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B D Clarkson

Publications and source records attributed to B D Clarkson.

At least 127 records · Page 7Linked to original sources
PubMed1980

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Adolescent↗
PubMed1980

Discrimination of human leukemia subtypes by flow cytometric analysis of cellular DNA and RNA.

A newly developed flow cytometry technique for simultaneous measurements of three features of individual cells--DNA, RNA, and nuclear diameter--using acridine orange as a fluorescent metachromatic dye, has been applied to cell-cycle analysis. DNA stemline determination, and to classification of 102 cases of human leukemias in adults. Acute lymphoblastic leukemia (L1-2) was characterized by moderately increased RNA of G0/1 cells as compared to normal lymphocytes; acute nonlymphoblastic leukemia (M 1-5) by very high RNA of G0/G1 cells. Both had either diploid or aneuploid DNA stemlines. Chronic lymphocytic leukemia showed diploid DNA, very low proliferation, and low RNA, similar to that found by use to be typical for normal B cells. In chronic myelogenous leukemia, two cell populations were distinguished, one with high RNA, the other with very low RNA and elongated nuclear diameter due to stripped, unfolded nuclei of polymorphonuclear leukocytes. The number of leukemic blast cells, identified by aneuploid DNA values, correlates well with conventional microscopy counts and could be followed during the course of treatment. Thus, acridine orange flow cytometry can be used to discriminate subtypes of human leukemias, to determine cell cycle stages, and to detect and monitor aneuploid leukemia stemlines.

Blood Cell Count↗
PubMed1980

Abnormal responsiveness of granulocyte-macrophage committed colony-forming cells from patients with chronic myeloid leukemia to inhibition by prostaglandin E1.

The formation of myeloid colonies in soft-agar cultures of normal human marrow was markedly inhibited by prostaglandin E. Morphological characterization of colonies in the presence or absence of prostaglandin E1 showed that inhibition was restricted to monocytoid rather than neutrophil differentiation. Myeloid colony formation by granulocyte-macrophage-commited colony-forming cells from patients with chronic myeloid leukemia was not inhibited even by high concentrations of prostaglandin E and was independent of colony morphology. The altered sensitivity of leukemic colony-forming cells to prostaglandin E was observed at all stages of the disease and persisted following chemotherapy-induced reversion to a partial or complete Philadelphia chromosome-negative bone marrow status. This evidence suggests that altered myeloid stem cell sensitivity to a normal regulatory factor may play a role in the pathophysiology of chronic myeloid leukemia.

Bone Marrow↗
PubMed1980

Restoration of nonclonal hematopoiesis in chronic myelogenous leukemia (CML) following a chemotherapy-induced loss of the Ph1 chromosome.

After intensive chemotherapy, marrow cells of some patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) become partially or completely Ph1-negative. However, without a second marker for the neoplastic clone, it could not be determined if these Ph1-negative cells arose from normal progenitors or were still members of an abnormal clone. In the present study, a patient with Ph1-positive CML, also heterozygous for glucose-6-phosphate dehydrogenase (G6PD), was studied before and after intensive chemotherapy. Prior to treatment only G6PD type B was detected in the patient's red cells, platelets, and granulocytes, and all unstimulated marrow metaphases had Ph1. After four cycles of chemotherapy, 76% of marrow cells were Ph1-negative, and approximately 80% of the granulocytes were nonclonal by G6PD analysis. Thus, the frequency of nonclonal cells by G6PD analysis correlated closely with that of the Ph1-negative cells. The data indicate that intensive chemotherapy can restore nonclonal and presumably non-neoplastic hematopoiesis in CML.

Adult↗
PubMed1980

Phase I and II trial of 4'-(9-acridinylamino)methanesulfon-m-anisidide in patients with acute leukemia.

Patients with acute leukemia in relapse were given 5'-(9-acridinylamino)methanesulfon-m-anisidide at a dosage of 75 to 200 mg/sq m as a daily bolus infusion of 5 consecutive days. None of the 11 patients treated at 75 to 150 mg/sq m daily for 5 days achieved remission. Ten patients with acute lymphoblastic leukemia and 21 with acute nonlymphoblastic leukemia were given treatment at 200 mg/sq m daily for 5 days. Six of these patients achieved complete remission, three with acute lymphoblastic leukemia and three with acute nonlymphoblastic leukemia. Neutropenia and thrombocytopenia were seen in all patients and in the responders lasted a median of 39 and 41 days, respectively. Stomatitis was the most significant nonhematopoietic toxicity noted. occurring in 80% of the patients. Hyperbilirubinemia was seen in 25% of the patients treated. Since 4'-(9-acridinylamino)methanesulfon-m-anisidide will induce remission in heavily pretreated patients with acute leukemia, consideration should be given to exploring its use in combination with other active drugs.

Adolescent↗
PubMed1980

Characterization of B-cell leukemias: a tentative immunomorphological scheme.

Analysis of the morphological and immunologic [surface (Sm Ig) and cytoplasmic (Cy Ig) immunoglobulin, faintness (f.imfl) or brightness (b.imfl) of surface immunofluorescence, rosette formation with mouse erythrocytes (MR), or sheep red cells coated with C3 (EAC)] characteristics of the neoplastic lymphocytes involved in 137 cases of B-cell leukemias allowed the differentiation of the following cytologic categories: B1 small lymphocytes (71); SM Ig+, f.imfl., Cy Ig-, MR+, EAC+; B2 prolymphocyte (4): SM Ig+, b.imfl., Cy Ig-, MR+, EAC+. B3 plasmacytoid lymphocyte (2): Sm Ig+, b.imfl., Cy Ig+/-, MR+!-, EAC+/- B4 small cleaved lymphocyte (23): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC+. B5a large cleaved and B5b noncleaved lymphocytes (14): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC-. B6 small noncleaved "Burkitt-like" lymphocyte (5): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC-. B7 plasma cell (2): Sm Ig+, MR-, EAC-. B8 hairy cell (16): Sm Ig+, b.imfl., Cy Ig-, MR-, EAC-, also exhibiting ingestion or attachment of particulate material, not seen in other types. Improved delineation of the heterogeneous group of B-cell leukemias might be of developmental significance in lymphocyte differentiation and improve current prognostic and therapeutic criteria.

Animals↗
PubMed1980

Fatal graft-versus-host disease following blood transfusion in Hodgkin's disease documented by HLA typing.

Fatal graft-versus-host disease (GVHD) developed in a patient with Hodgkin's disease treated with combined chemotherapy and radiotherapy following the transfusion of 2 U of packed red blood cells. Clinical features of the GVHD included the development of exfoliative dermatitis, progressive hepatic dysfunction, aplastic anemia, and finally progressive fatal pneumonia. GVHD was documented by skin biopsy and chimerism by HLA typing. The HLA phenotype of the patient's skin fibroblasts [A3, Bw44 (w4)/A2, B15 (w4)] was appropriate for parental haplotypes and probably represented her true HLA phenotype. Lymphocytes from the patient (peripheral blood and lymph node biopsy) were of a different HLA phenotype (A3; Bw35, w38, w4, w6; Cw4), which was inappropriate for parental HLA haplotypes but identical to the HLA phenotype of one of the blood donors. The HLA-DR typing of the patient's family and of the blood donor demonstrated that the patient and the donor probably were HLA-DR identical (DRw5/DRw6), although no B lymphocytes could be obtained from the patient for direct DR typing. We are currently irradiating all blood products administered to patients with Hodgkin's disease receiving intensive treatment. Further observations will be necessary to determine whether transfusions to other cancer patients with immunodeficiency states should be restricted to irradiated blood products.

Adolescent↗
PubMed1979

The coexistence of acute myeloblastic leukemia and diffuse histiocytic lymphoma in the same patient as demonstrated by multiparameter analysis.

Measurement of cellular DNA content by flow cytometry demonstrated presence of two distinct aneuploid neoplasms in a patient who developed acute myeloblastic leukemia (AML) 4 mo after diagnosis of a diffuse histiocytic lymphoma (DHL). A lymph node aspirate contained peroxidase-negative, "null," hyperdiploid (2.6C) DHL cells, while the bone marrow (BM) contained 84% primitive peroxidase-positive tetraploid AML cells (4.0C). Minor populations of hyperdiploid HDL and normal diploid cells could be detected by flow-cytometry in the BM, and all three populations were also seen in the peripheral blood.

Adult↗
PubMed1979

Macrophage-like cell transformation and CFU(c) fluctuations in normal and leukemic human marrow cultures treated by phorbol diester.

Bone marrow from normal and chronic myeloid leukemia donors was grown in liquid cultures without feeder layers and with and without 12-u-tetradecanoyl-phorbol-13-acetate (TPA). In 24-96 hours most of the cells (60-70%) cultured with 10(-7) M and 10(-8) M TPA stuck to the bottom of the flasks and had a peculiar shape resembling macrophages possessing strong phagocytizing activity and surface markers of monocyte-macrophage lineage of differentiation. 10(-7) M and 10(-8) M TPA fully inhibited CFU(c) in cultures of normal marrow as well as of chronic myeloid leukemia (CML) patients; 10(-9) M and 10(-10) M exhibited individually varied partial suppression. Cultivation of bone marrow with 10(-11) M to 10(-13) M TPA led in some cases to statistically significant increase of CFU(c) on day 4 and day 7.

Bone Marrow↗
PubMed1978

The L-5 protocol: intensive treatment for patients with chronic myeloid leukemia.

An aggressive treatment program combining splenic irradiation, splenectomy and intensive cytotoxic combination chemotherapy was used in 37 patients with Ph1 chromosome positive chronic myelogenous leukemia. Cytogenetic Ph1 chromosome determination on marrow cells revealed a significant but transient decrease in the Ph1 positive cell population in 12/37 (32%) cases. Survival duration appears longer in patients who show a reduction in the Ph1 positive population. Blastic transformation occurred in 18/37 (49%) cases, not different from our historical control.

Adolescent↗