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J Finke

Publications and source records attributed to J Finke.

At least 37 records · Page 2Linked to original sources
PubMed2004

Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index.

BACKGROUND: To evaluate the long-term benefit from high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT), as part of the initial treatment for patients with chemosensitive, high-grade B non-Hodgkin's lymphoma (hg B-NHL), stratified according to the age-adjusted International Prognostic Index (aaIPI). PATIENTS AND METHODS: Eligible patients were 33 consecutive hg B-NHL patients responding to first-line chemotherapy and fulfilling at least one of the following criteria: stage III or IV, bulky disease, elevated lactate dehydrogenase or failure to achieve complete remission (CR). Twenty-two of 33 patients (67%) had two or three risk factors with respect to the aaIPI. All patients received HDCT with ASCT after a minimum of 6 weeks of VACOP-B standard therapy and VIP-E for mobilization. RESULTS: After ASCT, 31 patients (94%) achieved CR. No treatment-related death occurred. The cumulative incidence of relapse at a medium follow-up of 10 years is 16% for 31 of 33 patients achieving CR. Twenty-five of 33 patients are in sustained CR with a disease-free survival of 76% [95% confidence interval (CI) 67% to 86%]. The overall survival at a median follow-up of 122 months (range 86-148) is 79% (95% CI 68% to 89%). CONCLUSIONS: The results suggest that up-front HDCT with ASCT may improve long-term outcome in high-risk patients with chemotherapy-sensitive hg B-NHL when compared to historic populations treated solely with dose-intense chemotherapy. We observed that long-term survival of high-risk (two to three risk factors) patients is comparable to low-risk (zero to one risk factor) patients after HDCT and ASCT with a low incidence of late relapse.

Adult↗
PubMed2004

Treatment with granulocyte colony-stimulating factor increases interleukin-1 receptor antagonist levels during engraftment following allogeneic stem-cell transplantation.

BACKGROUND: The effect of treatment with granulocyte colony-stimulating factor (G-CSF) on interleukin-1 receptor antagonist (IL-1ra) plasma concentrations as well as the role of IL-1ra on leucocyte recovery and parameters of infection within the first 30 days after haematopietic stem-cell transplantation (HSCT) are not well known. MATERIAL AND METHODS: Twenty-seven patients undergoing myeloablative therapy followed by allogeneic SCT for various haematological disorders were either treated with (n = 18) or without (n = 9) G-CSF. IL-1ra plasma levels were serially determined by ELISA starting at day - 1 and continued until patients were engrafted. RESULTS: Patients receiving G-CSF had significantly shorter neutropenic periods and significantly lower mean C-reactive protein serum levels during the first 3 weeks succeeding bone marrow transplantation (BMT). Importantly, starting at day + 11 and paralleling the rise of peripheral blood leucocytes, increasing IL-1ra plasma concentrations were observed in both treatment groups. However, the magnitude of the IL-1ra surge was far greater in the G-CSF treatment group. Peak IL-1ra plasma level observed on day + 19 was 882.3 +/- 879.2 pg mL(-1) (mean +/- SD) in patients receiving G-CSF compared with 285.8 +/- 175.2 pg mL(-1) (mean +/- SD) in patients not receiving G-CSF (P = 0.0130). Furthermore, a direct correlation of IL-1ra with peripheral blood leucocytes was verified by the Spearman rank test (P = 0.0025). CONCLUSION: Granulocyte colony-stimulating factor-mediated acceleration of neutrophil recovery following myeloablative therapy correlated with increased IL-1ra plasma concentrations. Our data suggest that IL-1ra constitutes an intrinsic component of the anti-inflammatory and neutrophil differentiating efficacy of G-CSF and, thus, IL-1ra may be required for the in vivo activity of G-CSF.

Bone Marrow Transplantation↗
PubMed2004

Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry.

OBJECTIVE: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. METHODS: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.

Adolescent↗
PubMed2003

Quantitative analysis of mixed chimerism following allogeneic bone marrow transplantation using telomere flow-FISH.

Assessment of mixed chimerism is of particular interest for allogeneic bone marrow or peripheral blood stem cell transplantation with reduced-intensity conditioning in order to study contribution of donor-type and host-type lymphohematopoiesis. Because the length of telomere repeat sequences is frequently shorter in leukemic compared to normal hematopoietic cells, this telomere repeat polymorphism might be a useful marker to analyze mixed chimerism in selected patients with short telomeres. Recently, fluorescence in situ hybridization and flow cytometry (flow-FISH) have been shown to be valuable tools to analyze the mean telomere length in hematopoietic cells. Here, we demonstrate in a case study on a patient with chronic lymphocytic leukemia (CLL) that telomere flow-FISH can in principle be exploited to quantitate the amount of donor- and host-type cells for chimerism analysis based on distinct histogram distributions which reflect cell populations with different telomere length.

Bone Marrow Transplantation↗
PubMed2003

Patients with acute lymphoblastic leukaemia allografted with a matched unrelated donor may have a lower survival with a peripheral blood stem cell graft compared to bone marrow.

We analysed data for 213 patients with ALL and AML who received either peripheral blood stem cells (PBSC) (n=74) or bone marrow (BM) (n=139) from an HLA-matched unrelated donor (EBMT acute leukaemia registry; January 1994 to January 1999). The two groups of patients (by cell source) were comparable with respect to age, sex, disease status, year at transplant and graft T cell depletion. Engraftment was achieved in about 90% regardless of stem cell source or leukaemia type. Kinetics of neutrophil and platelet recovery, similar for both sources in ALL patients, were faster for PBSC in AML patients. The incidence of acute graft-versus-host disease was similar for both sources in AML patients, but higher for PBSC in ALL patients (74 vs 54%, P=0.05). The 1-year probability of chronic graft-versus-host disease was 40 and 45% (P=0.66) in ALL patients compared to 49 and 35% (P=0.13) in AML patients (PBSC vs BM). In AML patients, none of the following differed significantly with cell source: transplant-related mortality, relapse incidence, leukaemia-free survival and overall survival. In ALL patients, the transplant-related mortality for PBSC vs BM was 61 vs 47% (P=0.13), the relapse incidence was 47 vs 39% (P=0.17), the leukaemia-free survival was 21 vs 32% (P=0.04) and the overall survival was 24 vs 34% (P=0.04). These data suggest that the short-term outcome of allogeneic PBSC is not significantly different from that of BM in AML patients who underwent a transplant from a matched unrelated donor but, conversely, that survival with PBSC may be decreased in ALL patients. In conclusion, the source of transplant cells needs to be evaluated by disease, especially when dealing with unrelated donors.

Adolescent↗
PubMed2003

Surveillance of nosocomial infections in adult recipients of allogeneic and autologous bone marrow and peripheral blood stem-cell transplantation.

To identify overall and site-specific rates of nosocomial infections (NIs) during the neutropenic, as compared to the non-neutropenic stage of treatment in adult recipients of allogeneic and autologous bone marrow transplantation (BMT) and peripheral blood stem-cell transplantation (PBSCT), a prospective, 54-month study was started at the Haematological Stem Cell Transplantation Unit of the University Hospital of Freiburg, Germany. NI types were identified using modified CDC definitions. A total of 351 patients (14 256 in-patient days, 5026 neutropenic days) were investigated (316/90% allogeneic, 35/10% autologous; BMT: 119 patients, PBSCT: 234 patients). The mean length of neutropenia was 14.3 days (range: 0-66). Antimicrobial prophylaxis for allogeneic transplantation consisted of ciprofloxacin, trimethoprim/sulpha-methoxazole, fluconazole, and metronidazole. In total, 239 NIs were identified in 169 patients (48.1%), and of these 171 (71.5%) occurred during neutropenia (34.0 NIs per 1000 days at risk). The main pathogens were coagulase-negative staphylococci (36.3%), Clostridium difficile (20.4%), and enterococci (10.0%). Site-specific incidence densities during neutropenia vs non-neutropenia were: 13.9 vs 1.6 bloodstream infections (all central line-associated), 11.9 vs 1.8 pneumonias, 3.0 vs 2.9 gastroenteritis, and 1.6 vs 0.3 urinary tract infections. The greatest number of NI in BMT and PBSCT recipients is acquired during neutropenia, and multicentre surveillance programmes should focus on this.

Adult↗
PubMed2003

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation.

In a 36-year-old male with ileocolic Crohn's disease (CD) no long-lasting remission was obtained by treatment with corticosteroids, mesalazine, azathioprine and antibiotics. Surgical interventions due to relapsing fistulae and abscesses resulted in the removal of >1.5 m of small bowel and left only 40 cm of large bowel. In July 2000, a new fistula and abscess developed. The combination of corticosteroids, mesalazine, ciprofloxacin, metronidazol, azathioprine, formula diet and anti-TNF-alpha antibody largely reduced clinical activity, and resection of fistula and abscess were successful. Despite clinical remission, histology showed activity in the small bowel and the colon. In March 2001, stem cell mobilization chemotherapy with cyclophosphamide was performed. It induced an endoscopic remission for 9 months, which was maintained on azathioprine and corticosteroids. After relapse, in March 2002, high-dose chemotherapy with cyclophosphamide and reinfusion of T-cell-depleted autologous peripheral CD34+ blood stem cells were performed. This led to a complete clinical, endoscopical and histological remission for 9 months without any treatment. Thereafter, endoscopy showed initial aphthous lesions with minimal histological signs of inflammation. The patient is asymptomatic, but low-dose prednisolone and methotrexate are prophylactically given. Immunoablative chemotherapy followed by autologous peripheral blood stem cell transplantation may be a beneficial therapeutic option in complicated refractory CD.

Adult↗
PubMed2003

ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML).

Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.

Acute Disease↗
PubMed2003

Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning.

Allogeneic stem cell transplantation (SCT) using reduced-intensity conditioning (RIC) has potential to be a promising treatment of aggressive chronic lymphocytic leukemia (CLL). Since available clinical data obtained with this novel approach are very limited, we have performed a survey on this issue. Data of 77 patients were collected from 29 European Group for Blood and Marrow Transplantation centers. Median age was 54 (30-66) years, and the median number of previous chemotherapy regimens was 3 (0-8). HLA-identical sibling donors were used in 81% of the cases. Moderate conditioning regimens (mainly low-dose total body irradiation (TBI) or fludarabine-cyclophosphamide combinations) were administered to 56% of the patients, whereas the remainder received more intense conditioning consisting of fludarabine-busulfan or high-dose melphalan combinations. In 40% of the patients, in vivo T-cell depletion (TCD) with anti-thymocyte globulin or CAMPATH-1H was part of the conditioning regimen. Cumulative treatment-related mortality (TRM) was 18% (95% CI 9; 27) after 12 months. Complete chimerism as well as best response was not achieved immediately post-transplant but took a median of 3 months to develop. The 2-year probability of relapse was 31% (95% CI 18; 44), with no event occurring later than 12 months post transplant in the absence of TCD. With one exception, relapses were not observed after onset of chronic graft-versus-host disease. Event-free and overall survival at 24 months were 56% (95% CI 43; 69) and 72% (95% CI 61; 83), respectively. The median follow-up was 18 (1-44) months. Donor lymphocyte infusions or secondary transplants were performed in 19 patients with insufficient disease control and/or incomplete donor chimerism post-transplant, leading to a response in seven patients (37%). Preliminary multivariate analysis identified less than PR at transplant (hazard ratio (HR) 3.5; P&<0.01) and alternative donor (HR 3.1; P=0.02) as significant risk factors for relapse, whereas number of previous regimens >2 (HR 5.4; P=0.03), TBI (HR 2.5; P=0.05), and alternative donor (HR 2.3; P=0.08) were risk factors for survival. We conclude that RIC might favorably influence the outcome after allogeneic SCT for CLL by reducing TRM while preserving graft-versus leukemia activity.

Adult↗
PubMed2002

Allogeneic hematopoetic stem-cell transplantation for patients with relapsed or refractory lymphomas: comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens.

BACKGROUND: Allogeneic hematopoetic stem-cell transplantation (alloHSCT) has curative potential for poor risk lymphoma patients due to the graft-versus-lymphoma effect. High non-relapse mortality with conventional high-dose conditioning indicates the necessity for less toxic transplant strategies. PATIENTS AND METHODS: Between 1992 and 1999, 25 patients [median age 37 (20-60) years] with relapsed or refractory non-Hodgkin's lymphoma (NHL, n = 20) or Hodgkin's disease (HD, n = 5) received an alloHSCT in our institution. Patients were grafted from HLA matched (17) or mismatched (2) related, or matched unrelated donors (MUD) (6). NHL histological subtypes were lymphoblastic (6), high grade B/T-cell lymphomas (5), follicular (3), mantle cell (2) and CLL, immunocytic, composite lymphoma and panniculitic T-NHL in one patient each. Patients had received a median of four (range three to six) different therapies before alloHSCT, and 10 patients had relapsed after high-dose chemotherapy and autologous (9) or allogeneic (1) HSCT. Remission status prior to allogeneic SCT was CR1 (1), CR2 (1), relapse (11), partial remission (5) or primary refractory induction failure (7). Conventional myeloablative conditioning (cc) regimens contained total body irradiation 12 Gy (5), busulfan 16 mg/kg (7) or BCNU/VP16 (1). Twelve patients received reduced-intensity conditioning (ric) regimens with fludarabine (FLU) plus alkylating agents. Graft-versus-host disease prophylaxis consisted of cyclosporin A +/- prednisone or methotrexate. Six patients also received anti-T-lymphocyte globulin. RESULTS: Twenty-four patients engrafted. Best response after alloHSCT was complete remission in 16 of all patients [64%: 95% confidence interval (CI) 44% to 84%] and in 16 of 22 evaluable patients (73%: 95% CI 53% to 93%), partial remission in three of 25 (12%), and no change in three of 25 (12%) patients. Early death prevented response evaluation in three of 25 patients. Non-relapse mortality was 54% (95% CI 15% to 78%) in patients after cc and 17% (95% CI 0% to 41%) after FLU-based ric (P = 0.03). Six patients died due to progressive disease or relapse. Four patients with HD died, three in complete remission due to non-relapse mortality and one with progressive disease. Eleven of 25 patients are alive with a median follow up of 618 days (range 383-2815), with an overall survival of 44% (95% CI 23% to 65%) at 1 year for all patients, while eight of 12 (67%: 95% CI 35% to 98%) patients are alive after ric compared with three of 13 (23%; 95% CI 0% to 50%) after cc (P <0.02). CONCLUSIONS: AlloHSCT induces high rates of complete remission in advanced lymphoma patients, even when the tumor had relapsed after autologous HSCT. It should be considered earlier as part of the therapeutic options in poor risk patients to avoid non-relapse mortality associated with extensive pretreatment. Our novel reduced conditioning regimens show promising results, especially in heavily pretreated patients, and improve survival after allogeneic transplantation.

Adult↗
PubMed2001

Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells.

The present paper summarizes the results of the second German consensus meeting on immunogenetic donor search for allotransplantation of hematopoietic stem cells held in Essen in November 1999 under the auspices of the German Society for Immunogenetics (DGI) and the German Working Party for Blood and Marrow Transplantation (DAG-KBT). Immunogeneticists and transplant physicians from all over the country agreed to update the national standards for: (1) search strategy including the role of unrelated and extended family donor search after unsuccessful core family donor search, (2) histocompatibility loci to be typed, (3) histocompatibility typing techniques to be used (HLA serology vs DNA-based HLA typing, cellular tests, serum cross-match), and (4) acceptable HLA mismatches in the context of a defined underlying disease, donor type, and conditioning regimen.

Aging↗
PubMed2001

2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial.

BACKGROUND: The authors undertook a prospective evaluation of the clinical value of 2-fluoro [18-]-2-deoxyglucose positron emission tomography (FDG-PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB). METHODS: Fifty-two consecutive patients with untreated malignant lymphoma were evaluated prospectively in a bicenter study. FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal manifestations and bone marrow infiltration. Thirty-three percnt of the discrepant results were verified by biopsy, magnetic resonance imaging, or clinical follow-up (range, 4-24 month). RESULTS: Altogether, 1297 anatomic regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT scans were compared by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve were as follows: lymph nodes, 0.996 (PET) and 0.916 (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and 0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these analyses, FDG-PET was significantly superior to CT (P < 0.05), except in infradiaphragmatic regions, in which the two methods produced equivalent results. In detecting bone marrow infiltration, FDG-PET was superior to CT and was equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a change of therapy. CONCLUSIONS: Noninvasive FDG-PET is very accurate in the staging of malignant lymphoma. Compared with standard staging modalities (CT and BMB), PET was significantly superior and led to changes in the therapy regimen for 8% of patients.

Adolescent↗
PubMed2001

5. Report on workshop: Primary CNS lymphoma.

The increase in primary CNS lymphoma (PCNSL) has resulted in a growing interest in this disease. Despite efforts to optimize the management of PCNSL, several therapeutic questions remain unanswered. Due to methodological pitfalls in the clinical trials published thus far, particulary their uni- or oligocenter setting and the small number of patients, it has been difficult to draw definitive conclusions. Future efforts should concentrate on identifying optimal chemotherapy combinations, evaluating the efficacy of modern therapy options such as high-dose chemotherapy supported by autologous blood stem cell transplantation, and clarifying the impact of radiotherapy delay in complete responders to chemotherapy. Standardized neuropsychological testing and quality-of-life assessment are indispensable in future PCNSL trials. Important questions regarding management of PCNSL should be preferably addressed in large multicenter prospective randomized trials.

Antineoplastic Agents↗
PubMed2001

[Conflict-centered individual therapy or integration of psychotherapy methods. Process of change in client-centered psychotherapy with and without behavioral exposure therapy in agoraphobia with panic disorder].

The mechanisms of change due to different psychotherapeutic treatments of anxiety disorders are the subject of the present study. Sixty-eight patients with agoraphobia and panic (DSM III R No. 300.21, ICD 10 No. F 40.01) were included, exclusively treated with client-centered treatment (n = 28) or with additional behavioral exposure treatment (n = 40) in an inpatient setting. The patients were examined on admission, at discharge, and at 6 and 12 months follow-ups with the Structured Clinical Interview for DSM III R (SKID), the Freiburg Personality Inventory (FPI R), and the Giessen Test (GIESS). Both treatment modalities significantly reduced panic and avoidance. Differences were found in personality scales. The support of autonomy was superior by client-centered treatment alone: client-centered treated (CCT) patients felt less dependent on the expectations of others, less under stress, and had fewer psychosomatic complaints. Patients with additional exposure treatment feel accepted by their social environment earlier. The results are discussed with regard to open questions of therapy integration and different mechanisms of change.

Adult↗
PubMed2001

Analysis of stem cell apheresis products using intermediate-dose filgrastim plus large volume apheresis for allogeneic transplantation.

Previously, a dose-dependent influence of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on CD34+ mobilization was demonstrated. In this single-center prospective analysis, 52 healthy donors were investigated to determine the efficacy of intermediate-dose rhG-CSF 2x8 microg/kg donor body weight (bw) and intermediate large volume apheresis (LVA, median 12 l) to mobilize peripheral blood progenitor cells (PBPC) for allogeneic transplantation. The median number of CD34+ cells in apheresis products was 0.45% and 2.2x10(6)/kg recipient bw per single apheresis. A total of 5.4x10(6)/kg CD34+ cells were collected with two (range: one to three) LVA. In the analysis of donor subgroups, higher peripheral blood (PB) and apheresis results were obtained in male vs female donors; however, donor weight significantly differed in both groups. Heavier donors displayed higher PB and apheresis CD34+ counts; however, when CD34+ cells/kg were adjusted to a constant bw, similar harvest results were calculated in males and females, demonstrating that gender per se does not, whereas bw does affect apheresis results. Younger donors had significantly higher PB CD34+ counts, higher CD34+ numbers per single apheresis, increased CFU, more T, B, and CD61+, comparable NK, and less CD14+ cells. A correlation analysis of donor age and apheresis results displayed an age-related decline of 0.46x10(6)/kg CD34 cells per decade of donor aging. Cell subsets in apheresis products were CD14 (49%), CD3 (22%), CD4 (13%), CD8 (7%), CD61 (20%), CD19 (5%), and CD16/56+ (3%) cells, with increasing CD14+ cells and decreasing CD3, CD4, CD8, CD61, CD19, and CD16/56+ cells on subsequent days of apheresis. Compared to our previous analysis using high- (2x12 microg) and low-dose (1x10 microg) rhG-CSF for allogeneic PBPC mobilization, the intermediate-dose showed a similar CD34+ mobilization potential to 1x10 microg rhG-CSF; however, with use of LVA, two instead of three (p<0.05) aphereses were sufficient to mobilize > or =4x10(6)/kg bw CD34+ cells in most donors. Taken together, our results demonstrate that intermediate-dose rhG-CSF sufficiently mobilizes > or =4x10(6)/kg x bw CD34+ cells with use of LVA and that especially younger donors display increased CD34+ cell numbers.

Adult↗
PubMed2001

Phase I and II trials of subcutaneously administered rIL-2, interferon alfa-2a, and fluorouracil in patients with metastatic renal carcinoma.

PURPOSE: A phase I followed by a phase II trial utilizing rIL-2, IFN alpha, and 5-FU were conducted in patients with unresectable and/or metastatic renal cell carcinoma. METHODS: Treatment consisted of: rIL-2 at 5.0 x 10(6) IU/m2 SQ on days 1-5 for 4 weeks, rHUIFN alpha-2a at 5.0 x 10(6) U/m2 SQ on days 1, 3, and 5 for 4 weeks, and 5-FU by IV bolus on days 1-5 during week 1. In the phase I study, patients were treated at varying doses of 5-FU: I-none, II-250 mg/m2, III-300, and IV 375. A phase II trial was then conducted utilizing the same schedule and maximum tolerated dose (MTD) for 5-FU. RESULTS: Twenty patients were entered into the phase I trial. Dose-limiting toxicity included grade III nausea and vomiting, and one sudden cardiac death. The MTD for 5-FU was determined to be 300 mg/m2. In the phase II trial, a median of two cycles of therapy was administered to 25 evaluable patients. Toxicity was moderate and consisted primarily of fevers, chills, fatigue, nausea/vomiting, and anorexia. Grade IV thrombocytopenia, consistent with ITP, developed in one patient each on the phase I and phase II trial. Seven partial responses were seen among 25 patients treated in the phase II trial for a 28% (CI 12-49%) response rate. CONCLUSIONS: The addition of 5-FU to rIL-2 and rHuIFN alpha-2a appears to increase the toxicity of this therapy. Randomized trials will be required to determine if efficacy is enhanced.

Adult↗
PubMed2001

GM-CSF safety and effects in the management of advanced/refractory multiple myeloma patients: a phase I trial.

PURPOSE: Some limitations of effective therapy in multiple myeloma include the low growth fraction of the malignant plasma cells, multi-drug resistance, and the presence of other concurrent diseases in this patient population. A phase I study was conducted to evaluate the toxicity of granulocyte macrophage colony stimulating factor (GM-CSF) in myeloma patients as well as the potential effect on the plasma cell labeling index (PCLI). Relapsed patients with multiple myeloma were eligible. METHODS: The first phase of this trial assessed the toxicity (including the effect on disease progression) of escalating doses (125-500 microg/m2 SC, days 1-5) of GM-CSF, and the effects of this cytokine on PCLI. Patients whose PCLI doubled and increased to > or = 1.7% were treated with chemotherapy including cyclophosphamide, vincristine, prednisone, and GM-CSF. Twenty-two patients were enrolled. RESULTS: The toxicity of GM-CSF was mild, and no dose-limiting side effects were seen. Twenty-five percent of patients (5/20) achieved the target PCLI, and 4/5 proceeded to receive chemotherapy. No relationship of GM-CSF dose to increases of the PCLI was noted. All patients who received chemotherapy responded. CONCLUSIONS: GM-CSF has acceptable toxicity in patients with multiple myeloma and produced increases of PCLI in selected individuals. Further studies of GM-CSF alone or in combination with chemotherapy are indicated.

Alanine Transaminase↗