Complex treatment experience in a cohort of children and adolescents with Hodgkin’s lymphoma
Daria A. Zvyagintseva2, Andrew V. Kozlov1, Asmik G. Gevorgian1, Ilya V. Kazantsev1, Polina S. Tolkunova1, Tatiana V. Iukhta1, Ludmila S. Zubarovskaya1, Boris V. Afanasyev1
1 Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint
Petersburg State Medical University, St. Petersburg, Russia
2 N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia
Contact: Dr. Daria A. Zvyagintseva
The use of modern standard risk-adapted therapy programs is accompanied by a relatively favorable prognosis for Hodgkin’s lymphoma (HL) in both adult and pediatric patients. Most patients can be cured, and long-term overall survival (OS) reaches 80-85%. However, 15-20% of patients do not respond to standard therapy, or have a relapse. In these cases, the use of intensive chemotherapy regimens, including high-dose polychemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HDCT), allows stabilization and a change in the prognosis of the disease. Our aim was to assess the survival of in standard and high-risk Hodgkin’s lymphoma patients based on the therapy received.
Patients and methods
In this study, we analyzed the treatment results of 175 patients aged 3 to 18 years with Hodgkin’s lymphoma. Most patients (n=143) received in 1993-2015 standard treatment regimens according to DAL-HD and SPbHL protocols in Pediatric Oncology Department at the N. N. Petrov Research Institute of Oncology. The induction regimen consisted of 2 to 6 polychemotherapy courses, then local irradiation of primary lesions locations was performed. Some patients (n=32, 18%) with primary resistant or relapsed disease belonged high-risk group and received more intense treatment including high-dose chemotherapy (HDCT) with autologous hemopoietic stem cell transplantation (auto-HSCT) performed in R. M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantation in 2012 to 2017. In most cases, BEAM (22%) and BeEAM (63%) HDCT regimens were employed, 15% of patients received other treatment regimens. The median follow-up is 10 years for primary patients and 2.5 years for the HDCT group.
The long-term overall (OS) and event-free survival rates (EFS) of the primary patients treated according to DAL-HD and SPbHL protocols were 88% and 77%, 93% and 87%, accordingly. There were no significant differences in overall and relapse-free survival depending on the treatment protocol used (p=0.5). The immediate treatment toxicity was mostly hematological (Gr IV neutropenia in 23% in DAL-HD and 11.8% of cases in SPbHL therapy regimens recipients). OS and EFS in primary resistant/relapsed patients receiving HDCT with auto-HSCT were 57% and 42%, accordingly. The main cause of death was relapse/progression of the disease (n=3), although 9% of patients died of transplant-related complications. The immediate HDCT toxicity effects were mostly febrile neutropenia (87% of cases), gastrointestinal mucositis of different grade (50%), which was in 6% of cases complicated by bleeding. In one case, a subarachnoid hemorrhage was registered.
Modern programs of complex HL therapy allow curative rates of more than 80% in the patients with HL. Therefore, some further efforts should be devoted to treatment-associated toxicity reduction. However, there is still a group of patients with extremely unfavorable prognosis, in whom the treatment results are still unsatisfactory (57 vs 42%), even after dose-intensive consolidation. The high-risk group treatment programs are also associated with considerable toxicity. These results may be significantly improved by the use of targeted drugs and immunotherapy (immune control checkpoints inhibitors, allogeneic HSCT).
Hodgkin lymphoma, children and adolescents, high-dose polychemotherapy, autologous hematopoietic stem cell transplantation, overall and event-free survival, treatment toxicity.