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

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.

Children's Oncology Group's 2013 blueprint for research: Hodgkin lymphoma

“…In parallel with efforts to capitalize on a prognostic scoring system to stratify therapy for newly diagnosed HL (described above), a risk-stratified algorithm for approaching pediatric and AYA patients with refractory HL has been developed. Patients will be divided into low, intermediate, and high risk based on duration of initial CR [60], initial response to prior therapy [61,62], and initial CHIPS score. Historically, retrieval therapy for these three groups has resulted in markedly divergent probabilities of long-term overall survival (OS), ranging from OS <30% among the highest-risk group to OS above 95% in the low-risk group.…”

Results of the AHOD0431 trial of response adapted therapy and a salvage strategy for limited stage, classical Hodgkin lymphoma: A report from the Children's Oncology Group

“…The rationale for our approach was that many patients with limited stage cHL who relapse with low disease burden after chemotherapy alone can be successfully retreated with further chemotherapy and involved-field radiation therapy (IFRT) without the use of high-dose chemotherapy/stem cell rescue or higher dose radiation therapy. 9,10 Our objective was to investigate a response-directed treatment paradigm that delivered minimal initial chemotherapy, with low-dose radiation reserved for those who did not achieve a complete response (CR), and integrating a conventional chemotherapy/low-dose radiation salvage regimen for protocol-defined, low-risk recurrence. We also evaluated the role of response measured by a fluorodeoxyglucosepositron emission tomography scan after 1 cycle of chemotherapy (PET1 response) as a marker of chemosensitivity.…”

Ifosfamide, gemcitabine, and vinorelbine is an effective salvage regimen with excellent stem cell mobilization in relapsed or refractory pediatric Hodgkin lymphoma

“…Other pediatric salvage regimens followed by ASCT have reported OS rates of 60% to 70%. [5][6][7][8][9][10][11][12][13][14][15][16] A Children's Oncology Group phase 1 trial evaluated use of ifosfamide with vinorelbine in 66 patients, 20 of which the majority were at first relapse. The ORR was 72%, with CR rate of 26% after two cycles, although response was assessed by combined metabolic and anatomic criteria.…”

“…to ≤ 12 months and > 12 months after completion of therapy, respectively. 13 Following SCT, this patient had further disease progression and was treated with brentuximab followed by nivolumab.…”

“…[1][2][3][4] Of those who fail initial therapy, salvage approaches, consisting of a range of chemotherapy regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), have demonstrated a five-year overall survival (OS) of 60% to 70% in pediatric patients. [5][6][7][8][9][10][11][12][13][14][15][16] The combination of ifosfamide, vinorelbine, and gemcitabine (IGEV) was first reported in adults with refractory and relapsed HL in 2001. 17 Abbreviations: ASCT, autologous stem cell transplant; CR, complete response; HL, Hodgkin lymphoma; IGEV, ifosfamide, gemcitabine, vinorelbine; ORR, overall response rate; PR, partial response.…”