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:complete remission (CR) rates (40-50%) with median overall survivals of 18-24 months and progression-free survivals (PFS) of 12-25% in patients with breast cancer We investigated the outcomes of patients with breast cancer undergoing induction chemotherapy, mobilizresponsive to conventional induction chemotherapy. 1-6 A recent randomized phase III trial demonstrated the superioration of peripheral blood stem cells (PBSC) and highdose chemotherapy (HDC) with PBSC infusion. One ity of two cycles of HDC with peripheral blood stem cell (PBSC) support compared to conventional-dose treatment hundred and fourteen patients with untreated stage IV breast cancer, with a median age of 46 years (range 24-in patients with newly diagnosed metastatic breast cancer. 7Although HDC with PBSC support may be superior to 62), were entered on a phase II trial consisting of: (1) doxorubicin, 5-flurouracil, methotrexate (AFM) × 4 conventional-dose chemotherapy, the majority of patients will relapse and die of progressive disease or of attempts courses at 2 week intervals; (2) A phase II study was designed to enroll patients with stage IV breast cancer at diagnosis and to evaluate outThere was one infectious death after AFM and all other deaths were associated with progressive disease. Fiftycomes following the sequential administration of induction chemotherapy, chemotherapy and growth factor mobiliztwo patients (46%) are alive, 21 (18%) without progression, at a median 31 months (range 22-47). The ation of PBSC and HDC followed by PBSC infusion. Outcomes were analyzed and reported on an intent to treat basis probabilities of survival and progression-free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 with a minimum follow-up of 24 months from enrollment. patients with visceral disease and/or a prior history of doxorubicin adjuvant therapy have relapsed or proPatients and methods gressed. We conclude that the sequential administration of AFM, CEP and CTCb followed by PBSC resulted in Between March 1992 and January 1994, 120 patients with untreated stage IV breast cancer were enrolled in a phase long-term PFS only in patients who were NED, had bone-only disease or had lymph node or soft tissue dis-II trial of chemotherapy induction, chemotherapy and filgrastim mobilization of PBSC, HDC and infusion of PBSC. ease with or without bone disease. Other strategies, aimed at improving responses to initial therapy, Patients were eligible if they had newly diagnosed and untreated breast cancer (except for adjuvant therapy), were improving HDC regimens and/or developing immunomodulatory therapies, will be necessary to improve PFS 65 years of age or less, had an ECOG performance of 0-1 and evidence of adequate hepatic, renal and cardiac funcfor patients who fail doxorubicin adjuvant or who have visceral disease.tion. Pre-menopausal women could be entered on the study without a previous trial of hormonal therapy. All patients Keywords: high-dose chemotherapy for breast cancer signed a protocol-specific informed consent appro...

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.

Summary:Keywords: high-dose chemotherapy; non-Hodgkin's lymphoma; autologous stem cells The outcomes for patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) infusion by practicing oncologists in community cancer centersPatients with recurrent or refractory non-Hodgkin's lymin the United States were determined. Eighty-three phoma (NHL) may respond to further conventional treatpatients with NHL, who had failed conventional chemoment but few are cured. 1 It has been known for more than therapy, underwent mobilization of PBSC with chemoa decade that high-dose chemotherapy (HDC) or chemotherapy and a recombinant growth factor in an outradiotherapy followed by autologous stem cell infusion patient facility. At a median of 40 days (range 26-119) results in long-term event-free survival (EFS) in a signifiafter mobilization chemotherapy all received carmuscant fraction of patients with NHL who have failed chemotine (300 mg/m 2 × 1), etoposide (150 mg/m 2 twice a day therapy. 2-6 A large body of data has been accumulated over × 4 days), cytarabine (100 mg/m 2 twice a day × 4 days) the past decade that confirmed these observations. ively. The probabilities of OS and EFS for 27 patientsDespite the curative potential of HDC and autologous in untreated first relapse were 0.52 and 0.44, respectstem cell infusion, many patients with NHL who fail ively, as compared to 0.56 and 0.32, respectively, for 18 chemotherapy in the United States do not have access to patients who had reinduction attempts prior to receivthis therapy because of geographic barriers, high cost assoing mobilization chemotherapy (P = 0.81 for OS and ciated with treatment and the perception that the morbidity 0.99 for EFS). No significant risk factors for the outand mortality of treatment requires referral to a tertiary comes of TRM, relapse/progression, OS or EFS could bone marrow transplant center. 23,24 However, the developbe identified. These data demonstrate that approximent of autologous peripheral blood stem cell (PBSC) mately 40% of patients with NHL who have failed coninfusion has made the delivery of some HDC regimens a ventional chemotherapy become long-term disease-free relatively safe therapeutic procedure allowing clinical trials survivors after mobilization chemotherapy, high-dose to be carried out in community cancer centers by practicing BEAC and PBSC infusion administered in an outpatient oncologists. 6,[25][26][27][28] setting in community cancer centers, with the major The purpose of this analysis was to report the outcome cause of failure being relapse. Results obtained in this of 83 patients with NHL who had failed chemotherapy and study are comparable to published data in similar received HDC with BEAC followed by autologous PBSC patient populations receiving therapy as inpatients, suginfusion in an outpatient private practice setting. gesting that clinical trials involving well-tested HDC regimens can be carried out safely in this setting.

Summary:with low-grade NHL, the role of high-dose therapy with autologous stem cell support is less well defined. 2-4 Several reports of high-dose therapy and autologous stem cell supForty-nine patients with low-grade non-Hodgkin's lymphoma (NHL) received high-dose chemotherapy (HDC) port for patients with NHL have included patients with lowgrade histology. [5][6][7][8][9][10][11] In addition, several recent studies have with busulfan and cyclophosphamide (BUCY) or carmustine, etoposide, cytarabine and CY (BEAC) followed specifically evaluated the outcome of patients with lowgrade NHL who have received high-dose therapies with stem by unpurged autologous peripheral blood stem (PBSC) infusion. All patients had failed initial chemotherapy or cell support after failure of conventional therapy. 3,4,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] One study has evaluated cyclophosphamide (CY) and TBI with progressed after an initial remission. Peripheral blood stem cells were mobilized with CY alone (n = 1), CY, stem cell support in patients with follicular lymphoma treated during first remission. 82). It was concluded that BUCY isBetween January 1991 and July 1995, 49 patients with lowan active regimen for the treatment of patients with lowgrade NHL failing to achieve a complete remission (CR) grade NHL.with initial induction chemotherapy or relapsing following Keywords: high-dose chemotherapy; non-Hodgkin's an initial remission were enrolled on a protocol involving lymphoma; autologous stem cells either BUCY or BEAC. This was not a randomized trial and the choice of protocols was decided by the treating oncologist.Patients were required to have an ECOG performance It is generally accepted that patients with intermediate-or status of 0-2, be age 65 years or less, and have evidence high-grade non-Hodgkin's lymphoma (NHL) who fail of adequate hepatic, renal and cardiac function. All patients chemotherapy benefit from high-dose chemotherapy (HDC) signed informed consent approved by the institutional or HDC combined with total body irradiation (TBI) folreview board of the hospital where the therapy was lowed by autologous hematopoietic stem cell support.