Publications (485)3694.69 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Immunoadsorption columns capable of specifically removing antibodies show promise as an alternative treatment to plasma exchange. Most columns are designed to be perfused with plasma and it is necessary to use a plasma separation device (filtration or centrifugation) for the procedure. This increases the cost and complexity of the immunoadsorption procedure. We have adapted immunoadsorption columns capable of removing anti-A or anti-B red cell antibody from plasma to a whole blood perfusion system by coating the silica with a thin layer of collodion and incubating with albumin (1%). Patients were given heparin, 25 units/kg intravenously, followed by a continuous infusion of 3% citrate and heparin, 10 units/ml, to achieve a ratio of 1:16–1:20 (anticoagulant to whole blood) before delivery through the columns. Effective and specific removal of anti-A or anti-B antibody was achieved with this technique. Effects on coagulation parameters and the complement system were acceptably small.
- [Show abstract] [Hide abstract] ABSTRACT: Bone marrow transplant recipients require central venous catheterization for a variety of fluids. They are also particularly susceptible to infection. Here we discuss the use of double lumen catheters to reduce the number of invasions necessary. We make particular reference to infection, neutropenia, prophylactic antibiotics, additional catheters, and presence of graft vs host disease.
- [Show abstract] [Hide abstract] ABSTRACT: A patient with pancytopenia and paroxysmal nocturnal haemoglobinuria (PNH) following exposure to insecticide spray developed complete marrow failure after inhalation of vapours containing benzol. There was no sign of spontaneous recovery after more than 6 mth of conventional and supportive therapy. The patient was treated with the immunosuppressive agent cyclophosphamide, 50 mg/kg on each of four days, followed in 36 hr by transplantation of marrow from a sibling compatible at the major human histocompatibility locus (HL-A). Intermittent methotrexate therapy was given for 102 days after grafting to prevent graft-versushost disease. The patient showed prompt haemopoietic engraftment indicated by restoration of marrow cellularity and a rise in peripheral blood cell counts beginning on day 11 after the graft. The patient is alive and well with normal haemopoietic function and continued absence of PNH more than 1 yr and 4 mth after transplantation.
- [Show abstract] [Hide abstract] ABSTRACT: Twenty patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Four patients remain alive in complete remission from 153 to 784 days after transplant. The reason for failure in eight cases was persistence or relapse of lymphoma. In the other eight cases, death was due to a complication of the transplant procedure including interstitial pneumonia, veno-occlusive disease of the liver, graft-versus-host disease, or infection. These results appear similar to those previously observed in patients with acute leukemia in relapse in that a small but significant proportion of patients with otherwise end-stage disease may achieve prolonged complete remission after intensive chemoradiotherapy and allogeneic marrow transplantation.
- [Show abstract] [Hide abstract] ABSTRACT: The current status of autologous and allogeneic marrow transplantation for acute leukemias and malignant lymphoma is reviewed and compared to the current status of conventional chemotherapy. Based on the reviewed literature, it is concluded that marrow transplantation and conventional chemoradiotherapy are not mutually exclusive and that for most young patients with acute hematological malignancies the question is not if, but rather when to intervene with a marrow transplant treatment. Thus marrow transplantation and conventional chemoradiotherapy can work as complimentary units in the complex therapeutic approach needed to cure most patients with hematological malignancies.
- [Show abstract] [Hide abstract] ABSTRACT: There is evidence that pentoxifylline (PTX) and ciprofloxacin (Cipro) may protect patients from the effects of chemotherapy and radiation, which could allow further drug dose escalation. This study was conducted to determine whether oral and intravenous (IV) PTX and Cipro permits increased dose levels of oral busulfan (BU) with a fixed dose of IV cyclophosphamide (CY) in patients with breast cancer receiving autologous or syngeneic hematopoetic cell transplantation. Sixty-seven patients received PTX and Cipro with CY of 150 mg/kg and escalating doses of BU. The BU dosing began at 15 mg/kg, escalating in 1 mg/kg increments in groups of 4 patients. If no grade 3 or 4 regimen- related toxicities (RRT) were observed, the next 4 patients were treated at a higher dose. Excessive RRT was not observed until BU 21 mg/kg was reached. Two patients at this dose level had RRTs and their BU steady-state concentration (Css) were 1,414 and 1,545 ng/ml. At a BU dose of 20 mg/kg , average BU Css 1,280 ng/ml, 0/4 had RRT. Among 10 patients who had BU Css targeted to 1,350 ng/ml, RRTs occurred in 2 (20%). In this preliminary study with PTX and Cipro, the maximum tolerated dose of BU that can be given with CY (150 mg/kg) was 20 mg/kg, a BU Css of approximately 1,300 ng/ml. A randomized trial is necessary to determine whether PTX and Cipro reduce the toxicities of this regimen.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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 microg/kg/day s.c., GM-CSF 250 microg/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 x 10(9) per liter (median of 11 vs14 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 x 10(6) kg per apheresis, P = 0.0001) and a higher percentage achieved 2.5 x 10(6) CD34 cells per kilogram (94% vs 78%, P = 0.21) and 5 x 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.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to compare the effects of filgrastim, sargramostim, or sequential sargramostim and filgrastim on CD34(+) cell yields and morbidity after myelosuppressive mobilization chemotherapy (MC). One hundred fifty-six patients were randomized to receive filgrastim (n = 51), sargramostim (n = 52), or sargramostim for 5 days followed by filgrastim (n = 53) after MC with either cyclophosphamide and etoposide (n = 75) or paclitaxel and cyclophosphamide (n = 81). Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 x 10(9)/L or greater (a median of 11 v 14 days; P =. 0001), with fewer patients requiring RBC transfusions (P =.008), fewer patients with fever (18% v 52%; P = 0.001), fewer hospital admissions (20% v 42%; P =.013), and less intravenous antibiotic therapy (24% v 69%; P =.001). Patients who received filgrastim yielded more CD34(+) cells (median, 7.1 v 2.0 x 10(6)/kg/apheresis; P =.0001), and a higher fraction achieved 2.5 x 10(6) (94% v 78%; P =.021) and 5 x 10(6) (88% v 53%; P =.001) or more CD34(+) cells/kg with fewer aphereses (median, 2 v 3; P =.002) and fewer days of growth-factor treatment (median, 12 v 14; P =.0001). There were no major differences in outcomes between the filgrastim alone and the sequential regimens. After high-dose chemotherapy, patients who had peripheral-blood stem cells (PBSCs) mobilized with filgrastim or the sequential regimen received higher numbers of CD34(+) cells and had faster platelet recovery (P =.015), with fewer patients (P =.014) receiving fewer platelet transfusions (P =.001) than patients receiving sargramostim-mobilized PBSCs. It was concluded that filgrastim alone or sequential sargramostim and filgrastim were superior to sargramostim alone for the mobilization of CD34(+) cells and reduction of toxicities after MC.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to determine outcomes for patients with operable noninflammatory stage IIIA/B locally advanced breast cancer (LABC) with positive axillary lymph nodes receiving high-dose chemotherapy (HDC) with peripheral blood stem cell (PBSC) support. One hundred fifteen patients with LABC who were no evidence of disease (NED) after initial surgery received standard dose induction chemotherapy, chemotherapy for mobilization of PBSC, and high-dose cyclophosphamide, thiotepa, and carboplatin with PBSC support for adjuvant therapy. Following hematopoietic recovery, all patients were scheduled to receive radiation therapy and tamoxifen was administered if the primary tumor was estrogen receptor/progesterone receptor (ER/PR) positive. Eighty-eight percent of patients were admitted to the hospital following HDC for a median of 11 days (range 3-26) and 12% were treated entirely as outpatients. There was one treatment-related death (0.9%) from infection occurring on day 8 after HDC. Forty-four (38%) have relapsed at a median of 20 months (range 10-55) from diagnosis, 11 (10%) with local-regional and 33 (28%) with metastatic disease. The probabilities of overall (OS) and event-free survival (EFS) for all 115 patients at 3 years were 0.73 and 0.61, respectively, with a median follow-up of 42 months (range 10-89) from diagnosis. In univariate and multivariate analyses, no factors could be identified that were statistically predictive for OS or EFS. However, there were trends for patients with ER/PR-negative primary tumors to have worse OS (p = 0.16) and EFS (p = 0.10) than patients with ER/PR-positive tumors. This adjuvant combined modality strategy incorporating HDC is safe and compares favorably to historical studies of neoadjuvant or adjuvant treatment for LABC. Further attempts to improve outcomes of patients with LABC receiving HDC are warranted.
- [Show abstract] [Hide abstract] ABSTRACT: Several studies have clearly documented a more rapid hematopoietic recovery with growth factor-mobilized PBSC than with bone marrow. Time to engraftment for neutrophils and platelets average 8-12 days in contrast to 2-4 weeks after bone marrow. This rapid hematopoietic recovery with PBSC has decreased the duration of hospitalization, transfusion requirements, and costs. Although growth factors alone may mobilize enough PBSC for high-dose chemotherapy, administration of growth factor after submyeloablative chemotherapy increases the yield of CD34+ cells. Based on the current data, CD34+ cell content of PBSC appears to be the single most powerful predictor of hematopoietic recovery. Infusion of > or =5 x 10(6) CD34+ cells/kg is associated with a rapid engraftment of neutrophils and platelets, although successful engraftment has also been reported with infusion of 2.5-5 x 10(6) CD34+ cells/kg. Age, prior radiotherapy, marrow involvement, and prior chemotherapy regimens are important factors influencing the yield of stem cells. Therefore, using these pa-rameters, we may identify the patients who will fail to mobilize sufficient numbers of PBSC before collection and use new strategies for stem cell mobilization. Because of the ease of collection and rapid engraftment after myeloablative therapy, PBSC have replaced bone marrow for autologous transplantation and may supplant bone marrow for allogeneic transplantation in the near future.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study is to determine outcomes for patients with high-risk nonmetastatic breast cancer undergoing high-dose chemotherapy with peripheral blood stem cell support. Forty-three patients with stage II-III disease, five to nine positive axillary lymph nodes, and a median age of 44 years (range, 27-60 years) were enrolled in a study that included: 1) standard dose doxorubicin, 5-fluorouracil, and methotrexate adjuvant therapy; 2) cyclophosphamide, etoposide, filgrastim, and peripheral blood stem cell harvest; and 3) high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by peripheral blood stem cell infusion. All 43 patients received doxorubicin, 5-fluorouracil, and methotrexate, 42 (98%) received etoposide, and 41 (95%) received CTCb. Thirty-two patients (74%) are alive, 28 (65%) without relapse at a median of 55 months (range, 41-87 months). Two died (5%) of treatment-related causes, (subclavian catheter complication after etoposide and late radiation pneumonitis), and nine other deaths (21%) were associated with recurrent breast cancer. The probabilities of overall and event-free survival at 4 years were 0.77 and 0.67, respectively, compared with 0.82 and 0.69, respectively, for 72 similar patients with 10 or more positive axillary nodes receiving the same sequence of therapy. Thus, patients with five to nine positive axillary lymph nodes have a similar risk of failure after high-dose chemotherapy and peripheral blood stem cell support as patients with 10 or more positive axillary lymph nodes.
- [Show abstract] [Hide abstract] ABSTRACT: 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/m2 (n = 52) or 250 mg/m2 (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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
University of PaviaTicinum, Lombardy, Italy
Fred Hutchinson Cancer Research Center
Seattle, WA, United States
- Division of Clinical Research
University of Washington Seattle
Seattle, Washington, United States
- Department of Medicine