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.

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.

Long-Term Outcome after LACE (Lomustine, Ara-C, Cyclophosphamide, Etoposide) Conditioned Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Lymphoma: A Single Centre Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5502-5502
Author(s):  
Jolanta B. Perz ◽  
Chrissy M. Giles ◽  
Donald MacDonald ◽  
Jane F. Apperley ◽  
Edward J. Kanfer
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
Secondary Malignancy ◽  
High Dose ◽  
Long Term Outcome

Abstract Introduction: The majority of patients with Hodgkin’s lymphoma are cured with initial therapy. However, in patients with primary refractory or relapsed disease, high-dose therapy followed by autologous stem cell transplantation has been shown to be the best option. We analysed patients (pts) who underwent autologous stem cell transplantation (ASCT) following LACE (Lomustine 200 mg/m2, Ara-C 4 g/m2, Cyclophosphamide 4.8 g/m2, Etoposide 1 g/m2) conditioning for relapsed or refractory Hodgkin’s lymphoma at the Hammersmith Hospital, London, between 1991 and 2004. Patients and methods: 67 pts (46 m, 21 f) initially diagnosed with Hodgkin’s lymphoma (stage I; n=2, stage II; n=29, stage III; n=22 and stage IV; n=14) received first-line chemotherapy with ABVD or COP/ABVD (n=20), BEMOP-CA (n=29), COPP or similar (n=14) or mantle radiotherapy alone (n=4). High dose chemotherapy (HDC) with LACE and ASCT was undertaken in 45 of these pts in 1st relapse, 15 pts in 2nd or subsequent relapse and 7 pts with refractory disease. Median age at the time of HDC was 32 y (17 – 70 y). Prior to ASCT further chemotherapy achieved a complete or partial remission in 41 pts (chemosensitive), but 26 pts had no significant response (chemoresistant). Stem cells were mobilised with Etoposide (1.8 g/m2) and G-CSF in 56 pts, and bone marrow harvest was performed in the other 11 pts. Results: Two pts suffered a treatment-related mortality (TRM) within the first 100 days (3%). Two pts (3%) developed secondary malignancy (acute myeloid leukaemia). With a median follow-up of 43.3 months (range 0.5 – 145.5 months) the cumulative probabilities of overall survival (OS) and progression free survival (PFS) at both 5 and 10 years was 70% and 62% respectively. Pts who had chemosensitive disease at the time of ASCT had a better OS (p=0.008) and PFS (p=0.08) when compared with pts who had chemoresistant disease. Median PFS has not yet been reached for chemosensitive pts but was 23.4 months for chemoresistant pts. Median OS has not yet been reached for either group. Conclusions: The outcome for patients with relapsed or refractory Hodgkin’s lymphoma following high dose chemotherapy and ASCT has been sufficiently encouraging to suggest that ASCT should be considered early in chemosensitive patients. However, new therapeutic strategies are needed to improve the clinical outcome of patients with chemoresistant disease.

The Revised High-Dose Regimen of Beacop in the Primary Treatment of the Advanced Hodgkin's Lymphoma: A Interim Report

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4783-4783
Author(s):  
Peng LIU ◽  
Yuankai Shi ◽  
Zhao Wang
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Standard Dose ◽  
Primary Treatment ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Similar Response ◽  
Good Tolerance ◽  
Asian Patients ◽  
Advanced Hodgkin’S Lymphoma

Abstract Abstract 4783 Objective In the study, we compared the efficacy between the revised high-dose and standard-dose of the revised BEACOP regimen (Bleomycin, Etoposide, Epidoxorubicin, Cyclophophamide, Vincristine, Prednisione) in the treatment of the advanced Hodgkin's lymphoma (HL). Patients and methods Patients with HL of Stage III/IV were 1:1 randomized into either the standard-dose BEACOP regimen (the same to the BEACOPP regimen in GHSG-HD9 study except procarbazine) in the control arm or the revised high-dose BEACOP regimen (different from BEACOPPesc regimen in GHSG-HD9 study, excluding procarbazine, increasing the dose of cyclophophamide and doxorubicin, with the standard-dose of etoposide, and without the preventive G-CSF support) in the experimental arm. Patients with large tumor or residual tumor after 6 to 8 cycles chemotherapy would be received local radiotherapy. All patients were evaluated by imaging examination every 2 cycles during treatment and were followed up every 3 months from the end of the treatment. Results 33 cases with advanced HL completed whole cycles chemotherapy and were followed-up a medium time of 12 months. The interim analysis showed that, patients received revised high-dose BEACOP had better response than those with standard-dose BEACOP. After 2 cycles chemotherapy, 2/17 cases had complete response (CR), and 8/17 cases had reduced more than 75% in the tumor size in the experimental arm; while none of 16 cases in the control arm achieved the similar response. After 6 cycles chemotherapy, 13/17 cases in the experimental arm achieved CR/CRu, compared with 8/16 cases in the control arm. Simultaneously, adverse drug reactions, such as neutropenia, nausea and vomiting, were observed significantly increased in the experimental arm. However, no related death and SAE occurred. All the patients showed good tolerance in the study. Conclusions In the HD9 study, asian patients received with BEACOPPesc were not tolerated enough to complete the whole chemotherapy, because of the serious toxicity such as long-term bone marrow suppression. In our study, we demonstrated that revised high-dose BEACOP in the primary treatment of the advanced HL would achieved the more high rate of CR/CRu compared with standard-dose BEACOP, and patients with revised high-dose BEACOP showed good tolerance and controllable acute hematotoxicity, even without the preventive use of G-CSF. Therefore, the revised high-dose BEACOP regimen might be a potential choice for Asian patients with advanced HL. However, more cases and long-term follow-up should be needed in the future to evaluate the long-term overall survival (OS) rate, efficacy and toxicity. Disclosures: LIU: Research Project of Cancer Hospital, CAMS: Research Funding.

Dose Intensity of Chemotherapy in Patients With Relapsed Hodgkin's Lymphoma

2010 ◽  
Vol 28 (34) ◽  
pp. 5074-5080 ◽  
Author(s):  
Andreas Josting ◽  
Horst Müller ◽  
Peter Borchmann ◽  
Joke W. Baars ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Stage Iv ◽  
Dose Intensity ◽  
High Dose Chemotherapy ◽  
Observation Time ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Significant Difference ◽  
Multiple Relapse ◽  
The Impact

Purpose High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy. Patients and Methods Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points. Results From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001). Conclusion Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.

Early Interim 18f-FDG PET In Hodgkin's Lymphoma: Evaluation on 304 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3879-3879
Author(s):  
Pier Luigi Zinzani ◽  
Luigi Rigacci ◽  
Vittorio Stefoni ◽  
Alessandro Broccoli ◽  
Benedetta Puccini ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Conflicts Of Interest ◽  
Early Recognition ◽  
Early Stage ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Advanced Stage ◽  
Interim Pet

Abstract Abstract 3879 Purpose. The use of early (interim) positron emission tomography (PET) restaging during front-line therapy in Hodgkin's lymphoma (HL) has considerably increased in clinical practice as an early recognition of treatment failure allows patients to be addressed to more intensive treatment regimens. Patients and Methods. Between June 1997 and June 2009, 304 newly-diagnosed Hodgkin's lymphoma patients (147 early-stage and 157 advanced-stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent to a PET staging and restaging at baseline, after 2 cycles of therapy and at the end of the treatment. Results. 53 patients showed a positive interim PET and only 13/53 (24.5%) achieved a complete response (CR), whereas 251 patients showed a negative PET and 231/251 (92%) remained in CR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival (p=0.0000) and 9-year overall survival (p=0.0000), with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET and only 4 (21%) achieved a CR; among the 128 negative interim PET patients, 122 (97.6%) obtained a CR. In the advanced-stage subset, 34 patients showed a persistently positive PET (with only 9/34, 26.4% in CR), whereas 123 showed a negative interim PET, with 109 (88.6%) remaining in CR. Conclusions. Our results confirm the role of early PET as a significant step forward for the management of both early and advanced-stage HL patients, offering the potential for an immediate switch to high-dose treatments, if required. Disclosures: No relevant conflicts of interest to declare.

A Pilot Study of Combined Escalated BEACOPP-ABVD Therapy for Advanced Hodgkin’s Lymphoma Patients with High IPS Score: The Israel Cooperative Lymphoma Group.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4576-4576
Author(s):  
Abraham Avigdor ◽  
Shlomo Bulvik ◽  
Noga Shemtov ◽  
Itai Levi ◽  
Miriam Berkowicz ◽  
...  
Keyword(s):  
Pilot Study ◽  
Hodgkin’S Lymphoma ◽  
Intensive Therapy ◽  
Hodgkin's Lymphoma ◽  
Who Grade ◽  
Term Survival ◽  
Advanced Hodgkin’S Lymphoma ◽  
Grade Iii

Abstract ABVD is widely considered as the gold standard treatment for advanced Hodgkin’s lymphoma (HL), although about 40% of patients relapse or do not respond to initial treatment. Recently, the HD9 trial of the German Hodgkin’s Lymphoma Study Group has shown that escalated (esc) BEACOPP regimen can achieve better disease control than ABVD, but has a high incidence of acute and long-term toxicities including high occurrence of AML/MDS. In an attempt to decrease toxicity while preserving the potential benefit of upfront intensive therapy, we conducted a pilot study, which tested the feasibility, toxicity and efficacy of combined escBEACOPP-ABVD regimen as therapy for newly diagnosed patients with high risk (IPS≥3) stage III–IV HL. Patients initially received 2 cycles of escBEACOPP followed by reevaluation with CT and gallium or PET/CT-FDG scans. When complete response (CR) or partial response (PR) was achieved, patients continued to receive 4 cycles of ABVD, while those failing to achieve a response were withdrawn from the study. Since August 2001, 21 patients entered the study and at the time of present analysis four of them are still receiving therapy. Three (18%) of 17 patients, who completed chemotherapy, received consolidative radiotherapy. Median age at diagnosis was 26 years (range 18–56) and 11 (57%) were males. Stage IV and B symptoms were evidenced in 19 (90%) and 17 (81%), respectively, and 7 (33%) had bulky mediastinal mass. Histology included nodular sclerosis in 18 patients (86%), mixed cellularity in 2 (10%) and lymphocyte predominance in 1 (5%). Following the first 2 cycles of escBEACOPP the overall response rate (CR+PR) was 100%. At the end of all therapy 15 patients (88%) were in CR, one patient in PR and only a single patient had progressive disease. With a median follow-up of 20 months no patient relapsed or died. Toxicity included WHO grade III–IV granulocytopenia in 15 patients (88%) and grade III–IV infection in one patient. Hospitalization for intravenous antibiotics was necessary in 10 patients (59%). Almost all of these events occurred during the first two cycles of escBEACOPP, while acute toxicity during the ABVD phase was mild. In conclusion, the combined escBEACOPP-ABVD regimen is well tolerated and is associated with a high CR rate when used in advanced HL patients with high IPS scores. Further follow-up is obviously required in order to determine long-term survival and late complications of this regimen.

ESAP-Lenalidomide - a Highly Active Regimen in Refractory or Relapsed Hodgkin's Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4797-4797
Author(s):  
Adrian Tempescul ◽  
Jean-Christophe Ianotto ◽  
Gaelle Guillerm ◽  
Christian Berthou
Keyword(s):  
Fdg Pet ◽  
Hodgkin’S Lymphoma ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Salvage Regimen ◽  
Highly Active

Abstract Abstract 4797 Hodgkin's disease (HD) is a commonly cured lymphoma. Unfortunately between 10 and 20% of patients are refractory or relapse after a first line of treatment. There is evidence that for these patients the best approach is salvage chemotherapy followed by high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Existing salvage regimens of chemotherapy, mainly based on platines or aracytine, have a response rate between 60-85%. Usually is associated a toxicity resulting in delay of chemotherapy or dose reduction. It is very important to achieve complete remission before HDC/ABSCT. It has been proved that 18-FDG PET has a predictive value on Hodgkin's lymphoma. Into the pathophysiology of HD are implicated various cytokines like IL6, IL12, IL13, NFkB and angiogenic factors. Immunomodulatory drugs have an impact on microenvironment, altering cytokine secretion and the expression of adhesion molecules which can result in apoptosis of malignant B-cell. Lenalidomide, having both immunomodulatory and antiangiogenic activity, proved to be highly active into the treatment of myeloma and some forms of non-Hodgkin's lymphoma. Into a phase two studies, Lenalidomide administrated as a single agent, proves to be also active into the refractory or relapsed Hodgkin's lymphoma. During a period of one year, we identified eight patients with refractory ore relapsed HD. We have treated these patients with classical salvage chemotherapy regimen – ESAP- in which we associated Lenalidomide, administrated continuously during the whole period of treatment. We evaluate the response by 18-FDG PET, early, after two or three cycles of ESAP-Lenalidomide association. We obtained seven complete remissions and one very good partial remission (minimal residual disease in PET SCAN). The toxicity was essentially hematological, neutropenia and trombocytopenia. This small study proves that Lenalidomide, a new drug with both immunomodulatory and antiangiogenic effects, associated to a classical salvage regimen of chemotherapy is highly active on refractory or relapsing Hodgkin's lymphoma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High-dose chemotherapy and auto-SCT in elderly patients with Hodgkin's lymphoma

2011 ◽  
Vol 46 (10) ◽  
pp. 1339-1344 ◽  
Author(s):  
N Puig ◽  
M Pintilie ◽  
T Seshadri ◽  
K al-Farsi ◽  
N Franke ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
High Dose
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