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Several prognostic factors have been recognized in patients with multiple myeloma (MM). Among the most important are: the serum levels of β2-microglobulin, albumin, and LDH; the labeling index; and an abnormal karyotype. Patients with amyloidosis (AL) have poor prognosis; however, little is known concerning the prognostic significance of AL associated to MM. In 201 consecutive patients with de novo MM, we performed a fat-pad biopsy needle aspiration (FPBNA) that was stained with Congo red. Sixty eight (34%) patients had AL and a poorer prognosis disease: lower performance status, presence of B symptoms, higher LDH and calcium values, and worse response to chemotherapy. Cox regression model for overall survival detected three variables having independent prognostic significance: the presence of AL (RR = 3.4, P < 0.004), serum albumin levels <3.5 g/dl (RR 3.2, p < 0.005), and patients not achieving complete remission or very good partial remission (RR 2.9, p < 0.02). In 28% of patients with de novo MM, FPBNA was useful to detect incidental amyloidosis. During follow-up, 69% of these patients had symptoms of AL. Excluding 16 patients with obvious symptoms of AL at diagnosis, overall survival was worse in patients who developed later symptoms of AL. MM-associated AL represents a poorer prognosis disease even in the absence of symptoms at diagnosis, and this specific association may be considered as an independent high-risk prognostic factor. The routine study of periumbilical fat-pad tissue should be mandatory in all patients with MM. [ABSTRACT FROM AUTHOR]

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 μg/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±14.9×106/l vs 70.1±46.1×106/l, P<0.02). DCs were mobilized significantly with a 5.9-fold increase in DC2 (15.1±30.3×106/l vs 89.8±81.0×106/l, P<0.02) and a 2.6-fold increase for DC1 (41±42.5×106/l vs 109.5±58.0×106/l, P<0.04). Patients received a mean of 3.1±1.2×107/kg NK cells, 1.3±0.9×107/kg NKT cells, 0.41±0.29×107/kg DC1, 0.2±0.22×107/kg DC2, and 1.8±1.9×107/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. [ABSTRACT FROM AUTHOR]

To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) ± VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6×106/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5×107/kg NKT cells and less than 1.7×106/kg DC2 for disease-free survival (DFS), and a dose of less than 3×107/kg NK cells, less than 1.5×107/kg NKT cells, less than 3×106/kg DC1, and less than 1.7×106/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8×106/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT. [ABSTRACT FROM AUTHOR]

Between December 1993 and November 2001, 30 patients with chronic myeloid leukemia who relapsed after stem cell transplantation were studied. Seventeen patients were not treated before donor lymphocyte infusion (DLI), eight patients received interferon-α (IFN-α), and five underwent chemotherapy. The method of DLI was the bulk dose regimen. The median time between DLIs was 6 weeks. The median number of infusions was three; the median time from transplant to relapse was 17 months and from relapse to DLI 2 months. Eleven patients (37%) were in molecular/cytogenetic relapse, 14 (47%) in chronic phase, and five (16%) in accelerated or blastic phase. Seventeen patients (57%) developed acute graft-versus-host disease (GVHD). Chronic GVHD was observed in 15 of 24 (62%) patients. Four (13%) patients developed cytopenia after a median of 30 days. Nineteen (63%) patients achieved response, 15 of them developed GVHD. The response rate according to the disease phase was molecular or cytogenetic relapse: 91%, chronic phase: 57%, and accelerated or blastic phase: 20%. The median time to response was 6 months. Patients treated with IFN-α or no treatment as well as those who were in molecular/cytogenetic relapse and those who received a CD3+ cell dose <1×108/kg and CD4+ <8×107/kg had better survival. We conclude that patients who receive lower doses of lymphocytes have better survival. In some patients IFN-α seems to be a good choice to potentiate the graft-versus-leukemia (GVL) effect. [ABSTRACT FROM AUTHOR]