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R Arrieta

Publications and source records attributed to R Arrieta.

At least 19 recordsLinked to original sources

Analysis of factors affecting PBPC collection in low-weight children with malignant disorders.

BACKGROUND: PBPC collection in children weighing </=25 kg is hampered by technical and clinical problems related to vascular access, low total blood volume, anticoagulation, side effects, and psychological impact. The aim of this study was to analyze several clinical and technical factors, other than pre-apheresis CD34(+) count, that may affect PBPC collection in these low-weight children. METHODS: Data from 88 leukaphereses performed in 45 children were analyzed, including pre-apheresis CD34(+) cell count, COBE Spectra software (version 4.7 versus 6.0), apheresis volume [standard versus large-volume leukapheresis (LVL)] and patient's diagnosis, age, weight and sex. RESULTS: The median number of PBPC collected was 6.68 mononuclear cells (MNC)x10(8)/kg (range 2.36-19.05) and 1.69 CD34(+) cellsx10(6)/kg (range 0.08-13.79). Multivariate analysis showed that factors independently associated with the CD34(+) cell yield per apheresis were pre-apheresis CD34(+) cell count (P<0.001), diagnosis (P=0.008) and apheresis volume (P=0.009). Recruitment of CD34(+) cells was also independently affected by the apheresis volume, being higher in the LVL group (P=0.008). DISCUSSION: We have demonstrated that, apart from the well-known influence of the pre-apheresis CD34(+) cell count, two other factors have a major impact on the CD34(+) cell yield: patient's diagnosis and apheresis volume. In addition, taking into account that side effects were mild and tolerable, we have confirmed that LVL is a safe and effective procedure in children </=25 kg, and that AutoPBSC software could be reliably used in these patients, provided that an experienced team performs the procedure.

Antigens, CD34↗

Secondary acute myeloid leukemia and myelodysplasia after autologous peripheral blood progenitor cell transplantation.

Secondary myelodysplastic syndrome (MDS) and acute leukemia (AL) are well-known complications of antineoplastic therapy. The incidence of these serious complications after autologous hematopoietic transplantation ranges from 1.1% to 24%. Prior chemotherapy is its most likely cause, but other variables related to these long-term complications are seriously discussed. There is evidence that priming of progenitor cells isolated from peripheral blood with chemotherapy is also related to a higher risk of secondary MDS/AL. Whether progenitor cells isolated from bone marrow or peripheral blood after mobilization only with cytokines are related to higher risk is a controversial issue. In this paper, we analyze the incidence and variables related to these complications in a series of 99 patients diagnosed with lymphoma or multiple myeloma who underwent autologous transplantation using hematopoietic progenitors isolated from peripheral blood mobilized with granulocyte colony-stimulating factor (G-CSF). The probability of MDS/AL in patients alive 5 years after transplant in our series is 8.58%, similar to that reported in other series using bone marrow grafts. The total dose of cyclophosphamide ( p=0.099), the number of chemotherapy cycles ( p=0.04) received before transplant, and the total dose of mononuclear cells infused at the time of transplant were the only variables associated with secondary MDS/AL. Autologous transplantation with progenitor cells isolated from peripheral blood after mobilization with cytokines has probability and risk factors for secondary MDS/AL development similar to bone marrow grafts when compared with other published series.

Acute Disease↗

A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.

In a previous phase II trial of the synthetic topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), given as a 72-h infusion, we identified modest single agent activity of 9% in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Preclinical studies suggested that a more prolonged continuous infusion of the drug might lead to greater antitumor activity. A phase I study recommended a phase II dose of 25 microg/m2/hr for 120 h (3000 microg/m2 over 5 days), administered for 2 consecutive weeks of a 3-week cycle. We utilized this schedule and enrolled 13 chemotherapy-naïve patients with Stage IIIB and IV NSCLC in this trial: median age 67 (range 57-74); 46% male; 92% stage IV; and median performance status 1. Twelve patients are available for response and toxicity evaluation after 2 cycles of therapy. One patient achieved a partial response. Four patients had stable disease while seven patients had progressive disease. Patients with stable or progressive disease after two cycles received no additional 9-AC, and were offered conventional chemotherapy. The median survival time was 10.2 months and the one-year survival rate 28% (95% confidence interval, 5-58%). Significant toxicities included myelosuppression, fatigue, and anorexia. One patient had grade 4 neutropenia following the first week of cycle 2, and did not receive additional therapy. There were no neutropenia-related infections. These data suggest that this prolonged schedule is unlikely to increase 9-AC's very modest activity in NSCLC above that seen with the simpler 72-h administration schedule. Further evaluation of 9-AC in NSCLC is not recommended.

Aged↗

Donor age-related differences in PBPC mobilization with rHuG-CSF.

BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of 5 days (range, 4-6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B, respectively. Fifty-six percent of Group A donors needed only one apheresis to achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001). CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.

Adolescent↗

Identification of factors associated with poor peripheral blood progenitor cell mobilization in Hodgkin's disease.

BACKGROUND AND OBJECTIVES: Although the use of drugs which damage stem cells is common in patients with Hodgkin's disease (HD), factors affecting peripheral blood progenitor cell (PBPC) mobilization have not been clearly established in this group of patients. The aim of this study was to identify factors associated with poor PBPC mobilization in patients with HD. DESIGN AND METHODS: In order to address this issue we have evaluated in 54 patients with HD mobilized with G-CSF alone the following factors: sex, age, histologic subtype, B symptoms at diagnosis, status of remission, previous chemotherapy and radiotherapy, interval from diagnosis and last chemotherapy cycle to harvest, and dose of G-CSF. Univariate analysis was performed using Student's t-test, Pearson's correlation and Spearman's correlation. A stepwise regression model was used to determine which of the variables was the most predictive of PBPC mobilization. RESULTS: In univariate analysis poorer PBPC mobilization was observed in patients who had previously received at least two courses of mini-BEAM (p=0.006), a high number of different chemotherapy regimens (p=0.002), a chemotherapy score >30 (p=0.02) and more than 9 months of alkylating agents (p=0.07). We did not find radiotherapy to be a significant factor affecting progenitor cell yield (p=0.59). In the stepwise regression model, only the previous administration of two or more mini-BEAM cycles predicted a poor PBPC yield (p=0.006). INTERPRETATION AND CONCLUSIONS: Previous chemotherapy, principally exposure to a mini-BEAM regimen, seems to be the principal factor affecting collection of PBPC in patients with HD mobilized with G-CSF alone. Since mini-BEAM is an effective salvage regimen in relapsed or refractory HD, collection of PBPC should be planned when there has been no or only minimal exposure to a mini-BEAM regimen.

Adolescent↗

Factors influencing collection and engraftment of CD34+ cells in patients with breast cancer following high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation.

Although autologous PBPC transplantation is being used increasingly for the treatment of breast cancer, there are few data on factors influencing mobilization and engraftment in these patients. We have analyzed these factors in 70 patients with advanced or metastatic breast cancer undergoing autologous PBPC transplantation. All patients were mobilized after stimulation with G-CSF, and a median of 3.16 x 10(6)/kg CD34+ cells (range 0.75-23.33) were infused. All patients received conditioning with a combination of cyclophosphamide, thiotepa, and carboplatin, and postinfusion G-CSF was administered to 60 patients. The median times to reach 0.5 x 10(9)/L and 1 x 10(9)/L neutrophils were 10 and 11 days, respectively. The median times to obtain 20 x 10(9)/L and 50 x 10(9)/L platelets were 12 and 18 days, respectively. An analysis of factors that influence CD34+ cell collection was performed by linear regression. Previous radiation therapy and increasing age were associated with lower numbers of CD34+ cells collected. Those variables that could influence the tempo of engraftment were examined by multivariate analysis using Cox regression models. The number of CD34+ cells infused was found to influence both neutrophil and platelet recovery. The use of G-CSF after transplant, accelerated neutrophil recovery, and having more than six cycles of previous chemotherapy was an unfavorable factor for recovering >50 x 10(9)/L platelets.

Adult↗

A prospective randomized trial of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in adults.

In order to assess the potential clinical benefit of filgrastim (G-CSF) after peripheral blood stem cell (PBSC) autotransplantation a randomized study was begun in our center in July 1997: 62 patients were involved (30 received filgrastim after PBSC infusion and 32, the control group, received no cytokines). All were adults (median 40 years, range 18-65). Patients with one of three different pathologies were recruited: 28 had advanced breast carcinoma, 23 had lymphomas (12 Hodgkin's disease and 11 non-Hodgkin's lymphoma) and 11 had de novo AML. All of them were transplanted using myeloablative chemotherapy conditioning regimens. G-CSF was administered subcutaneously from day +5 in the treated group at a dose of 5 microg/kg body weight/day. The numbers of CD34+ and mononuclear (MNC) cells infused were similar in each group. Only minor differences regarding the use of G-CSF could be inferred from the analysis of the data. Faster granulocyte engraftment was evident in the treated group (mean of 10 vs 12 days to achieve >0.5 x 109/l granulocytes, P = 0.0008), without differences in incidence and severity of infections, days of fever or duration of antibiotic treatment between groups. There was slightly slower platelet engraftment (mean of 15 days in the group with G-CSF vs 12 days in the other group to achieve >20 x 109/l platelets, P = NS) in this series, but there were no differences in incidence and severity of haemorrhage or platelet transfusion support. Considering the economical costs, the median expenditure per inpatient stay was Eur5961 (range Eur4386-Eur17186) in the G-CSF group compared with Eur5751 (range Eur3676-Eur15640) in the control group (P = 0.47). From our data it could be concluded that for adult patients transplanted with PBSC there is no clear beneficial impact of post-infusion G-CSF administration.

Adolescent↗

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry. Spanish Group of Allo-PBT.

A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.

Adolescent↗

Hematopoietic cell transplantation using plasma and DMSO without HES, with non-programmed freezing by immersion in a methanol bath: results in 213 cases.

A simplified cryopreservation method for bone marrow (BM) and peripheral blood progenitor cells (PBPC) was utilized in hematopoietic cell transplantation of 213 patients with hematological or solid neoplasms after ablative chemotherapy (187 with peripheral blood progenitor cells and 26 with bone marrow). Cells were cryopreserved, after addition of autologous fresh plasma with DMSO, without HES, by freezing to -80 degrees C in a methanol bath and non-programmed freezer. For the patients autotransplanted with PBPC, the median period necessary for recovery of more than 0.5 x 10(9)/l granulocytes was 11 days (range 6-44), and 15 (8-204) days were required to obtain more than 20 x 10(9)/l platelets. For the patients autotransplanted with BM, the median period necessary to recover >0.5 x 10(9)/l granulocytes was 12 days (range 9-33), and 24 (12-57) days to obtain more than 20 x 10(9)/l platelets. These results support this method as being very effective in achieving high-quality cryopreservation. The procedure, which uses a non-programmed freezer, simplifies and reduces enormously the cost of the technical measures currently in use, enabling its adoption in almost any clinical oncological institution.

Adolescent↗

Haploidentical peripheral blood stem cell transplantation with a combination of CD34 selection and T cell depletion as graft-versus-host disease prophylaxis in a patient with severe combined immunodeficiency.

Severe combined immunodeficiencies are a group of rare genetic disorders characterized by a profound impairment in both cellular and humoral immune functions. This disorder is rapidly fatal without bone marrow transplantation. Unfortunately, most children lack a histocompatible donor. The development of T cell depletion allows for haploidentical transplantation with reduced risk of GVHD. In the present article, we discuss the case of a child diagnosed with X-linked severe combined immunodeficiency for whom haploidentical peripheral blood stem cell transplantation was performed by selecting CD34-positive cells followed by depletion of T cells. Both selection and purging were performed using immunoselection by the biotin-avidin system (CEPRATE System). The CD34-enriched T cell-depleted product contained 5.05 x 10(6)/kg CD34+ cells with only 0.01 [corrected] x 10(6)/kg CD3+ cells, achieving a T cell depletion of 4.2 log.

Antigens, CD34↗

Single-centre experience of peripheral blood stem cell transplantation using cryopreservation by immersion in a methanol bath.

A simplified method to remove and cryopreserve peripheral blood stem cells (PBSC) was utilised to restore the bone marrow in 31 patients with haematological or solid neoplasms after ablative chemotherapy. Mobilization was performed with subcutaneous G-CSF, starting 4 days before the first PBSC harvest and continuing to the last day of harvest. Cryopreservation was carried out by freezing cells to -80 degrees C after addition of autologous fresh plasma with DMSO, in a methanol bath and non-programmed freezer. The PBSC were reinfused in all cases. The mean quantity of CD34 cell (x 10(6)/kg) infused was 6.5 +/- 6.7. The mean number of procedures needed to harvest an appropriate number of PBSC was 3.6 +/- 1.3. The mean times necessary to recover more than 0.5 x 10(9)/l granulocytes were 11 +/- 4 (8-30) days and 23 +/- 13 (8-55) days to obtain more than 20 x 10(9)/l platelets. These results confirm our method as very effective in achieving a high-quality harvest, and it was used in paediatric and adult patients without problems. This procedure, using a non-programmed freezer, simplifies and reduces enormously the cost of the technical measures currently used, enabling their adoption in almost any clinical oncological institution.

Adolescent↗

[Severe hemolytic anemia caused by anti-AB in renal transplantation with minor ABO incompatibility].

A 54 year-old woman subjected to renal transplant with minor ABO incompatibility developed clinically severe anti-AB haemolytic anaemia. On the 13th day after transplantation the patient had: haemoglobin, 7.5 g/dL, unconjugated bilirubin, 393 mumol/L (23 mg/dL), and undetectable haptoglobin levels. Positive direct antihuman globulin test was found, and an IgG antibody capable of binding complement and with anti-AB specificity was found upon studying the eluate. Immunosuppressive therapy improved the clinical picture, although antibodies could still be detected one month later. Clinically significant immune haemolysis after renal transplantation appears in about 10-15% of those cases having antibodies against the host's antigens. The peak red-cell destruction is seen one to two weeks after grafting, and haemolytic signs may last for about three weeks. Although self-limited, this condition may achieve high severity. The duration and severity of haemolysis depend upon the density of antigen sites on the surface of the host's red-cells, his secretor trait, the presence or absence of complement activation and the immunosuppressive therapy including cyclosporin. Several cases of anti-A and anti-B specificity have been reported, but anti-AB specificity had not been previously found; this fact is probably related to the scarce interest paid to its search thus far.

ABO Blood-Group System↗