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PubMed2006

The clinical study of autologous peripheral blood stem cell transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI).

PURPOSE: To investigate the effects and safety of autologous peripheral blood stem cell (PBSCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). METHODS: 70 patients with AMI were allocated to two groups, one was PBSCs transplantation group (n=35) that received optimal post-infarction medical treatment (standard drug and coronary artery intervention therapy) and intracoronary transplantation of PBSCs; the other was control group (n=35) that received optimum post-infarction medical treatment (standard drug and coronary artery intervention therapy). The PBSCs transplantation group received granulocyte colony-stimulating factor (G-CSF: Filgrastim, 300 microg) with the dose of 300-600 microg/day to mobilize the stem cell, and the duration of administration G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then, the suspend liquid was transferred into the infarct-related artery (IRA) by occluding the over-the-wire balloon and infusing artery through balloon center lumen. In the process of the mobilization, separation and intracoronary infusion of PBSCs, the complications have been investigated. Changes in left ventricular function were assessed at 6-month follow-up. RESULTS: 35 cases had finished follow-up in the treated group, while 23 cases in control group. After 6 months, within the treated group, there was a significant improvement in global left ventricular function ejection fraction (EF) from a baseline of 50.0+/-8.2% to 57.1+/-7.8% (P<0.0001), wall motion score index (WMSI) from 1.219+/-0.190 to 1.101+/-0.118 (P<0.0001), left end-systolic volume (ESV) from 63.8+/-23.9 ml to 52.6+/-20.3 ml (P=0.01) and left end-diastolic volume (EDV) from 134.2+/-36.7 ml to 119.2+/-30.3 ml (P=0.07); in the control group, there was no significant improvement in EF, WISM, EDV and ESV (P=0.490, 0.259, 0.117, 0.395). After 6-month follow-up, according to treatment group vs. control group, there was a significant improvement in EF from 57.1+/-7.8 to 52.6+/-5.7 (P=0.041) and WISM from 1.101+/-0.118 to 1.184+/-0.138 (P=0.034). There were a total of 25 cases with complications during the mobilization, separating and infusion of PBSC. The incidence of complications relating to mobilization was 37.1% (13/35), relating to separating was 14.3% (5/35) and relating to intracoronary infusion was 20.0% (7/35). No death was observed. CONCLUSION: Autologous PBSCs transplantation by intracoronary infusion is feasible and safe, and it can improve left ventricular function in the 6-month follow-up.

Aged↗
PubMed2004

The impact of granulocyte colony stimulating factor at content of donor lymphocytes collected for cellular immunotherapy.

BACKGROUND AND OBJECTIVES: Donor lymphocyte infusions (DLI) have become widely used for prevention or treatment of relapse after allogeneic hematopoietic stem cell transplantation. Increasing use of reduced intensity conditioning regimens (RICR) and subsequent application of DLI forced the hemapheresis centers to collect donor lymphocytes in certain quantity and quality. The place of growth factors especially granulocyte colony stimulating factor (rhG-CSF, filgrastim) in allogeneic hemapoietic stem cell (HSC) collection is established, but there is no consensus about the role of rhG-CSF. We aimed to clarify the dose effect of rhG-CSF on lymphocyte subpopulations (CD3+, CD3+4+, CD3+8+, CD19+, CD3-16+56+) cells and CD34+ HSC. DONORS AND METHODS: Major indications for DLI (mean volume: 180+/-52 ml) were for relapse or transplants using RICR mainly in patients with acute leukemia (n=20) or chronic myeloid leukemia (n=15). In four years we performed 40 lymphocyte apheresis (LA) on 30 healthy (med. age 28, M/F 21/9) donors using continuous flow cell separators by processing 2-2.5 times of their total blood volume (TBV). The apheresis data is divided into three groups according to rhG-CSF dose used for priming. Donors in Group I (n=18), Group II (n=9) and Group III (n=13) received no rhG-CSF (steady state), rhG-CSF 5 microg/kg/dsc x 5 days and rhG-CSF 10 microg/kg/dsc x 5 days, respectively. There was no difference within groups concerning TBV processed and recipient body weight. RESULTS: A total of 11,565 ml (+/-3700) of blood was processed in 216 min (+/-36.5) at an inlet of 56.8 ml/min (+/-10.6) using 999 ml (+/-307) ACD. The CD34+ HSC increased with increasing rhG-CSF dose as expected. Median CD3+ lymphocyte yield per recipient body weight in Group I, II and III were 0.9 x 10e8/kg (range: 0.1-2.1), 2.9 x 10e8/kg (range: 1.6-4.3) and 2.1 x 10e8/kg (range: 0.6-6.9), respectively. The primed donors T lymphocyte yield was 2-3-fold more in comparison to Group I. This gain was most significant between Group I and III in terms of mean CD3+ (1.09 x 10e8/kg vs 2.41 x 10e8/kg, p=0.02), CD3+4+ (0.64 x 10e8/kg vs 1.44 x 10e8/kg, p=0.02) and CD3+8+ (0.42 x 10e8/kg vs 0.89 x 10e8/kg, p=0.03) cells, respectively. CONCLUSION: Though the yield of lymphocyte subsets in G-CSF primed donors exceeds the non-primed donors, the target range of 1 x 10e7-1 x 10e8/kg CD3+ lymphocytes could be achieved in the majority of the apheresis procedures without rhG-CSF priming. The yield of T and B lymphocyte subsets are increased by G-CSF stimulation but not on a logarithmic scale, which did not correlate into a clinical relevance.

Adult↗
PubMed2002

Prophylactic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy: a meta-analysis.

PURPOSE: Several studies have evaluated the efficacy of the recombinant colony-stimulating factors in reducing the severity and duration of neutropenia and the risk of infection associated with dose-intensive cancer chemotherapy. We performed a meta-analysis to define better the magnitude of this effect and to assess the generalizability of the results among different diseases and types of treatment. MATERIALS AND METHODS: We used electronic databases and citation lists to identify controlled clinical trials of the prophylactic efficacy of the colony-stimulating factors on neutropenic complications. We selected randomized trials of the use of recombinant colony-stimulating factors before the onset of fever or neutropenia following systemic chemotherapy for solid tumors or malignant lymphomas. RESULTS: We identified eight controlled trials (n = 1144 patients) of prophylactic colony-stimulating factors, including five trials of filgrastim (recombinant granulocyte colony-stimulating factors) and three studies of lenograstim (glycosylated granulocyte recombinant colony-stimulating factors). Five trials were double-blind and placebo-controlled; three included untreated controls. Use of recombinant colony-stimulating factors was associated with a reduced risk of febrile neutropenia (odds ratio [OR] = 0.38; 95% confidence interval [CI]: 0.29 to 0.49), documented infection (OR = 0.51; 95% CI: 0.36 to 0.73), and infection-related mortality (OR = 0.60; 95% CI: 0.30 to 1.22), but a greater risk of bone pain (OR = 2.9; 95% CI: 1.6 to 4.8). CONCLUSION: In this meta-analysis, recombinant colony-stimulating factors were effective in reducing the risk of febrile neutropenia and documented infection associated with several malignancies and dose-intensive treatment regimens.

Antineoplastic Agents↗
PubMed2001

Challenging the platinum combinations: docetaxel (Taxotere) combined with gemcitabine or vinorelbine in non-small cell lung cancer.

The limited single-agent activity of cisplatin, its toxicity profile, and the inconvenience involved in hydrating patients has compelled researchers to investigate other treatments as possible alternative therapies in non-small cell lung cancer. More recently, interest has focused on the potential of nonplatinum combinations. Phase II studies show that the combination of docetaxel (Taxotere; Aventis, Antony, France) and gemcitabine is active in stage IIIB/IV non-small cell lung cancer not previously treated by chemotherapy. Response rates of up to 54% and a median survival time of 13 months have been reported. These data are comparable with the achievements of cisplatin-based combinations. A randomized phase II trial of docetaxel plus gemcitabine versus docetaxel plus cisplatin found that the two regimens were equally active in terms of response rate, median, and 1-year survival. However, the combination of docetaxel with gemcitabine produced significantly less neutropenia and nonhematologic toxicities. In combination, from 80% to 100% of the full single-agent gemcitabine and docetaxel doses can safely be administered once every 3 weeks. The combination of docetaxel plus vinorelbine is also active in non-small cell lung cancer and preliminary data suggest that this schedule with prophylactic filgrastim may optimize tolerability and dose intensity. In a phase II study using this approach, a confirmed response rate of 51% was obtained in 35 patients. At 12 months, the predicted median survival is 14 months and the predicted 1-year survival rate is 60%. Excessive lacrimation, fatigue, and onycholysis were cumulative toxicities. However, the incidence of mucositis and neuropathy was low with the combination of docetaxel and vinorelbine. Docetaxel combined with other new agents, particularly gemcitabine, may offer another useful alternative to cisplatin-based chemotherapy in patients with good performance status.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Current management of chemotherapy-induced neutropenia: the role of colony-stimulating factors.

Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms. One important consequence, chemotherapy-induced neutropenia (CIN), places patients at risk of developing fever and life-threatening infections. These complications have substantial economic impact and may severely affect the quality of life of patients undergoing treatment of cancer. Currently, CIN is managed by delaying and reducing chemotherapy treatment with hematopoietic growth factors and with intravenous antibiotic therapy. Reducing chemotherapy may compromise treatment outcomes in potentially curable malignancies, such as early stage breast cancer and non-Hodgkin's lymphoma. Randomized clinical trials have clearly shown that granulocyte colony-stimulating factor (filgrastim) and the longer-acting pegylated granulocyte colony-stimulating factor pegfilgrastim, when administered 24 hours after chemotherapy before the occurrence of CIN, are effective in reducing the incidence and severity of neutropenia and its complications, including administration of full doses of chemotherapy without treatment delay. Dose-dense chemotherapy, ie, the administration of standard-dose chemotherapy in shorter cycles (made feasible with growth factor support), has recently been shown to improve outcomes in early stage breast cancer and non-Hodgkin's lymphoma. This review summarizes the clinical consequences of CIN and describes current best practices for the management of patients at risk for CIN.

Antineoplastic Agents↗
PubMed2000

Rescue of haemopoiesis by a combination of growth factors including stem-cell factor.

We observed an unexpectedly rapid rise in platelet counts with complete haematological recovery after a BEAM regimen, in a patient who could not be rescued by autologous transplant but who received filgrastim, epoetin alfa, and ancestim. We feel that these results may be attributed to this specific growth factor combination, including ancestim, a cytokine known to act on primitive stem cells. If confirmed, this observation may open new possibilities in intensive chemotherapy for patients for whom haematopoietic progenitors are difficult to harvest. This may also represent an alternative to ex-vivo expansion and deserves further investigation.

Adult↗
PubMed2005

Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.

BACKGROUND: Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial. METHODS: Patients with at least nine positive nodes were randomly assigned either two courses of accelerated (2-week intervals, with filgrastim support), conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy (epirubicin, cyclophosphamide, and thiotepa supported by peripheral-blood progenitors) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide, methotrexate, and fluorouracil. The primary endpoint was event-free survival. Analyses were done both by intention to treat and per protocol. FINDINGS: 403 patients were enrolled; 201 were assigned high-dose chemotherapy and 202 conventional treatment. The mean number of positive nodes was 17.6, and median follow-up was 48.6 months. 4-year event-free survival (intention-to-treat analysis) was 60% (95% CI 53-67) in the high-dose chemotherapy group and 44% (37-52) in the control group (p=0.00069). The corresponding overall survival was 75% (69-82) versus 70% (64-77; p=0.02). There were no treatment-related deaths. INTERPRETATION: Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies. The discrepancy might be due partly to design differences (tandem, brief induction) between our regimen and those studied in other trials. This approach merits further study.

Adult↗
PubMed2000

Phase II trial of induction high-dose chemotherapy followed by surgical resection and radiation therapy for patients with marginally resectable non-small cell carcinoma of the lung.

The combination of carboplatin and paclitaxel is an active regimen in non-small cell lung cancer (NSCLC). Historically, patients with stage III disease have manifested higher response rates than patients with metastatic disease, and patients achieving a pathologic complete response to induction chemoradiation therapy prior to surgery have shown better long-term outcome. Based upon our pilot data using high-dose carboplatin and paclitaxel, we designed a phase II trial in patients with marginally resectable stage IIIA NSCLC. Ten patients, with bulky nodal stage IIIA disease, initially received etoposide (2 g/m2) and granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC). Two cycles, 28 days apart, of carboplatin (AUC 12 in seven patients; AUC 16 in three patients) and paclitaxel (250 mg/m2) were administered with filgrastim (5 microg/kg) and PBSC support. After re-evaluation, patients underwent a thoracotomy followed by radiotherapy (44-60 Gy) if deemed resectable, or radiotherapy alone (60 Gy) if not resectable. The median age was 58.5 years (48-66) with a median ECOG performance status of 0 (0-1). Histology was adenocarcinoma in seven patients; the remainder had either squamous cell, large cell or bronchoalveolar carcinoma. Based on CT radiography, the overall response rate was 40%. Eight of ten patients underwent resection with four right pneumonectomies, three right upper lobectomies and one wedge resection of the right upper lobe. Six patients had a complete resection. Of eight patients resected, four were downstaged by induction therapy, three remained unchanged and one was found to have more extensive disease. The remaining two patients developed metastatic disease while receiving chemotherapy. The median dose of postoperative radiotherapy was 54 Gy (35-66 Gy). Actual median follow-up for all patients was 89 weeks (25 to 136+). The actuarial median overall survival was 124 weeks (25 to 136+) and time to progression was 57 weeks (17 to 136+). The median dose of carboplatin delivered expressed as mg/m2 was 779 (615-1540). Neutropenic fever occurred in two patients during the initial mobilization cycle only. The median number of units of RBC and/or platelets transfused was 0 (0-2 and 0-6, respectively). There were no significant non-hematologic toxicities. High-dose induction chemotherapy with stem cell rescue is feasible and safe with an acceptable response rate. Thoracotomy, including pneumonectomy and postoperative radiotherapy, were well tolerated by patients after undergoing high-dose induction chemotherapy with no apparent increase in peri-operative morbidity. The pathologic complete response rate was low--one out of ten patients. These results indicate that dose escalation of induction chemotherapy does not improve response rates even in this highly selected patient population. Accordingly, the complexity and potential toxicity of high-dose chemotherapy, as delivered in this trial as neoadjuvant treatment of non-small cell lung cancer, is not warranted.

Adenocarcinoma↗
PubMed1997

[Economic evaluation of the use of haematopoietic factors in managing malignant hemopathies].

Economic evaluation of haematopoietic growth factors in the treatment of malignant hemopathies was undertaken along with clinical trials or retrospectives studies. The cost of the sole treatment was estimated to be 2,302 US$ per cycle. Cost-minimization analyses compared the cost of a treatment course (chemotherapy, bone marrow transplantation with and without haematopoietetic growth factors), and cost-effectiveness analyses estimated the cost per episode of averted febrile neutropenia. Results appear to be contradictory and do not allow definite conclusions about the existence of extra costs or of cost savings due to the introduction haematopoietetic growth factors, except in the case of filgrastim-mobilized peripheral blood progenitor cell transplantation.

Cost-Benefit Analysis↗
PubMed2003

Treatment of human immunodeficiency virus-related lymphoma with haematopoietic stem cell transplantation.

The advent of highly active antiretroviral therapy (HAART) and its co-administration with chemotherapy in patients with human immunodeficiency virus (HIV)-related lymphoma has lead to the exploration of potentially curative combination chemotherapy and myeloablative therapy followed by autologous haematopoietic stem cell transplantation (ASCT). Applying the same principles used for patients with HIV-negative aggressive lymphoma, in 1998 we developed a program of high-dose therapy and ASCT at City of Hope for patients with HIV-related lymphoma and Hodgkin's disease. Our studies have primarily included patients with chemosensitive lymphoma in relapse or first remission with poor-risk features at diagnosis. Filgrastim (G-CSF)-primed peripheral blood stem cell mobilization and apheresis have been successful while patients were receiving HAART and chemotherapy. To date, ASCT has been performed in 19 patients with HIV-related lymphoid malignancies, representing the largest single-institution experience reported to date. Most patients received a chemotherapy-based conditioning regimen consisting of high-dose carmustine, etoposide and cyclophosphamide. Early infections, namely bacteremias and neutropenic fever were similar to those observed in the HIV-negative transplant setting. Opportunistic infections were rare and easily treatable. There were three early deaths, two from relapsed lymphoma and one from multi-organ failure in an older patient. The remaining 16 patients are alive and in remission. In summary, ASCT is well tolerated, can result in long-term remissions, and is potentially curative in selected HIV-related lymphoma patients with chemosensitive relapse and high-risk disease in first remission defined by the age-adjusted International Prognostic Index criteria (i.e., two or three of the following: elevated LDH, advanced stage, and poor performance status). Acquisition of resistance to HAART remains as a potential problem for HIV-positive patients who are cured of their lymphoma.

Antineoplastic Agents↗
PubMed2002

The effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet recovery in breast cancer patients undergoing autologous bone marrow transplantation.

OBJECTIVE: To assess the safety and efficacy of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) administered after autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Two randomized, double-blind, placebo-controlled studies were done. In the phase 1/2 study, 75 breast cancer patients underwent a bone marrow harvest and myeloablative STAMP V chemotherapy and were randomized to receive placebo or one of three doses of PEG-rHuMGDF. In the phase 3 study, 64 patients were randomized to receive placebo or the minimally effective dose of PEG-rHuMGDF. The study drug was administered daily starting on the day of bone marrow infusion until the platelet count was greater than or equal to 50 x 10(9)/L (without transfusion) or for a maximum of 28 days. All patients received 10 microg/kg/day filgrastim starting on day 2 until neutrophil count recovery. RESULTS: PEG-rHuMGDF appeared to be safe and well tolerated. No significant differences were noted in mortality or disease progression rates. Antibodies to MGDF were not observed. In the phase 1/2 study, the time to platelet recovery to greater than or equal to 20 x 10(9)/L and platelet transfusion requirements were significantly reduced for patients treated with PEG-rHuMGDF compared with placebo (p < 0.05). In the phase 3 study, no significant differences in the kinetics of early thrombopoiesis or platelet transfusions after ABMT were observed. CONCLUSIONS: PEG-rHuMGDF was not consistently efficacious in reducing the duration of severe thrombocytopenia. The maximum platelet counts for PEG-rHuMGDF-treated patients occurred a median of 2 weeks after the last dose of drug, suggesting that the biologic effects of this hematopoietic cytokine are delayed compared with other hematopoietic cytokines.

Adult↗
PubMed2003

A randomized multicenter comparison of CD34(+)-selected progenitor cells from blood vs from bone marrow in recipients of HLA-identical allogeneic transplants for hematological malignancies.

OBJECTIVE: Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone marrow transplantation (BMT) vs PBPC transplantation (PBPCT) using CD34(+) selection for T-cell depletion (TCD) in both study arms. PATIENTS AND METHODS: Between January 1996 and October 2000, 120 patients with a diagnosis of acute leukemia, myelodysplasia, multiple myeloma, or lymphoma were randomized to receive either filgrastim-mobilized PBPC or BM from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Patient characteristics did not differ between study arms. RESULTS: Recipients of PBPC received more CD3(+) T cells (median: 3.0 vs 2.0 x 10(5)/kg, p<0.0001) and more CD34(+) cells (median: 3.6 vs 0.9 x 10(6)/kg, p<0.0001). Neutrophil and platelet recoveries occurred significantly faster after PBPCT. The cumulative incidence of acute GVHD grades II-IV was 37% after BMT vs 52% after PBPCT and was most significantly (p=0.007) affected by the number of CD3(+) T cells in the graft. Acute GVHD appeared strongly associated with increased treatment-related mortality (TRM) in a time-dependent analysis. Higher numbers of CD34(+) cells were associated with less TRM. With a median follow-up of 37 months (range: 12-75), overall survival at 4 years from transplantation was 60% after BMT and 34% for recipients of PBPCT (p=0.04), which difference was largely due to increased GVHD and TRM in PBPC recipients receiving T-cell dosages greater than 2 x 10(5)/kg. CONCLUSION: Outcome following T cell-depleted PBPCT critically depends on the number of CD3(+) T cells, whereby high T-cell numbers may blunt a favorable effect of higher CD34(+) cell numbers.

Adolescent↗
PubMed1998

Successful treatment of pustulosis palmaris et plantaris with granulocyte colony stimulating factor in a patient with hereditary neutropenia.

A 26-year-old female with hereditary neutropenia had Pustulosis Palmaris et Plantaris. Drug administration did not improve her symptoms. Following administration of granulocyte colony stimulating factor (G-CSF; filgrastim), her neutrophil count increased from 300 to 58,000/microliters, and her dermatosis improved. Pustulosis Palmaris et Plantaris has been described as a representative second lesion of focal infection. Neutropenia may be one cause of Pustulosis Palmaris et Plantaris due to refractory focal infection. In the present case, increase in neutrophils with G-CSF may have improved focal infection, resulting in improvement in refractory Pustulosis Palmaris et Plantaris.

Adult↗
PubMed1996

Time to resolution of morbidity: an endpoint for assessing the clinical cure of community-acquired pneumonia.

Clinical trials of new therapeutics for community-acquired pneumonia (CAP) have typically used a subjective endpoint of clinical response. However, as this endpoint is not quantitative, it is subject to observer bias and renders the conduct of multicenter trials difficult. For the purposes of conducting a clinical trial of filgrastim, as an adjunct to antibiotics for the treatment of CAP, a set of clinical criteria were developed prospectively to determine the time when a clinical cure was achieved, based on respiratory rate, temperature, oxygenation and roentgenographic findings, which was termed the time to resolution of morbidity (TRM). The TRM was evaluated on the first 100 patients entered in this clinical trial. As no clear reference standard exists, the predictive value for the duration of parenteral antibiotics (AB) and the length of hospital stay (LOS) was compared with that provided by a widely used classification system for severity of disease, APACHE II. The TRM was found to correlate significantly better with AB or LOS than APACHE II (P < 0.001). Furthermore, TRM offers the benefit over the endpoints of LOS and AB of being specifically designed to measure the patient's response to therapy, and, in fact, may aid physicians in determining the duration of parenteral antibiotic therapy. Hence, TRM is relevant to the clinician and is a useful tool to ensure uniformity in the assessment of the response to a new therapeutic in a multicenter clinical trial.

Adult↗
PubMed1996

High-dose melphalan with re-infusion of unprocessed, G-CSF-primed whole blood is effective and non-toxic therapy in multiple myeloma.

In order to shorten the pancytopenic period following high-dose melphalan 140 mg/m2 (HDM) treatment of multiple myeloma patients, we studied the effects of re-infusing granulocyte colony stimulating factor (G-CSF) [Filgrastim, Neupogen]-primed unprocessed whole blood. 30 patients with multiple myeloma were treated with HDM. One litre of blood after 5 or 6 days stimulation with G-CSF (10 micrograms/kg) was drawn, kept unprocessed for 1 day and re-infused 24 h after chemotherapy. Time to granulocyte recovery (> 0.5 x 10(9)/1) and platelet recovery (> 20 x 10(9)/1) were assessed as well as length of hospital stay, number of transfusions and antibiotic use. These 30 patients were compared with 20 historical control patients who were similarly treated but without stem cell support. The response rate was 75% (21/28) including a complete remission (CR) rate of 29% (8/28). Two early deaths due to Aspergillus pneumonia were observed. The median overall survival after HDM has not been reached after a median follow-up of 14 months. 10 patients showed progression at a median of 7 months. Currently, 23 patients are alive with a median follow-up time of 14 months. Haematological recovery was significantly faster in the study group as compared to the historical control group. The neutrophil count reached 0.5 x 10(9)/1 at a median of 14 days after infusion of 1 litre of unprocessed whole blood compared with 38 days in the historical control group. A platelet count of 20 x 10(9)/1 was reached at a median of 26 days compared with 36 days in the historical control group. Length of hospital stay decreased from a median of 43 to 18.5 days. The number of days with antibiotics was reduced from a median of 21 to 6 days. HDM is effective therapy for multiple myeloma. Toxicity of the regimen is considerably reduced by the use of G-CSF-stimulated unprocessed whole blood, an easy to perform and cheap technique to mobilise and collect stem cells.

Adult↗
PubMed2000

Immunotherapy with rituximab during peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Peripheral blood stem cell grafts from patients with lymphoma are often contaminated with neoplastic cells. Administration of a lymphoma-specific monoclonal antibody before collecting stem cells may be one way of reducing the contamination. Similarly, an antibody after transplantation at a time of minimal residual disease may increase the efficacy of the procedure. The objective of this study was to determine the safety of using rituximab as both an in vivo purging agent and a posttransplantation adjuvant. Eligible patients with lymphoma received 375 mg/m2 rituximab intravenously IV) on day 1, 2.5 g/m2 cyclophosphamide IV on day 4, and 10 microg/kg per day filgrastim starting on day 5 and continuing until completion of leukapheresis. Patients subsequently received a standard preparative regimen and then received 375 mg/m2 rituximab IV 7 days after platelet independence was achieved. Twenty-five patients (14 men, 11 women; median age, 51 years) were enrolled. Of the 25 patients, 23 received transplants after at least 2.0 x 10(6) CD34+ cells/kg were harvested. As determined with a sensitive polymerase chain reaction assay, 6 of 7 stem cell products tested were free of tumor contamination. All patients engrafted promptly, and the rituximab infusions were well tolerated. Transient neutropenia of uncertain etiology occurred in 6 patients a median of 99.5 days post-transplantation. An additional patient developed progressive pancytopenia. Rituximab used as an in vivo purging agent and adjuvant immunotherapy with peripheral blood stem cell transplantation for non-Hodgkin's lymphoma is a well-tolerated regimen. However, the ultimate determination of efficacy will require the results of ongoing studies.

Adult↗
PubMed2003

Low-dose total body irradiation, fludarabine, and antithymocyte globulin conditioning for nonmyeloablative allogeneic transplantation.

Nonmyeloablative allogeneic peripheral blood progenitor cell transplantation with low-dose total body irradiation (TBI; 200 cGy) plus fludarabine followed by cyclosporine and mycophenolate mofetil results in modest graft rejection rates. Acute and chronic graft-versus-host diseases (GVHD) are also seen and may not differ substantially from those that occur after fully ablative transplantation. Adding antithymocyte globulin (ATG) to pretransplant conditioning produces substantial immunosuppression. Because of its persistence in the circulation, ATG can achieve in vivo T-cell depletion. Twenty-five patients who were not eligible for conventional fully ablative allogeneic stem cell transplantation by virtue of age or comorbidities underwent nonmyeloablative allogeneic transplantation with ATG 15 mg/kg/d days -4 to -1, TBI 200 cGy on a single fraction on day -5, and fludarabine 30 mg/m(2)/d on days -4 to -2. Oral mycophenolate mofetil 15 mg/kg every 12 hours and cyclosporine 6 mg/kg every 12 hours were started on day -5. Grafts were unmanipulated peripheral blood progenitor cells mobilized with filgrastim 10 microg/kg/d and collected on day 5. The median age of the recipients was 57 years (range, 30-67 years); diagnoses were non-Hodgkin lymphoma (n = 11), acute myeloid leukemia (n = 6), multiple myeloma (n = 3), acute lymphoblastic leukemia (n = 2), severe aplastic anemia (n = 1), paroxysmal nocturnal hemoglobinuria (n = 1), and myelodysplastic syndrome (n = 1). The median CD34(+) and CD3(+) contents of the grafts were 7.6 x 10(6)/kg and 1.6 x 10(8)/kg, respectively. Five patients received voluntary unrelated donor grafts. Three patients, 2 with voluntary unrelated donor grafts and 1 with a sib donor, received a 1 antigen-mismatched graft. The rest were fully matched. Twenty-two of 25 patients were evaluable for chimerism. Sixteen had >/=95% donor chimerism. Four patients displayed 80% to 90% donor chimerism, 1 displayed 78%, and 1 displayed 64%. Eleven patients relapsed with their original disease. One patient rejected the graft at 180 days. The median hospital stay was 27 days. Complications included GVHD in 6 patients (3 patients had grade I or II GVHD of skin and liver, and 3 patients had grade III or IV GVHD of liver and gut). Two of the patients with GVHD had mismatched grafts. Transplant-related toxicity was seen in 4 patients and infection in 5 patients. The median length of follow-up was 162 days (range, 17-854 days). Complete remissions were seen in 10 patients. Four patients remained in complete response (CR) at 280 to 595 days. One patient relapsed with non-Hodgkin lymphoma after a CR of 728 days. Of the 25 patients, 16 died (6 of relapsed disease, 4 of GVHD, 3 of infection, and 3 of transplant-related toxicity) and 9 are alive (6 with CR-2 of them after donor leukocyte infusion-and 3 with relapsed disease). The addition of ATG to low-dose TBI and fludarabine nonmyeloablative conditioning was well tolerated and resulted in >80% donor engraftment in this small cohort. As in other series of truly nonmyeloablative transplantation, a high rate of relapse was observed. Donor engraftment may be facilitated by the addition of ATG to low-dose TBI and fludarabine conditioning.

Adult↗
PubMed1997

A randomized study of epirubicin monotherapy every four or every two weeks in advanced breast cancer. A Hellenic Cooperative Oncology Group study.

PURPOSE: To evaluate the impact on the response rate in patients with advanced breast cancer (ABC) of the doubling of the dose intensity (DI) of epirubicin monotherapy. PATIENTS AND METHODS: From January 1991 until April 1996, 167 patients with ABC were randomized to receive epirubicin (110 mg/m2) either every four (81 patients, group A) or every two weeks (86 patients, group B). Filgrastim (5 micrograms/kg/daily) was administered prophylactically on days 2-12 of each cycle. RESULTS: The two groups were equally balanced in terms of major patient and tumor characteristics. Even though the median cumulative dose of epirubicin was identical in the two groups (651 mg/m2), the median DI of epirubicin was doubled in group B (27.2 vs. 52.9 mg/m2/wk, respectively). The complete response (CR) rate was significantly increased in group B (5%, 95% CI: 0.16%-9.84% vs. 17%, 95% CI: 8.9%-25.08%, P = 0.011), although overall response rates were similar (49% vs. 53%, P = 0.5957). Also, there was no significant difference in the incidence of grade 3-4 toxicity between the two groups. After a median follow-up of 25 months (range, 0.43-43.3+) no significant difference was observed in the duration of response (median, 10 months vs. 8.5 months, P = 0.5130), time to progression (median, 7.2 months vs. 7.4 months, P = 0.2970) or survival (median, 14.6 months vs. 14.9 months, P = 0.4483). Logistic regression analysis showed that performance status was a significant variable for response (P = 0.0068) and multivariate analysis using the Cox proportional hazards model revealed that performance status was significant for survival (P = 0.0049), while the presence of multiple metastases (P = 0.0020) was significant for time to progression. CONCLUSION: Doubling the planned DI of epirubicin monotherapy significantly increases the CR rate but has no influence on time to progression or survival in patients with ABC.

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