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Biomedical subjects

V Caggiano

Publications and source records attributed to V Caggiano.

At least 19 recordsLinked to original sources
PubMed1997

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Abnormalities in immune regulation precede the development of multiple myeloma.

Immunosuppression of immunoglobulin synthesis seen in patients with multiple myeloma is in part due to immunosuppressive CD5 positive B cells. In a 13 year longitudinal study of an IgA-deficient blood donor who developed multiple myeloma, the presence of immunosuppressive CD5 positive B cells and T cells preceded the diagnosis of overt multiple myeloma and the appearance of immunosuppressive monocytes. These data argue that certain immune defects may be involved in the development of myeloma and are not simply a consequence of overt malignancy.

Antibody Formation↗
PubMed1992

Factors affecting the in vitro evolution of a myeloma cell line.

A continuously growing plasma cell line has been established from the bone marrow of a multiple myeloma patient. Initial growth of the cells was dependent on the presence of bone marrow stromal cells. Following initial outgrowth the cells were maintained by transfer onto non-autocthonous bone marrow stromal cultures. Following approximately one year of continuous growth, a subline was derived which could be grown independently of feeder cells. These stromal-cell-independent myeloma cells nevertheless retained dependence for a growth factor present in stromal-cell-conditioned media. The relevant factor in the conditioned media was determined to be interleukin-6 (IL-6). The cells also ultimately became independent of the conditioned media. These latter cells were shown to contain mRNA for IL-6 and eventually began to secrete IL-6. This cell line has thus progressed from complete dependence on stromal cells to IL-6-dependent growth in the absence of stromal cells to complete self sufficient growth. This in vitro progression may reflect an in vivo pattern of myeloma development.

Bone Marrow↗
PubMed1991

CD5 positive immunoregulatory B cells in spleen populations from multiple myeloma patients.

CD19+CD5+ lymphocytes constitute a minority of peripheral blood B cells. In view of the importance of these cells in the pathogenesis of the immunoregulation of myeloma, their incidence in another lymphoid organ was determined. CD5+ B cells were studied in 9 spleens from patients with multiple myeloma and in 10 spleens from normal individuals removed secondary to trauma. The total number of CD19+ B cells were increased in myeloma spleens (44.4% +/- 12.6%) as compared to normal spleens (20.4% +/- 7.4%). Likewise, the percentage of CD19 cells which co-expressed CD5 were increased in myeloma (25.3% +/- 12.4%) versus normal (4.4% +/- 2.3%) spleen. CD5+ B cells isolated from myeloma spleens, but not normal spleens, inhibit production of immunoglobulin in a pokeweed mitogen driven assay. Thus the spleen appears to be an important source of immunoregulatory B cells in multiple myeloma.

Antigens, Differentiation↗
PubMed1990

High-dose cisplatin and mitomycin C in advanced non-small cell lung cancer: a phase II study of the Northern California Oncology Group.

To investigate chemotherapeutic dose intensity in advanced non-small-cell lung cancer (NSCLC), we evaluated a pharmacokinetically designed schedule of high-dose cisplatin (200 mg/m2 per 28-day cycle) plus mitomycin C. Between March 1987 and March 1989, 62 patients were registered for a phase II study of the Northern California Oncology Group (NCOG). The treatment schedule consisted of cisplatin in hypertonic saline given on a divided days 1 and 8 schedule (100 mg/m2 on each day) plus mitomycin C given at a dose of 8 mg/m2 on day 1 of each cycle. In 61 patients evaluable for response analysis, the overall response rate was 39% (24/61), with a complete response being achieved in 6% (4/61) of cases and a partial response, in 33% (20/61). The response according to reviewed histologic subtype included squamous, 53% of patients (10/19); large cell, 31% (4/13); and adenocarcinoma, 34% (10/29). The median survival for all patients was 29.3 weeks. The mean cisplatin and mitomycin C delivered dose intensities in this study were 45 mg/m2 per week (90% of the projected dose) and 1.5 mg/m2 per week (75%). The toxicity of this combination regimen in the 62 enrolled patients was significant but manageable. Leukopenia (WBC, less than 1,000/mm3) and thrombocytopenia (platelets, less than 25,000/mm3) occurred in 3% and 8% of patients treated, respectively. Dose-limiting renal toxicity and clinically significant ototoxicity developed in 8 patients each (13%), and a peripheral sensory neuropathy was observed in 17 cases (27%). Whether this type of dose-intensive therapy results in an improved therapeutic index in NSCLC is currently being evaluated in a randomized comparative trial versus standard-dose cisplatin therapy.

Adult↗
PubMed1988

CD5 positive immunoregulatory B cell subsets.

B-chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease often expressed as a clonal expansion of CD5+ B cells. We report the characterization of CD5+ B cells from two unique B-CLL patients. Cells from patient 1 coexpressed CD5 (leu-1), CD19 (Leu-12), CD20 (B1), and HLA-DR; they were CD10 (J5), CD21 (B2), CD22 (Leu-14), CD25 (IL2-R1), PCA-1, surface, and cytoplasmic Ig negative. They suppressed normal peripheral blood lymphocyte (PBL) pokeweed mitogen (PWM) -stimulated immunoglobulin (Ig) synthesis greater than 80%. Cells from patient 2 were CD5 (Leu-1), CD19 (Leu-12), CD20 (B1), CD21 (B2), CD22 (Leu-14), HLA-DR, IgM, and kappa positive. They were negative for CD10 (J5), CD25 (IL2-R1), and PCA-1. These cells did not suppress normal PBL PWM-stimulated Ig synthesis but produced a monoclonal IgM kappa protein with rheumatoid factor-like activity. These observations suggest that there are different CD5+ B cell subsets, one immunosuppressive and the other autoreactive.

Antibodies, Monoclonal↗
PubMed1987

Effects of plasmapheresis on peripheral blood mononuclear cell populations from patients with macroglobulinemia.

Effects of plasmapheresis on peripheral blood T-cell, B-cell, monocyte, and natural-killer-cell populations were studied in ten macroglobulinemia patients with hyperviscosity syndrome. Following plasmapheresis, there was a transient decrease in the number of T4+ helper cells and a longer-lasting decrease in the number of Leu-7+ natural killer cells and Mo2+ monocytes. In addition, there was a greater than 50% decrease in the in vitro ingestion capacity of monocytes. Although no significant changes in the numbers of IgM+, B1+, B4+, or PCA+ B cells (P greater than .05) were detected, there was a highly significant (P less than .01) increase in I2 antigen density on the surface of IgM+ B cells and in the bromodeoxyuridine uptake by these cells 7-9 days after plasmapheresis. These findings suggest that following plasmapheresis, IgM+ B cells are activated. Using flow cytometry to determine when maximum IgM+ B cell activation occurs by measuring I2 antigen density on the cell surface may be useful in determining the postplasmapheresis timing of chemotherapy in macroglobulinemia patients with hyperviscosity syndrome who require more aggressive treatment.

B-Lymphocytes↗
PubMed1985

Peripheral T-cell lymphoma. A clinicopathologic study of a morphologically diverse entity.

We analyzed the clinicopathologic features of 13 patients with immunologically confirmed peripheral T-cell lymphoma. The lymphomas were classified into poorly differentiated lymphocytic, mixed cell, and large cell types. Marked morphologic heterogeneity was noted within the mixed cell and large cell categories, and the various subtypes are described. Twelve of the 13 patients received multiagent chemotherapy. Only three of the nine patients with poorly differentiated or mixed cell lymphomas achieved a complete remission, and the median survival for this group was 11 months. In contrast, all three of the treated patients with large cell lymphomas achieved a complete remission, two of whom are alive without disease (14 and 29 months, respectively). Classification of peripheral T-cell lymphomas into lymphocytic, mixed cell, and large cell types, as well as further subclassification within the heterogeneous groups, is suggested so that pathologic features of prognostic significance can be identified.

Adult↗
PubMed1983

Thrombotic thrombocytopenic purpura: report of fourteen cases--occurrence during pregnancy and response to plasma exchange.

Thrombotic thrombocytopenic purpura (TTP), a syndrome of diverse etiology probably related to factors regulating platelet-vessel wall interaction, is predominantly a disorder of women. We report our experience with 14 patients in an 11-year period. Thirteen were female and aged between 25-69 years. Four were postmenopausal, and of the nine premenopausal women three were pregnant, one was immediately postpartum, and three were taking estrogen-containing oral contraceptives. A review of the literature confirms the two to one female/male preponderance and that TTP is reported in 56 women who are pregnant or recently postpartum. While this association with possible hormonal events has been noted, it has previously received little comment. We stress the similarity between TTP and some occurrences of preeclamptic toxemia, and that this may suggest not only a common etiology but that therapeutic attempts should be similar. While no single therapeutic modality is universally successful, our experience is that plasma exchange is the most effective, with five of seven patients so-treated obtaining prolonged remission; four of five patients responded to splenectomy and corticosteroids, but one died of infection postoperatively. Five patients, including two treated exclusively with antiplatelet aggregating agents, died without achieving remission. The frequency of successful therapy is not changed by the concurrent pregnancy, but the fetal loss is high. There does seem to be an increased risk of recurrence of TTP in a subsequent pregnancy, and this might be considered when counseling premenopausal patients who have achieved remission of TTP.

Adrenal Cortex Hormones↗
PubMed1978

Effects of abnormal cation transport on deformability of desiccytes.

We have studied the deformability of subpopulations of red cells from a patient with "desiccytosis," a disorder characterized by increased membrane permeability to potassium and associated with a probable increase in sodium-sodium exchange. Cells become increasingly dehydrated after maturation because of continued potassium loss without compensatory sodium gain, and they exhibit a progressive increase in mean cell hemoglobin concentration (MCHC). This increase in MCHC causes the cells to become underformable at shear stress values which result in extensive deformation of normal cells. Reduction of MCHC to approximately normal levels by suspending the cells in hypotonic medium restores normal deformability to all but 0.1--0.2% of the cells. These results suggest that the major factor leading to premature destruction in this disorder is whole cell rigidity conferred by increased intracellular hemoglobin concentrations, rather than any associated membrane rigidity.

Anemia, Hemolytic↗
PubMed1978

Multiple myeloma: an immunologic profile. II. Bone marrow studies.

Bone marrow mononuclear cell populations were studied in 35 patients without myeloma, 39 patients with multiple myeloma, and 15 patients with benign monoclonal gammopathy. Bone marrow mononuclear cell receptors, responses to mitogens or allogeneic stimuli, and suppressive effects on in vitro peripheral blood lymphocyte (PBL) function were studied. In bone marrow cell populations from patients with untreated multiple myeloma, the percent of complement receptor-bearing cells and the pokeweed mitogen- and concanavalin A-stimulated responses were significantly greater than were those in bone marrow cell populations from patients without myeloma. Sheep red blood cell receptor-bearing cells were significantly greater in marrow populations from treated multiple myeloma patients compared to those from untreated multiple myeloma patients. Sheep red blood cell receptor-bearing cells from the bone marrow of multiple myeloma patients suppressed responses of the multiple myeloma patients' PBL's to autologous mitomycin C-treated bone marrow plasma cells and to allogeneic stimuli in one-way mixed leukocyte culture. Complement receptor-bearing cells suppressed the response to pokeweed mitogen. The presence of lymphocytes in the marrow compartment that are capable of suppressing the response of myeloma patients' PBL's to plasma cell antigens may be significant in the pathogenesis of multiple myeloma.

Bone Marrow↗