Intensive Salvage Therapy With High-Dose Chemotherapy for Patients With Advanced Hodgkin's Disease in Relapse or Failure After Initial Chemotherapy: Results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial

2002 ◽  
Vol 20 (2) ◽  
pp. 467-475 ◽  
Author(s):  
C. Ferme
2002 ◽  
Vol 20 (2) ◽  
pp. 467-475 ◽  
Author(s):  
Christophe Fermé ◽  
Nicolas Mounier ◽  
Marine Diviné ◽  
Pauline Brice ◽  
Aspasia Stamatoullas ◽  
...  

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin’s disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P = .0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P = .0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.


2005 ◽  
Vol 23 (25) ◽  
pp. 6181-6189 ◽  
Author(s):  
Günther Schellong ◽  
Wolfgang Dörffel ◽  
Alexander Claviez ◽  
Dieter Körholz ◽  
Georg Mann ◽  
...  

Purpose To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin’s disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients’ median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis. Results Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission. Conclusion The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin’s disease in childhood/adolescence.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 612-612
Author(s):  
Guenther Schellong ◽  
Wolfgang Doerffel ◽  
Alexander Claviez ◽  
Dieter Koerholz ◽  
Georg Mann ◽  
...  

Abstract To evaluate the efficacy of a salvage therapy (ST-HD-86) developed for children and adolescents with progressive or relapsed Hodgkin’s disease (HD) who were primarily treated in the pediatric DAL/GPOH studies. The essential chemotherapeutic elements were ifosfamide, etoposide, prednisone (IEP) and doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD). 176 patients with progression (N=51) or first relapse (N=125) were enrolled by 67 centers from six countries between 1986 and 2003. The median time from initial diagnosis to progression/relapse was 1.1 (range, 0.02–17.1) years and the median patients age at the diagnosis of progression/relapse was 14.7 (range, 4.3–24.5) years. Salvage therapy consisted of 3–5 alternating cycles of IEP and ABVD, supplemented in part by 1–2 cycles of cyclophosphamide, vincristine, procarbazine, prednisone (COPP) or CCNU, etoposide, prednimustine (CEP). Radiotherapy was given to involved areas using individualized dosages. In the 1990ies, high-dose high dose chemotherapy with stem cell support was introduced for patients with unfavorable prognostic criteria. Disease-free survival (DFS) and overall survival (OS) at 10 years after initiation of salvage therapy are 63±4% and 74±4%. Second events occurred in 70 of 176 pts (40%). Risk factor analysis revealed the time until progression/relapse as the most discriminating prognostic factor (p=.0001). Patients with progression had an inferior outcome (DFS 41±7%, OS 51±8%), whereas patients with late relapses (>12 months after end of therapy) do very well (DFS 87±4%, OS 90±4%). The result of study ST-HD-86 with a long-term survival of 74% in this large cohort of patients with progressive or relapsed HD can be considered favorable. While the salvage strategy for patients with progression has to be further optimized, a reduction of intensity might be considered for those patients with late relapses following HD in childhood or adolescence.


1997 ◽  
Vol 75 (7) ◽  
pp. 1044-1048 ◽  
Author(s):  
C Rubio ◽  
ME Hill ◽  
S Milan ◽  
MER O'Brien ◽  
D Cunningham

Author(s):  
A. M. Carella ◽  
G. Santini ◽  
F. Frassoni ◽  
A. Santoro ◽  
P. Coser ◽  
...  

2000 ◽  
Vol 18 (13) ◽  
pp. 2615-2619 ◽  
Author(s):  
A. Santoro ◽  
H. Bredenfeld ◽  
L. Devizzi ◽  
H. Tesch ◽  
V. Bonfante ◽  
...  

PURPOSE: To explore the use of gemcitabine for the treatment of patients with relapsing or refractory Hodgkin’s disease. PATIENTS AND METHODS: Eligible patients had measurable disease and more than one previous chemotherapy regimen. Patients previously treated with high-dose chemotherapy with autologous bone marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250 mg/m2, was administered as a 30-minute intravenous infusion on days 1, 8, and 15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any dose of gemcitabine that could not be given on time was omitted. Patients who had not experienced any hematologic or nonhematologic toxicity after one complete cycle of therapy were permitted to have subsequent doses increased by 20%: that is, from 1,250 mg/m2 to 1,500 mg/m2. RESULTS: Of the 23 enrolled patients, 22 were assessable for response; all 23 patients were included in the efficacy analysis. Disease status for two patients (9%) reached a state of complete remission, and seven patients (30%) achieved a partial response, for an overall response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of achieving a response was not influenced by a patients’ main pretreatment characteristics or by their response to their last prior chemotherapy. The median duration of response was 6.7 months (range, 2 to 33+ months), and the median overall survival time was 10.7 months (range, 4 to 34.7+ months). In general, toxicities were mild; no treatment-related deaths occurred, and only one life-threatening adverse event was reported for this study. CONCLUSION: Gemcitabine was shown to be active in heavily pretreated patients with Hodgkin’s disease, producing a response rate of 39%. Additionally, drug-related toxicities were mild, which thus suggests the possible inclusion of gemcitabine in an earlier phase of treatment.


1989 ◽  
Vol 7 (12) ◽  
pp. 1791-1799 ◽  
Author(s):  
K M Taylor ◽  
S Jagannath ◽  
G Spitzer ◽  
J A Spinolo ◽  
S L Tucker ◽  
...  

To determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate granulocyte recovery after high-dose combination chemotherapy with autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease, we performed a nonrandomized phase II study using historical controls as a comparison. Eighteen relapsed/refractory Hodgkin's disease patients who received cyclophosphamide at 1.5 g/m2/day (days -6 to -3), carmustine (BCNU) at 300 mg/m2 (day -6), and etoposide (VP-16) at 125 mg/m2 every 12 hours (days -6 to -4), followed by ABMT (day 0) were treated with rhG-CSF at 60 micrograms/kg/day for a maximum of 28 days beginning on day 1. rhG-CSF dosage was gradually diminished and stopped once an adequate granulocyte count was maintained. rhG-CSF significantly accelerated absolute granulocyte count (AGC) compared with historical controls recovery to the 100/microL level (median, 9 days v 13 days; P = .103 x 10(-4), 500/microL level (median, 13 days v 22 days; P = 0.189 x 10(-2), and 1000/microL level (median, 16 days v 30 days levels; P = .125 x 10(-5). Platelet recovery to 50,000/microL was not significantly altered (P = .370). rhG-CSF was well tolerated, bone pain and myalgia being the only side effects noted. rhG-CSF hastens granulocyte recovery after high-dose chemotherapy with ABMT in patients with relapsed/refractory Hodgkin's disease without significant toxicity.


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