BACOPP-D - An Etoposide-Free Dose-Escalated Polychemotherapy Regimen in Advanced Hodgkin Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2317-2317
Author(s):  
Ralph Naumann ◽  
Katrin Wetzko ◽  
Annette Haenel ◽  
Kai Friedrichsen ◽  
Ernst Zschuppe ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Observation Time ◽  
Hypopharyngeal Carcinoma ◽  
High Dose ◽  
Who Grade ◽  
Fdg Uptake ◽  
Pet Scans ◽  
Grade Iii

Abstract Introduction: The development of the escalated BEACOPP regimen let to an improved outcome in patients with advanced Hodgkin Lymphoma (HD9 study of the GHSG). However, the application of high dose etoposide (cumulative 4,8 g/m2 per 8 cycles) seems to be associated with an increased incidence of secondary MDS and AML, respectively. Therefore, the aim of our multicenter pilot study was to evaluate the efficacy and toxicity of the etoposide free as well as dose intensified BACOPP-D protocol. Methods: Since May 2000 a total of 115 patients with Hodgkin Lymphoma (HL) stage IIB, III, and IV were treated with BACOPP-D which included cyclophosphamide 1250 mg/m2 (d1), adriamycin 25 mg/m2 (d1+2), dacarbazine 250 mg/m2 (d1-3), procarbazine 100 mg/m2 (d1-7), prednisolone 40 mg/m2 (d1-14), bleomycin 10 mg/m2 (d8) and vincristine 1,4 mg/m2 (maximum 2 mg, d8) at three-weekly intervals with granulocyte colony-stimulating factor (G-CSF). A consolidating involved field radiation (30 Gy) was performed only in patients who achieved less than CR following chemotherapy. Post-treatment follow-up included PET imaging. Results: Until now 97 patients (median age 35 years, range 17-65; 61 male, 36 female) are assessable for toxicity and treatment outcome. We analyzed the acute toxicity for 728 cycles of BACOPP-D. CTC/WHO grade III/IV haematological toxicities per patient were observed as follows: leukopenia 93%, anemia 39%, and thrombocytopenia 33%. CTC grade III/IV non-haematological side effects included documented infection (4%) and lung toxicity (one patient). A total of 85 patients (88%) achieved complete remission, 9 patients (9%) achieved partial remission, three patients (3%) had progressive disease. At a median observation time of 39 months (0,9-77 months), five patients have relapsed, and nine deaths were documented (4 HL-specific and 3 treatment related deaths, 1 death due to ruptured Meckel diverticulum with peritonitis, one 65 year-old woman died in CR following myocardial infarction). One patient developed a second neoplasia (hypopharyngeal carcinoma in an alcoholic). The overall survival and freedom from treatment failure rates at 39 months were 91% and 85%, respectively. FDG-PET scans after BACOPP-D chemotherapy were performed in 68 of 97 patients. PET scans revealed no increased FDG uptake in 48/68 patients (71%), in 20 patients (29%) increased FDG uptake was detected. In the group of patients with increased FDG uptake, one patient developed progressive disease and four patients relapsed. In the group with PET-negative findings no patient relapsed. Diskussion: BACOPP-D regimen appears as a feasible and effective treatment which induced a complete morphologic and metabolic remission in a high proportion of patients with advanced HL. The treatment was associated with moderate acute toxicity. No secondary AML or MDS occurred until now.

BACOPP-D - An Etoposide-Free Dose-Escalated Polychemotherapy Regimen In Advanced Hodgkin‘s Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1754-1754
Author(s):  
Ralph Naumann ◽  
Diana Kluge ◽  
Annette Haenel ◽  
Katrin Wetzko ◽  
Nadja Friedel ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Hodgkin’S Lymphoma ◽  
Conflicts Of Interest ◽  
Observation Time ◽  
Hodgkin's Lymphoma ◽  
Hypopharyngeal Carcinoma ◽  
Secondary Malignancy ◽  
High Dose ◽  
Advanced Hodgkin’S Lymphoma ◽  
Grade Iii

Abstract Abstract 1754 Introduction: The development of the escalated BEACOPP regimen let to an improved outcome in patients with advanced Hodgkin‘s lymphoma (HD9 study of the GHSG). However, the application of high dose etoposide (cumulative 4,8 g/m2 per 8 cycles) seems to be associated with an increased incidence of secondary MDS and AML, respectively. Therefore, the aim of our multicenter pilot study was to evaluate the efficacy and toxicity of the etoposide-free as well as dose-intensified BACOPP-D protocol. Methods: From May 2000 until August 2008 a total of 139 untreated patients with Hodgkin‘s lymphoma (HL) stage IIB, III, and IV were treated with BACOPP-D which included cyclophosphamide 1250 mg/m2 (d1), adriamycin 25 mg/m2 (d1+2), dacarbazine 250 mg/m2 (d1-3), procarbazine 100 mg/m2 (d1-7), prednisolone 40 mg/m2 (d1-14), bleomycin 10 mg/m2 (d8) and vincristine 1,4 mg/m2 (maximum 2 mg, d8) at three-weekly intervals with granulocyte colony-stimulating factor (G-CSF). A consolidating involved field radiation (30 Gy) was performed only in patients who achieved less than CR following chemotherapy. Post-treatment follow-up included PET imaging. Results: All patients (median age 34 years, range 16–65; 86 male, 53 female) are assessable for toxicity and treatment outcome. We analyzed the acute toxicity for 1060 cycles of BACOPP-D. CTC grade III/IV haematological toxicities per patient were observed as follows: leukopenia 92%, anemia 40%, and thrombocytopenia 35%. CTC grade III/IV non-haematological side effects included documented infection (8%) and lung toxicity (one patient). Consolidation radiotherapy was given in 73 patients (52,5%). A total of 125 patients (89,9%) achieved complete remission, 9 patients (6,5%) achieved partial remission, five patients (3,6%) had progressive disease. At a median observation time of 46 months (5-109 months), 9 patients (6,5%) have relapsed, and 11 deaths were documented (4 HL-specific and 4 treatment related deaths, 1 death due to ruptured Meckel diverticulum with peritonitis, one 65 year-old woman died in CR following myocardial infarction and 1 death due to secondary malignancy). Only two patients developed a second neoplasia (hypopharyngeal carcinoma in an alcoholic; melanoma). The overall survival and progression free survival rates at 46 months were 89,7% and 85,9%, respectively. Discussion: BACOPP-D regimen appears as a feasible and effective treatment which induced a complete morphologic remission in a high proportion of patients with advanced HL. The treatment was associated with moderate acute toxicity. No secondary AML or MDS occurred so far. Disclosures: No relevant conflicts of interest to declare.

PVAG (Prednisone, Vinblastine, Doxorubicin and Gemcitabine) In Elderly Patients with Intermediate or Advanced Stage Hodgkin Lymphoma: Final Results of a Phase II Study of the German Hodgkin Study Group (GHSG).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2827-2827
Author(s):  
Boris Böll ◽  
Teresa Halbsguth ◽  
Helen Görgen ◽  
Henning Bredenfeld ◽  
Hans Eich ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Advanced Stage ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Abstract 2827 About 20% of all patients diagnosed with Hodgkin lymphoma (HL) are older than 60 years. These patients have a rather poor prognosis, particularly when presenting in intermediate or advanced stages. Besides a biologically more aggressive disease, the main reason is a drastically increased toxicity of chemo- and radiotherapy resulting in a higher treatment-related mortality and insufficient dosing of the applied treatment. In the GHSG-HD9 trial, elderly patients did not benefit from the BEACOPP regimen in terms of overall survival due to a high toxicity related death rate. In order to improve tolerability, the PVAG regimen (prednisone, vinblastine, doxorubicin, and gemcitabine) was developed. This is a modification of the ABVD regimen in which bleomycin and dacarbazine were replaced by prednisone and gemcitabine. Here we report for the first time on the final analysis of this multi-center phase II study for elderly HL patients. 61 patients were recruited between 2004 and 2007. 2 patients were excluded due to histology review not confirming HL, resulting in 59 patients with intermediate- or advanced-stage HL aged between 60 and 75 years. Treatment consisted of 6 cycles PVAG in patients achieving a complete remission (CR) after 4 cycles or 8 cycles PVAG in case of partial remission (PR) after 4 cycles. Patients who did not achieve CR after the end of chemotherapy received additional radiotherapy. Primary endpoints were administration of adequate dose without excessive delays, and response rate 3 months after end of treatment. Secondary endpoints included WHO grade III/IV toxicities, and occurrence of early progression. 59 patients with a median age of 68 years were evaluated, of which 59% were male and 93% had advanced stage disease. The relative dose intensity (relative dose divided by relative chemotherapy duration) was at least 80% in 44 patients (76%). Regarding the single cycles, of which 85% started without major delay (max. 1 day), the mean relative dose of all agents was slightly decreasing over time but always exceeded 90%. WHO grade III/IV toxicities were documented in 43 patients (75%). Only 3 patients terminated CT because of excessive toxicity. 10 Patients (17%) received consolidating radiotherapy. In total, 46 patients responded with CR/CRu (78%; 95% CI: 65% to 88%), 2 with PR (3%), 2 with no change (3%) and 4 with progressive disease (7%). 3 patients died before restaging with unknown response and in 2 patients treatment outcome is unknown. With a median observation time of 37 months, 6 patients (10%) had progressive disease and 9 patients (15%) relapsed. In total, 10 patients died from relapsing or progressing HL, 2 from second malignancies (one of lung cancer after 23 months, and one of AML after 25 months) and 5 patients due to other reasons. Overall 17 patients (29%, 95% CI: 18% to 42%) have died so far. In conclusion, PVAG is safe and feasible in Hodgkin patients older than 60. The PFS indicates activity of this regimen in this poor prognosis patient cohort. However, a controlled randomized trial to determine the best treatment in this patient population is warranted. This trial was registered at www.clinicaltrials.gov as #NCT00147875. Disclosures: No relevant conflicts of interest to declare.

Use of Palifermin for the Prevention of High-Dose Methotrexate-Induced Oral Mucositis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4445-4445
Author(s):  
Eva Schmidt ◽  
Nils H. Thoennissen ◽  
Annika Rudat ◽  
Ralf Bieker ◽  
Christoph Schliemann ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Oral Mucositis ◽  
Wilcoxon Test ◽  
Clinical Activity ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Who Grade ◽  
Dose Methotrexate ◽  
Grade Iii

Abstract Oral mucositis is a frequent problem in high-dose methotrexate (HD-MTX) based chemotherapy, impairing the patient’s quality of life, leading to higher rates of infections and delaying subsequent chemotherapy. Numerous substances have been used to prevent or treat oral mucositis, but none of them has proven clinical benefit. Palifermin, a recombinant human keratinocyte growth factor, can lead to a prevention of oral mucositis by different effects. Clinical activity of palifermin has been proven in a controlled randomized study with patients undergoing high-dose therapy with autologous stem cell rescue. The purpose of this report is to describe the effect of palifermin in patients treated within the GMALL-B-ALL 2002 protocol containing HD-MTX who developed a severe mucositis in cycles A1 or B1. Ten patients who were treated within this protocol developed a severe WHO grade III–IV oral mucositis in cycles A1 or B1. Before and after the subsequent similar or identical cycles A2 or B2 palifermin was given to reduce the risk of mucositis. Thus, patients serve as their own control for efficacy of palifermin. All ten patients developed a grade III–IV mucositis in cycles A1 or B1 without palifermin, whereas only 2/10 developed a grade III–IV mucositis in corresponding cycles A2 or B2 with palifermin (Mann-Whitney-Wilcoxon-test p < 0.05). Five patients were treated with a lower palifermin dose than recommended. Also these patients did not develop a higher grade mucositis. Only 4/10 patients showed infections in the cycles with palifermin compared to 10/10 patients without palifermin. The duration of mucositits in patients who aquired a higher-grade (III, IV) mucositis despite treatment with palifermin could be reduced from 12.9 days (median) without to 10.4 days with palifermin. In conclusion, palifermin can significantly reduce the incidence and severeness of oral mucositis and may influence clinical sequelae such as infection and quality of life.

Febrile Neutropenia, Mucositis and Duration of Hospitalization Are Reduced After Pegfilgrastim Following Autologous Peripheral Blood Stem Cell Transplantation (PBSCT) for Malignant Lymphopathies: Report of 683 PBSCTs From a Single Institution.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3410-3410
Author(s):  
Sophie Auger ◽  
Philippe Quittet ◽  
Marie Cecile Bozonnat ◽  
Salahedine Bouya ◽  
Tarik Kanouni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Daily Injection ◽  
High Dose ◽  
Platelet Recovery ◽  
Duration Of Hospitalization ◽  
Grade Iii

Abstract Abstract 3410 Poster Board III-298 Granulocyte colony-stimulating factor (G-CSF) has been shown to decrease time to neutrophil recovery following PBSCT. Now, 3 products are available: 2 standard G-CSFs (filgrastim and lenograstim), and pegfilgrastim (PegG-CSF). In order to determine whether a single subcutaneous injection of Peg-G-CSF is as effective as a daily injection of standard G-CSF, in terms of haematological recovery, febrile neutropenic episodes (FN), antibiotic usage, hospitalization duration, mucositis, progressive free survival (PFS) and overall survival (OS), we retrospectively analyzed series of 558 patients having myeloma and lymphoma who underwent 683 PBSCT between 2000 and 2008 in our institution. Statistical analysis included univariate, Wilcoxon and χ2 fisher tests, logrank test for PFS and OS, and Cox model for multivariate analysis. From January 2000 and April 2005, 359 patients received standard G-CSF (filgrastim or lenograstim) and from May 2005 to December 2008, 298 patients received PegG-CSF. 26 patients did not receive G-CSF for any reasons. 427 PBSCTs have been performed for multiple myeloma (MM) after high dose melphalan, 197 for Non Hodgkin Lymphoma (NHL) and 59 for Hodgkin lymphoma (HL) with BEAM conditioning regimen. 133 patients underwent 2 or 3 PBSCT (130 MM and 3 HL). The mean of CD34 dose infused was 5.2 106 /kg (1.2-26.9) with 96% of the grafts containing more than 2.5 106 CD34/Kg. The median number of days of standard G-CSF given to reach an absolute neutrophil count (ANC) ≥500/ml was 9 days (0-29). Median time to neutrophil engraftment (ANC of 500/ml) was 11 days (5-30) in each group. The platelet recovery (platelet>20 000/mL) was 10 days (0-54) in each group. The platelet and RBC transfusion requirement are stastitically lower in the PegG-CSF than in the standard G-CSF group. As listed on the table, we have analyzed the following parameters for all patients: number of FN and their beginning and duration, number of antibiotic lines, duration of hospitalization, duration of mucositis, and the percentage of grade III and IV mucositis. Median, (range) Peg G-CSF standard G-CSF None G-CSF N 298 359 p 26 FN rate (%) 91.7 96.4 <0.01 96.16 Duration of FN (days) 2 (0-27) 2 (0-18) 0.62 2 (0-13) First day of FN (day) 5 (-3-16) 4 (-5-17) <0.01 4 (0-11) Number of antibiotic lines 1 (1-5) 2 (0-5) <0.01 3 (0-4) Duration of hospitalization (days) 17 (8-62) 19 (8-65) <0.01 24 (18-35) Duration of mucositis (days) 0 (0-75) 6 (0-60) <0.01 7.5 (0-10) Mucositis grade III, IV (%) 17.7 40.28 <0.01 ND The same significantly differences are observed in MM, NHL and HL patients. The use of standard G-CSF or PegG-CSF did not modify OS at 1 and 5 years for both NHL and HL patients. In MM population PFS was unmodified but OS appeared better in the PegG-CSF group compared to standard G-CSF: respectively 1 y OS at 1 year, 96% versus 92%, OS at 5 years: 79% versus 53% (p= 0.034). Such a difference could be explained by the early use of bortezomib regimen for induction therapy before PBSCT more frequently in PegG-CSF group and this feature has been analyzed. Among patients undergoing autologous stem cell transplantation the use of Peg G-CSF seems to show an advantage in terms of duration of hospitalization and reduce the percentage of grade III, IV mucositis and the number of febrile neutropenic episodes. Disclosures: No relevant conflicts of interest to declare.

Front-Line Treatment of Low-Grade Non-Follicular Non-Hodgkin Lymphoma (Final Report of Gisl LL02 Trial).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2332-2332
Author(s):  
Maria Goldaniga ◽  
Francesco Merli ◽  
Caterina Stelitano ◽  
Vincenzo Callea ◽  
Fiorella Ilariucci ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Report ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Indolent Non-follicular non-Hodgkin Lymphoma (NFo-NHL) is a group of relatively frequent lymphoproliferative diseases, nevertheless extended clinical and prognostic studies are still lacking. In 2002 the Gruppo Italiano Studio Linfomi (GISL) initiated a LL02 prospective multicenter phase II trial, with the aim to evaluate the efficacy and safety of FC combination in the first-line therapy of NFo-NHL patients younger than 70 years. Between July 2002 and September 2006, 58 adult patients (35 males and 23 females, median age 64 yrs, range 40–75) affected by NFo-NHL in active disease phase, were consecutively enrolled in 12 GISL Hematological Centres. Patients were treated with a dose of 25 mg/mq Fludarabine plus 250 mg/mq Cyclophosphamide administred intravenously daily for 3 days; each cycle was repeated every 28 days for 6 courses. During the treatment patients received oral thrimethoprim-sulphametoxazole prophylaxis. After the intermediate evaluation, 48/58 patients (82.8%) had an objective response (ORR) with a 20.7% of complete remission (CR) plus 62.1% of partial remission (PR); at the final evaluation the ORR percentage was 84.5% with a 41.4% of CR (24 pts) and 43.1% of PR (25 pts); three patients were in progressive disease (5.2%) and one in stable disease (1.7%). The median overall survival (OS) was not reached with an 88% and 84% at 12 and 24 months; the progression free survival (PFS) was 89% and 77% and the event free survival (EFS) was 81% and 66% at 12 and 24 months respectively.About the toxicity profile, the major toxicity was hematological with a 18% cases of WHO grade III or IV anemia, 40% leucopenia, 33% neutropenia and 10% piastrinopenia. The 12% of patients had an infective episode wich a 7.7% of WHO grade III–IV.In conclusion the FC chemotherapy is a useful chance for advanced untreated non follicular low-grade NHL, with an optimal ORR, CR and PFS. The crucial point of FC remains OS, that not seems to be significantly improved in comparison with fludarabine alone or with standard therapy, even though the better quality of responses; Rituximab plus FC association is growing in literature as the probably key to find a real improvement also in this aspect.

Acute toxicity analysis of patients receiving surgery, Gliadel wafer implantation, and postoperative daily temozolomide with radiation therapy for primary high-grade glioma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 11504-11504 ◽  
Author(s):  
C. R. Heery ◽  
A. Desjardins ◽  
J. A. Quinn ◽  
J. N. Rich ◽  
S. Gururangan ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Acute Toxicity ◽  
High Grade Glioma ◽  
Wound Complications ◽  
Hematologic Toxicity ◽  
Who Grade ◽  
Initial Surgery ◽  
Grade 3 ◽  
Who Grade Iii ◽  
Grade Iii

11504 Background: Treatment of patients with newly diagnosed malignant glioma using Gliadel wafer implantation at initial surgery has been shown to increase survival (Westphal et al 2003). Similarly, administration of temozolomide during and after radiotherapy has also been shown to increase survival in this patient population (Stupp et al 2005). Accordingly use of both Gliadel and temozolomide may be advantageous for these patients although it is possible that the toxicity of these two approaches used together might be prohibitive. Methods: The Preston Robert Tisch Brain Tumor Center at Duke has occasionally treated with this approach over the last several years, and we now present an analysis of the observed acute toxicity. We retrospectively reviewed the Duke patients treated with surgery plus Gliadel wafer placement followed by daily temozolomide (75 mg/m2-150 mg/m2) and radiation therapy. Results: Of 28 patients reviewed, four patients were diagnosed with AA (WHO grade III), two patients were diagnosed with AO (WHO grade III) and the remaining 22 patients were diagnosed with glioblastoma multiforme (WHO grade IV). Two of the 28 7.1%) patients experienced grade 3 or 4 hematologic toxicity during radiation and daily temozolomide therapy. This is similar to the 7% of patients found to have hematologic toxicity reported by Stupp et al (2005). Three patients (10.7%) had grade 3 or 4 seizure activity. Two patients (7.1%) had grade 4 pulmonary emboli. No events of cerebral edema or wound complications were noted in this review of patient events following Gliadel wafer placement. Conclusions: In summary, the addition of Gliadel wafer placement at the time of surgery followed by radiation therapy with concurrent daily low dose temozolomide does not appear to have significant acute toxicity over that observed with radiation therapy and daily temozolomide. Future formal trials combining these therapeutic strategies may allow evaluation of the possible survival advantage associated with this approach. [Table: see text]

High Dose Chemotherapy with Autologous Stem Cell Support Is Effective in Resistant and Refractory Hodgkin Lymphoma. A Single Center Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5506-5506
Author(s):  
Emilia Cocorocchio ◽  
Fedro Peccatori ◽  
Simona Bassi ◽  
Federica Gigli ◽  
Davide Radice ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Therapeutic Option ◽  
High Dose Chemotherapy ◽  
Late Relapse ◽  
High Dose ◽  
Standard Chemotherapy ◽  
Refractory Hodgkin Lymphoma

Abstract We report retrospective data concerning 49 relapsed or refractory Hodgkin lymphoma pts, treated from 1995 in our institution with high dose chemotherapy (HDCT) with autologous peripheral blood stem cell (aPBSC) support. 41/49 had resistant disease, because presenting an early relapse (14/41), a late relapse (12/41) after CR induced by standard chemotherapy (CT) or persistence of disease (15/41) after initial CT. 8/49 had refractory disease, presenting stable or progressive disease within three months after the end of first line CT. Median age at transplantation time of 32 yrs (range 18–58 yrs). Before high dose chemotherapy, all pts received at least a standard chemotherapy (hybrid regimen for 4–6 cycles ± RT, according to the extension of disease). At the time of transplantation, 13 pts were in complete remission, 31 were in partial or very good partial remission and 5 were in stable /progressive disease. We used as myeloablative regimen mainly HDBEAM. Radiotherapy was performed in 9 pts after transplantation. In the subgroup of the 26 relapsed pts, 21 achieved a CR, 2 a PR and 3 a PD/SD; with a median follow up of 23 months from transplant (range 2 – 112 months), expected DFS and OS at 10 years are 90.5% and 76.9%, respectively. Analyzing separately early versus late relapsed patients, DFS expected at 10 years are 81.8% and 100%, respectively, and the OS expected are 71.4 and 83%, respectively. 11/15 pts with persistence of disease after initial CT achieved a CR, 2 PR, 2 presented SD/PD; with a median follow-up of 32 months from transplant (range 2 – 88 months), expected DFS and OS are 90.9% and 75%, respectively. Finally, 5/8 refractory pts achieved a CR (two of them progressed after transplant), 2 pts a PR (both progressed and died after transplant), 1 patient obtained a SD (progressed and died after transplant). No toxic deaths or second cancer or other severe late toxicity were recorded. Autologous transplantation is a safe procedure, considering the manageable early and late toxic effect; the clinical results achieved indicate that HDCT with aPBSC support is to be considered the first therapeutic option for those pts who present an early or late relapse after standard chemotherapy. The low number of refractory pts doesn’t allow any definitive conclusion about its role in this subgroup, but the relative high number of events observed seems to suggest that further analysis of biological features are warranted in order to better define the best therapeutic option.

Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma

Blood ◽  
2011 ◽  
Vol 118 (24) ◽  
pp. 6292-6298 ◽  
Author(s):  
Boris Böll ◽  
Henning Bredenfeld ◽  
Helen Görgen ◽  
Teresa Halbsguth ◽  
Hans T. Eich ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Observation Time ◽  
Advanced Stage ◽  
Phase 2 ◽  
Who Grade ◽  
Stage Disease ◽  
Phase 2 Study ◽  
Grade 3

Abstract Approximately 20% of all Hodgkin lymphoma (HL) patients are older than 60 years and have a poor prognosis, mainly because of increased treatment-related toxicity resulting in reduced overall dose intensity and more treatment-related mortality. To possibly improve the treatment of elderly HL patients, the German Hodgkin Study Group developed a new regimen, PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine). In this multicenter phase 2 study, elderly HL patients in early unfavorable and advanced stages received 6 to 8 cycles of PVAG and additional radiotherapy if they were not in complete remission (CR) after chemotherapy. Endpoints included feasibility, acute toxicity, and response rate. Fifty-nine patients 60 to 75 years of age (median, 68 years) were eligible for analysis; 93% had advanced stage disease. WHO grade 3/4 toxicities were documented in 43 patients; 46 patients responded with CR/CR uncertain (78%). Within 37 months median observation time, 15 progressions or relapses and 17 deaths were observed, of which 8 were related to HL and 1 was the result of treatment-related toxicity. The 3-year estimates for overall survival and progression-free survival were 66% (95% CI, 50%-78%) and 58% (95% CI, 43%-71%), respectively. We conclude that PVAG is safe and feasible in elderly HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00147875.

Intermediate Intensity Conditioning Followed by Allogeneic Peripheral Blood Stem Cell Transplantion for Treatment of High Risk Relapse of Aggressive Lymphoma. Interim Analysis of the DSHNHL R3 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3043-3043
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Peter Dreger ◽  
Martin Gramatzki ◽  
Joerg Schubert ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Cell Lymphoma ◽  
Observation Time ◽  
High Dose ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
To Receive ◽  
Relapse Rates

Abstract High dose therapy (HDT) followed by autologous stem cell support has poor outcome in patients with primary progressive lymphoma or relapse after primary HDT due to high relapse rates and failure free survival below 20%. Allogeneic SCT may help these patients by exerting an GVL effect. Its use however, is followed by high incidence of severe GVHD and treatment related mortality (TRM) in this population. The anti-CD20 monoclonal antibody rituximab has been claimed to solve this problem. We initiated a randomized phase II study using intermediate conditioning (Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg) followed by GVHD prophylaxis with short term mycophenolat mofetil plus tacrolimus. Patients were randomized to receive two times four doses of rituximab (375 mg/m2) post transplant starting day +28 and day +175 or no further GVHD prophylaxis. Here we report the results of a first interim analysis. From January 2005 to August 2007 sixty patients (pts) with aggressive NHL were enrolled. Thirty one pts had diffuse large B cell NHL, 9 patients follicular lymphoma grade 3, 8 pts blastic mantle cell lymphoma, one patient aggressive marginal zone lymphoma and 11 patients peripheral T cell lymphoma. The median number of prior treatment regimens was 3 (range 1 to 6). 43 (72%) pts received at least one cycle of high-dose therapy and autologous SCT prior to alloSCT; 79% had early relapse (< 12 months) or primary progressive disease, 58% chemo-refractory disease and 52% had progressive disease with high or high intermediate age adjusted IPI immediately prior to conditioning. Allo-PBPC were obtained from HLA-identical siblings in 16 pts, from fully matched unrelated donors in 32 pts and from 1 locus mismatched unrelated donors in 12 pts. Engraftment of leukocytes was rapid (median 10 days, range 8–27) and all patients achieved complete (> 95%) donor type chimerism after alloSCT. Median observation time is 8 months (range 1–35 months). 32 pts died, in 20 patients death was attributed to treatment related causes. After one year, estimated overall survival is 47%, failure free survival is 43%, TRM is 37%, relapse rate is 33% and incidence of GVHD > grade 1 is 57%. With an observation time precluding final analysis, there are no significant differences between patients randomized to receive rituximab post transplant and those who were not. There was a trend to lower relapse rates in patients with GVHD > grade 1 (25% vs 44%, p=0.14). Intermediate intensity conditioning followed by allogeneic SCT is a valuable treatment option in patients with high-risk relapse of aggressive NHL. The basic incidence of GVHD and TRM is high. Due to the short observation time, a definitive conclusion regarding the impact of post transplant Rituximab cannot be drawn. The study will be continued.

Comparison of ICE (Ifosfamide-Carboplatin-Etoposide) Versus DHAP (Cytosine Arabinoside-Cisplatin-Dexamethasone) as Salvage Chemotherapy in Patients with Relapsed or Refractory Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4438-4438
Author(s):  
Yuksel Urun ◽  
Huseyin Abali ◽  
Berna Oksuzoglu ◽  
Burcin Budakoglu ◽  
Nuriye Yildirim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Response Rates ◽  
Salvage Chemotherapy ◽  
World Health ◽  
High Dose ◽  
Salvage Regimen ◽  
Who Grade ◽  
Group Response ◽  
Refractory Lymphoma ◽  
Grade Iii

Abstract Background: High dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is currently the treatment of choice for relapsed or refractory lymphoma patients. However, the optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP and ICE regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkin’s disease (HD) (n=13) or non-Hodgkin lymphoma (NHL) (n=40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 were female and the median age was 43 years. In the evaluable ICE group (n=22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n=27) rates of CR, PR, and ORR were 18%, 30% and 48% (p=0,24, for ORR). Of the 40 patients with NHL, 15 patients received ICE and 25 patients received DHAP. In the ICE group response could be evaluated in 12 patients, 3 (25%) achieved CR and 5 (42%) PR, leading to an ORR of 67%. In DHAP group, response could be evaluated in 24 patients, 5 (21%) achieved CR and 7 (29%) PR, which makes an ORR of 50%. Although response rate for ICE tends to be higher than DHAP, this difference was not statistically significant (p=0,48). Thirteen patients with HD had an ORR of 62%. One patient had a major response (CR + PR) in DHAP group (33%). In the ICE group of 10 patients with HD, ORR rate was 70%. The response rates for ICE for patients with NHL and HD were not statistically different (p=1,0). Toxicity with both regimens was within acceptable limits. The major grade III–IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to be more effective in terms of response rates than DHAP regimen in whole cohort and subgroups but this difference was not statistically significant. Response of relapsed or refractory lymphoma patients to salvage chemotherapy regimens response ICE (n=22) n,% DHAP (n=27) n,% CR: complete response, PR: partial response, PBSC: peripheral blood stem cell CR 6 (27) 5 (18) PR 9 (41) 8 (30) CR+PR 15 (68) 13 (48) Failure 7 (32) 14 (52) Attempt to mobilize PBSC 8 (36) 2 (7) Successful mobilization 8 (36) 2 (7) Toxicity profiles of salvage chemotherapy regimens used for relapsed or refractory lymphoma patients ICE (n=25),n (%) DHAP (n=28), n (%) WHO: world health organization RBC: red blood cell, TX: transfusion PLT: platelet,G-CSF: granulocyte colony-stimulating factor No. of courses administered 1 3 (12) 7 (25) 2 5 (20) 4 (50) ≥3 17 (68) 7 (25) Total No. of courses administered 73 59 Toxicities (WHO grade III–IV) n=73 n=59 Neutropenia 13 (18) 8 (14) Thrombocytopenia 9 (12) 6 (10) Anemia 5 (7) 9 (15) Febrile neutopenia 6 (8) 6 (10) treated in patient 5 (7) 5 (8) Renal 4 (6) 4 (7) Total RBC TX (unit) 11 23 Total PLT TX (unit) 48 43 G-CSF 8 (11) 6 (10) TDDT 4 (6) 7 (12)

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