The complex intensive therapy regimen as curative therapy in patients with primary-resistant and relapsed neuroblastoma: R.M. Gorbacheva Memorial Institute for Children Oncology, Hematology and Transplantation experience

I. V. Kazantsev; Казанцев И. В.; A. G. Gevorgyan; Геворгян А. Г.; T. V. Yukhta; Юхта Т. В.; P. S. Tolkunova; Толкунова П. С.; D. A. Zvyagintseva; Звягинцева Д. А.; A. V. Kozlov; Козлов А. В.; M. S. Golenkova; Голенкова М. С.; E. V. Babenko; Бабенко Е. В.; P. S. Kuga; Куга П. С.; A. N. Shvetsov; Швецов А. Н.; I. Yu. Nikolaev; Николаев И. Ю.; E. V. Morozova; Морозова Е. В.; S. A. Safonova; Сафонова С. А.; Yu. A. Punanov; Пунанов Ю. А.; L. S. Zubarovskaya; Зубаровская Л. С.; B. V. Afanasyev; Афанасьев Б. В.

doi:10.24287/1726-1708-2020-19-2-129-140

The complex intensive therapy regimen as curative therapy in patients with primary-resistant and relapsed neuroblastoma: R.M. Gorbacheva Memorial Institute for Children Oncology, Hematology and Transplantation experience

Authors: Kazantsev I.V.¹, Gevorgyan A.G.¹, Yukhta T.V.¹, Tolkunova P.S.¹, Zvyagintseva D.A.¹, Kozlov A.V.¹, Golenkova M.S.¹, Babenko E.V.¹, Kuga P.S.¹, Shvetsov A.N.¹, Nikolaev I.Y.¹, Morozova E.V.¹, Safonova S.A.¹, Punanov Y.A.¹, Zubarovskaya L.S.¹, Afanasyev B.V.¹
Affiliations:
1. R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
Issue: Vol 19, No 2 (2020)
Pages: 129-140
Section: ORIGINAL ARTICLES
Submitted: 01.07.2020
Accepted: 01.07.2020
Published: 01.07.2020
URL: https://hemoncim.com/jour/article/view/347
DOI: https://doi.org/10.24287/1726-1708-2020-19-2-129-140
ID: 347

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Abstract

About 20% of initially high-risk patients with neuroblastoma (NB) develop primary resistant to chemotherapy and more than 50% of them subsequently have a relapse. There is currently no uniform approach to therapy in this group and long-term outcomes are dismal. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. A total of 78 patients with a median age of 5 (1–20) years with primary resistant (n = 33) or (n = 45) relapsed NB receiving treatment in R.M. Gorbacheva Memorial Center were included in this study. In 20 cases the 2nd-line therapy including topotecan (n = 10) or irinotecan (n = 10) was used, 58 patients received combined chemo- and targeted therapy (RIST regimen: rapamycin, irinotecan, sirolimus, temozolomide). Nineteen patients with primary resistant disease (n = 4) or systemic relapse (n = 15) subsequently underwent an allogeneic hemopoietic stem cell transplantation from haploidentical donor (haplo-HSCT). In all cases fludarabin-based reduced intensity conditioning (RIC) regimens were used. Ten patents received modified graft (immunomagnetic selection or depletion), in 9 unmodified graft with subsequent post-transplant cyclophosphamide (PTCM) was used. Also, 16 of 19 haplo-HSCT recipients had post-transplant therapy. The clinical effect was seen in 79% of patients. The median event-free survival (EFS) in 2nd-line therapy and RIST recipients was 2.5 (1–11) and 8 (1–76) months, accordingly. The complete of good partial response in 2nd-line therapy or RIST recipients was seen in 5% and 15%, 14% and 31% of cases accordingly. The therapy toxicity was comparable in both groups. The median EFS for haplo-HSCT recipients was 15 months with 2-year OS and EFS in this group bring 44% and 21% accordingly. Seven of 19 (37%) patients are currently alive and 4 (21%) of 19 maintain response. All long-term responders have history of posttransplant therapy. There was no statistically significant difference based on graft-versus-host disease prophylaxis used (graft modification or PTCM) or KIR compatibility. Combined chemo- and targeted therapy (RIST) is characterized by acceptable toxicity and effective even in some previously resistant cases. In 20% of responders a long-term effect may be achieved by subsequent haplo-HSCT and post-transplant therapy.

Keywords

neuroblastoma, resistance/relapse, chemotherapy, targeted therapy, haploidentical hematopoietic stem cell transplantation

About the authors

I. V. Kazantsev

R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation

Author for correspondence.
Email: Ilya_Kazantsev@inbox.ru
ORCID iD: 0000-0002-3818-6213

Pediatric Oncologist 2nd Pediatric Transplant Department, Chair,

Russia, 197022, St. Petersburg, Rentgen st., 12

Russian Federation

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