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Biomedical subjects

L Penchansky

Publications and source records attributed to L Penchansky.

At least 37 records · Page 2Linked to original sources

Down's syndrome and mixed acute leukemia in infants.

The routine use of panels of monoclonal antibodies has been complementary to the French-American-British (FAB) leukemia classification, and has unmasked the occurrence of mixed acute leukemia (myeloid-lymphoid). It is widely accepted that children with Down's syndrome (DS) have a high incidence of acute leukemia. There is an extensive body of literature emphasizing the cytogenetic findings in these children. However, information as to the immunophenotype is often limited to the lymphoid surface determinants. The authors report two children with DS whose leukemic blasts were studied with a panel of 17 monoclonal antibodies (myeloid, lymphoid, and megakaryocytic) by flow cytometric examination and were classified as biphenotypic acute leukemia. The blast population coexpressed myeloid and T-cell surface markers. The lymphoid origin was ruled out on the basis of negative terminal deoxynucleotidyl transferase and molecular analysis demonstrating germline configuration for the JH and beta TCR genes.

Antibodies, Monoclonal↗

Multiple lineage reactivity in childhood leukemia.

The leukemia cells from 63 children with acute leukemia were evaluated by flow cytometry with a panel of monoclonal antibodies that included lymphoid and myeloid lineage-specific antigens. Surface markers from patients with acute lyphocytic leukemia (ALL) did not correlate with their FAB classification except for L3 leukemia. Myeloid leukemias of FAB class M1-M4 were positive for CD13 and CD33, whereas CD14 and MY8 were only detected in FAB class M4 leukemia. Mixed leukemias were subclassified as intralineage (B+T+) or interlineage (B+ or T+/M+). Interlineage leukemias represented 5.6% of ALLs, and all patients are alive after treatment with ALL protocols. Interlineage mixed leukemias represent 7.9% of all leukemias occurring in 3.7% of ALLs and 33% of acute myeloid leukemias (AMLs). All children with mixed interlineage leukemias are alive after treatment with the protocol for the dominant leukemia; however, follow-up periods are too short to predict final outcome. The high proportion of mixed interlineage leukemias in AMLs supports Greaves' theory of lineage promiscuity, that is, there is a normal period of hematopoietic development when individual cells co-express multiple lineage antigens on the cell surface.

Acute Disease↗

Three infants with acute megakaryoblastic leukemia simulating metastatic tumor.

The diagnosis of acute megakaryoblastic leukemia (AMKL) (M7, French-American-British [FAB] classification) has rarely been made in children due, in part, to its pleomorphic morphology and ability to mimic other malignancies common in the pediatric age group. Three infants are described who had thrombocytopenia and the classical criteria of metastatic solid tumor in the bone marrow: patchy infiltration by cohesive clusters of cells with high nuclear cytoplasmic ratio and myelofibrosis in the bone marrow biopsy infiltrated area. This finding prompted clinical evaluation for solid tumor. The megakaryocytic lineage was ascertained by immunocytochemical studies and/or electron microscopic examinations of the bone marrow aspirates. The blasts in all three patients showed cytogenetic abnormalities that also were demonstrated by quantitative DNA analysis. None of the infants had Down's syndrome. Two of the patients are alive; one is off of therapy and the other is in remission. The third patient was transferred to another institution and lost to follow-up. Two children had wheezing that disappeared in remission. It is proposed that the clinical symptoms may be due to a substance produced, stored, or released by the leukemic cells.

Adolescent↗

Immunophenotyping in the classification of acute leukemia in adults. Interpretation of multiple lineage reactivity.

Fifty-nine adult patients with acute leukemia were classified using a combination of the French-American-British (FAB) criteria and characterization by immunophenotyping using flow cytometric study. The authors identified 51 patients with acute myeloblastic leukemia and eight with acute lymphoblastic leukemia. This procedure permitted lineage assignment in leukemias that otherwise might have been unclassifiable. In addition, the authors demonstrated that the leukemic blasts of 29% of patients with myeloblastic disease exhibited one or more T-cell antigens on their surface. The use of immunophenotyping has greatly enhanced the authors' ability to correctly identify the lineage of acute leukemias. The data, however, must be interpreted with caution with respect to diagnosing acute mixed lineage leukemias and must be integrated with the morphologic and cytochemical evaluation of traditional classification schemes. The possible significance of T-cell markers in myeloblastic leukemia is discussed.

Adult↗

Microgranular promyelocytic leukemia: a multiparameter examination.

Six cases of microgranular variant acute promyelocytic leukemia (M3v) were studied by use of a multiparameter approach including morphology, cytochemistry, flow cytochemistry, flow cytometry, cytogenetics, and gene rearrangement. Three of six cases demonstrated both myeloid and monocytoid associated surface markers by flow cytometry. One of six cases had strong alpha-naphthyl-butyrate esterase (alpha-NBE) activity in addition to myeloperoxidase activity. There was no correlation between percentage of positive monocytoid surface markers and intensity of cytoplasmic alpha-NBE activity. Four of six cases also had a T-cell-associated surface antigen. Further studies indicated that the T-cell markers appeared to be on the promyelocytes and that the T-B receptor gene was not rearranged. Similarly, cytogenetics studies indicated only one clonal abnormality t(15q+; 17q-). Whether these cases represent true "lineage infidelity" remains to be answered. Future important studies are needed on normal hematopoietic progenitor cells at early stages of development and childhood to study lineage-specific characteristics and to determine whether co-expression normally exists during early development.

Adult↗

Thrombocytosis as a presenting feature of acute lymphoblastic leukemia in childhood.

To determine the incidence of thrombocytosis at presentation in acute lymphoblastic leukemia (ALL), medical records of all children diagnosed at the Children's Hospital of Pittsburgh from 1980 to 1987 were reviewed. Out of 217 such patients, 7 (3.2%) had platelet counts greater than 400,000/mm3. All of the seven were boys compared with a male:female ration of 1.4:1 in the entire ALL population. Other than sex, no characteristics were clearly associated with thrombocytosis, including white blood cell count, hemoglobin, lymphoblast morphology, and immunologic or chromosomal markers. Apart from ALL, no inflammatory or infectious process which might have caused a thrombocytosis, was detected in any of these patients. The period of induction therapy was notable for the preservation of platelet counts greater than 20,000/mm3 in all patients. However, of the seven children with thrombocytosis, two had major induction complications: one, a cavernous sinus thrombosis; and the other, gastrointestinal bleeding with duodenal perforation. We conclude that thrombocytosis at diagnosis can be seen in children, particularly boys, with ALL. Based on small numbers, this group of patients may be at risk for major events during induction therapy. Large numbers, longer follow-up, and platelet function studies on similar patients will be of interest.

Biopsy↗

Immunogold staining in bone marrow aspirate for the study of surface markers in acute lymphoblastic leukemia.

The diagnostic value of phenotyping acute lymphoblastic leukemia (ALL) of childhood using the immunogold staining method (IGS) was assessed in 34 consecutive new ALL patients seen at Children's Hospital of Pittsburgh during a 14-month period. IGS proved to have considerable value in the diagnosis and classification of ALL. It allowed a sharp and clear identification of surface antigens, documented surface antigen heterogeneity in normal and abnormal cells, and provided a permanent record. The combination with cytochemistries allowed further cytoplasmic identification and correlation. This method does not require sophisticated equipment and can be performed in any laboratory, thus enabling results from different institutions to be more readily compared.

Adolescent↗

Flow cytometry in the diagnosis of acute leukemia.

Fifty cases of acute leukemia were analyzed by means of flow cytometry. The results obtained were correlated with morphology and routine cytochemistries. The panel selected was useful in classifying an acute leukemia as acute lymphocytic (ALL) or acute nonlymphocytic (ANLL), which is of primary importance for therapeutic considerations. Common ALL (CALLA) (J5) was a good marker for classifying the leukemia as ALL. Monoclonal antibodies (MoAbs) T1 and/or T11 further delineated the lymphoid leukemia as T-cell ALL while MoAbs B4 or B1 delineated the lymphoid leukemia as non-T-cell ALL. Eighteen cases of ALL were diagnosed and consisted of five cases of T-cell ALL and 13 cases of non-T-cell ALL. Both the T-cell ALL cases and non-T-cell ALL cases were found to be heterogeneous and could be further subgrouped by phenotypic expression with additional MoAbs in the panel. A monoclonal antibody panel consisting of My4, My7, My9, Mo1, and Mo2 was useful in characterizing an acute leukemia as ANLL. This panel was less useful in distinguishing myeloid from monocytic subtypes although My4, Mo1, or Mo2 when present, appeared to favor a monocytic component. Of interest, a case of biclonal leukemia with two distinct blast populations on the flow cytogram was discovered. Morphology alone was successful in diagnosing ALL from ANLL in 35 cases (70%). It was not useful in distinguishing non-T-ALL cases from T-ALL cases. The ambiguous cases could be resolved by cytometric means. Flow cytometry has much to offer as a diagnostic aid in the evaluation of acute leukemia.

Acute Disease↗

Use of the Technicon H-1 in the characterization of leukemias.

The Technicon H-1 is a hematology analyzer that performs a complete blood cell count and white blood cell differential using both cytochemistry and flow technology. Two white blood cell cytograms are produced based on peroxidase activity and nuclear characteristics of the cells. Ninety cases of leukemia were studied. The 25 cases of acute lymphocytic leukemia (ALL) could be distinguished from the 39 cases of acute nonlymphocytic leukemia as the lymphocyte percentage was greater than 50% in the ALL cases and the mean peroxidase index value was 0 in 80% of the cases. The ALL cases and the chronic lymphocytic leukemia cases also had different cytogram patterns. Subtypes of acute nonlymphocytic leukemia could not be absolutely distinguished, although promyelocytic leukemias (M3) had characteristic cytograms and a monocyte percentage above 15% suggested a monocytic component (M4 or M5). Chronic myelogenous leukemia likewise seemed to have a recognizable pattern. Since a sample takes only 60 s to process, information is readily available. The unique data available from this instrument should provide a significant advancement in the automated hematology field.

Adolescent↗

Simultaneous evaluation of terminal deoxynucleotidyl transferase and myeloperoxidase in acute leukemias using an immunocytochemical method.

The classification of acute leukemia is important for the selection of optimal therapy. Classification often rests on morphologic, cytochemical, and immunologic criteria, and the marker enzyme terminal deoxynucleotidyl transferase (TdT) has been considered to be a reliable indicator of lymphoblastic leukemias. Because TdT-positive cells sometimes are seen in leukemias otherwise identified as myeloblastic, the authors evaluated blasts identified as myeloid by the presence of myeloperoxidase (MPO) for the simultaneous expression of TdT. The blasts in the bone marrow aspirate or peripheral blood of unselected patients with hematologic malignancies were evaluated and 60 cases are shown. The French-American-British system and, in some patients, cytochemical and immunologic studies were used to classify the leukemias. The authors demonstrated that blasts simultaneously contained MPO and TdT in 29% of patients with acute myeloblastic leukemia and 3% of patients with acute lymphocytic leukemia (ALL). This finding supports the hypothesis that TdT is an expression of cell primitivity rather than a marker for lymphoblastic cells.

Adolescent↗

Characterization of lymphocyte subpopulations in human cord blood using the immunogold staining technique.

Lymphocyte subpopulations in human cord blood have been examined using monoclonal antibodies, visualized with immunogold. The proportions of T11, T4, T8, and B1 cells in cord blood are very similar to values in adult peripheral blood. Some evidence of lymphocyte immaturity in cord blood is suggested by the presence of 12% CALLA-positive cells and the sum of T4 and T8 cells significantly exceeding the number of T11 cells; however, there were no TdT-positive cells. The presence of CALLA-positive lymphocytes in normal cord blood should be borne in mind when investigating blood smears from neonates for congenital leukemia.

Antigens, Surface↗

Terminal deoxynucleotidyl transferase activity in acute leukemia: a study of 100 cases comparing an immunoperoxidase (PAP) vs immunofluorescent method.

A comparison between the immunofluorescent (IF) method for terminal deoxynucleotidyl transferase (TdT) activity and the immunoperoxidase (IP) method by peroxidase-anti-peroxidase (PAP) technique was done for 100 cases of acute leukemia. For the acute lymphoblastic leukemias (ALL) there was agreement in 93% of the cases. However, the IP method detected 51/55 (93%) TdT+ cases versus 47/55 (85%) by the IF method. For the acute nonlymphocytic leukemias (ANLL), there was an agreement in 89% of the cases. The IP method detected 8/36 (22%) TdT-positive cases while IF detected 4/36 (11%) positive cases. If a figure of 10% TdT+ cells is considered significant in the marrow of the ANLLs, then the IP method would detect eight additional cases for a total of 16/36 (44%) TdT+ cases. This latter figure questions the ability of the IP TdT assay as a single test adequately to determine the lineage of a cell line. It may be rather that TdT is a marker that is expressed in a stem cell.

Acute Disease↗

Phagocytic macrophages in the bone marrow biopsies of children with Hodgkin's disease.

Phagocytic macrophages in bone marrow aspirates have been described as normal and are frequently observed in autoimmune disorders. They are rarely seen in bone marrow biopsies. We observed phagocytosis of leukocytes and nuclear debris by macrophages in the bone marrow biopsies in 20 of 26 children with Hodgkin's disease before therapy. In contrast, phagocytic activity was present in only 1 of 16 children with solid tumors and 4 of 17 children receiving chemotherapy for neoplasia other than Hodgkin's disease. In all groups the marrow was not directly involved by tumor. The presence of macrophage activity did not correlate with clinical stage or histological type of Hodgkin's disease or with the peripheral blood count. Its increased frequency in patients with Hodgkin's disease may reflect abnormal macrophage function in those patients.

Adolescent↗

Bone marrow response to chemotherapy in acute lymphocytic leukaemia and acute non-lymphocytic leukaemia.

Histopathologic changes in core bone marrow biopsies were reviewed in 33 patients with acute leukaemia during chemotherapy to compare the changes in acute lymphocytic leukaemia (ALL) with acute non-lymphocytic leukaemia (ANLL). Cellular, stromal, and bony changes were evaluated with regard to diagnosis and time of biopsy from initiation of chemotherapy. A significant difference was noted in the plasma cell response. Plasmacytosis was present in 19/19 cases of ANLL, but in only 2/14 cases of ALL. Cellular depletion was also significantly less frequent in ALL. Other stromal changes such as haemorrhage, dilatation of sinusoids and fat regeneration, as well as osteoblastic bone activity occurred with similar frequencies in all cases of treated acute leukaemia. Fibrosis, necrosis, and serous atrophy were uncommon. Differing chemotherapeutic regimens and differing patient ages were both correlated with the plasma cell response, but not with the difference in cellular depletion.

Acute Disease↗

Bone marrow biopsy in the metastatic work-up of solid tumors in children.

The bone marrow biopsy has an established role in the evaluation of nonhematologic malignancies in adults. The results of the trephine bone marrow biopsy (BMB) and bone marrow aspiration (BMA) in 42 children with solid tumors were reviewed. Bone marrow biopsies were done for the following indications: (1) "dry tap," (2) equivocal presence of tumor in the BMA, (3) definitely no tumor in the BMA, (4) protocol requirements. Of the 42 children, 19 (45%) had metastases in the BMB; 9 (21%) had a positive BMA and BMB, and 10 (23%) had a positive BMB and a questionable or negative BMA. Patients were divided into two groups, according to the presence or absence of metastases in the biopsy. Their clinical, hematologic, and pathologic findings were reviewed. Comparison was made between patients with and those without metastases. No single hematologic parameter was predictive of bone marrow metastases. Nevertheless, percentages of hemoglobin and platelet counts were lower in patients with metastases. This study indicates that, in children as in adults, aspiration and biopsy are complimentary procedures in the workup for metastases in patients with solid tumors.

Biopsy↗