Bone Marrow Transplantation for Fanconi Anemia Using Fludarabine-Based Conditioning

Abstract

In the mid-1990s, we introduced a fludarabine (Flu)-based conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with Fanconi anemia (FA).The aim of this study is to compare Flu-based conditioning to alternative regimens in patients with FA. Forty-one patients with FA (aged 0.5-31, median, 10.3 years) who underwent allogeneic HSCT were included in this retrospective study. Hospital records were reviewed for conditioning regimens, engraftment data, and toxicity. The median (range) follow-up was 32 (0.5-149) months. Flu-based conditioning regimens were used in 24 patients: 17 patients were treated with alternative conditioning regimens including a radiation-based regimen/cyclophosphamide and busulfan regimen. The disease-free survival (DFS) after Flu-based regimens is 83% (20/24) versus 35% (6/17) for the alternative regimens (P = .002). Toxicity was significantly lower in patients who received Flu-based conditioning (modified Bearman toxicity score [P = .001]). Seven patients received transplants from matched unrelated donors without irradiation (5 of whom are currently alive and well). All patients who survived are disease free and in good clinical condition. We conclude that a combination of fludarabine with antithymocyte globulin (ATG) and low-dose cyclophosphamide (Cy) and/or busulfan (Bu) is safe, demonstrates low rejection rates, and is well tolerated by FA patients.

Hematopoietic 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 Immunology

“…В настоящее время для пациентов с АФ удалось раз-работать наименее токсичные, но при этом эффективные режимы кондиционирования с включением флудараби-на [20,21,27,29], которые показали эффективность и в нашей когорте пациентов. Применение подобных современных режимов и адекватной профилактики РТПХ способствовали улучшению исходов ТГСК.…”

“…Было показано, что комбинация флударабина и циклофосфамида дает схожие по эффективности результаты в сравнении с применением ТАО [28,29]. В настоящее время в ряде исследований показатели длительной (до 8 лет) ОВ превышают 90 % [27].…”

Allojenik Hematopoietik Kök Hücre Transplantasyonunda Hazırlık Rejimleri

“…FAA hazırlık rejimlerinin çoğu Siklofosfamid (5-10 mg/kg/gün, 4 gün) içermektedir. Günümüzde FAA'nde sekonder malignite gelişme riski nedeniyle TBI (400-450 cGy) içeren hazırlık rejimlerinden uzaklaşılmış; Siklofosfamid'e ATG ve düşük doz Busulfan veya Fludarabin eklenmesiyle başarılı sonuçlar elde edilmiştir [15][16] .…”

“…Allojenik HKHT; otolog HKHT yapılmasına rağmen hastalık relapsı veya progresyonu olması durumunda tercih edilebilir. Toksisiteyi azaltmak için Flu/Mel, Flu/Bu, Flu/TBI gibi düşük yoğunluklu hazırlık rejimleri (RIC) kullanılarak yapılan allojenik HKHT ile başarılı sonuçlar bildirilmektedir [12][13][14][15][16][17] .…”

HLA-matched related-donor HSCT in Fanconi anemia patients conditioned with cyclophosphamide and fludarabine

“…To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning through non-irradiation-based regimens. [4][5][6][7][8][9] A reduced conditioning regimen based on CY (60 mg/kg) alone was proposed by Bomfim et al 10 Survival rates were excellent, but some patients experienced primary (n 5 1) or late (n 5 4) graft failure (11% of the patients). Moreover, mucositis was a major problem, in that 25 patients (60%) presented grade 3/4 mucositis.…”