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R Brunning

Publications and source records attributed to R Brunning.

7 recordsLinked to original sources
PubMed1990

Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia.

The National Cancer Institute (NCI) sponsored a workshop to develop a set of standardized diagnostic and response criteria for acute myeloid leukemia (AML) clinical trials. The French-American-British (FAB) classification was retained for diagnosing AML, with the addition of patients with bone marrow morphologic features of a myelodysplastic syndrome and less than 30% bone marrow blasts, but with greater than or equal to 30% blasts in the peripheral blood. In this report, there are four important subgroups of AML not defined in the FAB classification that are discussed: undifferentiated acute leukemia, MO (AML lacking definitive myeloid differentiation by morphology or conventional cytochemistry but with ultrastructural or immunophenotypic evidence for AML), mixed lineage leukemia, and hypocellular AML. Definitions of response for clinical trials are presented to facilitate comparisons among different studies. Complete remission is considered the only response worth reporting in phase III trials, since lesser responses do not improve survival. Partial remissions may be of interest to identify active new agents in phase I and II studies. Monoclonal antibodies and cytogenetic studies are not part of the routine assessment of remission or reassessment at relapse, and their role in the evaluation of patients with AML is currently being evaluated in clinical trials. Although we recognize that some of the definitions in this report are arbitrary, generalized use of these guidelines will make results of clinical trials more comparable and interpretable.

Antibodies, Monoclonal↗
PubMed1989

Mature T-lineage leukemia with growth factor-induced multilineage differentiation.

We report an acute T-lymphoblastic leukemia with a predominantly mature CD3+ CD7+ WT31+ phenotype that was induced to differentiate into different cell lineages by various recombinant human growth factors. In the presence of IL-3 or GM-CSF, the leukemic cells gave rise to myeloid and monocytic cells including terminally differentiated, partially functional, segmented neutrophilic granulocytes as assessed by morphologic, cytochemical, immunophenotypic, and functional criteria. In the presence of IL-2, leukemic granulated lymphoid cells exhibiting MHC-unrestricted cytotoxicity and expressing a CD2+ CD3+ CD5+ CD7+ CD8+ CD33+ WT31+ Leu19+ phenotype arose. Leukemic cell cultures initiated with IL-3 yielded growth factor-independent cells with a mixed lineage phenotype and morphologic and cytochemical evidence of immature blasts. These were T lymphocyte and myeloid surface antigen (CD2,CD3,CD5,CD7,CD13,CD33,WT31) positive. Identical rearrangements of the constant region of the TCR-delta gene and of the joining regions of the TCR-beta, -gamma, and -delta genes were observed in the fresh and all cultured leukemic cells, indicating that they were derived from the same malignant clone. Consistent with the molecular genetic data, the cytogenetic analyses of the GM-CSF-, IL-3-cultured and the growth factor-independent leukemic cells showed the presence of multiple, closely related abnormal clones, all of which had an interstitial deletion of part of the long arm of chromosome 6 and a complex 1;10;12 translocation. In conclusion, these data demonstrate the involvement of a multipotent leukemic precursor cell in this predominantly mature CD2+ CD3+ CD5+ CD7+ WT31+ T-ALL. This multipotent leukemic precursor may be susceptible to various growth factors and respond with ordered differentiation and maturation.

Adult↗
PubMed1988

Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission.

Seventy-three patients with acute nonlymphocytic leukemia in first complete remission (CR) have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. The first 36 patients received a preparative regimen consisting of cyclophosphamide, 60 mg/kg/d (days -6 and -5), and 750 cGy single-dose total-body irradiation (TBI) (day -1). Subsequently, 37 patients received cyclophosphamide 60 mg/kg/d (days -6 and -5), and 165 cGy fractionated TBI administered twice daily for a total dose of 1,320 cGy (days -4, -3, -2, and -1). Survivors have been followed from 9 to 124 months (median, 40 months). The 61% (95% confidence interval [CI], 45% to 77%) projected disease-free survival (DFS) of 41 children less than 18 years old does not differ significantly from the 62% (95% CI, 49% to 73%) projected DFS of 32 adults at 84 months (P = .89). Similarly, the 15% (95% CI, 1% to 29%) projected relapse rate seen in children does not differ from the 9% (95% CI, 0% to 21%) seen in adults (P = .69). Multivariate Cox regression analysis of presenting features demonstrates that a presenting WBC count greater than 20,000/m3 is associated with decreased DFS (P = .01). When compared with other French-American-British (FAB) subtypes, presentation with FAB M4 or M5 morphology is significantly associated with relapse in multivariate analysis (P = .014). Other presenting features such as preparation with single-dose or fractionated TBI, interval from diagnosis to CR or CR to BMT, donor or recipient sex, and donor or recipient cytomegalovirus serology do not correlate independently with either DFS or relapse. When included in the stepwise multivariate analysis of presenting patient features, two posttransplant events, development of grades 2 to 4 acute graft-v-host disease (GVHD) (P less than .03) and development of interstitial pneumonitis (P less than .001), also correlate independently with poor DFS. Allogeneic BMT provides equivalent, prolonged DFS in both children and young adults when performed in first CR and should be considered the therapy of choice for all first CR patients under 45 years of age with a suitable donor. Continued efforts to prevent and treat acute GVHD and pneumonitis as well as efforts designed to prevent relapse in patients presenting with FAB M4 and M5 morphology should further improve outcome.

Age Factors↗
PubMed1976

Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin and iron.

Relations among circadian rhythms in serum iron, glucagon and insulin and urinary cyclic AMP excretion differ drastically when diurnally active, nocturnally resting human adults consume all daily food for one week as breakfast only and for another week as dinner only - a finding of interest to diverse fields, e.g., for optimizing certain kinds of therapy or for a better utilization of calories.

Circadian Rhythm↗
PubMed1975

Congenital neutropenia: impaired maturation with diminished stem-cell input.

Children with congenital neutropenia (Kostman disease) present a syndrome of recurrent and eventually fatal bacterial infections. The disease is uniformly lethal and the mean age at death is 24 months. To attempt to better understand the nature of this inborn error, we have studied marrow and peripheral blood of 3 children with the disease. Along with classic morphologic analysis we have used the technic of soft agar bone marrow culture in vitro. All 3 patients showed marked deficiency of numbers of neutrophils in the peripheral blood, intermittent monocytosis especially with infection, and predominant nitroblue tetrazolium (NBT) dye staining in monocytes during infection. The marrow of all 3 patients showed evidence of maturation arrest at the promyelocyte stage and very few or no neutrophils. Two cases showed no neutrophils in the Rebuck skin window inflammatory study. The 3rd case, however, developed small numbers of neutrophils in the peripheral blood, up to 6%, but the first 2 patients, although studied on many occasions, did not show neutrophils above 1%. Evidence from soft agar culture of bone marrow in 1 patient was compatible with the view that development of committed neutrophil stem cells is defective. This patient did not develop neutrophils in soft agar culture and showed loose colonies developing only to promyelocytes. In the 2nd case, where depression of neutrophil development was somewhat less severe clinically, culture of the marrow in soft agar yielded normal neutrophil colonies and none of the loose colonies showing arrested maturation were seen. These findings suggest that the basic mechanism underlying the congenital neutropenias may differ from patient to patient.

Agranulocytosis↗