Comparison of two prognostic models for acute pulmonary embolism: clinical vs. right ventricular dysfunction-guided approach.

BACKGROUND: Recently, some prognostic models for acute pulmonary embolism (PE) have been proposed. We investigated whether the Pulmonary Embolism Severity Index (PESI) and the European Society of Cardiology (ESC) prognostic approaches result in different prognoses. METHODS: Consecutive adult patients with acute PE were included. According to the ESC guidelines, high-risk patients were identified by the presence of shock/hypotension, intermediate-risk patients by elevated troponin I or right ventricular dysfunction as assessed by echocardiography, and low-risk patients by the absence of any of the above. In the PESI model, 11 clinical variables, easily accessible at the bedside, were used to generate three risk classes. The main outcomes were all-cause and PE-related in-hospital mortality. RESULTS: Forty-one patients (8%, 95% confidence interval [CI] 5.8-10.8) of 510 died. According to the ESC model, 40% were at low risk of short-term mortality, 54% at intermediate risk, and 6% at high risk. The distribution according to the PESI model was 31% (P < 0.05 vs. ESC), 49% and 20% (P < 0.05 vs. ESC), respectively. Mortality increased through the risk classes (P < 0.01), without significant differences between the models. The ESC model identified with higher accuracy than the PESI model both high-risk and low-risk patients (P < 0.05 for both). When patients with shock/hypotension were excluded, the PESI model stratified patients into classes with increasing PE-related mortality (0.7%, 4.3%, and 11.6%, P < 0.05). Troponin I and right ventricular dysfunction added incremental prognostic value to the PESI model, particularly in normotensive patients at intermediate risk. CONCLUSIONS: The ESC model showed higher accuracy than the PESI model in identifying high-risk and low-risk patients. In normotensive patients, the PESI model could guide clinical management as well as troponin I and echocardiography testing.

High-dose epirubicin, preceded by dexrazoxane, given in combination with paclitaxel plus filgrastim provides an effective mobilizing regimen to support three courses of high-dose dense chemotherapy in patients with high-risk stage II-IIIA breast cancer.

SUMMARY: We verified the possibility of collecting large amounts of peripheral blood stem cells (PBSCs) to support three courses of adjuvant high-dose dense chemotherapy (HDDC) with high-dose epirubicin, preceded by dexrazoxane, and high-dose paclitaxel, in patients with high-risk breast cancer (>/=9 positive nodes). The mobilizing regimen consisted of high-dose epirubicin 150 mg/m(2), preceded by dexrazoxane 1000 mg/m(2) (day 1), given in combination with paclitaxel 175 mg/m(2) (day 2), plus filgrastim. Of the 25 patients enrolled, one went off study due to a severe hypersensitivity reaction to paclitaxel, another did not undergo leukapheresis due to fever persistent after hematological recovery, while in 23 patients an adequate number of PBSCs was collected by a single leukapheresis. The median number of CD34+, CD34+/CD33-, and CD34+/CD38- cells collected per patient was 17 x 10(6)/kg, 13.4 x 10(6)/kg, and 1.5 x 10(6)/kg, respectively. Neutropenia was the only grade 4 toxicity and lasted a median of 3 days. High-dose epirubicin, preceded by dexrazoxane for the first time used in mobilizing regimen, and paclitaxel plus filgrastim are effective in releasing large amounts of PBSCs, which can then be safely employed to support multiple courses of HDDC.

Relationships between total CD34+ cells reinfused, CD34+ subsets and engraftment kinetics in breast cancer patients.

BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate the correlation between the number of CD34+ cells transfused and the duration of hypoplasia, and the relationship between various CD34+ subsets (CD34+/33-; CD34+/38-; CD34+/ HLA-DR-; CD34+/Thy-1+) and engraftment kinetics in a series of patients with breast cancer treated with high doses of thiotepa and melphalan. DESIGN AND METHODS: We treated 42 consecutive patients: 19 in an adjuvant context (>= 4 positive axillary nodes) and 23 for metastatic disease. A combination of thiotepa 600 mg/m(2) and melphalan 140-160 mg/m(2) was administered as the conditioning regimen. All patients received peripheral blood progenitor cells (PBPC) and growth factors for hematopoietic rescue. RESULTS: In univariate analysis, we found a significant relationship between the number of CD34+ cells reinfused and the time to hematologic recovery and the duration of hospital stay. We observed an inverse correlation between the number of CD34+ cells reinfused and the units of platelets transfused. Cox multivariate analysis confirmed that the number of CD34+ cells reinfused is the most effective predictor of time to hematologic recovery. CFU-GM resulted to be a better predictor of the duration of hospitalization. INTERPRETATION AND CONCLUSIONS: We found a significant relationship between the number of PBPC reinfused and the time to hematologic recovery after high doses of thiotepa and melphalan. In our experience, the numbers of subsets of CD34+ cells infused did not give compared additional information to that provided by the total number of CD34+ cells infused.

Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF and G-CSF alone in patients with non-Hodgkin's Lymphoma?

We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2, group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg, group B) as a mobilizing regimen, could result in harvesting different numbers of CD34+ cells, committed progenitors and CD34+ cells subsets. The number of CD34+ cells considered as the target for each high-dose chemotherapy was > or = 2 x 10(6) /Kg/bw. Fifteen leukaphereses procedures were necessary in group A, while 16 procedures were performed in group B. We did not observe any difference between the two groups in terms of CD34+ cells/microl in the peripheral blood (117 vs 78; p = NS), whereas in the aphereses product we found a significant difference between the two groups of patients in terms of CD34+ cells (6.41 vs 2.89 x 10(6) /Kg/bw; p = .009), CFU-GM (82.5 vs 52.3 x 10(4) /Kg/bw; p = .04). Interestingly, we noted a different distribution of CD34+/33- cells between the 2 groups (mean value 39% vs 65%; p < .05), whereas we did not find any differences regarding CD34+/38-, CD34+/Thy1+, CD34+/HLADR-. The higher number of CFU-GM/Kg/bw collected in the former group did not translate into a superior plating efficiency (27.75 vs 30.29). Furthermore, we observed a strong correlation between CD34+ cells/microl in the peripheral blood and the total number of CD34+ cells in the leukaphereses product (r = 0.97), whereas this correlation was not found in group B (r = 0.15). In both groups of patients the number of CD34+ cells collected correlated well with CFU-GM (r = 0.93; r = 0.94), but definitely we did not observe any correlation between CD34+ cells/microl and CFU-GM in patients mobilized with G-CSF alone and this did not allow us to predict the harvest accurately. Finally, we evaluated the engraftment kinetics and we did not observe any statistically significant difference between the two groups of patients.