Consolidation with high-dose chemotherapy for responding patients to standard chemotherapy in advanced, metastatic soft tissue sarcoma (STS): A randomized trial from FNCLCC-French Sarcoma Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10505-10505
Author(s):  
N. N. Binh ◽  
C. Chevreau ◽  
N. Penel ◽  
J. Bay ◽  
J. Coindre ◽  
...  
Keyword(s):  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Surgical Removal ◽  
High Dose ◽  
Logrank Test ◽  
Peripheral Blood Stem Cells ◽  
Intention To Treat ◽  
Blood Stem Cells ◽  
New Treatment ◽  
Grade 3

10505 Background: Whether high dose (HD) chemotherapy improves disease-free (DFS) or overall (OS) survival has been suggested in phase II trial, but never explored in a randomized setting. This randomized, open, phase III study was designed to assess whether or not an HD chemotherapy with peripheral blood stem cells (PBSC) would improve OS in patients with advanced or metastatic STS responding to MAID chemotherapy. Methods: Pts aged 18 to 65 and with advanced STS were enrolled. After 4 courses of MAID, patients in PR or CR, or in whom complete surgical removal of all lesions was performed, were proposed for randomisation between 2 more cycles of MAID (control arm) vs 1 MAID followed by an intensification with MICE, ie: mesna (3.6g/m2, d1–5), ifosfamide (4g/m2, d1–4), carboplatin (UCA5, d2–4) and etoposide (300mg/m2, d1–4), followed by PBSC (HD arm). The primary endpoint was OS and the study was designed to detect by logrank test a 25% difference between the arms. Results: From 03/00 to 06/08, 266 patients were included and 87 were randomised (15 centres); low accrual and new treatment concepts lead to an IDMC in 11/08 who analysed 45 treated in the control arm (41 with full treatment) and 40 in the HD arm [only 21 received MICE, because consent withdrawal (6), insufficient PBSC harvest (5), tumor reprogression (4)]. Baseline characteristics (pts and tumors) were similar between treatment arms. With a 39 months follow-up, 25 pts were alive in the control arm, and 19 in the HD arm. The 3 years OS was 45.5% for control arm versus 35.8 for HD arm (HR = 1.12; 95% CI 0.58, 2.14; p = 0.72 Intention to treat analysis); PFS was 29.9% and 12.1 respectively (HR = 1.48; 95% CI 0.87, 2.53; p = 0.14). Higher rate of grade 3 - 4 hematologic (87% vs 46%), and digestive toxicity (33% vs 0%) were observed in the HD arm. Two treatment-related deaths occurred, both in the HD arm. Conclusions: In this study, HD chemotherapy for STS patients didn't improve OS and DFS. Consolidations with new concepts have to be explored. [Table: see text]

Randomized Trial of Filgrastim, Sargramostim, or Sequential Sargramostim and Filgrastim After Myelosuppressive Chemotherapy for the Harvesting of Peripheral-Blood Stem Cells

2000 ◽  
Vol 18 (1) ◽  
pp. 43-43 ◽  
Author(s):  
Charles H. Weaver ◽  
Kevin A. Schulman ◽  
Barbara Wilson-Relyea ◽  
Robert Birch ◽  
William West ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Hospital Admissions ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Platelet Recovery ◽  
Blood Stem Cells ◽  
Sequential Regimen ◽  
Chemotherapy Patients

PURPOSE: 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). PATIENTS AND METHODS: 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). RESULTS: Compared with those who received sargramostim, patients who received filgrastim had faster recovery of an absolute neutrophil count of 0.5 × 109/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 × 106/kg/apheresis; P = .0001), and a higher fraction achieved 2.5 × 106 (94% v 78%; P = .021) and 5 × 106 (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. CONCLUSION: 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.

Front-Line High-Dose Chemotherapy (HDT) Combined with Rituximab for Adults with Aggressive Large B-Cell Lymphoma (DLBCL) : Goelams 074 Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 902-902 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Thierry Lamy ◽  
Philippe Casassus ◽  
Eric Deconninck ◽  
Remy Gressin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pilot Trial ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Front Line ◽  
Peripheral Blood Stem Cells ◽  
Autologous Transplant ◽  
Blood Stem Cells ◽  
Intent To Treat

Abstract Background: The beneficial effect of adding rituximab to CHOP has been shown for elderly patients with DLBCL (Coiffier et al, N.E.J.M 2002). We have shown that HDT with autologous stem cell transplantation is superior to CHOP in young adults with DLCL ( Milpied et al GOELAMS 072 trial, N.E.J.M 2004). The feasibility of adding rituximab to front-line HDT remains to be established. Methods: A prospective pilot trial was proposed to patients with DLBCL, with intermediate-high or high adjusted IPI, up to the age of 60 y.o. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375/mg/m2) on day 1 of each course, followed by rituximab on d 22, harvest of G-CSF mobilised peripheral blood stem cells on d 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabin. For patients who achieved at least a PR after these 3 courses, a BEAM regimen started on d 66 to 80 followed by the infusion of stem cells. Results: Between 04/2002 and 05/2003, 42 pts gave their informed consent and were included in that trial. Median age was 50 y.o (18–60 y.o), 23 had WHO PS ≥ 2, the LDH level was >N in 41 pts and 38 had stage III or IV disease. The age-adjusted IPI was intermediate-high in 23 and high in 19 pts. The program was completed in 30 pts (71%), 3 pts died of toxicity before the BEAM regimen, 8 pts failed to achieve at least a PR after the first 3 courses and 1 refused the autologous transplant. On an intent-to-treat basis, the response rate at the end of the treatment was CR/Cru=64%, PR=7%, less than PR or progression= 22% and toxic death=7%. No toxic death was directly attributable to the addition of rituximab. With a median FU of 19 m, the KM 2y probability of OS and EFS are 79% and 59% respectively, these figures compare to those achieved without rituximab in the previous trial as shown on the table: Conclusion : The addition of 4 doses of rituximab to this HDT program is feasible with no unexpected toxicity, allows the harvesting of sufficient numbers of stem cells to support an autologous transplant with a BEAM regimen in responding patients. This treatment is now being randomly prospectively compared with CHOP-14-rituximab in youg adults with DLBCL (Goelams 075 trial).Supported in part by Roche which kindly provided rituximab for that trial and by DRC Nantes programme N°:02/2N 2002. GOELAMS 072 (IPI 2 only) GOELAMS 074 (IPI 2–3) 2y OS 80% 79% 2y EFS 60% 59%

Mobilization, Harvesting and Transplantation of Peripheral Blood Stem Cells in Patients with Severe Refractory Systemic Lupus Erythematosus - A Single Center Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5107-5107
Author(s):  
Yi Xiao ◽  
Hanyin Sun ◽  
Jianfeng Zhou ◽  
Wenli Liu ◽  
Yicheng Zhang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
Salvage Treatment ◽  
High Dose ◽  
Systemic Lupus ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells

Abstract The prognosis for patients with severe refractory systemic lupus erythematosus (SLE) is poor; High dose chemotherapy with hematopoietic stem cell support is a salvage treatment under investigation for these patients. In our center, 17 patients with severe refractory SLE received autologous peripheral blood stem cells transplantation (PBSCT); Peripheral blood stem cells were mobilized with cyclophosphamide 4g/m2 and granulocyte colony-stimulating factor (G-CSF) 5 μg/kg/day. Enough PBSC were collected in all patients. There’s no mobilization-related mortality, while 3 patients developed active lupus after mobilization which was controlled by slightly increasing the dosage of steroids. Following conditioning with cyclophosphamide 6g/m2 plus anti-thymocyte globulin (ATG, 20mg/kg/d, 5 days), cryopreserved PBSC (mean MNC 4.28×108/kg and CD34(+) cell 2.48×106/kg) were infused. Median ANC and platelet engraftment time were days +11 and +12 after transplantation, respectively. Treatment related complications include mucositis (14/17), infection (12/17), liver malfuction (10/17), edema or/and heart failure (3/17), renal failure (2/17), bleeding (5/17); One patient died from cerebral hemorrhage. Median follow-up is 22 months (9–28 months); All the patients improved with the SLEDAI score reduced from 25.2±6.6 before to 9.7±1.2 3 months after transplantation; Steroids were stopped or maintained at very low dose (equal to 5 to 7.5 mg/d predinisone). One patient had overt lupus relapse 8 months following transplant Conclusions Mobilization, harvesting and transplantation of peripheral blood stem cells in patients with severe refractory systemic lupus erythematosus is safe; The short-term result of the approach is effective in this group of patients; More patients needed to enroll a control study to validate the role of high-dose chemotherapy/PBSCT as the salvage treatment for severe SLE.

A Phase III Randomized, Double Blind, Placebo Controlled Multi-Center Study Of Panobinostat For Maintenance Of Response In Patients With Hodgkin Lymphoma Who Are At Risk For Relapse After High Dose Chemotherapy and Autologous Stem Cell Transplant: Final Results After Early Trial Discontinuation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4648-4648 ◽  
Author(s):  
Bastian von Tresckow ◽  
Aleksander Skotnicki ◽  
Igur Lisukov ◽  
Shivani Srivastava ◽  
David S. Morgan ◽  
...  
Keyword(s):  
At Risk ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Double Blind ◽  
Grade 3

Introduction High dose chemotherapy with autologous stem cell transplant (ASCT) is the treatment of choice for Hodgkin Lymphoma (HL) patients suffering from relapse or progression after first line therapy. However, patients with recurrence after ASCT have a very poor prognosis. Thus, the oral deacetylase inhibitor panobinostat was evaluated as maintenance therapy for patients at risk for relapse after ASCT to prevent recurrences. Methods HL patients after ASCT with at least one of the risk factors: primary refractory disease, early relapse (<12 months), multiple relapses, stage III/IV disease or hemoglobin <10,5 g/dl at relapse prior to transplant were randomized to receive oral panobinostat (45mg three times a week, every other week, QOW) or placebo (2:1 randomization) in this phase III randomized, double blind, placebo controlled multi-center trial. As per the original protocol, disease-free survival (DFS) was the primary endpoint. However, the trial was terminated prematurely due to slow recruitment and the new primary objective was the provision of drug to ongoing patients randomized to panobinostat in an open label phase and to the evaluation of safety in the whole patient population. Results The study was closed to enrollment and data were unblinded with only a total of 41 patients out of the planned 367 patients enrolled; 27 patients in the panobinostat arm and 14 patients in the placebo arm. Three patients (1 from the panobinostat arm and 2 from the placebo arm) never received treatment. Data are reported for patients treated during the randomized phase and no formal statistical analyses were conducted. The median duration of treatment was longer in the placebo arm (217 days) than in the panobinostat arm (176 days, randomized phase). The majority of patients in both treatment arms had an exposure of ≥ 24 weeks (53.8% in the panobinostat arm, 75% in the placebo arm). In the panobinostat arm, the most common reasons that patients discontinued were due to withdrawal of consent (29.8%) and adverse events (22.2%), whereas in the placebo arm, patients most commonly discontinued due to disease progression (28.6%). Most adverse events (AEs) occurred more frequently in the panobinostat arm (randomized phase). The most frequently reported AEs as compared to the placebo arm included: diarrhea (88.5%/25%), nausea (57.7%/8.3%), vomiting (46.2%/25%), fatigue (34.6%/25%), neutropenia (26.9%/33.3%), thrombocytopenia (26.9%/8.3%), oropharyngeal pain (26.9%/0%), headache (23.1%/0%), nasopharyngitis (19.2%/0%), upper respiratory infection (19.2%/8.3%), decreased appetite (15.4%/16.7%), pyrexia (15.4%/8.3%), influenza like illness (15.4%/0%) and sinusitis (15.4%/8.3%). Overall, the incidence of grade 3/4 AEs was 65.4% in the panobinostat arm during the randomized phase and 41.7% in the placebo arm. In the panobinostat arm, the most frequently reported grade 3/4 AEs were neutropenia (26.9%), thrombocytopenia (15.4%), and diarrhea, vomiting and fatigue (all 11.5%). In the placebo arm, the most frequently reported grade 3/4 AEs were neutropenia (33.3%), leukopenia (16.7%) and herpes zoster (16.7%). Although efficacy could not be formally evaluated due to the small number of patients in this trial, it is interesting to note that more patients from the placebo arm discontinued from the study due to disease progression (28.6% vs. 14.8% panobinostat patients). Conclusion The safety observations from this study were consistent with the general safety profile known for panobinostat. The use of panobinostat in a maintenance setting in a QOW schedule appeared to have acceptable tolerability in a population of patients with HL who are at risk for relapse after high dose chemotherapy and ASCT. Disclosures: von Tresckow: Takeda: Honoraria, Reimbursement of congress, travel, and accommodation costs , Reimbursement of congress, travel, and accommodation costs Other; Novartis: Consultancy, Honoraria. Szer:Novartis: Membership on an entity’s Board of Directors or advisory committees. Sureda:Novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Engert:Seattle Genetics, Inc.: Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Takeda: Honoraria.

Pegfilgrastim after High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cells Transplantation. A Single-Centre Experience in 15 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4213-4213 ◽  
Author(s):  
Carole Soussain ◽  
Laure Marec ◽  
Wajed Abarah ◽  
Christian Allard ◽  
Hassina Mallek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Stem Cells Transplantation

Abstract The efficacy of Pegfilgrastim (PF) in decreasing the duration of neutropenia has been proved after standard dose of chemotherapy. Results of PF after high dose chemotherapy (HDC) and autologous peripheral blood stem cells transplantation ASCT) are lacking. We studied the efficacy of PG in patients receiving HDC and ASCT for lymphoproliferative disease. Fifteen consecutive patients (8 males; 7 females) were onrolled in the study from September 2003 through March 2004. Median age of the patients was 56 years. Diseases were multiple myeloma in 5 patients, diffuse large cell non-Hodgkin’s lymphoma (NHL) in 3 patients, follicular lymphoma in 4 patients, mantle cell lymphoma in one patient, and primary central nervous system lymphoma PCNSL) in 2 patients. All patients were eligible for HDC and ASCT per institutional criteria. Stem cells were collected with peripheral blood pheresis after high dose cyclophosphamide (7 cases); high dose Ara-c (5 cases); ifosfamide (1 case); CHOP-like chemotherapy (1 case); or in steady state (1 case). All the patients received daily G-CSF (5 to 10 mcg/kg). Three different conditioning regimens were used. Patients with multiple myeloma received high dose melphalan (200 mg/m²), patients with PCNSL received a combination of high dose Thiotepa (750 mg/m²), Busulfan (12 mg/kg), and Cyclophosphamide (120 mg/kg), and patients with NHL received a BEAM chemotherapy. PF was administered as a single subcutaneous injection of 6 mg at day +3 after stem cell infusion, except for one patient whose injection was done on day 4. No adverse event attributable to PF was observed. There were no toxic death on study. All patients engrafted neutrophils and platelets. The median time to neutrophils engraftment (&gt; 500/mm3) was 7 days (range, 4–12). Febrile neutropenia was almost constant (14/15) but never exceed OMS grade 2. Median number of days with IV antibiotics was 7 days (range 5–22). These preliminary data show that a fixed dose of 6 mg of PF given subcutaneously at day +3 after HDC and ASCT is safe and effective. A cost efficacy study is warranted to compare PF and daily dose of standard G-CSF after ASCT.

Cell-Freezing Devices Are Not Strictly Needed to Start an Autologous Hematopoietic Transplantation Program: Non-Cryopreserved Peripheral Blood Stem Cells Can be Used to Restore Hematopoiesis after High Dose Chemotherapy: A Multicenter Experience in 268 Autografts in Patients with Multiple Myeloma or Lymphoma. Study on Behalf of the Latin-American Bone Marrow Transplantation Group (LABMT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 849-849 ◽  
Author(s):  
Amado J Karduss-Urueta ◽  
Guillermo J. Ruiz-Arguelles ◽  
Rosendo Perez ◽  
Guillermo J Ruiz-Delgado ◽  
Angelica Maria Cardona ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Median Time ◽  
Latin American ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Transplantation Program ◽  
Blood Stem Cells

Abstract Storage of peripheral blood stem cells (PBSC) at 4ºC is a simple and inexpensive alternative to cryopreservation for preserving the clonogenic capacity of progenitors cells in the autologous transplant setting, however it has been perceived as unsafe and has deserved little attention. We present the experience of two Latin-American centers using refrigerated, non-cryopreserved stem cells after conditioning with high dose melphalan, CBV or BEAM in a large group of lymphoma and myeloma patients Materials and Methods PBSC were mobilized with filgrastim 5 mg/kg/BID for three to six days.One to three apheresis procedure were employed; the cells were stored at 4ºC for 5 to 6 days in patients who received BEAM or CBV and for 3 days in those given melphalan. All of the conditioning regimens were administered preserving the full intensity of dose (Table 1). After the autograft all patients received filgrastim or pegfilgrastim Table 1 BEAM D-5 D-4 D-3 D-2 D-1 BiCNU 300 mgs/m2 X Etoposide 200-400 mgs/m2 X X X X Citarabine 300-400 mgs/m2 X X X Melphalan 140 mgs/m2 X CBV BiCNU 300 mgs/m2 13 patients received carboplatin 900 mgs/m2 instead BiCNU X Etoposide 300 mgs/m2 X X X Ciclophosphamide 2.000 mgs/m2 X X X Melphalan Melphalan 200 mgs/m2 X Melphalan 100 mgs/m2 X X Results 102 lymphoma patients: 48 Hodgkin`s lymphoma (HL) and 54 non-Hodgkin´s lymphoma (NHL) received BEAM (71) or CBV (31). A median of 3.3 millions/kg of CD34 was infused; the median viability of the cells after 5-6 days of refrigeration (trypan blue exclusion) was 82%. 101 out of 102 patients engrafted, median time to achieve 500/ul neutrophil or more was 12 days, 100 were evaluable for thrombopoiesis, 99 of them had a self- sustained platelet count of 20.000 or more at a median of 17 days. The OS at 5 years was 59% and 42% for patients with Hodgkin and lymphoma respectively 151 patients with multiple myeloma received melphalan 200 mgs/m2. After 72 hours of refrigeration, a median of 2.6 millions/kg of CD34 cells were infused, the viability in all cases being > 90%. Three patients were not evaluable because early death. Median time to achieve 500 neutrophil or more and 20.000 platelets was 12 (9-50) and 15 (7-50) days. The OS at 5 years was 50% 21 patients with NHL and HL received as conditioning regimen melphalan 200 mgs/m2. After 72 hours of storage, a median of 1.75 millions/kg of CD34 cells were transplanted, 100% of them engrafted, median time to 500 neutrophils and 20.000 platelets was 11.9 and 15 days respectively There were no cases of secondary engraftment failure in any of the three groups Conclusion In this series of 268 patients, we have shown that autologous PBSC can be kept at 4ºC in a conventional blood bank refrigerator for up to six days and use them to rescue high-dose chemotherapy in both multiple myeloma and lymphoma patients. Avoiding freezing procedures results in substantial cost savings. The availability of freezing devices for hematopoietic stem cells is not anymore an obstacle to start a an autologous transplantation program This observation is critical in areas of underprivileged economic circumstances, where more than 50% of the inhabitants of the world live. Disclosures No relevant conflicts of interest to declare.

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