Search PubMed⌕ Search

Biomedical subjects

S Sica

Publications and source records attributed to S Sica.

At least 55 records · Page 3Linked to original sources
PubMed2000

Stem cell collection using the dideco excel continuous flow blood cell separator: parameters for optimal stem cell collection timing.

This study evaluates stem cell collection procedures performed with the Dideco Excel blood cell separator, with particular attention given to yields and separator collection efficiencies. Patients' blood precounts and yield parameters related to the harvest capacity of the collection system were investigated. Fifty-five collection procedures were analyzed in 32 patients suffering from hematological malignancies and solid tumors and mobilized with chemotherapy plus G-CSF. The median blood volume processed in each procedure was 15.8 liters (12-19.750), with a blood flow rate of 70 ml/min. Patients had the following median blood precount value: NC 7.81x10(9)/L, CD34+ cells 49.08x10(3)/ml. Leukapheresis procedures gave the following yields: NC 14.95x10(9), MNC 10.83x10(9), CD34+ cells 4.37x10(6); yields/kg, NC 0.21x10(9)kg, MNC 0. 15x10(9)/kg CD34+ cells 4.26x10(6)/kg. Procedures show the following collection efficiencies: NC 10.79%, MNC 29.06%, CD34+ 42.33%, PLT 26.5%. The RBC (red blood cell) contamination of the product was (median value) 20.9 ml for each procedure, and for platelets 1.76x10(11) per procedure. The CD34+ cell precounts strongly correlated with the CD34+ yields/kg (r=0.82. p=0.000). Furthermore the NC and MNC precounts correlated with the CD34+ yields/kg but only the MNC precount correlation is notable (r=0.57, p=0.000). The logistic regression analysis shows that CD34+ (p=0.008) but not NC (po=0.14), MNC (p=0.09), or PLT (p=0.53) precounts significantly influenced the collection of a sufficient dose of CD34+ cells for transplantation (> or =2.5x10(6)/kg). Eleven of the thirty-two patients have been transplanted till now, and all had a prompt and lasting trilineage engraftment NC >1x10(9)/L on day 12 (10-17). Our data show that the collection system analyzed in this report is able to collect large amounts of progenitor cells, harvesting >2.5x10(6)/kg CD34+ cells with a single procedure in 68.8% of patients and assuring complete recovery after stem cell transplantation.

Adolescent↗
PubMed1999

Optimal timing of G-CSF administration after CD34+ immunoselected peripheral blood progenitor cell transplantation.

G-CSF accelerates neutrophil recovery after autologous peripheral blood progenitor cell transplantation (aPBPCT), although the optimal timing for its administration is currently unknown. In order to establish the role and the optimal timing of administration of G-CSF after immunoselected CD34+ aPBPCT, we analyzed the data from 21 consecutive patients affected by haematological malignancies. Patients were randomized into three groups according to G-CSF administration after transplantation: day +1 (group B); day +7 (group C) or no G-CSF (group A). Serum G-CSF level was evaluated until engraftment. The CD34+ cell dose reinfused was similar (P = 0.48). G-CSF significantly reduced time to recovery of PMN >0.5 x 10(9)/l (11 vs 14 vs 20.5 days) (P= 0.00046); >1.0 x 10(9)/l (12 vs 15 vs 22) (P = 0.001). No difference was observed in the number of days with PMN <0.1 x 10(9)/l (5.5 vs 7 vs 8 days). Platelet count >50 x 10(9)/l and >100 x 10(9)/l, reticulocytes >1%, length of hospitalization, non-prophylactic antibiotic therapy, fever, incidence of sepsis and transfusion support did not differ. Early or delayed G-CSF after immunoselected CD34+ aPBPCT significantly accelerated PMN recovery but did not reduce the amount of supportive treatment or the duration of hospitalization. Delaying the initiation of G-CSF did not reduce the length of treatment (11.5 vs 12 days). Early or delayed G-CSF administration resulted in G-CSF peak serum levels 7 (early)-12 (delayed)-fold greater than an endogenous response to neutropenia.

Adolescent↗
PubMed1999

Severe thrombotic microangiopathy: an infrequent complication of bone marrow transplantation. Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Thrombotic microangiopathy (TMA) usually occurs during the first weeks following transplantation in the setting of systemic infections or graft-versus-host reaction. However, some cases without any evidence of other complications or after autologous transplantation have been reported. Transplant-associated TMA (BMT-TMA) incidence ranges from 0% to 74%, possibly due to different diagnostic criteria. The GITMO Group provided the opportunity to retrospectively study 4334 consecutive Italian patients who received bone marrow transplants (1759 allogeneic and 2575 autologous BMT), during the 1985-1995 period. The present report focuses on patients with severe TMA requiring specific treatment. We identified nine cases of TMA as a complication of allogeneic BMT (0.51%), whereas three patients developed the syndrome after ABMT (0.13%); four of the 12 patients were not receiving CsA at the time of TMA onset. Finally, it is noteworthy that TMA occurred in seven patients as a late complication (up to 90 days after BMT). Despite intensive treatment, five of the seven patients with thrombotic thrombocytopenic purpura died. One death was observed among the five cases with hemolytic uremic syndrome.

Adult↗
PubMed1999

Inappropriate antidiuretic hormone secretion after high-dose thiotepa.

High-dose thiotepa has been successfully included in a variety of conditioning regimens for stem cell transplantation in hematological and solid neoplasms. Toxicity of high-dose thiotepa mainly manifests as profound myeloablation and some degree of liver damage. We report a case of inappropriate secretion of antidiuretic hormone (SIADH) in a patient with primary CNS lymphoma who underwent therapy with high-dose thiotepa.

Adult↗
PubMed1999

Factor V Leiden and allogeneic bone marrow transplantation: chimerism as a confounding factor in genetic test interpretation.

Factor V Leiden is one of the most common genetic conditions predisposing to venous thrombosis. Diagnosis is currently made by plasma activity assay for activated protein C (APC) resistance or polymerase chain reaction (PCR)-based DNA assay. The occurrence of factor V Leiden is reported in a patient affected by acute myeloid leukaemia submitted to allogeneic bone marrow transplantation from an HLA identical sister. The donor was not affected by the factor V mutation. The patient did not develop thrombosis during induction and consolidation chemotherapy and the post-transplantation course was not complicated by thrombosis or veno-occlusive disease. At engraftment, PCR analysis showed the disappearance of factor V Leiden. Genetic tests on DNA after allogeneic marrow transplantation should be carefully interpreted as a result of donor chimerism.

Bone Marrow Transplantation↗
PubMed1999

Highly fluorescent reticulocyte count predicts haemopoietic recovery after immunosuppression for severe aplastic anaemia.

Highly fluorescent reticulocyte (HFR) counts are the most reliable and sensitive index of haemopoietic recovery after bone marrow or peripheral blood stem cell transplantation. We report the behaviour of HFRs during haemopoietic recovery in two patients who were affected by severe aplastic anaemia (SAA) and treated with horse antithymocyte globulin (ATG), cyclosporin A (CsA) and granulocyte colony-stimulating factor (G-CSF). A HFR value > 5% of the total reticulocyte count, a reticulocyte count > 30 x 10(9)/l, and a polymorphonuclear (PMN) count > 0.5 x 10(9)/l were found after 9 and 8, 20 and 46, and 16 and 22 days, respectively, after the end of ATG. HFR recovery to > 5% anticipated the rise of PMN > 0.5 x 10(9)/l by at least 7 and 14 days, respectively. Thus, HFR evaluation could be used as a reliable and early marker of response to immunosuppression in severe aplastic anaemia.

Adolescent↗
PubMed1999

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF): effects on lymphocyte phenotype and function.

Granulocyte colony-stimulating factor (G-CSF) can be administered to healthy donors to mobilize CD34+ peripheral blood progenitor cells (PBPC) for transplantation into HLA-matched allogeneic recipients. Current clinical trials report a similar incidence and severity of acute graft-versus-host disease (G-VHD) compared with transplantation of allogeneic bone marrow (BM) despite the infusion of 1-2 more logs of T lymphocytes. An overview of modulation of T cell function both in animal models and in humans receiving G-CSF is provided. The experimental evidence summarized in the present article highlights a powerful immunoregulatory action exerted by G-CSF, consisting of (1) increase in soluble immunoregulatory cytokines, (2) inhibition of lymphocyte proliferation, and (3) induction of lymphocyte partial activation after mitogenic challenge. These findings offer an experimental background for promising and innovative approaches to cytokine therapy.

Graft vs Host Disease↗
PubMed1999

Large volume leukapheresis for collecting hemopoietic progenitors: role of CD 34+ precount in predicting successful collection.

In this work we evaluated the efficacy of stem cell collection with Large Volume Procedures. (LVP), and analysed the importance of the CD34+ cell precount in promoting the collection of a sufficient number of CD34+ cells for transplantation, using the Univariate Logistic Regression analysis. Eighty-nine leukapheresis were performed in 49 patients with hematological malignancies and solid tumors, mobilized with chemotherapy plus Granulocyte Colony Stimulating Factor (G-CSF). For each procedure 15.8 liters of blood were processed. The median value of Nucleated Cells (NC) and CD34+ cells precount was respectively 8.29 x 10(9)/ml (range 1.13/45.4) and 43.08 x 103/ml (range 1.06/795.2). Results show the capability of LVP to collect large quantities of hemopoietic progenitors with a median CD34+ cell total yield of 215.02 x 10(6) (range 5.03/2210). The yields per patients' body weight were: CD34+ cells 3.23 x 10(6)/kg (range 0.081/41.58). The regression analysis between blood cell precounts and collection yields gave the following correlations: the CD34+ cell precount correlates with CD34+ yield (r = 0.78 p < 0.00) and with CD34+ cell yield/kg (r = 0.76 p < 0.00). The number of CD34+ cells processed correlated with the number of CD34+ cells collected/kg (r = 0.83 p < 0.000). To investigate the importance of CD 34+ cell precount in promoting CD34+ cell yields > or =2.5 x 10(6)/kg we performed a Univariate Logistic Regression analysis that showed in our patients a probability of collecting > or =2.5 x 10(6) CD34+/kg that rose from 0.6 to 0.95 for CD 34+ precounts that oscillated from 30 to 40 x 10(3) CD34+ cells/ml, respectively. The Univariate Logistic Regression gave a probability of collecting > or =2.5 x 10(6) CD34+ cells/kg that oscillated between 0.64/0.98 for values of CD34+ cells processed from 6 x 10(6)/kg to 8 x 10(6)/kg, p < 0.000. Sixty-three percent of patients reached the target dose of 2.5 x 10(6) CD34+ cells/kg with only one LVP. Until now 12 patients have been transplanted and all have had a prompt and complete lasting recovery. These results confirm the efficacy of LVP in harvesting hemopoietic progenitors and their ability in reconstituting hemopoiesis of transplanted patients, enabling the estimation of CD34+ precounts and CD34+ cells processed values, highly predictive for the collection of > or =2.5 x 10(6) CD34+ cells/kg. Furthermore, the Logistic Model suggests that the best strategy to plan a successful CD34+ cell collection procedure is to identify for each patient the amount of CD34+ cells/kg to be processed rather than the fixed processing of 3/5 blood volumes in all patients.

Adolescent↗
PubMed1999

Autologous transplantation in multiple myeloma: a GITMO retrospective analysis on 290 patients. Gruppo Italiano Trapianti di Midollo Osseo.

BACKGROUND AND OBJECTIVE: Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions we assessed the results of autologous transplantation in a large cohort of patients whose data were reported to the GITMO registry. DESIGN AND METHODS: We retrospectively analyzed data from 290 patients with MM (M = 150; F = 140; median age 52 years, range 19-70; stage I = 34, stage II = 75, stage III = 167) reported to the GITMO. At the time of autograft, 20% were in CR, 66% in PR, while the remaining had non-responsive or progressive disease. Median time between diagnosis and transplant was 16 months (1-90). Seventy-two patients (26%) had been planned to receive a double autograft, but this was actually done in only 35 (12%). The conditioning was chemotherapy in 90%. Peripheral blood was the only source of stem cells in 94%, and purging was applied in 10% of cases. For statistical analysis of data, differences between patient subsets were analyzed using the chi-square test, while the Kaplan-Meier method was used to estimate event-free survival (EFS) and survival (OS) probabilities. The Cox model was used for multivariate analysis. RESULTS: Following the autograft, 116 patients (40%) were in CR, 144 (50%) in PR, 24 (8%) did not respond or progressed and 6 (2%) died before response evaluation. Transplant-related mortality occurred in 3%. At a median follow-up of 23 months, 223 (77%) patients are alive, 71 (24%) of them in CR, and 67 (23%) patients have died at a median time of 20 months (0-70). OS and EFS at 6 years are 47% and 28%, respectively, but the EFS curve shows no plateau. In multivariate analysis, age, beta2-microglobulin level and status at transplant emerged as significant prognostic factors for both OS and EFS, while time from diagnosis to transplant showed borderline significance. INTERPRETATION AND CONCLUSIONS: Based on the prognostic factors identified in multivariate analysis, we were able to assess the weight of a single prognostic factor or their combinations on transplant outcome. We also calculated the probability of OS and EFS by the number of factors at the time of autograft. Autologous transplantation is a safe and effective procedure, not only in sensitive patients, but also in resistant cases, provided they are <55 years of age and have low beta2-microglobulin. It should be applied early after the diagnosis of multiple myeloma, following the delivery of brief primary chemotherapy.

Adult↗
PubMed1999

The application of two different blood cell separators to harvest CD34+ cells in patients suffering from non Hodgkin's lymphoma.

From January 1996 until now, thirty-eight PBSC procedures were carried out on 20 patients suffering from NHL, mobilized by polichemotherapy regimens plus recombinant human Granulocyte-Growth Factor (rhG-CSF). Patients were enrolled in PBSC procedures using Dideco Excel (group A) and Cobe Spectra v.4.7 (group B) blood cell separators. Twelve patients were enrolled in group A (6 males and 6 females, median age 33) and 9 patients in group B (5 males and 4 females, median age 55). The mean White Blood Cell (WBC) and Mononuclear Cells Fraction (MNC) peripheral blood counts were not statistically different in either group and neither were blood CD34+ cell peripheral counts. CD34+ cell peripheral value was predictive of the CD34+ yield while mean values of harvested CD34+ cells were not significantly different. CD34+ cell efficiencies were statistically the same. The CD34+ cell purity of the apheresis harvest was statistically different between the two groups (group A = 3.0+/-2.2%; group B = 1+/-0.9%) p = 0.001. High CD34+ cell yields were observed in both groups which confirms that both blood cell separators are able to harvest hematopoietic progenitor cells from peripheral blood.

Adolescent↗
PubMed1999

Long-term immune recovery after CD34+ immunoselected and unselected peripheral blood progenitor cell transplantation: a case-control study.

BACKGROUND AND OBJECTIVE: CD34+ stem cell selection induces extensive T-cell depletion as a consequence of ex vivo manipulation. The impact of T-cell depletion on long-term immunologic recovery after autologous CD34+ peripheral blood progenitor cell transplantation (CD34+ PBPCT) is not well characterized. We compared the long term immunologic recovery in two groups of patients submitted to CD34+ PBPCT or unselected autologous peripheral blood progenitor cell transplantation (uPBPCT). DESIGN AND METHODS: Eight patients in both groups were closely matched for diagnosis, age, disease status at transplantation and conditioning regimen and lymphocyte phenotype was prospectively evaluated during long-term post-transplantation follow-up. RESULTS: At a median of 18 months after transplantation, CD3+ lymphocyte subset remained below the normal range in both groups. CD19+ B lymphocytes subset after CD34+ PBPCT was within the normal range in both groups. CD4+ lymphocytes were depressed while the CD8+ lymphocyte subset was increased in group A and in the normal range in group B. As a result, inversion of CD4/CD8 ratio was documented in both groups. T-activated lymphocytes (CD3DR+) and natural killer (CD16/56+) cells were increased in both groups. INTERPRETATION AND CONCLUSIONS: Long-term immune recovery appears to be unaffected by extensive ex vivo manipulation in this adult population when compared to recovery after unmanipulated PBPCT. CD34+ selection, although causes an extensive depletion of T lymphocytes in the graft does not represent a risk factor for delayed CD4+ recovery late after transplantation. Elevated numbers of NK cells and activated T-cells, which have antineoplastic activity, are maintained late after autologous CD34+ transplantation.

Adult↗