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

Blood ◽  
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.

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

2005 ◽  
Vol 23 (25) ◽  
pp. 6181-6189 ◽  
Author(s):  
Günther Schellong ◽  
Wolfgang Dörffel ◽  
Alexander Claviez ◽  
Dieter Körholz ◽  
Georg Mann ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
Primary Treatment ◽  
Salvage Chemotherapy ◽  
Late Relapse ◽  
High Dose ◽  
First Relapse

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.

scholarly journals 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 ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1137-1145 ◽  
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.

scholarly journals 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 ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1137-1145 ◽  
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.

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

2002 ◽  
Vol 20 (2) ◽  
pp. 467-475 ◽  
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.

Survival and long-term toxicities of biochemotherapy for metastatic melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8553-8553
Author(s):  
D. R. Minor ◽  
J. Miller ◽  
M. Kashani-Sabet
Keyword(s):  
Residual Disease ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Consecutive Series ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Survivors ◽  
Disease Free

8553 Purpose: Because long-term survival after therapy for advanced stage IV melanoma is rare, we thought it would be useful to examine our series of survivors treated with biochemotherapy for melanoma to analyze the characteristics of survivors and their chronic toxicities. Patients and Methods: We reviewed our previously reported (J Clin Oncol. 2005:23:16s suppl, abstract 7547) consecutive series of 38 patients treated between 9/02 and 7/04. They received 6 cycles of inpatient temozolomide, cisplatin, vinblastine, decrescendo high- dose iv IL-2 , and interferon followed by maintenance immunotherapy using IL-2 and sargramostim using the O’Day regimen (Clinical Cancer Res. 2002:8:2775).Two of the ten long-term survivors received surgery for resection of residual disease after achieving a partial response with biochemotherapy. Maintenance immunotherapy was given for 6 to 24 months after biochemotherapy. Results: The median progression- free survival was 7.3 months. No patient developed progression later than 17 months after the start of therapy with the progression-free survival curve level at 24%. Median overall survival was 16.2 months. 10 of the 38 patients are alive and disease-free off therapy after an average of 3.3 years follow-up. Durable complete responses were seen in visceral sites including lung, bone, and pericardium, with 8 of 10 long- term survivors having M1B or M1C disease. 3 patients have significant lymphedema related to prior surgery, radiation therapy, or both. 2 patients, one with pre-existing diabetes, have significant persisting neuropathy. 5 of the 10 patients are hypothyroid. Menstrual function returned in the three women under age 45 in this study. Conclusion: This series supports the findings from other series that biochemotherapy, like high-dose IL-2, can give prolonged disease-free survival. Survivors have a high incidence of hypothyroidism but neuropathy and lymphedema, which affected a minority of patients, were the most bothersome long-term toxicities. No significant financial relationships to disclose.

A Single Institution Long-Term Experience Using Autologous Stem Cell Transplantation for the Management of Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5233-5233
Author(s):  
Barry S. Skikne ◽  
Narotham Thudi ◽  
Delva Deauna-Limayo ◽  
Siddhartha Ganguly ◽  
David Bodensteiner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Primary Induction ◽  
Induction Failure

Abstract Patients with stage III – IV Hodgkin’s lymphoma (HL), and those with bulky stage I/II disease have a disease relapse rate of 30–40% after primary treatment. High dose chemotherapy with stem cell transplantation is a treatment option after relapse or in those with primary induction failure. In the present study, we retrospectively examined long term outcomes in 45 relapsed/primary induction failure HL patients undergoing autologous peripheral stem cell (25 patients), bone marrow (17 patients) or combination (3 patients) transplantation between 1985 and December 2003. The median age was 32 yrs(16–64), 38 had Nodular Sclerosing HL, 17 patients had stage I/II, 13 stage III and 15 stage IV disease, and 33 had B symptoms at diagnosis. Twenty patients were previously treated with 1–2 prior regimens, while 25 had ≥3 treatment regimens. Sixteen patients had sensitive disease to salvage therapy given prior to transplantation, 27 had resistance to salvage therapy while 2 did not undergo salvage therapy prior to transplantation. Five patients had primary resistant disease, 33 had evidence of relapsed disease and 7 patients were in CR at the time of transplantation. CBV was used in 30 patients, BEAM in 9 patients and 5 patients received CY/TBI based regimens. Six patients (13%) had early mortality (< 100 days) directly attributable to the procedure. Four of these deaths were cardiac related and two were due to infection. The overall response was 93% with CR achieved in 28 (62%) and incomplete response in 14 (31%). The median overall survival (OS) was 5.5 yrs, the median disease free survival (DFS) was 1 yr with DFS at 5 yrs of 26%. For patients achieving a CR after transplantation, 67% remain alive at a median of 7 yrs from transplant, however, the median progression free survival in these patients was 3.7yrs. For 15 patients not achieving CR after transplantation, 3(20%) have survived, the median time to death in this group was 20 months. Seventeen patients are alive, 2 are lost to follow-up and 21 patients have died. Fourteen patients died from disease progression (31%), 2 (4%) died from MDS/AML occurring after 32 and 66 mnths, 2 died of late occurring infections, 2 related to respiratory failure and a further patient from late cardiac failure. OS and DFS did not differ between peripheral stem cell vs bone marrow transplantation, those with B symptoms at diagnosis, sex differences, age <20yrs vs >20yrs, high dose therapy regimens but a difference in OS (p=0.04) and DFS (p=0.03) was seen in patients transplanted in CR vs active disease at transplantation. Patients whose disease displayed sensitivity to salvage therapy immediately prior to transplant did show a trend towards improved OS and DFS, but this was not statistrically significant. High dose chemotherapy and autologous stem cell transplantation can be expected to lead to long term DFS in approximately 25–35% of patients. Cardiac mortality (11%) appears to be a higher than expected complication in this patient group.

Role of High-Dose Chemotherapy with Autologous Haematopoetic Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5432-5432
Author(s):  
Ambuj Kumar ◽  
Benjamin Djulbegovic ◽  
Heloisa P. Soares
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Meta Analysis ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Conventional Chemotherapy ◽  
Free Survival

Abstract Background: Hodgkin disease (HD) is a potentially curable lymphoma with overall survival exceeding 60% at 10 years. However, patients with relapsed Hodgkin’s disease have a dismal prognosis when treated with conventional salvage chemotherapy. The primary objective of our systematic review/meta-analysis was to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with relapsed Hodgkin’s disease which has not been done before. Methods: Data search of published studies included Medline (1966–2006), Cochrane library and hand search of references. Studies were included if they were randomized controlled trials of HSCT versus conventional chemotherapy only. Data were extracted on benefits as well as harms (overall survival, event-free survival, and treatment related mortality). All data extraction was done in duplicate independently. Results: Out of 47 identified studies only 2 met the inclusion criteria of the current systematic review. Overall survival was similar for HSCT and conventional chemotherapy arms (see figure 1) with a pooled hazard ratio (HR) of 0.69 (95%CI 0.40, 1.18, p=0.2). However, the event-free survival was better in the HSCT arm than the conventional chemotherapy alone group (HR = 0.59, 95%CI 0.41, 0.85, p=0.005). Treatment related mortality was similar in both groups. (HR = 0.40, 95%CI 0.11, 1.44, p=0.2). Conclusion: Results from our meta-analysis indicate that treatment with HSCT compared with conventional chemotherapy only improves event free survival without excessive toxicity. However, overall survival was not affected by the HSCT therapy. In summary patients with relapsed Hodgkin’s disease should be offered HSCT therapy. Role of transplant in relapsed or resistant hodgkin’s disease Role of transplant in relapsed or resistant hodgkin’s disease

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