Dufour C, Rondelli R, Locatelli F, Miano M, Di Girolamo G, Bacigalupo A, Messina C, Porta F, Balduzzi A, Iorio A P, Buket E, Madon E, Pession A, Dini G, Di Bartolomeo P
Department of Paediatric Haematology-Oncology and BMT Unit, IRCCS G. Gaslini, Largo G. Gaslini 5, 16148 Genoa, Italy.
Br J Haematol. 2001 Mar;112(3):796-805. doi: 10.1046/j.1365-2141.2001.02572.x.
Twenty-seven consecutive Italian patients with Fanconi's anaemia (FA) underwent stem cell transplantation (SCT) from an HLA-matched related donor in 10 Italian centres of the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP), Gruppo Italiano di Trapianto di Midollo Osseo (GITMO). Twenty-two patients (81.5%) were conditioned with low-dose (median 20 mg/kg) cyclophosphamide (Cy) and thoraco-abdominal or total body irradiation (median dose 500 cGy), five patients (18.5%) with high-dose Cy (median 120 mg/kg). Graft-vs.-host disease (GVHD) prophylaxis was carried out with cyclosporin A in 26 cases; methotrexate (MTX) was added in eight cases. One patient received MTX alone. The median follow-up was 36 months. Ninety-two percent of patients (25 out of 27) engrafted, grade II and III acute GVHD occurred in 28% and 8% of patients, respectively, with chronic GVHD in 12.5%. Conditioning-related toxicity was mild: 4% of patients had grade III mucositis, 7.4% had grade II haemorrhagic cystitis, 14.8% had grade III liver toxicity and 11.1% had grade III renal toxicity. Transplant-related mortality at 12 months was 19.2%, survival at 36 months was 81.5%, with a median Karnofsky score of 100%. No late tumours occurred after a mean follow-up of the survivors of 5 years. None of the studied variables significantly affected the survival, including conditioning regimen, acute GVHD and clinical non-haematological phenotype. Among the studied variables, only conditioning regimens containing high-dose Cy and the presence of genital abnormalities were significantly (P < 0.05) associated with an increased rate of acute GVHD. Our study demonstrates that the Italian FA patients undergoing SCT from an HLA-matched related donor have a very good outcome. These patients, when compared with others of different ethnic origin who underwent allogeneic bone marrow transplantation, showed a less severe non-haematological phenotype, raising the possibility that this milder phenotype may have, at least in part, contributed to the outcome. Our data may provide a useful tool for further studies aiming to correlate genotype with phenotype.
27例连续性意大利范可尼贫血（FA）患者在意大利儿科血液学和肿瘤学协会（AIEOP）、意大利骨髓移植组（GITMO）的10个意大利中心接受了来自人类白细胞抗原（HLA）匹配的相关供者的干细胞移植（SCT）。22例患者（81.5%）采用低剂量（中位剂量20 mg/kg）环磷酰胺（Cy）及胸腹部或全身照射（中位剂量500 cGy）进行预处理，5例患者（18.5%）采用高剂量Cy（中位剂量120 mg/kg）进行预处理。26例患者采用环孢素A预防移植物抗宿主病（GVHD）；8例患者加用甲氨蝶呤（MTX）。1例患者单独接受MTX治疗。中位随访时间为36个月。92%的患者（27例中的25例）植入成功，II级和III级急性GVHD分别发生在28%和8%的患者中，慢性GVHD发生率为12.5%。预处理相关毒性较轻：4%的患者发生III级黏膜炎，7.4%的患者发生II级出血性膀胱炎，14.8%的患者发生III级肝毒性，11.1%的患者发生III级肾毒性。12个月时移植相关死亡率为19.2%，36个月时生存率为81.5%，中位卡诺夫斯基评分100%。幸存者平均随访5年后未发生晚期肿瘤。包括预处理方案、急性GVHD和临床非血液学表型在内的所有研究变量均未显著影响生存率。在研究变量中，只有含高剂量Cy的预处理方案及存在生殖器异常与急性GVHD发生率增加显著相关（P<0.05）。我们的研究表明，接受来自HLA匹配相关供者SCT的意大利FA患者预后非常好。与接受异基因骨髓移植的其他不同种族患者相比，这些患者的非血液学表型较轻，这增加了这种较轻表型可能至少部分促成该预后的可能性。我们的数据可能为进一步研究基因型与表型的相关性提供有用工具。
