PO-02. High-dose chemotherapy and autologous hemopoietic stem cell transplantation effectiveness in patients with relapsed medulloblastoma: RM Gorbacheva Research Institute experience
Asmik G. Gevorgian, Ilya V. Kazantsev, Denis V. Kozlov, Polina S. Tolkunova, Tatiana V. Iukhta, Andrew V. Kozlov, Margarita S. Golenkova, Alexander N. Galimov, Olga I. Bogdanova, Alexander D. Kulagin, Yuri A. Punanov, Olga G. Zheludkova, Ludmila S. Zubarovskaya
RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
Polina S. Tolkunova, phone: +7 (963) 348-05-24, e-mail: firstname.lastname@example.org
Although central nervous system (CNS) tumors are a second most common malignancy in children, they are a leading cause of cancer-related death in pediatric population. Medulloblastoma (MB) is the most common pediatric CNS tumor and although current treatment standards allow achieving remission in most patients, there are still disease variants characterized by high relapse rate. In spite of general trends to increased survival, the prognosis in patients with MB relapse is still dismal. High-dose chemotherapy (HDCT) with subsequent autologous hemopoietic stem cell transplantation (auto-HSCT) may be an option able to improve results in this group. This is a summary of R. M. Gorbacheva Institute experience in performing HDCT with auto-HSCT within a prospective cohort of patients with relapsed MB.
Patients and methods
Over 2008-2021, a total of 62 patients (45 М/17 F) with relapsed MB received HDCT followed by auto-HSCT. The median age at diagnosis was 9 (2.5-34) years, and at the moment of auto-HSCT, 12 (4-38) years. The molecular variant evaluated in 18 patients was WNT in 1, SHH in 7, Gr. III in 1, and Gr. IV in 9 patients, accordingly. Only 11 patients were evaluated for MYCN amplification, 2 of these cases were positive. Prior to auto-HSCT all patients received chemotherapy achieving complete response (CR) in 21, partial (PR) in 34, and disease stabilization (S) in 7 cases. Most (n=59) patients received Carbo-Eto-Thio HDCT regimen, in 3 cases Thio-Tmz regimen was used. Afterwards, 7 patients with no signs of disease progression proceeded to radiation therapy.
Transplant engraftment was registered in 55/62 cases. The median time to engraftment was 13 (8-37) days. Seven patients died not reaching engraftment due to transplant-related complications. With a median follow-up of 27 (0.1-157) months after auto-HSCT, the 2-year event-free survival (EFS) is 49.6% (95% CI 36.5%-61.3%) and overall survival (OS) is 70.2% (95% CI 56.9%-80.1%), accordingly. Patients with CR and PR prior to auto-HSCT have better results compared to patients with S, which is valid for both overall (80% and 70.5% vs 35.7%, accordingly; p=0.04) and event-free (61.1% and 49.8% vs 14.3%, accordingly; p=0.006). Also, better results were registered in patients with classic and anaplastic MB compared to desmoplastic/nodular variant for overall (79.4% and 80% vs 27.8%, accordingly; p=0.001) and event-free (57.6% and 60% vs 0%, accordingly; p=0.003) survival. No statistically significant difference was found between different molecular subtypes of MB or MYCN amplified/non-amplified cases. Conditioning regimens had relatively high toxicity with Grade 4 (CTCAE V 5.0) complications developing in 19.4% cases. Cumulative transplant-related mortality was 11.3% (95% CI 1.0%-35.4%).
In spite of relatively high rate of toxic complication HDCT with auto-HSCT is still a curative option for a significant number of patients achieving at least partial response to prior chemotherapy. It is much less effective as salvage option. The small number of patients, in which molecular factors were evaluated, does not yet let us estimate the influence of these factors. For that a larger prospective cohort is required.
Medulloblastoma, relapse, high-dose chemotherapy, auto-HSCT.