Mobilization of peripheral blood stem cells with docetaxel and cyclophosphamide (CY) in patients with metastatic breast cancer: a randomized trial of 3 vs 4 g/m2 of CY.
(41/7058)
The purpose of this study was to develop a regimen of docetaxel, cyclophosphamide (CY) and filgrastim for mobilization of peripheral blood stem cells (PBSC) in patients with metastatic breast cancer (n = 66). A phase I trial of CY 2, 3 or 4 g/m2 with docetaxel 100 mg/m2, in consecutive cohorts of four patients each, did not reveal any dose-limiting toxicities and subsequent patients were randomized to receive 3 or 4 g/m2 of CY. The median yield of CD34+ cells from all patients was 11.06x10(6)/kg (range, 0.03-84.77) from a median of two aphereses (range, 1-7); 6.52x10(6) CD34+ cells/kg/apheresis (range, 0.01-52.07). Target CD34+ cell doses > or =2.5 and > or =5.0x10(6)/kg were achieved in 89% and 79%, respectively. There were no statistically significant differences in CD34+ cell yields or target CD34+ cell doses achieved following 3 or 4 g/m2 of CY. Patients with only one prior chemotherapy regimen yielded a median of 12.82x10(6) CD34+ cells/kg/apheresis compared to 5.85 for those receiving > or =2 regimens (P = 0.03). It was concluded that the combination of docetaxel, 100 mg/m2, CY 3 g/m2 without mesna could be administered with acceptable toxicity with collection of adequate quantities of PBSC from the majority of patients. (+info)
Ifosfamide in combination with paclitaxel or doxorubicin: regimens which effectively mobilize peripheral blood progenitor cells while demonstrating anti-tumor activity in patients with metastatic breast cancer.
(42/7058)
For patients with metastatic breast cancer (MBC) who undergo high-dose therapy with autologous peripheral blood progenitor cell (PBPC) transplantation, an important prerequisite is a mobilization regimen that efficiently mobilizes PBPCs while producing an effective anti-tumor effect. We prospectively evaluated ifosfamide-based chemotherapy for mobilization efficiency, toxicity and disease response in 37 patients. Patients received two cycles of the ifosfamide-based regimen; ifosfamide (5 g/m2 with conventional-dose cycle and 6 g/m2 with mobilization cycle) with either 50 mg/m2 doxorubicin (if limited prior anthracycline and/or progression more than 12 months after an anthracycline-based regimen) or 175 mg/m2 paclitaxel. For the mobilization cycle, all patients received additional G-CSF (10 microg/kg SC, daily) commencing 24 h after completion of chemotherapy. The target yield was >6x10(6) CD34+ cells/kg, sufficient to support the subsequent three cycles of high-dose therapy. The mobilization therapy was well tolerated and the peak days for peripheral blood (PB) CD34+ cells were days 10-13 with no significant differences in the PB CD34+ cells mobilization kinetics between the ifosfamide-doxorubicin vs. ifosfamide-paclitaxel regimens. The median PBPC CD34+ cell content ranged from 2.9 to 4.0x10(6)/kg per day during days 9-14. After a median of 3 (range 1-5) collection days, the median total CD34+ cell, CFU-GM and MNC for all 44 individual sets of collections was 9.2x10(6)/kg (range 0.16-54.9), 37x10(4)/kg (range 5.7-247) and 7.3x10(8)/kg (range 2.1-26.1), respectively. The PBPC target yield was achieved in 35 of the 37 patients. The overall response rate for the 31 evaluable patients was 68% with 10% having progressive disease. Thirty-three patients have subsequently received high-dose therapy consisting of three planned cycles of high-dose ifosfamide, thiotepa and paclitaxel with each cycle supported with PBPCs. Rapid neutrophil and platelet recovery has been observed. Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achieves effective mobilization of PBPC and anti-tumor activity with minimal toxicity. (+info)
Autologous stem cell transplantation for T and null cell CD30-positive anaplastic large cell lymphoma: analysis of 64 adult and paediatric cases reported to the European Group for Blood and Marrow Transplantation (EBMT).
(43/7058)
Anaplastic large cell lymphoma (ALCL) is a heterogeneous family of lymphoid tumours, among which the T and null cell types were recently listed in the REAL classification as a distinct entity. Reports on autologous stem cell transplantation (ASCT) in this group are only occasional. Sixty-four patients with T and null cell ALCL from 25 European centres had been registered with the European Group for Blood and Marrow Transplantation (EBMT) at the onset of this study. The median age was 25 years (range 3.2-53.0). Thirty of the 64 patients (47%) were in complete remission (CR), 18 (28%) in partial remission (PR), and the remaining 16 (25%) had a more advanced or chemotherapy-refractory disease at transplant. Eighty-one percent of the patients were conditioned with chemotherapy alone and 75% received marrow stem cells. All the patients transplanted in first CR (15), except one, maintained the CR over time; six of 15 transplanted in CR subsequent to first, six of 18 transplanted in PR and 14 of 16 transplanted in refractory or relapsed disease progressed. Actuarial overall survival (OS) at 10 years is 70%. Multivariate analysis showed that good status at transplant, younger age, absence of B symptoms and absence of extranodal disease indicated a better prognosis. These data suggest that ASCT should be considered as a possible treatment for chemosensitive patients in CR or PR. However, definitive conclusions cannot be drawn from this study and a prospective randomised trial between ASCT and conventional chemotherapy may be indicated. (+info)
Primitive hematopoietic progenitors within mobilized blood are spared by uncontrolled rate freezing.
(44/7058)
Uncontrolled-rate freezing techniques represent an attractive alternative to controlled-rate cryopreservation procedures which are time-consuming and require high-level technical expertise. In this study, we report our experience using uncontrolled-rate cryopreservation and mechanical freezer storage at -140 degrees C. Twenty-eight PBPC samples (10 cryovials, 18 freezing bags) from 23 patients were cryopreserved in a cryoprotectant solution composed of phosphate-buffered saline (80%, v/v) supplemented with human serum albumin (10%, v/v) and dimethylsulfoxide (10%, v/v). The cryopreservation procedure required on average 1.5 h. The mean (+/- s.e.m.) storage time of cryovials and bags was 344+/-40 and 299+57 days, respectively. Although cell thawing was associated with a statistically significant reduction of the absolute number of nucleated cells (vials: 0.3x10(9) vs. 0.2x10(9), P< or =0.02; bags: 14x10(9) vs. 11x10(9), P< or =0.0003), the growth of committed progenitors was substantially unaffected by the freezing-thawing procedure, with mean recoveries of CFU-Mix, BFU-E, and CFU-GM ranging from 60+/- 29% to 134+/-15%. Mean recoveries of LTC-IC from cryovials and bags were 262+/-101% and 155+/-27% (P< or =0.2), respectively. In 14 out of 23 patients who underwent high-dose chemotherapy and PBPC reinfusion, the pre-and post-freezing absolute numbers of hematopoietic progenitors cryopreserved in bags were compared. A significant reduction was detected for CFU-Mix (11 vs. 7.4x10(5)), but no significant loss of BFU-E (180 vs. 150x10(5)), CFU-GM (400 vs. 290x10(5)) and LTC-IC (15 vs. 16x10(5)) could be demonstrated. When these patients were reinfused with uncontrolled-rate cryopreserved PBPC, the mean number of days to reach 1x10(9)/l white blood cells and 50x10(9)/l platelets were 9 and 13, respectively. In conclusion, the procedure described here is characterized by short execution time, allows a substantial recovery of primitive and committed progenitors and is associated with prompt hematopoietic recovery following myeloablative therapy even after long-term storage. (+info)
Cord blood banking: volume reduction of cord blood units using a semi-automated closed system.
(45/7058)
Clinical evidence indicates that placental/umbilical cord blood (CB) is an alternative source of haematopoietic stem cells for bone marrow reconstitution. To establish a CB bank large panels of frozen, HLA-typed CB units need to be stored. Cryopreserved, unprocessed CB units require vast storage space. This study describes a method, using the Optipress II Automated Blood Component Extractor (Opti II) from Baxter Healthcare Corporation, to reduce the volume of the CB collection, preserving the quantity and quality of the progenitor cells, in a closed system. The CB collection was transferred to a triple bag system, centrifuged to produce a buffy coat layer and processed using a standard Opti II protocol to separate the whole blood into three components: plasma, buffy coat and buffy coat-depleted red cell concentrate. The buffy coat volume was standardised to 25 ml; mean reduced volume of 24.5 ml (s.d. 1.5 ml) with 53% red cell depletion. Good recovery of cells was observed: 92%, 98%, 96% and 106% recovery of nucleated, mononuclear, CD34+ and total colony-forming cells, respectively. Using this method for processing CB units reduces storage requirement by two-thirds but preserves the quantity and quality of the progenitor cells. (+info)
Pulmonary enterovirus infections in stem cell transplant recipients.
(46/7058)
In recent years, it has been recognised that the community respiratory viruses are a frequent cause of upper and lower respiratory tract infections in immunocompromised hosts such as bone marrow transplant recipients. By contrast, infections by non-polio enteroviruses have rarely been reported after stem cell transplantation. We present four cases of acute respiratory illness with enterovirus isolated as the sole pathogen from bronchoalveolar lavage. All four patients developed pneumonia and three died of progressive pneumonia, which reflects the severity of this complication. We conclude that enteroviral pulmonary infections may be a cause of severe pneumonia in immunocompromised hosts. (+info)
Busulphan level and early mortality in thalassaemia patients after BMT.
(47/7058)
The aim of the study was to correlate busulphan (BU) levels of thalassaemia patients with outcome of allogeneic transplant. BU levels were measured by gas chromatography mass fragmentography. All patients received a standardised dose of BU 16 mg/kg, and cyclophosphamide 150 or 200 mg/kg. For area-under-the-curve analysis (AUC), blood samples were obtained at 0, 1, 2, 3, 4 and 6 h after the first and fifth dose for all patients, and additional levels were measured after ninth and/or 13th dose in most patients. Outcome parameters examined included veno-occlusive disease of liver (VOD), idiopathic interstitial pneumonitis, chimerism, and day 90 survival. Twenty consecutive thalassaemia patients who underwent haematopoietic stem cell transplantation were studied. The median age at transplant was 11.2 years (range 3-21 years). Mean BU AUC levels were correlated with age at transplant (r = 0.58, P = 0.007). Nine patients developed VOD and six had mixed chimerism, but these did not correlate with mean BU AUC level. Four patients died before day 50 from VOD and interstitial pneumonitis. Patients with BU AUC levels greater than the median (908 micromol x min/l) had significantly lower probability of survival at day 90 (60%), whereas patients with BU AUC level less than the median all survived beyond day 90. No patient had graft rejection. In conclusion, a high BU AUC level was associated with a higher treatment-related mortality in thalassaemia patients after transplant. (+info)
A phase I study of paclitaxel for mobilization of peripheral blood progenitor cells.
(48/7058)
We conducted a phase I trial to determine the dose and schedule of paclitaxel, when given together with filgrastim, which would optimally promote mobilization of stem cells with tolerable toxicity. Dose escalation began at 275 mg/m2 3 h infusion. Dose-limiting neuropathy was observed at the 300 mg/m2 dose level. A second dose escalation was conducted utilizing 24 h infusion schedules, beginning at 225 mg/m2. Dose escalation was continued by 25 mg/m2 increments to 300 mg/m2, at which dose neuropathy was again dose-limiting. The recommended dose and schedule of paclitaxel for the purpose of mobilization of stem cells, when given together with filgrastim, are 275 mg/m2 as a 24 h infusion. The median stem cell yield after this dose of paclitaxel was 6.6 x 10(6) CD34+ cells/kg/apheresis (range 3.6 x 10(6)-7.7 x 10(6)). (+info)