Salvage Therapy of Progressive and Recurrent Hodgkin’s Disease: Results From a Multicenter Study of the Pediatric DAL/GPOH-HD Study Group

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.

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Salvage Therapy of Progressive and Recurrent Hodgkin’s Disease: Results from a Multicenter Study of the Pediatric DAL/GPOH HD-Study Group.

Blood ◽

10.1182/blood.v104.11.612.612 ◽

2004 ◽

Vol 104 (11) ◽

pp. 612-612

Author(s):

Guenther Schellong ◽

Wolfgang Doerffel ◽

Alexander Claviez ◽

Dieter Koerholz ◽

Georg Mann ◽

...

Keyword(s):

Salvage Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Disease Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Term Survival ◽

Free Survival ◽

First Relapse

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.

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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

Journal of Clinical Oncology ◽

10.1200/jco.20.2.467 ◽

2002 ◽

Vol 20 (2) ◽

pp. 467-475 ◽

Cited By ~ 81

Author(s):

C. Ferme

Keyword(s):

Salvage Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

High Dose Chemotherapy ◽

High Dose ◽

Advanced Hodgkin’S Disease

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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’Études des Lymphomes de l’Adulte H89 Trial

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.2.467 ◽

2002 ◽

Vol 20 (2) ◽

pp. 467-475 ◽

Cited By ~ 3

Author(s):

Christophe Fermé ◽

Nicolas Mounier ◽

Marine Diviné ◽

Pauline Brice ◽

Aspasia Stamatoullas ◽

...

Keyword(s):

Salvage Therapy ◽

Hodgkin's Disease ◽

Initial Treatment ◽

Cox Model ◽

Hodgkin’S Disease ◽

Intensive Therapy ◽

High Dose Chemotherapy ◽

High Dose ◽

Induction Failure ◽

Advanced Hodgkin’S Disease

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.

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The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Blood ◽

10.1182/blood.v81.5.1137.bloodjournal8151137 ◽

1993 ◽

Vol 81 (5) ◽

pp. 1137-1145 ◽

Cited By ~ 1

Author(s):

R Chopra ◽

AK McMillan ◽

DC Linch ◽

S Yuklea ◽

G Taghipour ◽

...

Keyword(s):

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Autologous Bone Marrow Transplantation ◽

Progression Free Survival ◽

Autologous Bone Marrow ◽

High Dose Chemotherapy ◽

High Dose ◽

Free Survival ◽

First Relapse ◽

Autologous Bone

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

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High-dose chemotherapy followed by autologous hematopoietic rescue for Hodgkin's disease patients following first relapse after chemotherapy

Annals of Oncology ◽

10.1093/oxfordjournals.annonc.a010542 ◽

1996 ◽

Vol 7 (2) ◽

pp. 151-156 ◽

Cited By ~ 66

Author(s):

P.J. Bierman ◽

J.R. Anderson ◽

M.B. Freeman ◽

J.M. Vose ◽

A. Kessinger ◽

...

Keyword(s):

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

High Dose Chemotherapy ◽

High Dose ◽

First Relapse

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The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Blood ◽

10.1182/blood.v81.5.1137.1137 ◽

1993 ◽

Vol 81 (5) ◽

pp. 1137-1145 ◽

Cited By ~ 237

Author(s):

R Chopra ◽

AK McMillan ◽

DC Linch ◽

S Yuklea ◽

G Taghipour ◽

...

Keyword(s):

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Autologous Bone Marrow Transplantation ◽

Progression Free Survival ◽

Autologous Bone Marrow ◽

High Dose Chemotherapy ◽

High Dose ◽

Free Survival ◽

First Relapse ◽

Autologous Bone

Abstract Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

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High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.7.1086 ◽

1992 ◽

Vol 10 (7) ◽

pp. 1086-1094 ◽

Cited By ~ 31

Author(s):

J M Tourani ◽

R Levy ◽

P Colonna ◽

B Desablens ◽

P Y Leprise ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Hodgkin's Disease ◽

Marrow Transplantation ◽

Hodgkin’S Disease ◽

Disease Free Survival ◽

Salvage Chemotherapy ◽

Adult Patients ◽

High Dose ◽

Intensive Chemotherapy

PURPOSE For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.

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