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K McCredie

Publications and source records attributed to K McCredie.

31 records · Page 2Linked to original sources
PubMed1983

Clinical course and response to treatment of patients with acute myelogenous leukemia presenting with a high leukocyte count.

The natural history and response to treatment of 46 patients with acute myelogenous leukemia and a pretreatment leukocyte count of 100,000/microliters or higher were reviewed to identify the clinical features and response characteristics to the treatment of this group of patients. While the response rate of 52% was similar to that of patients with lower leukocyte counts, remission durations were shorter and related inversely to the height of the initial leukocyte count and to the number of treatment courses necessary to achieve a complete remission. A high incidence of hemorrhagic deaths was observed during the first 8 days of treatment. These hemorrhages occurred at a time when the leukocyte count was falling secondary to chemotherapy and the platelet count was still greater than 15,000/microliters. Pretreatment coagulation disorders and poor performance status were factors associated with this fatal complication. Antimetabolites to rapidly arrest leukemic cell proliferation and leukapheresis to avoid further leukostatic plug formation may be useful immediate measures to reduce the incidence of these fatal hemorrhages until the underlying pathogenic mechanisms have been elucidated.

Adult↗
PubMed1979

Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia.

In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.

Adult↗
PubMed1979

Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

Bone Marrow↗
PubMed1975

Clinical and morphological correlations in acute promyelocytic leukemia.

Thirty adults with acute leukemia and greater than 20% bone marrow infiltrate by promyelocytes were studied. Eighteen patients had acute promyelocytic leukemia (APML) as defined by the presence of malignant promyelocytes, and the remaining 12 patients had acute myelocytic leukemia (AML) with an elevated percentage of normal promyelocytes. Malignant promyelocytes were characterized by abundant, abnormal, cytoplasmic granules, by Auer rods in meshwork pattern, and by splinter cytoplasmic granulations and dilatation of the cisternae of endoplasmic reticulum. Patients with APML had, in general, greater than 35% bone marrow infiltrate by promyelocytes. The degree of bone marrow infiltrate by these cells correlated with the clinical status of the patients. Diffuse intravascular coagulation with bleeding occurred in 61% of patients with APML, and the bone marrows of these patients had greater than 50% promyelocytes. No coagulation abnormalities were seen among patients with elevated bone marrow promyelocytes infiltrate and without APML. Coagulation abnormalities in patients with APML were only corrected by controlling the leukemia itself. When this occurred, patients with APML had an excellent rate of complete remission, and the duration of remission and survival were comparable to the results obtained in adults with AML.

Adult↗
PubMedDate not supplied

Hansenula anomala fungemia.

Fungi of the genus Hansenula have rarely been reported as pathogenic in humans. A case of catheter-related Hansenula anomala fungemia in a patient with acute leukemia in remission is presented, and the clinical features of 11 additional patients infected with Hansenula species are reviewed. The spectrum of disease with these organisms ranges from asymptomatic fungemia to life-threatening disseminated infection. Predisposing factors appear to be immunosuppression, use of intravenous devices, and previous treatment with antibacterial drugs. Clinical experience and limited in vitro susceptibility data show that amphotericin B remains the drug of choice in the treatment of hansenula infections.

Adult↗
PubMedDate not supplied

Rubidazone in adults with previously treated acute leukemia and blast cell phase of chronic myelocytic leukemia: a Southwest Oncology Group Study.

Rubidazone, a new anthracycline antibiotic, is the benzoyl hydrazone derivative of daunorubicin. The Southwest Oncology Group carried out a phase II study of the drug in 126 patients with previously treated acute leukemia; 116 patients were evaluable. Good-risk patients were given doses of 450 mg/m2, and poor-risk patients were given doses of 300 mg/m2 approximately every 3 weeks. No complete response was observed in 25 patients with chronic myelocytic leukemia blast cell transformation. In the remaining patients the overall complete response rate was 22% and the rate of complete plus partial response was 29%. In good-risk patients these rates were 27% and 35%, respectively. Toxicity was similar to that observed with other anthracyclines except that acute febrile reactions were more pronounced. On the basis of the results, there are plans for a large-scale comparison study of rubidazone versus doxorubicin, each in combination with cytarabine, vincristine, and prednisone.

Acute Disease↗