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.
Highlights
Научно-исследовательский институт детской онкологии, гематологии и трансплантологии им
Комбинированная химио- и таргетная терапия обладает благоприятным профилем токсичности и эффективности, в том числе у пациентов, не ответивших на предыдущие линии терапии
The clinical effect was seen in 79% of patients
Summary
Интенсивная комплексная терапия пациентов с первично-резистентным течением и рецидивами. В исследование включены 78 пациентов с первично-резистентной формой (n = 33) или рецидивом (n = 45) НБ, получавших лечение в клинике НИИ ДОГиТ им. Девятнадцати пациентам с первично-резистентным течением (n = 4) или системным рецидивом заболевания (n = 15) в дальнейшем была выполнена аллогенная трансплантация гемопоэтических стволовых клеток от гаплоидентичного донора (гапло-ТГСК). В дальнейшем 16 из 19 пациентов получили терапию после гапло-ТГСК. Медиана бессобытийной выживаемости (БСВ) в группе терапии 2-й линии составила 2,5 (1–11) мес, а в группе RIST – 8 (1–76) мес. В группе реципиентов гапло-ТГСК медиана БСВ составила 15 мес, а 2-летние ОВ и БСВ – 44% и 21% соответственно. Комбинированная химио- и таргетная терапия (схема RIST) обладает благоприятным профилем токсичности и эффективности, в том числе у пациентов, не ответивших на предыдущие линии терапии.
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