nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.17650/2311-1267-2016-3-1-23-34nodgo-186Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ/ОБЗОРЫ ЛИТЕРАТУРЫORIGINAL INVESTIGATIONS/LITERATURE REVIEWSТрансплантация гемопоэтических стволовых клеток у пациентов с анемией Фанкони: опыт РДКБ и ФНКЦ ДГОИ им. Дмитрия РогачеваHematopoietic stem cell transplantation in patients with Fanconi anemia: the experience of the Russian Children's Clinical Hospital and the Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and ImmunologyСкоробогатоваЕ. В.SkorobogatovaE. V.skorobog.e@mail.ruКиргизовК. И.KirgizovK. I.БалашовД. Н.BalashovD. N.ТрахтманП. Е.TrakhtmanP. E.СкворцоваЮ. В.SkvortsovaYu. V.ПристансковаЕ. А.PristanskovaE. A.НовичковаГ. А.NovichkovaG. A.МасчанМ. А.MaschanM. A.МасчанА. А.MaschanA. A.РумянцевА. Г.RumyantsevA. G.ФГБУ «Российская детская клиническая больница» Минздрава России; Россия, 117997, Москва, Ленинский просп., 117РоссияRussian Children's Clinical Hospital, Ministry of Health of Russia; 117 Leninskiy Prosp., Moscow, 117997, RussiaRussian FederationФГБУ «Российская детская клиническая больница» Минздрава России; Россия, 117997, Москва, Ленинский просп., 117 ФГБУ «Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России; Россия, 117997, Москва, ул. Саморы Машела, 1РоссияRussian Children's Clinical Hospital, Ministry of Health of Russia; 117 Leninskiy Prosp., Moscow, 117997, Russia Federal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia; 1 Samory Mashela St., Moscow, 117997, RussiaRussian FederationФГБУ «Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России; Россия, 117997, Москва, ул. Саморы Машела, 1РоссияFederal Research Center of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Ministry of Health of Russia; 1 Samory Mashela St., Moscow, 117997, RussiaRussian Federation201617042016312334Copyright © Скоробогатова Е.В., Киргизов К.И., Балашов Д.Н., Трахтман П.Е., Скворцова Ю.В., Пристанскова Е.А., Новичкова Г.А., Масчан М.А., Масчан А.А., Румянцев А.Г., 20162016Скоробогатова Е.В., Киргизов К.И., Балашов Д.Н., Трахтман П.Е., Скворцова Ю.В., Пристанскова Е.А., Новичкова Г.А., Масчан М.А., Масчан А.А., Румянцев А.Г.Skorobogatova E.V., Kirgizov K.I., Balashov D.N., Trakhtman P.E., Skvortsova Y.V., Pristanskova E.A., Novichkova G.A., Maschan M.A., Maschan A.A., Rumyantsev A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/186Введение

Введение. Анемия Фанкони (АФ) – редкий синдром, характеризующийся врожденными аномалиями, развитием аплазии кроветворения и повышенной частотой опухолей. Трансплантация гемопоэтических стволовых клеток (ТГСК) является единственным методом коррекции гемопоэтической недостаточности, однако стандартные мегадозные режимы кондиционирования у пациентов с АФ крайне токсичны.

Пациенты и методы

Пациенты и методы. За период с ноября 1994 по апрель 2014 г. трансплантации были выполнены 29 пациентам с АФ (18 девочек/11 мальчиков, медиана возраста – 9,5 года, разброс – 3,7–15,4 года). Показаниями для трансплантации были развитие трансфузионно-зависимой апластической анемии у 27 и трансформация в миелодиспластический синдром/острый миелоидный лейкоз у 2 пациентов. У 17 (58,6 %) больных были использованы HLA-совместимые семейные доноры, у 12 (41,4 %) – неродственные совместимые доноры. Источником трансплантата служил костный мозг (КМ) у 18, стволовые клетки периферической крови у 7, КМ + пуповинная кровь (ПК) у 3 и ПК у 1 пациента. Одна из родственных ТГСК была выполнена от донора, совместимого на 9/10, при неродственных трансплантациях совместимость 9/10 была у 2 доноров. Режим кондиционирования включал следующие препараты: бусульфан 4–8 мг/кг, циклофосфамид 20–40 мг/кг, флударабин 150 мг/м2 и антитимоцитарный глобулин. Профилактика реакции «трансплантат против хозяина» (РТПХ): циклоспорин А/такролимус, метотрексат 5 мг/м2 (дни +1, +3, +6, +11)/+/– микофенолата мофетил. У 3 реципиентов неродственных трансплантаций использовалась TCRα/β-деплеция трансплантата.

Результаты

Результаты. У всех пациентов было зафиксировано приживление трансплантата. Вторичное отторжение наблюдалось у 4 (13,8 %) пациентов – через 1, 2, 6 и 12 мес от ТГСК, при этом всем больным была выполнена повторная ТГСК c кондиционированием алемтузумабом, торакоабдоминальным облучением и флударабином. После 2-й ТГСК умерли 2 пациента – от РТПХ и аденовирусной пневмонии. У 18 больных острой РТПХ не было, острая РТПХ I–II степени развилась у 7 (24,1 %), III–IV степени – у 4 (13,7 %) пациентов. Ограниченная хроническая РТПХ развилась у 4 больных, экстенсивная – у 2. Медиана наблюдения составила 31,9 (3,8–246) мес. Общая 5-летняя выживаемость составила 67,4 %. У 2 пациентов развился плоскоклеточный рак полости рта. Всего умерло 11 больных – 10 от РТПХ и инфекций и 1 от плоскоклеточного рака языка.

Выводы

Выводы. ТГСК c аттенуированными высокоиммуносупрессивными режимами кондиционирования позволяет добиваться приживления трансплантата с минимальной висцеральной токсичностью у пациентов с АФ. Частота РТПХ и инфекционных осложнений остается высокой. Негемопоэтические опухоли являются причиной поздней смертности.

Background

Background. Fanconi anemia (FA) – rare syndrome characterized by congenital malformations, high risk of bone marrow failure andoncological diseases. Hematopoietic stem cell transplantation (HSCT) – is the only way of correction of hematopoietic insufficiency, but standard very intensive regimens of conditioning are highly toxic for patients with FA.

Patients and methods

Patients and methods. During the period from November 1994 to April 2014 transplantations were performed for 29 patients with FA (18 females/11 males, age median – 9.5 years, variation – 3.7–15.4). Indication for HSCT was the transfusion-dependent aplastic anemia at 27 patients and transformation to myelodysplastic syndrome/acute myeloid leukemia at 2 patients. At 17 (58.6 %) patients HLA-matched family donor were used, 12 (41.4 %) patients received unrelated graft. Source: bone marrow (BM) – 18 patients, peripheral blood stem cells – 7 patients, BM + umbilical cord blood (UCB) – 3 patients, UCB – 1 patient. One of the related HSCT was performed from 9/10 donor and 2 unrelated HSCT were from 9/10 donor too. Conditioning regimens: busulphan 4–8 mg/kg, cyclophosphamide – 20–40 mg/kg, fludarabine 150 mg/sq.m., anti-thymocyte globulin. “Graft versus host” disease (GvHD) prophylaxis: cyclosporine A/tacrolimus, methotrexate 5 mg/sq.m. (days +1, +3, +6, +11) /+/– mycophenolate mofetil. Three recipients of unrelated HSCT received TCRα/β grafts.

Results

Results. All patients engrafted. Secondary graft failure diagnosed at 4 (13.8 %) patients – after 1, 2, 6 and 12 months from HSCT. All these patients received second HSCT with conditioning with alemtuzumab, thoracoabdominal irradiation and fludarabine. Two patients died after the second HSCT, causes: GvHD and adenovirus pneumonia. Eighteen patients were free from GvHD, acute GvHD I–II gr. was revealed at 7 (24.1 %) patients, III–IV gr. – at 4 (13,7 %) patients. Limited chronic GvHD was observed at 4 patients, extensive – at 2 patients. Followup median is 31.9 (3.8–246) months. Overall 5 years survival was 67.4 %. Two patients suffered from oropharyngeal squamous cell cancer. Ten patients died in total – 10 from GvHD and one from the cancer.

Conclusion

Conclusion. HSCT with attenuated high immunosuppressive regimens of conditioning can obtain transplant engraftment with minimal visceral toxicity at patients with FA. Frequency of GvHD and infection complications remains high. Non-hematopoietic cancers are the cause of late mortality.

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The authors declare that there are no conflicts of interest present.