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Biomedical subjects

J P Lewis

Publications and source records attributed to J P Lewis.

At least 19 recordsLinked to original sources

Impact of polydonor mixed lymphocyte culture media on quantity and quality of myeloid metaphases.

A novel mitotic stimulator of myeloid hematopoietic cells was prospectively evaluated to detect enhanced quantity and quality of metaphases from bone marrow (BM) cultures for cytogenetic analysis. This polydonor mixed lymphocyte conditioned (PMLC) media decreased the culture failure rate, improved detection of chromosomal aberrations, and reduced technologists' analysis time. The conditioned media is recommended as a highly effective culture system for normal and neoplastic cells of myeloid lineage.

Bone Marrow

Clonal remission in aplastic anemia after treatment with antithymocyte globulin.

Aplastic anemia includes a group of disorders characterized by peripheral blood pancytopenia and marrow hypocellularity. The current report describes a patient who is an apparent constitutional mosaic and presented with marrow aplasia. Using cytogenetic analysis of bone marrow, skin, and peripheral T lymphocytes, we demonstrated the clonal nature of this patient's aplastic marrow, and, in addition, identify clonal evolution. The patient was treated with antithymocyte globulin (ATG) and achieved a complete remission, with disappearance of an abnormal evolved clone. This case illustrates that clonal cytogenetic abnormalities do not preclude a response to ATG and that aplastic anemia may be a nonmalignant clonal disorder with clonal evolution.

Aged

Analysis of mosaic states in amniotic fluid using the in-situ colony technique.

Appropriate counselling and clinical management of the pregnant woman with a mosaic amniotic fluid cell karyotype are difficult. The majority of the data on mosaicism and pseudomosaicism are derived from studies employing the flask technique for the analysis of amniotic fluid cell cultures. Since the majority of laboratories now utilize the in-situ technique, such data may not be relevant when analyzing results from the in-situ colony technique. We reviewed the incidence of mosaicism in 6339 amniotic fluid samples using the in-situ technique. Data are presented on the types of aberrations and clinical outcomes. A classification of mosaicism is presented that distinguishes mosaicism of clinical importance from that which is obviously of extrafetal origin or artifactual. This approach clarifies the significance of mosaic states detected by the in-situ colony technique and provides a rational foundation for genetic counselling and for planning clinical interventions.

Amniotic Fluid

Infusion carboplatin treatment of relapsed and refractory acute leukemia: evidence of efficacy with minimal extramedullary toxicity at intermediate doses.

Carboplatin (CBDCA) is a second-generation platinum analog with prominent myelotoxicity and modest extramedullary toxicity. We performed a phase I study of CBDCA in adult patients with relapsed acute leukemia. Therapy was administered as a five-day continuous infusion. The initial dose of 875 mg/m2 over five days was escalated in 15% increments to a final dose of 2,100 mg/m2 over five days. Twenty-eight patients received 35 induction courses of CBDCA, including two patients who achieved a complete remission (CR) following the first course, and received a second induction course at the time of relapse. Therapy was well tolerated. No grade 3 or 4 extramedullary toxicity was seen. Myelosuppression was regularly observed, with prolonged myelosuppression at 2,100 mg/m2 over five days being the indication to cease dose escalation. Eight of 28 patients (28.5%) responded to CBDCA therapy (six CR, two partial remission [PR]) or ten of 30 initial induction courses (33.3%). Continuous-infusion CBDCA has an advantage over other therapy for acute leukemia because of its highly selective myelotoxicity and minimal gastrointestinal and renal toxicity. A standard phase II study should be undertaken to establish a more accurate response rate.

Adult

Quantitation of erythropoietin stimulatory activity using [3H]thymidine uptake by K562 cells.

A microassay for erythropoietin (Ep) activity in serum using [3H]thymidine uptake by K562 cells is presented. The method is similar to that of Krystal except that cells of the K562 human pluripotent leukemia cell line replace spleen cells from phenylhydrazine-treated anemic mice. Response to the hormone by K562 cells and spleen cells was colinear. Using the Krystal bioassay, 14 young hemoglobin S homozygotes had Ep activity levels of 17.9-113.8 mU/ml serum, whereas the new method with K562 cells gave a range of 19.2-115.3 mU/ml. The correlation coefficient between the two sets of data (r) was 0.999 (p less than 0.001). With the modified technique we have assayed 34 sickle cell patients, whose sera ranged from 19.2 to 1400 mU of Ep/ml with corresponding hemoglobin concentrations of 10.7 g % to 3.0 g %. Values for normal subjects were 22.1 +/- 2.1 mU/ml (n = 7). The stimulation of [3H]thymidine uptake is significantly inhibited by an anti-Ep antiserum. The assay permits quantification of stimulatory activities in a large number of samples with relative ease and is also suitable to explore the interactions of erythropoietic factors with their appropriate receptors on stem cells.

Adolescent

Ring chromosomes in chronic myelogenous leukemia: an ominous finding.

Two cases of Philadelphia chromosome positive chronic myelogenous leukemia (CML) demonstrated ring chromosomes. The appearance of the ring coincided with evolution from the stable to the aggressive phase. A literature search yielded six other cases of ring chromosomes in CML; all were in or were entering the aggressive phase of the disease. Thus, as is the case with acute nonlymphocytic leukemia, in CML the finding of an acquired ring chromosome is associated with a poor prognosis.

Adult

Impact of reinduction regimens on the clinical course of adult acute nonlymphocytic leukemia.

All clinical studies in the English literature from 1976 to mid-1987 that address drug management of refractory or relapsed ANLL are reviewed and summarized. We conclude that, although many regimens may induce a CR, none is clearly superior. New drugs and or drug combinations must be sought if treatment outcomes are to be substantially improved. At present it appears that combination chemotherapy with VP-16 has not been extensively studied and may be active in non-cross-resistant regimens.

Adult

Improved approach to patients with normocytic anemia.

A precise cause for normocytic anemia can be determined through applied pathophysiology. Examination of the peripheral blood smear may yield evidence of renal disease, liver disease, hemolysis or megaloblastic anemia. A reticulocyte count is performed next; then the creatinine clearance is determined. Bone marrow aspiration with iron stain should further narrow the cause. Physical examination and family history remain important in determining the etiology of normocytic anemia.

Algorithms

Treatment of refractory chronic lymphocytic leukemia with prednimustine: a phase II study using strict response criteria.

Twenty-one patients with refractory chronic lymphocytic leukemia (CLL) were entered into this Northern California Oncology Group (NCOG) study of prednimustine, an ester of chlorambucil and prednisolone. All patients had active disease and were refractory to standard alkylating agent chemotherapy. Treatment consisted of prednimustine 100 mg/m2/day orally for 3 consecutive days every 2 weeks. By strict response criteria used in this study there was one complete remission (CR), no partial remissions (PR), and three cases of clinical improvement (CI) in 18 evaluable patients, for a total response rate of 22%. The median duration of response is 20+ months, with two patients continuing to respond. Toxicity of this intermittent prednimustine regimen consisted primarily of mild to moderate thrombocytopenia and neutropenia. No episodes of treatment-associated infection or hemorrhage occurred, and nonhematologic toxicity was minor. Using strict response criteria, this study fails to confirm previous reports of high response rates for prednimustine in patients with CLL refractory to standard therapy. The significance of the response category of clinical improvement in CLL is demonstrated by the substantial improvement in objective parameters and the long duration of response. This study also emphasizes the need for standardization of response criteria for this disease.

Alkylating Agents

Mast cell disease followed by leukemia with clonal evolution.

A 29-yr old woman developed urticaria pigmentosa which subsequently progressed through systemic mastocytosis to Philadelphia chromosome negative (Ph neg) chronic myelogenous leukemia (CML) with t(8;17). Further cytogenetic evolution occurred at the time of transformation to the aggressive phase of the disease. Unlike Ph-positive CML, chromosome number 9 was not involved, nor was the breakpoint cluster region located at band 22q11. This clearly separates this case from other Ph-negative CML patients who do have involvement of 9q34 or the breakpoint cluster region. Since this is the first case of its type to be reported with cytogenetic abnormalities, the clinical relevance of the unique chromosomal rearrangement t(8;17)(p11;q25) in the setting of systemic mastocytosis is unclear. Additional cases need to be reported to determine if this genetic rearrangement is a nonrandom marker of leukemia evolving in a setting of malignant mast cell disease.

Adult

The resolution of phenotypic ambiguity in a case of human leukemia using cytogenetics and immunoglobulin gene rearrangement.

A 28-year-old woman presented with acute leukemia. Surface antigen analysis showed monoclonal kappa immunoglobulin distribution. Morphology was consistent with either acute lymphoblastic leukemia or acute promyelocytic leukemia, hypogranular variant. This dilemma was resolved by examining the leukemic blasts for immunoglobulin gene rearrangement. None were found, ruling-out involvement of the B-cell lineage in this malignancy. Cytogenetic analysis showed a clonal abnormality diagnostic of acute promyelocytic leukemia. Immunoglobulin gene rearrangement in cytogenetics are invaluable in the care of patients with acute leukemia and can resolve ambiguities that result from phenotypic analysis.

Adult