Peripheral blood mobilization of different lymphocyte and dendritic cell subsets with the use of intermediate doses of G-CSF in patients with non-Hodgkin's lymphoma and multiple myeloma.

Between June 2003 and November 2004, we collected mobilized peripheral blood units from 29 patients with non-Hodgkin's lymphoma and multiple myeloma for autologous peripheral blood stem cell transplantation. They received granulocyte colony-stimulating factor (G-CSF) (16 micro g/kg/day) for a total of 5 days. Immediately before and 3 h after the fourth and fifth dose of G-CSF, we performed flow cytometry analysis to quantify: T cells (CD3+CD4+, CD3+CD8+), B cells (CD19+), NK cells (CD3-CD16+CD56+), NKT cells (CD3+CD16+CD56+), type 1 dendritic cells (DC1) (lin-HLA-DR+CD11c+), type 2 dendritic cells (DC2) (lin-HLA-DR+CD123+), regulatory T cells (Tregs) (CD4+CD25+), and activated T cells (CD3+HLA-DR+). All cell subsets were mobilized after G-CSF treatment with the exception of B, NK, and NKT lymphocytes. The median number of Treg cells before and after G-CSF was statistically different (29+/-14.9x10(6)/l vs 70.1+/-46.1x10(6)/l, P<0.02). DCs were mobilized significantly with a 5.9-fold increase in DC2 (15.1+/-30.3x10(6)/l vs 89.8+/-81.0x10(6)/l, P<0.02) and a 2.6-fold increase for DC1 (41+/-42.5x10(6)/l vs 109.5+/-58.0x10(6)/l, P<0.04). Patients received a mean of 3.1+/-1.2x10(7)/kg NK cells, 1.3+/-0.9x10(7)/kg NKT cells, 0.41+/-0.29x10(7)/kg DC1, 0.2+/-0.22x10(7)/kg DC2, and 1.8+/-1.9x10(7)/kg Tregs. In conclusion, intermediate doses of G-CSF induce mobilization of different lymphocyte subsets, with the exception of B, NK, and NKT cells. The mobilization of certain suppressive populations (DC2 and Treg) could be in theory deleterious, at least in patients with cancer.

CD4+ CD25+ lymphocyte and dendritic cell mobilization with intermediate doses of recombinant human granulocyte colony-stimulating factor in healthy donors.

We prospectively conducted a quantitative and phenotypic analysis of T, B, natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T cells, before and after mobilization with intermediate doses of granulocyte colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003, and December, 2004, we collected stem cells from 25 HLA identical sibling donors for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3 h after the fourth and fifth doses of G-CSF, blood samples were taken for blood counts and flow cytometry. The median number of regulatory T cells before and after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x 10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p < 0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x 10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/- 1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have demonstrated the mobilization of different lymphocyte subsets, in particular regulatory T cells and DC, which can be expanded later and used in the treatment of cancer and autoimmune diseases.

Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia.

Primary plasma cell leukemia (PPCL) is a rare form of disease accounting for 1-2 percent of myelomas. Between September 1990 and November 2000, among 540 patients with myeloma studied, 24 fulfilled the criteria of PPCL (4.4 percent). We found high frequencies of female patients (62 percent), Bence Jones proteinuria (79 percent), anemia (88 percent), bleeding (54 percent), confusional syndrome (42 percent), weight loss (71 percent), hepatomegaly (25 percent), splenomegaly (21 percent), leukocytosis (62 percent), and thrombocytopenia (71 percent). High serum levels of creatinine, calcium, lactate dehydrogenase (LDH), and beta(2)-microglobulin were detected in 50 percent, 37 percent, 58 percent, and 71 percent, respectively. Four patients were treated with vincristine, melphalan, cyclophosphamide, prednisone, and adriamycin (VMCPA), 12 with vincristine, adriamycin, and dexamethasone (VAD), and 8 with M-80 (oral melphalan 80 mg/m(2) plus dexamethasone 40 mg/m(2)). There was a trend toward lower values of Karnofsky score (P=0.07) and higher values of LDH (P=0.2) in the VAD group. Other clinical characteristics were comparable among the three groups. Complete plus partial responses were achieved in one and six patients treated with VMCPA and M-80, respectively. All patients treated with VAD failed to respond to treatment. Patients receiving the M-80 regimen experienced higher platelet toxicity (P=0.05), vomiting (P<0.0003), and mucositis. Also, the need for red blood cell transfusions was higher in the M-80 group. Median overall survival was 60 days. Overall survival was better in patients achieving complete or partial response. In conclusion, our study illustrates that intermediate doses of melphalan plus dexamethasone are an effective chemotherapy regimen for this aggressive disease. Response to treatment is the only prognostic factor for survival in these patients.

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a single center experience.

BACKGROUND: Bone marrow transplantation (BMT) is the therapy of choice for patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen (HLA)-identical donor and are under 50 years of age. METHODS: Here, 45 patients with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120 mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD) prophylaxis. RESULTS: We observed a high incidence of acute and chronic GVHD (69% and 67%, respectively). A multivariate analysis identified differences in the sex of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p = 0.0001) as significant adverse influences on disease-free survival. Age, sex, chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had no statistical significance. The 3-year probabilities of relapse, disease-free survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant-related mortality occurred in 31% of the cases. The high frequency of GVHD is explained by HLA determination by serological typing, differences in sex between the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch donors. CONCLUSIONS: BMT is a procedure feasible for patients with CML in early and late chronic phase and even in those with an HLA non-identical donor. Strategies directed to decrease acute GVHD could improve the outcome of these patients.

Patologia tumoral de mama. / Tumoral pathology of the breast

Se estudian 171 pacientes operadas por tumoraciones de mama en el Hospital Docente Ginecobstetrico de Matanzas durante los anos 1975-1980. Se analizan las afecciones que con mayor frecuencia se encontraron, asi como se estudia la relacion existente entre el resultado de las mamografias realizadas y el diagnostico histologico

Enfermedad hipertensiva del embarazo.Etiologia. / Hypertensive disease of pregnancy. Etiology

Se revisa de manera generai, el origen de la enfermedad hipertensiva del embarazo, haciendo enfasis en las teorias que tienen mas creditos actualmente, tales como la isquemia uteroplacentaria, el sistema renina-angiotensina-aldosterona y las prostaglandinas

Metodos anticonceptivos actuales. / Present contraceptive methods

Se realiza una revision actualizada de algunos metodos anticonceptivos, que se utilizan actualmente sobre todo los hormonales y aquellos que se encuentran en fase de experimentacion. En muchos de los metodos anticonceptivos se exponen sus efectos favorables y desfavorables.Como la mayoria de los metodos anticonceptivos revisados, de tipo hormonal, antes de analizar cada uno de ellos se hace una breve resena de la fisiologia de la menstruacion

Displasia mamaria. Estudio de 100 casos. / Breast dysplasia. Study of 100 cases

Se realiza un estudio de 100 pacientes que presentaron mediante diagnostico histico, displasia mamaria, durante el periodo comprendido de 1975-1980, en el hospital docente ginecobstetrico de Matanzas. En el estudio se encuentra la mayor incidencia de displasia mamaria en el grupo etareo de 15-24 anos, y en el diagnostico histico fue mas frecuente la displasia fibrosa y fibroquistica

Deficiencia probablemente heredada de factor X (Prower-Stuart). Presentacion de un caso y breve revision de la bibliografia. / Probably inherited factor X deficiency (Power-Stuart). Report of a case and brief review of the literature

Se reporta el caso de una mujer de 8 anos de edad, con el antecedente de un primo materno diagnosticado como "hemofilico".Muestra alargamiento en el tiempo de tromboplastina parcial, el de protrombina y la generacion de tromboplastina, con un nivel de factor X de 15%, deficiencia aparentemente de tipo familiar. Se hace una breve revision monografica del factor X y bibliografica de su deficiencia, senalando sus caracteristicas clinicas y de laboratorio