Purpose: To estimate the maximum tolerated dose of hyperfractionated total marrow irradiation (TMI) as a second consolidation after high-dose chemotherapy with autologous or syngeneic blood stem cell transfusion for patients with bone/bone marrow-based malignant disease.Patients and Methods: Fifty-seven patients aged 3-65 years (median, 45 years), including 21 with multiple myeloma, 24 with breast cancer, 10 with sarcoma, and 2 with lymphoma, were treated with 1.5 Gy administered twice daily to a total dose of 12 Gy (n = 27), 13.5 Gy (n = 12), and 15 Gy (n = 18). Median time between the 2 transplants was 105 days (range, 63-162 days).Results: All patients engrafted neutrophils (median, Day 11; range, Day 9-23) and became platelet independent (median, Day 9; range, Day 7-36). There were 5 cases of Grade 3-4 regimen-related pulmonary toxicity, 1 at 12 Gy, and 4 at 15 Gy. Complete responses, partial responses, and stabilizations were achieved in 33%, 26%, and 41% of patients, respectively. Kaplan-Meier estimates of 5-year progression-free survival and overall survival for 56 evaluable patients are 24% and 36%, respectively. Median time of follow-up among survivors was 96 months (range, 77-136 months).Conclusion: Total marrow irradiation as a second myeloablative therapy is feasible. The estimated maximum tolerated dose for TMI in a tandem transplant setting was 13.5 Gy. Because 20% of patients are surviving at 8 years free of disease, further studies of TMI are warranted. (c) 2006 Elsevier Inc.

Filgrastim alone and sequential sargramostim and filgrastim have been shown to be more effective than sargramostim alone in the mobilization of CD34 + cells after myelosuppressive chemotherapy (MC). We sought to compare costs and resource use associated with these regimens. Data were collected prospectively alongside a multicenter, randomized trial of filgrastim, sargramostim, and sequential sargramostim and filgrastim. Direct medical costs were calculated for inpatient and outpatient visits and procedures, including administration of growth factors and MC. We followed 156 patients for 30 days or until initiation of high-dose chemotherapy. The main outcome measures were resource use and costs of inpatient and outpatient visits, platelet and red blood cell transfusions, antibiotic use, and apheresis procedures. Hospital admissions, red blood cell transfusions, and use of i.v. antibiotics were significantly more common in the sargramostim group than in the other treatment arms. In univariate and multivariable analyses, total costs were higher for patients receiving sargramostim alone than for patients in the other groups. Mean costs in multivariable analysis for the filgrastim and sequential sargramostim and filgrastim arms were not significantly different. Filgrastim alone and sequential sargramostim and filgrastim are less costly than sargramostim alone after MC, as well as therapeutically more beneficial. Bone Marrow Transplantation (2002) 29, 159–164. doi:10.1038/sj.bmt.1703341

Myelosuppressive chemotherapy is frequently used for mobilization of autologous CD34 + progenitor cells into the peripheral blood for subsequent collection and support of high-dose chemotherapy. The administration of myelosuppressive chemotherapy is typically followed by a myeloid growth factor and is associated with variable CD34 cell yields and morbidity. The two most commonly used myeloid growth factors for facilitation of CD34 cell harvests are granulocyte colony-stimulating factor (G-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF). We performed a randomized phase III clinical trial comparing G-CSF, GM-CSF, and sequential administration of GM-CSF and G-CSF following administration of myelosuppressive chemotherapy. We evaluated CD34 yields, morbidity, and cost-effectiveness of the three cytokine schedules. One hundred and fifty-six patients with multiple myeloma, breast cancer, or lymphoma received cyclophosphamide with either paclitaxel or etoposide and were randomized to receive G-CSF 6 μg/kg/day s.c., GM-CSF 250 μg/m 2 /day s.c., or GM-CSF for 6 days followed by G-CSF until completion of the stem cell harvest. Compared with patients who received GM-CSF, patients who received G-CSF had faster recovery of absolute neutrophil count to 0.5 × 10 9 per liter (median of 11 vs 14 days, P = 0.0001) with fewer patients requiring red blood cell transfusions ( P = 0.008); fewer patients with fever (18% vs 52%, P = 0.001); fewer hospital admissions (20% vs 42%, P = 0.13); and less intravenous antibiotic therapy (24% vs 59%, P = 0.001). Patients who received G-CSF also yielded more CD34 cells (median 7.1 vs 2.0 × 10 6 kg per apheresis, P = 0.0001) and a higher percentage achieved 2.5 × 10 6 CD34 cells per kilogram (94% vs 78%, P = 0.21) and 5 × 10 6 CD34 cells per kilogram (88% vs 53%, P = 0.01) or more CD34 cells per kilogram with fewer aphereses (median 2 vs 3, P = 0.002) and fewer days of growth factor treatment (median 12 vs 14, P = 0.0001). There were no significant differences in outcomes between groups receiving G-CSF alone and the sequential regimen. After high-dose chemotherapy, patients who had peripheral blood stem cells mobilized with G-CSF or the sequential regimen received higher numbers of CD34 cells and had faster platelet recovery with fewer patients requiring platelet transfusions than patients receiving peripheral blood stem cells mobilized by GM-CSF. In summary, G-CSF alone is superior to GM-CSF alone for the mobilization of CD34 + cells and reduction of toxicities following myelosuppressive chemotherapy. An economic analysis evaluating the cost-effectiveness of these three effective schedules is ongoing at the time of this writing. Bone Marrow Transplantation (2001) 27, Suppl. 2 , S23–S29.

The aim of this study was to compare toxicity and efficacy of total body irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) vs busulfan, melphalan and thiotepa (Bu/Mel/T) in patients receiving autologous stem cell infusion (ASCI) for malignant lymphoma (NHL). Between September 1990 and July 1998, 351 patients with NHL were treated with TBI/CY/E (n = 221) or Bu/Mel/T (n = 130) followed by ASCI. Patients in first, or second remission, first responding or untreated relapse were defined as having less advanced disease before transplantation. The median follow-up was 5 years (range 1–9) and 3.5 years (1–6) for patients receiving TBI/CY/E and Bu/Mel/T, respectively. The cumulative probabilities of survival, event-free survival (EFS) and relapse at 5 years were 44%, 32%, 49% following TBI/CY/E and 42%, 34% and 42% following Bu/Mel/T. The probability of EFS at 5 years for patients who had prior dose-limiting radiation (n = 59) was 32% after Bu/Mel/T therapy. Transplant-related mortality was 16% for TBI/CY/E and 21% for Bu/Mel/T. In univariate and multivariate analyses, more advanced disease status was associated with poor outcome (TBI/CY/E: RR 0.70, CI 0.50 to 0.97 P = 0.04; Bu/Mel/T: RR 0.61, CI 0.39 to 0.97 P = 0.03). No significant differences in toxicities and outcomes were observed between these two regimens despite the inclusion of patients who had received dose-limiting irradiation in the Bu/Mel/T regimen. Bone Marrow Transplantation (2001) 28, 455–461.

The purpose of this trial was to determine the effects of paclitaxel in patients with newly diagnosed metastatic breast cancer scheduled to receive high-dose chemotherapy with peripheral blood stem cell support. Eighty-four patients received anthracycline-based induction and two doses of paclitaxel at 170 mg/m(2) (n = 52) or 250 mg/m(2) (n = 32). Eighty-two (98%) received cyclophosphamide and etoposide (n = 50) or paclitaxel and cyclophosphamide (n = 32) with granulocyte colony-stimulating factor for mobilization of peripheral blood stem cells, and 79 (94%) received cyclophosphamide, thiotepa, and carboplatin with peripheral blood stem cell support. One patient (1%) died of infection and 56 (67%) died of progressive disease. For patients with measurable disease, the complete response rate was 21% after induction and 29% after paclitaxel (p = 0.54). Results were compared with those of 125 patients who received the same sequence of therapy without paclitaxel. The complete response rate after high-dose chemotherapy was 54% for patients receiving paclitaxel and 62% for those not receiving paclitaxel (p = 0.60). The probabilities of overall survival and event-free survival at 3 years for patients receiving paclitaxel were 46% and 24%, respectively, compared with 54% and 22%, respectively, for patients not receiving paclitaxel (p = 0.62). Further trials evaluating this dose and schedule of paclitaxel in patients with metastatic breast cancer receiving high-dose chemotherapy are not warranted.

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 11.06 × 106/kg (range, 0.03–84.77) from a median of two aphereses (range, 1–7); 6.52 × 106 CD34+ cells/kg/apheresis (range, 0.01–52.07). Target CD34+ cell doses ⩾2.5 and ⩾5.0 × 106/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 12.82 × 106 CD34+ cells/kg/ apheresis compared to 5.85 for those receiving ⩾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.

The purpose of this study was to determine outcomes for 56 patients with inflammatory breast cancer (IBC) receiving high-dose chemotherapy (HDC) with cyclophosphamide, thiotepa and carboplatin (CTCb) with peripheral blood stem cell (PBSC) support. All patients received the same total amount of chemotherapy but there were differences in the sequence of therapy: 15 received induction chemotherapy, chemotherapy mobilization of PBSC and CTCb after surgery (adjuvant group) while 41 received induction chemotherapy with (n = 17) or without (n = 24) chemotherapy for mobilization of PBSC prior to surgery and CTCb after surgery (neoadjuvant group). Median time from diagnosis to HDC was 5.5 months (range 3.5–12.5). Fifty-one patients (91%) required admission to the hospital following HDC for a median of 11 days (range 5–25). There were two (4%) infectious deaths after HDC. Twenty-four patients (43%) have relapsed at a median of 18 months (range 8–50) from diagnosis resulting in death in 34%. The probabilities of overall (OS) and event-free survival (EFS) at 3 years for all 56 patients were 0.72 and 0.53, respectively, with a median follow-up of 44 months (range 15–76) from diagnosis. There were no differences in OS, EFS or patterns of relapse between patients in the adjuvant or neoadjuvant groups. These sequences of combined modality therapy incorporating HDC are comparable or superior to other intensive approaches for the treatment of IBC. Further improvements will be necessary to decrease systemic recurrences.

The effects of different doses of filgrastim on yields of CD34+ peripheral blood stem cells were evaluated in patients with breast cancer. 55 were randomized to receive filgrastim 10, 20, 30 or 40 μg/kg/d with more CD34+ cells/kg/apheresis harvested after the three highest dose levels. 35 additional patients were randomized to receive 10 or 30 μg/kg. The median number of CD34+ cells collected after 10 μg/kg (n= 31) was 0.7 × 106/kg/apheresis (range 0.1–4.4) as compared to 1.2 (range 0.1–6.8) after 30 μg/kg (n= 32) (P= 0.04). Among patients randomized to 10 v 30 μg/kg, more (50%) achieved 5.0 × 106 CD34+ cells/kg and less aphereses were required to achieve 2.5 × 106 CD34+ cells/kg after the higher dose (P= 0.04). In multivariate analyses, patients receiving 10 μg/kg (n= 31) had lower yields of CD34+ cells (P= 0.026) and had a 3.3‐fold increase in the probability of not achieving 5.0 × 106 CD34+ cells/kg as compared to patients receiving 20–40 μg/kg (n= 59). Patients who had received radiation had a 2.9‐fold probability of not achieving 2.5 × 106 CD34+ cells/kg. These data suggest that, in patients with good marrow reserves, doses of filgrastim > 10 μg/kg/d mobilized more CD34+ cells and may be useful when high numbers of CD34+ cells are desired.

The purpose of this study was to determine the optimal schedule of i.v. granisetron and dexamethosone for control of nausea and emesis in patients receiving high-dose chemotherapy (HDC). Seventy patients with breast cancer received high-dose cyclophosphamide, thiotepa and carboplatin (CTCb) for 3 consecutive days. All 70 received dexamethasone 12 mg i.v. and granisetron 1 mg i.v. prior to infusion of CTCb and were randomized to receive placebo (n = 37) or an additional identical dose of granisetron (n = 33) 12 h later. Beginning on day 2 of chemotherapy administration, 55 patients evaluable later self-administered a cocktail of diphenhydramine (benadryl), lorazepam (ativan) and dexamethasone (BAD). Fourteen of 37 patients (38%) receiving granisetron once a day and 15/33 (44%) receiving it twice a day had a complete response during the first 24 h following the first doses of chemotherapy (P = 0.52). In the 55 evaluable patients receiving BAD, 18 of 29 (62%) in the once daily group and 14/26 (54%) in the twice daily group required additional medications (P = 0.54). The median time to first emetic episode was 20 h (range 6.6–79.5) for patients receiving once a day and 21.4 hours (range 5.8–105.3) for patients receiving twice a day granisetron (P = 0.48). Five patients in the once daily and seven patients in the twice daily group had complete control of nausea and emesis throughout the study period (P = 0.37). It was concluded that there were no statistically significant differences in nausea and emetic control between dexamethasone with once daily or twice daily i.v. granisetron administration in patients receiving high-dose CTCb.

Forty-nine patients with low-grade non-Hodgkin’s lymphoma (NHL) received high-dose chemotherapy (HDC) with busulfan and cyclophosphamide (BUCY) or carmustine, etoposide, cytarabine and CY (BEAC) followed by unpurged autologous peripheral blood stem (PBSC) infusion. All patients had failed initial chemotherapy or progressed after an initial remission. Peripheral blood stem cells were mobilized with CY alone ( n = 1), CY, etoposide ( n = 19), or CY, etoposide and cisplatin ( n = 29) followed by granulocyte colony-stimulating factor. Twenty-two patients received BU, 16 mg/kg, and CY, 120 mg/kg. Twenty-seven patients received carmustine 300 mg/m 2 , etoposide 600 mg/m 2 , cytarabine 600 mg/m 2 , and CY 140 mg/kg. Four patients (8%) died of non-relapse causes, two (9%) in the BUCY group and two (7%) in the BEAC group. Twenty-seven patients (55%) relapsed or progressed at a median of 9.4 months (2–38) from PBSC infusion. Ten patients who relapsed are alive a median of 31 months (range, 6–47) after relapse. The probabilities of relapse at 3.6 years for patients receiving BUCY or BEAC were 0.57 and 0.70, respectively ( P = 0.92). Twenty-seven patients (55%) are alive at a median of 3.6 years (range, 1–5). The probabilities of survival at 3.6 years for patients receiving BUCY or BEAC were 0.58 and 0.55, respectively ( P = 0.72). The probabilities of EFS at 3.6 years for patients receiving BUCY or BEAC were 0.36 and 0.28, respectively ( P = 0.82). It was concluded that BUCY is an active regimen for the treatment of patients with low-grade NHL.

To the Editor: In November 1990, we reported the results of a randomized trial of two irradiation regimens used to treat patients with acute myeloid leukemia in first remission by allogeneic marrow transplantation.[1][1]Patients were treated between April 1985 and September 1988 and received marrow

The purpose of this study was to evaluate the addition of cisplatin to cyclophosphamide, etoposide, and granulocyte colony-stimulating factor (G-CSF) for the mobilization of peripheral blood stem cells (PBSC). Eighty-one patients with malignant lymphoma were randomized to receive either cyclophosphamide 4 g/m2 and etoposide 600 mg/m2 (CE), and G-CSF 6 microg/kg/day (n = 41), or the same drugs with cisplatin 105 mg/m2 (CEP; n = 40) followed by collection of PBSC. Seventy-eight of 81 patients (96%) had apheresis performed and 70 (86%) received high-dose chemotherapy (HDC) with PBSC support. The median number of CD34+ cells collected after CE was 19.77 compared with 9.39 x 10(6)/kg after CEP (p = 0.09). More patients receiving CEP had grade 3-4 gastrointestinal (p = 0.03) and neurologic toxicities (p = 0.05), had significant delays in recovery of neutrophils (p = 0.0001) and platelets (p = 0.009), and received more red blood cell (p = 0.03) and platelet (p = 0.08) transfusions than patients receiving CE. There were no significant differences in treatment-related deaths, relapse, survival, or event-free survival between patients receiving CE or CEP when all 81 patients or the 70 patients receiving HDC were evaluated. It was concluded that the addition of cisplatin to CE did not improve CD34+ cell yields, was associated with more morbidity and resource utilization, and was not associated with improvement in outcomes.

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 (ICC) method for detection of occult tumor cells, and infused after HDC without consideration of test results. Two hundred and four patients, 114 with stage II–III and 90 with stage IV disease who received only PBSC, that were tested by ICC were evaluated for time to relapse. Five hundred and eighty-one of 619 PBSC harvests (94%) from 223 patients were tested. Fifty-three of 581 harvests (9%), 8% from stage II–III and 10% from stage IV patients, were positive by ICC (P = 0.68). Forty-one of 223 patients (18%), 17/122 (14%) with stage II–III and 24/101 (24%) with stage IV disease, had positive harvests (P = 0.06). Eleven percent of patients who had 1–2 harvests tested were positive as compared to 32% of patients who had ⩾3 PBSC harvests tested (P < 0.001). 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 ICC-negative 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.

The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.

This study was designed to determine the maximum tolerated dose (MTD) of high-dose melphalan (HDM), with peripheral blood stem cell support, that could be given twice within 90 days to patients with multiple myeloma. Twenty patients received tandem HDM at 160, 180 or 200 mg/m 2 and a total of 55 were treated at the estimated MTD of 200 mg/m 2 . Seventeen of 55 (31%) did not receive cycle 2; six because of low CD34 + cell yields, three because of severe ( n = 1) or fatal toxicities ( n = 2) and eight for other reasons. The median interval between doses for 38 patients was 70 days (range 41–225). Three of 55 patients (5%) died of treatment-related causes. In patients completing two cycles of HDM, at any dose level, the complete remission rate improved from 15% following cycle 1 to 55% following cycle 2. The probabilities of survival, event-free survival and relapse or progression at 18 months for the 55 patients treated at the MTD were 0.84, 0.76 and 0.20, respectively, with a median follow-up of 19 months (range 9–36) from mobilization chemotherapy. It was concluded that two cycles of HDM, 200 mg/m 2 , could be administered to approximately 70% of patients under the age of 66 with multiple myeloma in a median interval of 70 days, with improvement in CR rates.

This study was undertaken to evaluate the relationship between the time to recovery of peripheral blood counts and CD34+ cells in the peripheral blood (PB) and apheresis collections of patients undergoing intensive chemotherapy followed by rhG-CSF. Twenty-three patients with a median age of 42 years (range 17-64) with malignancies underwent peripheral blood stem cell (PBSC) collection after cyclophosphamide (CY) 4 g/m2 and etoposide (600 mg/m2) followed by rhG-CSF (10 microg/kg/day). The WBC, platelet counts, CD34+ cell counts per ml of PB, and CD34+ cells in apheresis products were followed in all patients. The relationship of the time to recovery of WBC > 1,000/microl, >3,000/microl, >10,000/microl and platelets >20,000/microl and 50,000/microl was compared to the average daily CD34+ cells/ml in each patient using the Spearman Correlation test. The tempo of recovery of WBC and platelets were highly correlated with the average CD34+ cell count in blood. In order to derive some useful guidelines for the timing of apheresis, the patients were divided into two groups, early recover (ER) and late recover (LR) based on the median time (day 10) to reach WBC count greater than 1,000/microl. ER patients had an average daily PB CD34+ cell count of 9.04 x 10(4)/ml (range 0.44-17.5) and a median yield of CD34+ cells of 10.43 x 10(6)/kg (range 0.60-25.95) compared to LR patients, who had 1.87 x 10(4)/ml (range 0.32-5.44) in the PB (P = .001) and a yield 3.20 x 10(6)/kg CD34+ cells (range 0.037-9.39) (P = .001). Patients recovering their WBC to 1,000/ml within 10 days of completing this regimen may undergo PBSC collection and achieve minimum-target cell doses of >2.5 x 10(6) CD34+ cells/kg--100% of the time.

The purpose of this study was to develop a less toxic outpatient chemotherapy regimen for mobilizing peripheral blood stem cells (PBSC). Three hundred eighteen patients with newly diagnosed stage II-III breast cancer who had received conventional dose adjuvant chemotherapy were randomized to receive intermediate-dose cyclophosphamide (2 g/m2), etoposide (600 mg/m2), and granulocyte colony-stimulating factor (G-CSF) 6 micrograms/kg/day (ID-Cy, n = 162) or high-dose cyclophosphamide (4 g/m2) and the same doses of etoposide and G-CSF (HD-Cy, n = 156) followed by collection of PBSC. Three hundred seventeen of 318 patients had apheresis performed, and 315 received high-dose chemotherapy (HDC) followed by PBSC support. The median numbers of CD34+ cells collected in a median of two apheresis following ID-Cy and HD-Cy were 19.9 and 22.2 x 10(6)/kg, respectively (p = 0.04). The fractions of patients achieving CD34+ cell doses > or = 2.5 or > or = 5.0 x 10(6)/kg were not different between the two regimens. More patients receiving HD-Cy had grade 3-4 nausea (p = 0.001), vomiting (p = 0.03), and mucositis (p = 0.04). The fractions of patients having a neutrophil nadir < 0.5 x 10(9)/L following ID-Cy and HD-Cy were 0.83 and 0.95, respectively (p = < 0.001). The fractions of patients having a platelet nadir < 25 x 10(9)/L following ID-Cy and HD-Cy were 0.13 and 0.51, respectively (p = < 0.001). More patients in the HD-Cy group received platelet (p < 0.001) and red blood cell (p < 0.001) transfusions and were admitted to the hospital more frequently (p = 0.03) than patients receiving ID-Cy. Three hundred fifteen patients received HDC followed by infusion of PBSC. There were no significant differences in the incidence of transplant-related death or early survival between patients receiving ID-Cy or HD-Cy followed by HDC. It was concluded that a regimen of Cy 2 g/m2 with etoposide and G-CSF was effective for mobilization of PBSC with low morbidity and resource utilization in patients with limited prior chemotherapy exposure.

The authors determined outcomes for patients with localized high-risk breast cancer undergoing sequential outpatient treatment with conventional-dose adjuvant therapy, chemotherapy, and growth factor mobilization of peripheral blood stem cells (PBSC) and high-dose chemotherapy (HDC) with PBSC support in community cancer centers. Ninety-six patients with stage II-IIIB noninflammatory breast cancer with 10 or more positive lymph nodes and a median age of 46 years (range, 22-60 years) were treated with: 1) doxorubicin, 5-fluorouracil, and methotrexate (AFM), four courses at 2-week intervals; 2) cyclophosphamide (4 g/m2) and etoposide (600 mg/m2) (CE), followed by filgrastim (6 microg/kg per day) and PBSC harvest; and 3) cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb), followed by PBSC infusion. All 96 patients received AFM, 95 (99%) received CE, and 95 (99%) received CTCb with a median hospital stay of 12 days (5-34 days) for all phases of treatment. Sixty-nine patients (72%) are alive, 55 (57%) without relapse at a median follow-up of 53 months (range, 37-77 months). One patient (1%) died of acute myeloid leukemia and all other deaths were associated with recurrent breast cancer. The probabilities of event-free survival (EFS) at 4 years for patients with or without locally advanced disease were 0.37 and 0.69, respectively (p = 0.004), and 0.71 and 0.48 for patients who were estrogen/progesterone receptor (ER/PR) positive or ER/PR negative, respectively (p = 0.016). In multivariate analyses, locally advanced disease (relative risk, 2.3; p = 0.021) and ER/PR-negative hormone receptor status (relative risk, 2.2; p = 0.014) were the only adverse risk factors for EFS identified. Patients with zero, one, or two of these adverse risk factors had 4-year EFS of 0.80, 0.56, and 0.33, respectively. The sequential administration of AFM, CE, and CTCb followed by PBSC in an outpatient community setting was well tolerated in patients with high-risk stage II-III breast cancer. More intensive or more novel treatment strategies will be required to decrease relapses in patients who have ER/PR-negative tumors and/or have locally advanced disease.

The purpose of this study was to evaluate the efficacy of high-dose chemotherapy (HDC) with busulfan, melphalan and thiotepa (BUMELTT) followed by autologous PBSC infusion in treating patients with advanced ovarian cancer. Thirty-one patients, 18 with stage III/IIIc and 13 with stage IV ovarian cancer, were treated with BU (12 mg/kg), MEL (100 mg/m(2)) and TT (500 mg/m(2)) and autologous PBSC rescue. Fifteen patients were in clinical complete remission (CR) at treatment; 11 had platinum-sensitive disease. Sixteen patients were not in CR; two had platinum-sensitive disease. The probabilities of overall survival (OS), event-free survival (EFS) and relapse (R) for all patients at 18 months were 0.57, 0.30 and 0.63; for patients in CR, the rates were 0.87, 0.44 and 0.49 and for patients not in CR, 0.38, 0.13 and 0.81. Two patients (6.5%) died of treatment-related causes. Among the 13 patients with platinum-sensitive disease, all are still alive, with seven having relapsed 129-1021 days after PBSC infusion. OS, EFS and R were 1.00, 0.52 and 0.48. Of the 18 patients with platinum-resistant disease, four remain alive (two in remission), Six patients did not respond and eight relapsed from days 104-429. The OS, EFS and R were 0.33, 0.11 and 0.78. We conclude that BUMELTT is well tolerated in patients with advanced ovarian cancer and results are equivalent to other published HDC regimens.