Summary:cancer centers. [10][11][12][13][14] This report describes the 100-day treatment-related mortality (TRM) of the first 1000 consecutive patients receiving high-dose myeloablative chemotherapy High-dose chemotherapy (HDC) with autologous peripheral blood progenitor cell (PBPC) is being increaswithin a multicentered community-based clinical trials program. ingly utilized as a therapeutic modality for patients with chemotherapy-sensitive disease. Several published HDC regimens have become relatively widely used. The purpose of this analysis was to determine treatment-related Materials and methods mortality (TRM) following administration of five different HDC regimens in community cancer centers. A Patient selection retrospective evaluation of 1000 consecutive patientsBetween February 1989 and 15 September 1994, 1000 conwith leukemia, non-Hodgkin's lymphoma, Hodgkin's secutive patients were enrolled on protocols administering disease, multiple myeloma, sarcoma, ovarian cancer, or HDC. [10][11][12][13] Patients were eligible for study if they had a breast cancer who received one of five published HDC malignant disease that could potentially benefit from HDC, regimens followed by PBPC infusion over a 5-year perwere between age 18-65 years, had ECOG performance iod in community cancer centers was performed to status of 0-2 and evidence of adequate hepatic, renal and determine TRM. Fifty-nine patients (5.9%) died within cardiac function. Patients were treated on clinical protocols 100 days of PBPC infusion. Twenty-five patients (2.5%) designed by investigators of Response Oncology Inc (ROI) died predominantly of causes related to disease proand approved by the institutional review board of the hospigression. Thirty-four patients (3.4%) died of TRM, 15 tal where the therapy was administered and all patients patients (1.5%) died from infection and 19 (1.9%) died signed a protocol-specific informed consent. from regimen-related toxicities (RRT). In a logistic model, increasing age (P = 0.001) and lower numbers of CD34 + cells/kg (P = 0.003) were associated with an Treatment centers increased risk of 100-day TRM. High-dose cyclophosPatients analyzed for this report were treated in 28 medical phamide, thiotepa, and carboplatin was associated with centers in the US under the care of 159 community medical a lower risk of mortality than other regimens (P = oncologists. The median number of patients treated in each 0.0001). High-dose chemotherapy and autologous PBPC center was 29. Chemotherapy was administered and PBPC support can be performed in community cancer centers were collected in an outpatient facility. 10,13with relative safety. Patient age, the type of preparative regimen and the number of CD34 + cells infused were important determinates of mortality.Collection, cryopreservation and infusion of PBPC

Summary. The effects of different doses of filgrastim on yields of CD34þ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 mg/kg/d with more CD34 þ cells/ kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 mg/ kg. The median number of CD34 þ cells collected after 10 mg/ kg (n ¼ 31) was 0·7 × 10 6 /kg/apheresis (range 0·1-4·4) as compared to 1·2 (range 0·1-6·8) after 30 mg/kg (n ¼ 32) (P ¼ 0·04). Among patients randomized to 10 v 30 mg/kg, more (50%) achieved 5 5·0 × 10 6 CD34 þ cells/kg and less aphereses were required to achieve 5 2·5 × 10 6 CD34 þ cells/ kg after the higher dose (P ¼ 0·04). In multivariate analyses, patients receiving 10 mg/kg (n ¼ 31) had lower yields of CD34 þ cells (P ¼ 0·026) and had a 3·3-fold increase in the probability of not achieving 5 5·0 × 10 6 CD34 þ cells/kg as compared to patients receiving 20-40 mg/kg (n ¼ 59). Patients who had received radiation had a 2·9-fold probability of not achieving 5 2·5 × 10 6 CD34 þ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 mg/kg/d mobilized more CD34 þ cells and may be useful when high numbers of CD34 þ cells are desired.

Summary:The purpose of this study was to evaluate the frequency of detecting occult tumor cells in peripheral blood stem cell (PBSC) harvests and to determine the impact of infusing such cells on relapses after high-dose chemotherapy (HDC). Peripheral blood stem cell harvests from 223 patients with breast cancer were examined by an immunocytochemistry ( Nineteen patients who were infused with a mixture of ICC negative and untested PBSC harvests were excluded from analyses of relapse. The probabilities of relapse at 18 months for the 97 patients with stage II-III disease infused with ICC-negative and the 17 with ICC-positive PBSC were 0.19 and 0.13, respectively (P = 0.48). The probabilities of relapse at 18 months for patients achieving a CR or a CR in non-bone sites and improvement in bone lesions were 0.55 for the ICCnegative group (n = 30) and 0.45 for the ICC-positive group (n = 11) (P = 0.60). It was concluded that occult tumor cells were detected by ICC in PBSC harvests from a relatively small fraction of women with breast cancer, but were not associated with a significant increase in the probability of early relapse or progression when infused after HDC.

Summary:there was more rapid recovery of platelets in patients receiving the higher CD34 + cell doses. 4 Some patients receiving Ͻ2-2.5 × 10 6 CD34 + cells/kg have greatly Engraftment kinetics after high-dose chemotherapy (HDC) were evaluated in patients receiving autologous delayed platelet recovery as compared to patients receiving a higher cell dose. 3,5-7 peripheral blood stem cell (PBSC) infusions with a low CD34 ؉ cell content. Forty-eight patients were infusedIt has also been suggested that there are factors other than CD34 + cell dose involved in hematologic recovery with Ͻ2.5 ؋ 10 6 CD34 ؉ cells/kg; 36 because of poor harvests and 12 because they electively received only a after HDC and PBSC infusion. For example, in a series of 225 patients with multiple myeloma receiving HDC, the fraction of their harvested cells. A median of 2.12 ؋ 10 6 CD34 ؉ cells/kg (range, 1.17-2.48) were infused followinfusion of 2.0 × 10 6 CD34 + cells/kg resulted in rapid engraftment in patients who had received Ͻ6 months of ing one of seven different HDC regimens. All patients achieved absolute neutrophil counts у 0.5 ؋ 10 9 /l at a therapy with melphalan, but Ͼ5 × 10 6 CD34 + cells/kg were required for rapid platelet recovery in patients who had median of day 11 (range, 9-16). Forty-seven patients achieved platelet counts у 20 ؋ 10 9 /l at a median of day received Ͼ12 months of melphalan. 8 Target CD34 + cell doses of 2.5 or 5.0 × 10 6 /kg are easily 14 (range, 8-250). Nine of 47 (19%) had platelet recovery after day 21, 4/47 (9%) after day 100 and one died achievable in the majority of patients. [3][4][5] In a relatively small fraction of heavily pretreated patients, however, these on day 240 without platelet recovery. Twenty-six patients (54%) died of progressive disease in 51-762 cell doses are not obtainable. 3-5 Furthermore, sequential or tandem administration of HDC followed by the infusion of days; 22 (46%) are alive at a median of 450 days (range, 94-1844), 17 (35%) of whom are surviving disease-free a fraction of harvested PBSC can result in the administration of relatively low CD34 + cell numbers after each at a median of 494 days (range, 55-1263). No patient died as a direct consequence of low blood cell counts.treatment. The purpose of this analysis was to evaluate the These data demonstrate that PBSC products containing 1.17-2.48 ؋ 10 6 CD34 ؉ cells/kg resulted in relatively engraftment kinetics in 48 patients with malignancy given HDC followed by PBSC containing Ͻ2.5 × 10 6 CD34 + prompt neutrophil recovery in all patients but approximately 10% had delayed platelet recovery. cells/kg. Keywords: engraftment; low CD34 ϩ cells Patients and methodsThe CD34 + cell content of peripheral blood stem cells Patient selection (PBSC) has been shown to be an accurate and proven predictor of engraftment kinetics, especially of platelets, folRecords were reviewed of 2079 nonleukemia patients lowing high-dose chemotherapy (HDC). 1-5 Infusion of treated with HDC and PBSC infusion between March 1991 PBSC containing у5 × 10 6 /k...

HuM195 is a humanized, unconjugated, anti-CD33 monoclonal antibody. Fifty adult patients with relapsed or refractory AML were randomized to receive HuM195 at a dose of 12 or 36 mg/m 2 by intravenous infusion over 4 h on days 1-4 and 15-18. Patients with stable or responding disease received two additional cycles on days 29-32 and 43-46. HuM195 was given as first salvage therapy in 24 patients and as second or subsequent salvage therapy in 26 patients. Pretreatment blast percentage in the marrow was between 5 and 30% in 20 patients with the others having blast counts greater than 30%. The median age of patients was 62 years (range 26-86) and CD33 was detected in 95% of patients for whom immunophenotyping was available. Of 49 evaluable patients, two complete and one partial remission were observed. All three responses were in patients treated at the 12 mg/m 2 dose level and all had baseline blast percentages less than 30%. Decreases in blast counts ranging from 30 to 74% were seen in nine additional patients. Infusion-related events of fever and chills occurred in the majority of patients and were generally mild and primarily related to the first dose of antibody. No hepatic, renal or cardiac toxicities were observed and other adverse events such as nausea, vomiting, mucositis and diarrhea were uncommon or felt to be unrelated to HuM195. In addition, anti-HuM195 responses were not detected. HuM195 as a single agent has minimal, but observable, anti-leukemic activity in patients with relapsed or refractory AML and activity is confined to patients with low burden disease. No significant differences in clinical efficacy or toxicity were seen between the two dose levels of antibody. HuM195 was well tolerated with infusion-related fevers and chills the predominant toxicities seen. Meaningful clinical efficacy of this unconjugated monoclonal antibody may be realized only in patients with minimal residual disease, or in combination with chemotherapy.