting as an isolated cytopenia can be difficult to identify morphologically and because it may be accompanied by megakaryocytic hyperplasia, RTC may be confused with idiopathic thrombocytopenic purpura. A review of 1,220 cases of myelodysplastic syndromes at Mayo Clinic Jacksonville and Mayo Clinic Rochester from 1979 to 1990 yielded 9 cases (0.7%) of isolated thrombocytopenia (RTC) associated with clonal chromosome abnormalities. Review of 319 marrow chromosome analyses performed at the cytogenetics laboratory at Mayo Clinic Rochester from 1979 to 1990 for patients with low platelet count yielded two additional cases of RTC (0.6%). Of the 11 RTC cases, 3 previously had been misdiagnosed as idiopathic thrombocytopenic purpura. All patients had oval macrocytes in peripheral blood smears and abnormal megakaryocyte morphology in bone marrow aspirates, lacked antiplatelet antibodies, and did not have splenomegaly on clinical examination. The most common clonal chromosome abnormalities involved chromosomes 3, 5, 8, or 20. Steroid therapy was ineffective. Clinical and laboratory findings can establish the diagnosis of RTC and allow the physician to avoid recommending inappropriate therapy (steroids or splenectomy) for these patients.

Aged

Clinical-cytogenetic correlations in myelodysplasia (preleukemia).

Cytogenetic studies detected abnormalities in 107 (43%) of the 247 patients in this series. Some degree of overt clinical progression occurred in 55 patients (22%), this being 29% of those patients with cytogenetic abnormalities and 17% of those with normal chromosomes. The presence and complexity of a clonal cytogenetic abnormality correlated with shorter survival. In each clone category of a complexity classification (simple, complex, very complex), patients with some normal cells appeared to have better survival than those with none. In multiple regression analyses, the prognostic value of chromosomes was independent of (and second in importance to) the FAB type of myelodysplastic syndrome (MDS) whichever chromosome classification was used. Patients with refractory anemia (RA) had the lowest incidence of chromosome abnormalities and no cases were found to have only abnormal cells (AA). A greater proportion of patients with refractory anemia with an excess of blasts (RAEB) and RAEB in transformation (RAEB-t) had clonal abnormalities. Morphology alone is not at present able to distinguish between RA or refractory anemia with ringed sideroblasts and similar disorders that may not be MDS in the strict sense. Demonstration of a clonal cytogenetic abnormality remains a positive indication of the presence of the neoplastic nature of the disease.

Adult

Treatment of acute nonlymphocytic leukemia in the elderly with intermediate high-dose cytosine arabinoside.

Effective treatment of the elderly patients (greater than or equal to 65 years) with acute nonlymphocytic leukemia (ANLL) remains elusive and controversial. In the present study, single-agent Cytosine Arabinoside (ARA-C) was administered at an intermediate dose level (500 mg/m2 intravenously [I.V.] 1-hour infusion q12 hours for 12 doses) to 30 newly diagnosed and previously untreated patients. Complete remission was achieved in seven patients after the initial cycle of treatment, in two patients after retreatment, and in one patient after delayed recovery of his peripheral count over a 6-month period. The toxicity of this schedule was primarily hematologic, and the response rate was in keeping with that reported by other groups using aggressive multiagent regimens.

Age Factors

Chronic myelomonocytic leukemia: natural history and prognostic determinants.

A retrospective clinical review of 41 patients with chronic myelomonocytic leukemia revealed a median age of 66 years and a male:female ratio of 2.4:1. The disease was preceded by a myelodysplastic syndrome of a different subtype in 24% of the patients and transformed into acute leukemia in 24%. Splenomegaly was present in 54% of the patients and reached massive proportions in 24%. Chromosomal abnormalities occurred in 34% of those studied, most commonly in the younger age group; the most frequent were trisomy 8, monosomy 7, and deletions involving the long arms of chromosomes 20 and X. Polyclonal hypergammaglobulinemia was detected in 47% of the patients in whom serum protein electrophoresis was done. The median survival was 3 years. With use of univariate analysis, the statistically significant prognostic determinants were hemoglobin level, the "modified Bournemouth score," and bone marrow blast cell percentage. When these factors were subjected to a multivariate analysis, only bone marrow blast cell percentage was an independent prognostic determinant. Orally administered hydroxyurea controlled leukocytosis and splenomegaly in some patients without affecting the overall prognosis.

Adult

Immunocytochemical identification of cells in serous effusions. Technical considerations.

Immunocytochemical methods were evaluated in order to find a practical one for cell identification on cytologic preparation of body fluids. The effects of fixatives and Triton X-100 treatment on the preservation of cell-type-specific antigens and cell morphologic characteristics were also examined. The method using the alkaline phosphatase-antialkaline phosphatase (APAAP) complex as the indicator is recommended because of its high specificity and sensitivity. With this method, currently available and potentially useful monoclonal antibodies were examined, and the antibodies that were useful for the identification of normal and neoplastic cells commonly present in body fluids were selected for practical applications.

Antibodies, Monoclonal

Acute lymphoblastic leukemia in children: immunologic, cytochemical, morphologic, and cytogenetic studies in relation to pretreatment risk factors.

Thirty children with previously untreated acute lymphoblastic leukemia were studied prior to therapy to determine whether sheep erythrocyte (E)-receptor status correlated with clinical factors, cytochemical staining characteristics, FAB morphologic classification, and karyotype. Five patients (17%) with more than 50% E+ blasts had intense focal acid phosphatase staining and distinct clinical characteristics, including high leukocyte counts, mediastinal masses, and involvement of the central nervous system at diagnosis. Focal acid phosphatase activity was present in blasts of patients with greater than 20% E+ blasts, but this group had fewer poor risk factors. Morphologic and karyotypic features were not related to erythrocyte-receptor status, but the L2 morphologic appearance occurred more frequently in older patients (P less than 0.05). Erythrocyte receptors have both qualitative and quantitative clinical correlations in childhood acute lymphoblastic leukemia; however, E+ and E- groups are heterogeneous and E+ groups must be analyzed for other risk factors and relapse rates determined before firm conclusions can be made about erythrocyte rosetting as an independent risk variable.

Acid Phosphatase

Preleukemic syndromes.

Acute nonlymphocytic leukemia (ANLL) is preceded by a hematologic illness representing the "preclinical" stages of the disease in many patients. This "preclinical stage" or preleukemic stage is difficult to recognize by conventional hematologic morphologic techniques. A prospective study was carried out to determine whether cytogenetic studies would be helpful in the recognition of preleukemic states and whether the presence of cytogenetic abnormalities would have prognostic significance. A study of 284 patients with suspected preleukemia has yielded 62 patients with progression to overt ANLL. Cytogenetic abnormalities were found in 30% of suspected preleukemic patients, whereas 53% of the patients progressing to acute leukemia had cytogenetic abnormalities. These studies show that the presence of cytogenetic abnormalities aid in the recognition of preleukemia but are not specific for early leukemia. Patients with cytogenetic abnormalities are more likely to develop overt ANLL. Banded chromosome studies demonstrated cytogenetic abnormalities in the preleukemic phase in 13 of 26 patients. A variety of clonal chromosomal abnormalities were observed.

Acute Disease

Cytogenetics in malignant lymphoma.

There appear to be four primary areas of interest in the application of cytogenetic techniques to the study of malignant lymphomas: (1) the role of cytogenetics in the diagnosis of lymphoma in problem cases, (2) as an aid to the classification of malignant lymphomas, (3) whether specific chromosomal patterns will have prognostic significance for response to therapy or survival, and (4) the role of cytogenetics in staging of malignant lymphomas. A case of reactive lymphoid hyperplasia is reported in which cytogenetic studies demonstrated an aneuploid clone suggesting that cytogenetic abnormalities of lymphoma may precede the diagnostic histopathologic picture. The occurrence of 14q+ marker chromosomes in plasmacytic myeloma, plasma cell leukemia, malignant lymphomas, Burkitt's lymphoma, and ataxia-telangiectasia suggest that a common etiologic or pathogenetic mechanism may be present in some of these disorders. A preliminary pilot study of spleens removed at staging laparotomy for Hdgkin's disease suggests that cytogenetic studies may be able to detect Hodgkin's disease that is not apparent histologically. Further studies are required to provide answers to these areas of interest in cytogenetics in malignant lymphoma.

Chromosome Aberrations

Investigation of statistical decision rules for sequential hematologic laboratory tests.

A statistical data processing program for identifying patients who are likely to have abnormalities on various hematologic laboratory tests is described. The prediction of abnormal levels of serum vitamin B12, serum folate, transferrin saturation, and reticulocyte counts is based on a statistical analysis of the patient's age, sex, and routine blood cell measurements. The program was developed using data from normal-value studies and data from patients who had these laboratory abnormalities. The sensitivity and specificity of the program were evaluated in a controlled prospective study of about 5,000 ambulatory adult patients. The program's predictions also were compared with the laboratory tests requested by the patients' attending physicians. The program was most sensitive for predicting low serum vitamin B12 (74%) and low transferrin saturation (78%). In the prospective evaluation, the predictive values varied from 11% for predicting low serum folate to 65% for predicting low transferrin saturation.

Adult

Atypical lymphoid leukemia in ataxia telangiectasia.

We observed two sisters with ataxia telangiectasia, one of whom developed an atypical subacute lymphocytic leukemia characterized by atypical lymphocytes and absence of palpable lymphadenopathy or hepatosplenomegaly. The lack of organomegaly in this patient may have been due to the underlying ataxia telangiectasia, which was associated with lymphoid hypoplasia. Cytogenetic studies showed a marker chromosome 14 [t(14q11:14q34)] in both patients. The sister with leukemia had other complex chromosomal aberrations in addition to the marker chromosome 14 that were stable for more than 14 mo before the patient's death from complicating infection. The development of atypical T cell leukemia has not been previously described in ataxia telangiectasia. This case further illustrates the interesting interrelationships amoung immunosuppressed states, development of lymphoid malignancy, and an emerging pattern of a propensity to chromosome 14 abnormalities in various lymphoid malignancies.

Ataxia Telangiectasia

Platelet satellitism as a cause of abnormal hemalog D differential results.

Platelet satellitosis resulted in an elevated high-peroxidase-activity value (9.9% versus normal range 0 to 3.65%) of the automated leukocyte differential count performed by the Technicon Hemalog D. Platelet satellitism occurred in Wright-stained smears of EDTA-anticoagulated blood, as well as in the effluent of the peroxidase channel of the Hemalog D. All platelets took up the perosidase stain. The rosette-like clusters of platelets and neutrophils were interpreted as single, large, intensely stained leukocytes resulting in the elevated high-peroxidase-activity value.

Autoanalysis

Routine erythrocyte measurements in diagnosis of iron-deficiency anemia and thalassemia minor.

A study was made of the routine electronic measurements of erythrocyte size and hemoglobin concentration in blood samples from 122 patients with decreased transferrin saturation and 66 patients with elevated levels of hemoglobin A2 or F. The medical histories of these patients were reviewed to identify 52 cases of uncomplicated iron-deficiency anemia and 39 cases of uncomplicated thalassemia minor. Four decision functions were compared for separating these two disorders. The functions evaluated were: D.F'. = MCV--[5 X Hb]-RBC; ratio MCV/RBC; ratio MCH/RBC, and RBC. The rules performed better in the uncomplicated cases than in the routine laboratory defined cases. Only minor differences in the performances of the various decision functions were observed. None was sufficiently accurate for final diagnosis, but they should have value in screening patients and in determining which additional test should be considered.

Anemia, Hypochromic

Lymphocyte-epithelial cell interactions in oral mucosal inflammatory diseases.

Lymphocyte cytotoxicity for target cells is a method for evaluating specific lymphocyte stimulation. In vitro lymphocytotoxicity has been demonstrated in chronic ulcerative colitis and granulomatous colitis, polymyositis and dermatomyositis, systemic scleroderma, recurrent aphthous stomatitis, and periodontal disease. We have investigated lymphocytotoxicity in 36 patients with various oral inflammatory diseases using an automated cell-counting system. This investigation demonstrated in vitro lymphocytotoxicity for gingival epithelial target cells by aggressor lymphocytes harvested from patients with recurrent aphthous stomatitis and periodontal disease. This effect was not seen when the lymphocytes were harvested from normal subjects or from patients with other oral mucosal inflammatory diseases. The automated cell-counting system corresponded very well with the assay technique of exclusion of supravital dye.

Antigen-Antibody Reactions

Endomyocardiopathy with eosinophilia.

Five patients were seen at the Mayo Clinic over an 8-year period with the following complex of clinical and morphologic features; striking eosinophilia, cardiomyopathy, hepatosplenomegaly, and either a rapidly fatal or a prolonged, debilitating illness. In recent years, controversy has raged over the precise designation of this syndrome, with proposals ranging from eosinophilic leukemia to hypereosinophilic syndromes. To focus on the major target organ of the disease, we have favored the term endomyocardiopathy with eosinophilia. Experience with these five patients showed that (1) eosinophilia can persist for many years before symptoms appear; (2) progressive restrictive cardiac disease was the major cause of death and debility; (3) osmiophilic cytoplasmic inclusions are present in eosinophils of these patients and also in cells from other patients with marked eosinophilia; and (4) echocardiography may prove to be a useful noninvasive tool to diagnose and follow the progress of cardiac involvement. Although none of these patients was thought to have leukemia, intensive therapy with steroids or cytotoxic agents, or both, is considered necessary to control the progression of the disease.

Adolescent

Multiple myeloma and acute leukemia associated with alkylating agents.

Rapidly fatal acute myelomonocytic leukemia developed in five patients with multiple myeloma who were treated with melphalan for 28 to 54 months. In each patient, multiple myeloma responded to therapy and progress was satisfactory until the development of acute leukemia. At postmortem examination, leukemic infiltration of organs was seen, and there was little or no evidence of myeloma. Consideration of these cases and a review of the literature suggest that these circumstances represent the development of acute myelomonocytic leukemia rather than plasma cell leukemia; there also appears to be an increased incidence of acute leukemia in multiple myeloma, probably related to the alkylating agent.

Acute Disease

The platelets in preleukemia and myelomonocytic leukemia. Ultrastructural cytochemistry and cytogenetics.

Light and electron microscopic studies of platelets from 16 patients with myelomonocytic leukemia or "preleukemia" revealed major morphologic alterations in 15 and minor ones in 1. Although variable in severity from case to case, the changes present followed a distinct pattern. In most cases there were two platelet populations, one morphologically normal and one morpholigically abnormal. The most salient changes pertained to size (giant forms), shape (the platelets being rounded and probably spheroidal), decrease or absence of the microtubules, and increase in immature elements. A striking feature was the variation in size and shape of the granules, with truly giant forms (up to 2.5 mum) being present. In cytogenetic studies in 14 cases, there was no correlation between the chromosomal changes and the various types of platelet anomalies.

Adult