Сравнительная оценка влияния треосульфан- и бусульфан-содержащих миелоаблативных режимов кондиционирования на поздние осложнения аллогенных ТГСК при злокачественных заболеваниях у детей

Статья в Elpub

Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2018; 17: 28-38

Сравнительная оценка влияния треосульфан- и бусульфан-содержащих миелоаблативных режимов кондиционирования на поздние осложнения аллогенных ТГСК при злокачественных заболеваниях у детей

Скворцова Ю. В., Новичкова Г.А. , Масчан М.А. , Балашов Д.Н. , Папуша Л.И. , Шипицына И.П. , Шелихова Л.Н. , Воронин К.А. , Скоробогатова Е.В. , Масчан А.А.

https://doi.org/10.24287/1726-1708-2018-17-2-28-38

Аннотация

Треосульфансодержащие миелоаблативные режимы кондиционирования позволяют снизить трансплантат-ассоциированную летальность и раннюю токсичность аллогенной трансплантации гемопоэтических стволовых клеток (ТГСК), однако поздние осложнения таких режимов неизвестны. Мы провели сравнительный ретроспективный анализ отдаленных эффектов бусульфан- и треосульфансодержащих режимов кондиционирования у 135 детей, получивших аллогенную ТГСК по поводу злокачественных гематологических заболеваний в период с января 1994 по июль 2011 года и проживших после этого минимум год. Бессобытийная выживаемость к 5 годам после ТГСК составила 75,6% в группе с бусульфаном и 66,5% - в группе с треосульфаном в кондиционировании; 5-летние показатели летальности, не связанной с рецидивами, - 6 и 10,2% соответственно. Анализ отдаленных эффектов выявил, что треосульфан-содержащие миелоаблативные режимы кондиционирования позволяют снизить риск развития ряда поздних осложнений: кумулятивный риск гипергонадотропного гипогонадизма равен 0, а в группе пациентов, получивших бусульфан, - 32,8% (р = 0,012). Отмечена тенденция к уменьшению риска развития вторичного гипотиреоза и вторичной кардиомиопатии, снижается частота возникновения органической патологии центральной нервной системы. Таким образом, использование треосульфана в миелоаблативных режимах кондиционирования при аллогенной ТГСК у детей со злокачественными заболеваниями позволяет снизить частоту и изменить структуру поздних осложнений по сравнению с последствиями применения бусульфана и тем самым улучшить отдаленные результаты аллогенной ТГСК.

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Pediatric Hematology/Oncology and Immunopathology. 2018; 17: 28-38

Late effects after treosulfan- and busulfan-based myeloablative conditioning for allogeneic HSCT in children with malignant diseases: a comparative study

Skvortsova Y. V., Novichkova G. A., Maschan M. A., Balashov D. N., Papusha L. I., Shipitsina I. P., Shelikhova L. N., Voronin K. A., Skorobogatova E. V., Maschan A. A.

https://doi.org/10.24287/1726-1708-2018-17-2-28-38

Abstract

Treosulfan-based regimens used in conditioning for allogeneic HSCT (allo-HSCT) in children allow to reduce incidence of transplant-related mortality and early toxicity, but there are no data about long-term effects. We propose a retrospective comparative study of late complications after allo-HSCT in 135 children with hematologic malignancies, who got allo-HSCT between January 1994 and July 2011 and survived at least 1 year after HSCT. Five-year event free survival was 75.6% in the group of children who got busulfan and 66.5% in patients with treosulfan-based conditioning; 5-year nonrelapse mortality was 6% and 10.2%, respectively. Late effects analysis demonstrated that treosulfan-containing conditioning allowed to reduce the incidence of some late complications: hypergonadotropic hypogonadism cumulative incidence was 0 compared to 32.8% in busulfan-conditioning group (р = 0.012); the decrease in subclinical hypothyroidism, secondary cardiomyopathy and organic central nervous system pathology incidence was revealed. Thus treosulfan-based conditioning regimen is an effective approach in reducing of serious late complications after allogeneic HSCT when compared with data of busulfan-based conditioning long-term effects.

References

1. Miano M., Faraci M., Dini G., Bordigoni P. EBMT Paediatric Working Party. Early complications following haematopoietic SCT in children. Bone Marrow Transplant 2008; 41 Suppl 2: S39-42.

3. Ortega J.J., Olivé T., de Heredia C.D., Llort A. Secondary malignancies and quality of life after stem cell transplantation. Bone Marrow Trans-plant 2005; 35 Suppl 1: S83-7.

5. Giralt S. Reduced-intensity conditioning regimens for hematologic malignancies: what have we learned over the last 10 years? Hematology Am Soc Hematol Educ Program 2005: 384-9.

7. Casper J., Knauf W., Blau I., Ruutu T., Volin L., Wandt H., et al. Treosulfan/fludarabine: a new conditioning regimen in allogeneic transplantation. Ann Hematol 2004; 83 Suppl 1: S70-1.

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11. Fichtner I., Becker M., Baumgart J. Antileukaemic activity of treosulfan in xenografted human acute lymphoblastic leukaemias (ALL). Eur J Cancer 2003; 39 (6): 801-7.

13. Lanvers-Kaminsky C., Bremer A., Dirk-sen U., Jürgens H., Boos J. Cytotoxicity of treosulfan and busulfan on pediatric tumor cell lines. Anticancer Drugs 2006; 17 (6): 657-62.

Аннотация

Late effects after treosulfan- and busulfan-based myeloablative conditioning for allogeneic HSCT in children with malignant diseases: a comparative study

Abstract

События