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M Talpaz

Publications and source records attributed to M Talpaz.

339 records · Page 19Linked to original sources

Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia.

We investigated the antiproliferative effect of partially purified human leukocyte interferon (HuIFN-alpha) given in a dose of 9-15 X 10(6) U daily by intramuscular injection to 7 patients with chronic myelogenous leukemia (CML). Hematologic remission of the disease was obtained in 5 patients. Among the responding patients, the mean white blood cell count decreased from 97.4 X 10(3)/cu mm (range from 35 X 10(3)/cu mm to 239 X 10(3)/cu mm) to 4.2 X 10(2)/cu mm (range from 3.0 X 10(3) to 7.9 X 10(3) cu/mm). Parallel reduction occurred in serum B12, from a mean of 1,435 pg/ml to a mean of 726 pg/ml, and lactate dehydrogenase levels, from a mean of 325 mU/ml to 112 mU/ml. Enlarged spleens decreased in 3 of 3 patients. The 5 responding patients have been maintained on HuIFN-alpha, 3 X 10(6) U daily or every other day, for 6+-35+ wk.

Chromosome Aberrations↗

Characterization of human effector and suppressor T cells by their activity in mixed lymphocyte reaction and by monoclonal antibody phenotyping.

Human T effector and T suppressor cell subpopulations which are functionally operative in the local graft-versus-host reaction were enriched and separated on the basis of their respective ability to form (or not to form) rosettes with sheep red blood cells in the presence of theophylline. These subpopulations were then tested as stimulators and as responders in the allogeneic mixed lymphocyte reaction assay against the same mononuclear cells. Among 18 normal donors, theophylline resistant cells responded more vigorously to mononuclear cells (SI, 9.9 +/- 9.8) than theophylline-sensitive cells (6.7 +/- 5.7, p less than 0.08). In contrast, T-effector cells were poorer stimulators of the same MNC (SI, 4.0 +/- 5.6) when compared to the stimulatory capacity of T suppressor cells (SI, 7.1 +/- 9.8, p less than 0.05). Similar studies among 14 patients with disseminated cancer showed the same, but more pronounced differences. Thus, the theophylline-resistant T effector cells were vigorous responders (SI, 14.7 +/- 10.0) compared to the weak response of the theophylline-sensitive T suppressor cells to the same mononuclear cells (SI, 3.4 +/- 1.8, p less than 0.01). Again, in contrast, T effector cells stimulated mononuclear cells poorly (SI, 1.0 +/- 0.5) while T suppressor cells induced a weak but significant stimulation (SI, 3.2 +/- 2.1, p less than 0.05). Phenotyping of these two functionally distinct subpopulations with monoclonal antibodies to subsets of T cells (Leu I, II, III) and for the HLA-DR antigen (OKIal) showed no enrichment for any of the phenotypes as defined by these antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

Studies of natural killer cell activity and antibody-dependent cell-mediated cytotoxicity among patients with acute leukemia in complete remission.

Low natural killer (NK) cell activity against the K-562 leukemia cell line was observed in patients with acute leukemia in the early stages of remission, i.e., 2-4 months (11.3% +/- 7.95% specific target cell lysis). This parameter was found to be normal among leukemia patients after a longer time in remission (19.53% +/- 7.55%) when compared with healthy donors (18.46% +/- 12.98%). A similar pattern of activity was observed in studies of antibody-dependent cell-mediated cytolysis (ADCC) to the CEM lymphoid tumor cell line in the same group (37.58% +/- 12.4% vs. 51% +/- 6.79% specific target cell lysis). ADCC to chicken red blood cells (CRBC) and to human red blood cells (HRBC) was not significantly different from that for healthy controls at either duration of remission. Nine patients relapsed over a follow-up period of 9 months. They were found to have slightly lower NK activity (14.4% +/- 9.3%) and ADCC to CEM (41.4% +/- 8.5%) than the patients who remained in remission (17.1% +/- 6.8%; 48.7% +/- 9.7%, respectively). These data indicate a lymphocyte deficit which may persist for some time after remission has been induced, and which may be due to the effect of leukemic cell burden or the effect of aggressive chemotherapy.

Acute Disease↗

Comparative functional analysis of lymphocytes and monocytes from plateletapheresis.

Large numbers (2.9 +/- 1.2 X 10(9)) of mononuclear cells can be obtained from incidental samples collected during routine plateletapheresis. We conducted studies comparing characteristics and functions of mononuclear cells derived from venous blood samples and from routine plateletapheresis in the same normal donors. Cell viability was similar in both samples (96 +/- 1% plateletapheresis vs 97 +/- 2% venous blood). Higher concentration of monocytes were observed in the plateletapheresis samples (32.3 +/- 6%) than in the venous blood (14.3 +/- 4%). The procedure of plateletapheresis does not seem to alter lymphocyte or monocyte function. Thus, the functional integrity of these cell populations was demonstrated in terms of natural killer cell activity, blastogenic response to mitogens, local graft-versus-host reactions, monocyte-mediated antibody-dependent cellular cytotoxicity against human red cells, monocyte-mediated tumor cell cytotoxicity, latex phagocytosis, and monocyte-dependent lymphocyte blastogenesis. We conclude that monocytes and lymphocytes obtained during routine plateletapheresis are functionally intact.

Antibody-Dependent Cell Cytotoxicity↗

Immunological properties of melanoma tumor-infiltrating lymphocytes before and after IL-2-based biotherapies.

Immunological properties of melanoma TILs before and/or after IL-2-based biotherapies were investigated. TILs harvested before therapies, including those for adoptive transfer, proliferated well in culture with IL-2 and displayed cytotoxicity relatively restricted to autologous tumor cells. In contrast, TILs during or at the end of IL-2 based therapies did not proliferate in culture with IL-2. TILs from tumors even harvested 45 days after the end of IL-2 therapy modestly proliferated in culture with IL-2 and showed MHC-nonrestricted cytotoxicity. The number of live tumor cells that were yielded from melanomas during or at the end of IL-2-based therapies significantly decreased in all nine patients with metastatic melanomas, regardless of their clinical responses (2 PR, 2 MR, 2 SD, and 3 PD). Collectively, these results suggest that current IL-2-based therapies resulted in both transient nonresponsiveness of TILs to IL-2 and transient decrease in the number of live tumour cells in most melanoma patients.

Cell Count↗

Effects of interferon-alpha therapy on lymphocyte subpopulations in patients with chronic myeloid leukemia.

The mechanism of action of interferon-alpha (IFN-A) in chronic myelogenous leukemia (CML) is not known, but some evidence points at the immune modulation properties of IFN-A. We conducted a prospective analysis on 49 patients with CML in chronic phase treated with IFN-A in order to identify the effect of therapy on different lymphocyte subpopulations as determined by flow cytometric quantification and whether this effect is associated with the response to IFN-A. The absolute number of lymphocytes was similar in all patients regardless of response to IFN-A. In patients achieving a complete cytogenetic response (CCGR) there was a rebound of the absolute count of CD3+, CD4+, CD8+, and CD19+ lymphocytes after discontinuation of therapy with IFN-A. Patients with resistant disease, as well as patients with hematologic response but no cytogenetic response, showed a lower absolute number of CD19+ cells than patients with any cytogenetic response. Patients who achieved a CCGR had a higher absolute number of CD56+ cells than patients with lesser response or no response to IFN-A, and this persisted after discontinuation of therapy. We conclude that an increase in absolute number of CD19+ and CD56+ lymphocytes is observed in CML patients achieving a CCGR with IFN-A compared to patients with lesser responses. These changes could have functional consequences in the control of the disease.

Adult↗