Prognostic Models for Predicting Outcomes after Autologous Stem Cell Transplantation (ASCT) in Patients with Relapsed or Refractory Hodgkin’s Disease: How Predictive Are They?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5509-5509
Author(s):  
Jose F. Leis ◽  
Keith S. Hansen ◽  
Peter T. Curtin ◽  
Brandon M. Hayes-Lattin ◽  
Keith S. Lanier ◽  
...  
Keyword(s):  
Radiation Field ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Conditioning Regimen ◽  
Prognostic Models ◽  
Entire Group ◽  
High Dose ◽  
Poor Risk ◽  
Risk Patients ◽  
Advanced Hodgkin’S Disease

Abstract Multiple prognostic models for patients with advanced Hodgkin’s disease have been developed in an effort to identify high-risk individuals for ASCT and predict outcomes of high dose therapy and transplant. The utility of four of these models was examined in a cohort of patients transplanted in our program between 1993 and 2005. A total of 113 patients with relapsed or refractory Hodgkin’s disease received ASCT. Forty-five patients received a conditioning regimen of busulfan, melphalan, and thiotepa (BuMelTT) whereas 68 patients received other standard conditioning regimens (SCR) including Cy/TBI/VP (23), CBV (39), and other (6). Median age is 34.5 years for BuMelTT and 34.0 years for SCR patients. Ninety-eight percent of patients receiving BuMelTT had at least two or more prior regimens compared with 86% SCR patients. Eighty-seven percent of BuMelTT and 93% of SCR patients had chemosensitive disease prior to transplant. Median followup is 113 weeks for BuMelTT patients versus 201 weeks for SCR patients. To date 37% of the BuMelTT and 56% of SCR patients have relapsed (p<0.05) with a median time to relapse of 30 and 36 weeks (p=NS) respectively. Statistically significant factors differentiating the BuMelTT and SCR groups included median followup post-ASCT, total percent relapse after transplant, death after transplant, relapse in prior radiation field, and stage at salvage therapy pre-ASCT. Median OS, EFS, and RFS have not yet been reached for BuMelTT patients compared with 439 (p=0.03), 67 (p=NS), and 74 (p=NS) weeks for the SCR patients. TRM was five percent in both groups at five years. We investigated the predictive value of four prognostic models on the entire group, BuMelTT and SCR cohorts. Models evaluated included Roswell Park (RPCI), Memorial Sloan-Kettering, German Hodgkin’s Study Group, and Southwestern Oncology Group (SWOG). Each of these models has identified three negative prognostic indicators on the basis of multivariate analysis. Patients who had 0 or 1 factor were considered good risk and those that had 2 or 3 factors poor risk. Only the SWOG model (>2 prior regimens, relapse in previous radiation field, extranodal disease) was predictive for OS for the entire group (p<0.01) and for the BuMelTT (p=0.05) and SCR (p<0.01) cohorts. The SWOG model was also able to differentiate EFS between good and poor risk patients for the entire group (p=0.02) and SCR group (p=0.05) but not for the BuMelTT cohort. None of the models could differentiate between good and poor risk patients with regard to RFS. When good and poor risk were defined as 0 factors versus 1 to 3 factors, the RPCI model (chemotherapy-resistant disease, poor performance status, and 3 or more chemotherapy regimens prior to transplant) was predictive of OS (p=0.02) and EFS (p=0.02) but only for the BuMelTT cohort. These results suggest that BuMelTT may improve long-term outcomes in patients with advanced Hodgkin’s disease. The prognostic models evaluated had limited utility in our patient cohort with only the SWOG model being predictive of outcome. Large multi-institutional studies are needed to improve prognostic models for transplantation in advanced Hodgkin’s disease.

Assessment of the Stanford V Regimen and Consolidative Radiotherapy for Bulky and Advanced Hodgkin’s Disease: Eastern Cooperative Oncology Group Pilot Study E1492

2000 ◽  
Vol 18 (5) ◽  
pp. 972-972 ◽  
Author(s):  
Sandra J. Horning ◽  
Jovanne Williams ◽  
Nancy L. Bartlett ◽  
John M. Bennett ◽  
Richard T. Hoppe ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Chemotherapy Regimen ◽  
Hodgkin’S Disease ◽  
Eastern Cooperative Oncology Group ◽  
Institutional Setting ◽  
High Dose ◽  
Oncology Group ◽  
Bulky Disease ◽  
Consolidative Radiotherapy ◽  
Advanced Hodgkin’S Disease

PURPOSE: This study was performed, in a multi-institutional setting, to evaluate the efficacy and feasibility of the Stanford V chemotherapy regimen plus radiotherapy to bulky Hodgkin’s disease sites. PATIENTS AND METHODS: A two-stage design was implemented in a phase II study involving 47 patients with bulky mediastinal stage I/II or stage III/IV Hodgkin’s disease. Twelve weeks of the Stanford V chemotherapy regimen were given with consolidative radiotherapy (36 Gy) to lymph nodes ≥ 5 cm and/or macroscopic splenic disease. Treatment was administered in one of five institutions participating in the Eastern Cooperative Oncology Group. RESULTS: With a median follow-up of 4.8 years, 45 patients are alive and 40 have been continuously disease-free. The estimated freedom from progression was 87% at 2 years and 85% at 5 years. Overall survival was 96% at 2 and 5 years. There was one death from Hodgkin’s disease and one death from an M5 acute leukemia. Six of seven relapsed patients received high-dose therapy and autologous stem-cell transplantation. The freedom from second progression for the seven relapsed patients was estimated at 98% at 3 years. CONCLUSION: Stanford V chemotherapy and consolidative radiotherapy to bulky disease is effective in bulky and advanced Hodgkin’s disease in a multi-institutional setting. On this basis, an Intergroup study comparing doxorubicin, bleomycin, vinblastine, and dacarbazine with the Stanford V regimen has been initiated.

A Numerical Prognostic Index for Clinical use in Identification of Poor-Risk Patients with Hodgkin's Disease at Diagnosis

1992 ◽  
Vol 7 (sup1) ◽  
pp. 17-20 ◽  
Author(s):  
Stephen J. Proctor ◽  
Penny Taylor ◽  
M. J. Mackie ◽  
Peter Donnan ◽  
Richard Boys ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Prognostic Index ◽  
Clinical Use ◽  
Poor Risk ◽  
Risk Patients

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.

Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin's disease and non-Hodgkin's lymphoma.

1994 ◽  
Vol 12 (12) ◽  
pp. 2552-2558 ◽  
Author(s):  
S J Horning ◽  
R S Negrin ◽  
J C Chao ◽  
G D Long ◽  
R T Hoppe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Survival Rate ◽  
Total Body Irradiation ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
High Dose ◽  
High Dose Therapy ◽  
Poor Risk ◽  
Total Body

PURPOSE High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies. PATIENTS AND METHODS Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow. RESULTS The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at > or = 3 years. CONCLUSION The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses.

A numerical prognostic index for clinical use in identification of poor-risk patients with Hodgkin's disease at diagnosis

1991 ◽  
Vol 27 (5) ◽  
pp. 624-629 ◽  
Author(s):  
Stephen J Proctor ◽  
Penny Taylor ◽  
Peter Donnan ◽  
Richard Boys ◽  
Anne Lennard ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Prognostic Index ◽  
Clinical Use ◽  
Poor Risk ◽  
Risk Patients

Autologous Stem-Cell Transplantation for Hodgkin’s Disease: Results and Prognostic Factors in 494 Patients From the Grupo Español de Linfomas/Transplante Autólogo de Médula Ósea Spanish Cooperative Group

2001 ◽  
Vol 19 (5) ◽  
pp. 1395-1404 ◽  
Author(s):  
A. Sureda ◽  
R. Arranz ◽  
A. Iriondo ◽  
E. Carreras ◽  
J.J. Lahuerta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cooperative Group

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin’s disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Ósea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age ≥ 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.

High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.

1993 ◽  
Vol 11 (4) ◽  
pp. 704-711 ◽  
Author(s):  
M Crump ◽  
A M Smith ◽  
J Brandwein ◽  
F Couture ◽  
H Sherret ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Intensive Therapy ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Disease Status ◽  
High Dose ◽  
Bulky Disease ◽  
Therapy Regimen ◽  
Advanced Hodgkin’S Disease

PURPOSE To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm). RESULTS Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor. CONCLUSION Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.

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