High-Dose Therapy and Autologous Hematopoietic Stem-Cell Transplantation for Recurrent or Refractory Pediatric Hodgkin's Disease: Results and Prognostic Indices

Department of Pediatrics , Stanford University, Palo Alto, California, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2004; 22(22):4532-40. DOI: 10.1200/JCO.2004.02.121
Source: PubMed


To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT).
From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS).
At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation).
More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.

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Available from: Michael Link, Jan 07, 2016
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    • "Indications and dose of radiotherapy depends on primary therapy and relapse locations. Relapse outcome depends on first line treatment, stage at relapse, and time to relapse, but only a few reports have investigated long term results and determined factors associated with survival in children in the context of initial response, risk adapted strategy treatment, and ASCT in relapse (Williams et al, 1993; Baker et al, 1999; Verdeguer et al, 2000; Lieskovsky et al, 2004; Harris et al, 2011; Shafer et al, 2011). Given that the cumulative incidence of HL relapse is around 10%, collecting data over a long period is a challenge. "
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    ABSTRACT: There is little data available regarding children and adolescents with Hodgkin lymphoma (HL) who relapse after combined-modality treatment, even though they have a substantial chance of cure. The purpose of this national retrospective study was to evaluate the outcome of patients with recurrent/refractory HL and determine adverse prognostic factors. From 1990 to 2006, 70 patients (median age 13·9 years) with refractory (n = 31) or first relapse (n = 39) HL were identified. Median time from end of treatment to relapse was 6 months (3-56). Relapses occurred in irradiated areas in 43/70 patients. Salvage therapy consisted of chemotherapy and 50 patients received high-dose chemotherapy with autologous stem cell transplantation. Radiotherapy was performed in 29 cases, tandem autologous transplantation in five and allograft in three. With a median follow-up of 40 months (2-140), significant prognostic factors were time to progression/relapse and response to therapy before autograft. Event-free survival and overall survival in patients with refractory disease, early relapse and late relapse were 35 ± 9%, 67 ± 11%, 76 ± 10% and 48 ± 11%, 89 ± 7% and 80 ± 10%, respectively. As progression <3 months was a major adverse prognostic factor, novel therapeutic approaches are needed for this group of patients. By contrast, patients have substantial chance of long term second remission in case of relapse >3 months.
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    • "HD-SCT is increasingly used as salvage therapy also in pediatric patients with poor-risk HL [57, 58], although there are no randomized studies demonstrating improved outcomes for this approach as compared with conventional chemoradiotherapy. Information regarding the role of allogeneic SCT for HL in the pediatric population is very limited. "
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    ABSTRACT: Despite the favorable prognosis of most patients with Hodgkin's Lymphoma (HL), 15-20% of patients remain refractory to chemoradiotherapy, and 20-40% experience relapses following autologous stem cell transplantation (SCT) being used as salvage approach in this situation. Long-term survival of only 20% was reported for patients who failed this option. As some authors suggested the presence of a graft versus HL effect, allogeneic SCT was introduced as a further option. Myeloablative strategies were reported to be able to achieve cure in some younger patients, but high nonrelapse mortality remains a problem. Reduced intensity conditioning, in turn, was found to be associated with high posttransplant relapse rates. As there is currently no standard in the management of HL patients who failed autologous SCT, we here review the literature on allogeneic stem cell transplantation in HL patients with a special focus on the outcomes and risk factors being reported in the largest studies.
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    • "In the poor-risk group, the overall outcome was similar regarding primary refractory patients and poor-risk relapse the 5-year EFS rates were 40AE7% [95% confidence interval (CI) 28AE6–52AE5%] and 52AE2% (CI 39AE9– 43AE1%) respectively (P = 0AE2192). The multivariate analysis of a paediatric study of 41 children with relapsed or refractory HL and a median follow-up of 4 years identified the three following adverse prognostic factors for OS and EFS: extranodal disease, mediastinal mass at relapse and primary refractory disease (Lieskovsky et al, 2004). The time to relapse was also predictive for failure in 176 children (Schellong et al, 2005). "
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    ABSTRACT: Despite a high curability rate, some patients with Hodgkin lymphoma (HL) fail to respond to, or relapse after, primary conventional treatment. This review aims to identify prognostic factors at relapse and guidelines for treatment in relapsed HL. Patients with relapsed HL should be identified according to their prognostic factors at relapse (duration of remission and extranodal disease or stage). This enables relapsing patients to be separated in to three different prognostic groups; primary refractory patients should be included in the unfavourable group because of their poor prognosis. All relapsed HL should receive second-line chemotherapy and the response to this chemotherapy is crucial for the outcome. Benefit of autologous stem-cell transplantation (ASCT) has been shown in a large randomized study and, although is often proposed in relapsed HL, it may be not necessary in the rare group of patients with stage I/II and late relapse who can receive additional radiotherapy after response to chemotherapy. Patients with intermediate and unfavourable relapse should receive high-dose chemotherapy and ASCT when chemosensitive; the first goal is to achieve this chemosensitivity. For patients in the unfavourable group, including refractory patients, the role of tandem HDT or allogeneic SCT will be discussed and should be proposed for patients not in complete remission at the time of HDT.
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