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R Preti

Publications and source records attributed to R Preti.

11 recordsLinked to original sources

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer.

We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m2 and doxorubicin 50 mg/m2. The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC. Blood-derived stem cells were collected after the first HDC cycle, processed using CD34+ cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01). Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (>36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs < or = 13%, P < or = 0.0002) when compared with PBT-01 patients. Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients. Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation.

Adult↗

A phase II trial evaluating the safety and effectiveness of the AastromReplicell system for augmentation of low-dose blood stem cell transplantation.

To reduce the number of apheresis procedures and maintain the usual rate of hematopoietic recovery in patients treated with high-dose chemotherapy, we studied the effect of adding a small volume of ex vivo expanded bone marrow to low doses of CD34(+) blood stem cells. Thirty-four patients with breast cancer received G-CSF (10 microg/kg/day) priming followed by a limited volume (50-100 ml) bone marrow aspiration and standard 10-liter aphereses. Marrow was expanded ex vivo using the AastromReplicell system and infused along with low doses of blood-derived CD34(+) cells, collected in one apheresis. Thirty-one evaluable patients received a median CD34(+) blood stem cell dose of 0.7 x 10(6)/kg (range, 0.2-2.5) and 4.7 x 10(7) nucleated cells/kg (range, 1.98-8.7) of ex vivo expanded marrow. All patients recovered with normal blood counts and engrafted 500 neutrophils/microl and 20 000 platelets/microl in a median of 10 and 13 days, respectively. Multivariate analysis revealed that, in addition to CD34(+) lineage negative cell quantity, the quantity of stromal progenitors contained in the ex vivo expanded product correlated with engraftment outcome (r = 0.551, P = 0.004). Our results indicate that ex vivo expanded bone marrow is capable of facilitating engraftment when combined with low doses of mobilized blood derived CD34(+) cells.

Adult↗

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome.

Forty-five patients with metastatic breast cancer without clinically evident disease were treated with thiotepa 750 mg/m2, mitoxantrone 40 mg/m2 and carboplatin 1000 mg/m2 followed by stem cell transplantation to determine the safety and efficacy of CD34+ selection of peripheral blood stem cells. Of these, 15 patients' (group I) stem cells were processed through Baxter Isolex 300 device for CD34+ selection, whereas 30 patients (group II) received unmanipulated stem cells. Toxicity, progression-free survival and survival were compared between these two groups. There was no difference in transfusion requirements, white cell count and platelet recovery and non-hematologic toxicity between the two groups. The survival of patients in group I was 27 months compared to 38 months in group II (P = 0.8). The progression-free survival was 12 months and 13.5 months for group I and group II patients, respectively (P = 0.6). Our results indicate that while there is no adverse effect, there is also no significant advantage of CD34+ selection in terms of progression-free survival and survival in patients with metastatic breast cancer without clinically evident disease. Bone Marrow Transplantation (2000).

Adult↗

Transplantation of CD34+ peripheral blood cells selected using a fully automated immunomagnetic system in patients with high-risk breast cancer: results of a prospective randomized multicenter clinical trial.

Tumor contamination of autologous peripheral blood stem/progenitor cell grafts occurs in a substantial proportion of high-risk breast cancer patients, and the possibility that such contamination may contribute to relapse has focused attention on methods for removal of the contaminating cells prior to transplantation. One such approach is positive selection of CD34+ cells. A fully automated immunomagnetic cell selection system has recently been introduced to facilitate the positive selection process. A multicenter randomized clinical trial was designed to evaluate the capacity of CD34+ cells isolated using the fully automated system to support prompt hematopoietic reconstitution following high-dose chemotherapy in high-risk breast cancer patients, as well as to assess the safety and tolerability of the CD34+ cell transplants. In recipients of isolated CD34+ cells, the median time to an absolute neutrophil count > or =500/microl was 10 days, a value identical to that observed in patients receiving unfractionated apheresis collections. In the isolated CD34+ cell recipients median time to a platelet count > or =20 000/microl was 12 days, compared with 10 days in the unfractionated cell group. There were no statistically significant differences between the groups in median time to neutrophil or platelet engraftment. Infusion of autologous cells was well tolerated by the study groups. There were no inter-group differences in the incidence of infections, need for platelet transfusions, or duration of hospitalization. Isolated CD34+ cells were high in purity and sufficient in number for use in autologous transplantation. The fully automated immunomagnetic cell selection system affords an efficient and time-saving option for isolation of CD34+cells to be used as autologous grafts in high-risk breast cancer patients, and the isolated CD34+ cells support undelayed hematopoietic reconstitution.

Adult↗

Effects of long-term storage at -90 degrees C of bone marrow and PBPC on cell recovery, viability, and clonogenic potential.

Autologous BM and PB HPC are usually stored from weeks to months until reinfusion after myeloablative chemotherapy. HPC have been stored for up to 16 months at -90 degrees C, using a mixture of 5% DMSO, 6% hydroxyethyl starch (HES), and 4% HSA as a cryoprotectant. Long-term storage (LTS) has usually entailed rate-controlled freezing using 10% DMSO and preservation in liquid nitrogen. The effects of LTS at -90 degrees C on the in vitro cell recovery, viability, and colony-forming unit-granulocyte macrophage (CFU-GM) clonogenic potential of autologous HPC that were not transplanted was studied. Sixteen BM and sixteen PB HPC had been cryopreserved for a median of 53 months (range 27-71) and 35 months (range 26-78), respectively. Samples of frozen HPC were thawed after 48 h, and the nucleated cell count, viability by trypan blue exclusion, and culture for CFU-GM were obtained. Following LTS, the cells were thawed and examined using the same assays. No difference in the median percentage recovery of nucleated cells was found in either the BM or PB HPC between the samples stored for 48 h and after LTS (5.73 x 10(9) versus 5.61 x 10(9) and 6.20 x 10(9) versus 5.78 x 10(9), respectively). In addition, no difference in median percentage viability was found in either the BM or PB HPC sampled at 48 h and at the end of LTS (75% versus 74% and 75% versus 76%, respectively). Finally, the median number of CFU-GM cultured from BM HPC at 48 h was 2.41 x 10(5) (range 0.33-11.01 x 10(5)) and at the end of LTS was 1.93 x 10(5) (range 0.32-10.55), representing a median recovery of 93% (range 19%-308%). Similarly, the median number of CFU-GM cultured from PB HPC was 1.66 x 10(5) (range 0-50.57) and at the end of LTS was 0.93 x 10(5) (range 0-44.9), representing a median recovery of 80% (range 36%-165%). This difference in percentage recovery was not significant (p = 0.514). There was poor correlation between the number of nucleated cells harvested and the percentage recovery of nucleated cells, cell viability, or CFU-GM for either the BM or PB HPC. Similarly, there was poor correlation between the number of CFU-GM in the harvest and their percentage recovery following LTS for both BM and PB HPC. Finally, there was poor correlation between the storage time of the BM or PB HPC and the percentage recovery of nucleated cells, cell viability, and CFU-GM. These data suggest that LTS of HPC at -90 degrees C is not associated with decreased recovery of nucleated cells or in vitro viability and is associated with only a modest decrease in clonogenic potential. This indicates that storage of HPC at -90 degrees C for periods in excess of 3 years is possible.

Blood Preservation↗

[Right ventricular infarct and atrioventricular blocks].

Right ventricular infarction in inferior left ventricular infarction is very common. We have examined, by means of equilibrium gated radionuclide angiography, the relationship existing between right ventricular infarction and atrioventricular block. Seventy-two patients with inferior wall myocardial infarction were studied. Thirty-nine of them had ventriculographic evidence of right ventricular infarction. Fifteen of them (38%) had a-v block in the acute phase. Only 3 patients without right ventricular involvement (9%) had a-v block. The occurrence of a-v block is usually explained by the fact that the blood supply to the a-v node depends on the right coronary artery. In the patients with right ventricular involvement, the incidence of a-v block is high just because occlusion of the right coronary artery is proximal to the branch to the a-v node. However, the presence of collateral blood supply to the a-v node makes the occurrence of a-v node not so high as expected.

Adult↗

Platelet aggregation behaviour in patients treated with ticlopidine.

Thirty patients (18 women, 12 men) with permanent or paroxysmal atrial fibrillation were treated with a new antiplatelet drug, ticlopidine, in order to study platelet aggregation behaviour, to see whether the drug prevents thromboembolisms and to observe side-effects over a period of 6 months. A further comparative study of the effects of ticlopidine and dipyridamole + aspirin on platelet aggregation was carried out in 20 patients. All appropriate haematological parameters were tested every 3 months, while platelet aggregation curves with ADP were examined also after 15 days. At the end of the period an echocardiogram was performed to check for any sign of thrombosis. The reduction in the aggregation curves was statistically significant for all the ADP stimuli, except at low doses. In the comparison with dipyridamole + aspirin, ticlopidine gave better results; with the former there was no significant reduction in platelet aggregation. A more significant reduction was seen in patients who had showed hyperaggregation at the outset. Bleeding time was increased and platelet adhesivity was reduced. During the 6-month period a slight reduction in white blood cells and a slight increase in creatinine were observed, both remaining within the normal range. Some 33.3% of the patients experienced side-effects. No embolic event or thrombosis in the left atrium was seen. Ticlopidine seems to be an effective antiplatelet drug, especially for patients with hyperaggregation.

Adult↗