Complications of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation in children with solid malignant neoplasms: a single-center experience

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Abstract

High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a therapeutic option that allows potentiating the antitumor effect in patients with malignant neoplasms (MNs) belonging to the high-risk group. However, despite the effectiveness of this method, the risks of developing infectious and toxic complications in the early and late post-transplantation period are higher than the risks associated with treatment according to standard protocols and can significantly worsen the results of transplantation. We carried out a retrospective analysis of the results of auto-HSCT in a cohort of 156 patients with high-risk solid MNs treated at the L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation in 2020–2023. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology. The study included 78 (50%) boys and 78 (50%) girls, the median age of the patients was 8 years 7 months (9 months – 17 years 8 months). Auto-HSCT was performed in 90 (57.7%) patients with neuroblastoma, 25 (16.0%) – with Ewing's sarcoma, 16 (10.3%) – with germ cell tumors, 13 (8.4%) – with nephroblastoma, 7 (4.5%) – with retinoblastoma, 3 (1.9%) – with medulloblastoma, 1 (0.6%) patient with pleuropulmonary blastoma and 1 (0.6%) patient with sialoblastoma. We used the following conditioning regimens: treosulfan + melphalan (n = 116), carboplatin + thiotepa + etoposide (n = 17), melphalan (n = 13), carboplatin + thiotepa + etoposide + cyclophosphamide (n = 10). Depending on the clinical indications and the treatment protocol used, 136 (87.2%) patients underwent one course of HDCT, and 20 (12.8%) patients underwent tandem HDCT. In most patients, the median recovery time for granulocytes and platelets was 11 (8–19) days and 14 (12–21) days, respectively. The most common infectious complications in patients after auto-HSCT were mucositis (89.1%), neutropenic enterocolitis (76.9%), febrile neutropenia (71.2%), less often: catheter-associated bloodstream infection (9%), pneumonia (14.1%), acute respiratory distress syndrome (0.6%). As regards toxic complications, all patients had emetic syndrome, 98 (62.8%) had dermatological toxicity, 9 (5.8%) had hemorrhagic cystitis, 116 (74.3%) had hepatic toxicity, 14 (9%) had neurotoxicity, 102 (65.4%) had moderate nutritional insufficiency. Episodes of hemorrhagic syndrome due to thrombocytopenia were observed in 44.2% of patients. After auto-HSCT, most patients develop chemotherapy-induced (including infectious) complications, which can not only significantly disrupt the patients’ well-being and quality of life, but also, depending on the severity, pose a threat to their life. The correct choice of conditioning regimen, effective collection of hematopoietic stem cells, complex accompanying therapy, timely diagnosis and treatment of complications can significantly improve the results of auto-HSCT in children with high-risk solid MNs.

About the authors

T. Z. Aliev

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0003-1091-1521

Teymur Z. Aliev, a pediatric oncologist at the Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation 

23 Kashirskoe Highway, Moscow 115522, Russia

Россия

K. I. Kirgizov

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-2945-284X

Moscow

Россия

E. B. Machneva

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0003-2395-4045

Moscow

Россия

I. O. Kostareva

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0003-0179-2479

Moscow

Россия

K. A. Sergeenko

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0003-3225-8412

Moscow

Россия

D. S. Smirnova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0009-0007-2171-1951

Moscow

Россия

N. A. Burlaka

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-3289-223X

Moscow

Россия

Yu. V. Lozovan

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0003-0600-8962

Moscow

Россия

I. Yu. Trushkova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0009-0000-5828-8041

Moscow

Россия

A. Yu. Elfimova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-8143-5791

Moscow

Россия

K. V. Mitrakov

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-2010-5534

Moscow

Россия

T. I. Potemkina

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0009-0007-0074-7197

Moscow

Россия

M. D. Malova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-9112-5973

Moscow

Россия

R. R. Fatkhullin

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-5988-8428

Moscow

Россия

N. G. Stepanyan

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-7939-5129

Moscow

Россия

D. A. Kapkova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com

Moscow

Россия

G. B. Sagoyan

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com

Moscow

Россия

A. M. Suleymanova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-5489-1879

Moscow

Россия

N. V. Matinyan

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-7805-5616

Moscow

Россия

G. M. Muftakhova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-8487-1879

Moscow

Россия

A. P. Kazantsev

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-7309-1650

Moscow

Россия

O. M. Romantsova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-2310-0106

Moscow

Россия

M. V. Rubanskaya

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-1016-539X

Moscow

Россия

T. L. Ushakova

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0003-3263-6655

Moscow

Россия

A. D. Rodina

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-8356-0625

Moscow

Россия

V. V. Zhogov

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0009-0005-8755-486X

Moscow

Россия

V. Sh. Vanesyan

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-0138-3379

Moscow

Россия

Yu. V. Skvortsova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-0566-053X

Moscow

Россия

I. V. Kazantsev

The R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation of the I.P. Pavlov First Saint Petersburg State Medical University of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-3818-6213

Saint Petersburg

Россия

A. S. Slinin

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-2021-0465

Moscow

Россия

T. V. Gorbunova

The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0001-5805-726X

Moscow

Россия

T. T. Valiev

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-1469-2365

Moscow

Россия

V. G. Polyakov

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Email: timaliev118@gmail.com
ORCID iD: 0000-0002-8096-0874

Moscow

Россия

S. R. Varfolomeeva

The L.A. Durnov Research Institute of Pediatric Oncology and Hematology, the N.N. Blokhin National Medical Research Center of Oncology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: timaliev118@gmail.com
ORCID iD: 0000-0001-6131-1783

Moscow

Россия

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