Sequential treatment for allogeneic hematopoietic stem cell transplantation in Fanconi anemia with acute myeloid leukemia
Sequential treatment for allogeneic hematopoietic stem cell transplantation in Fanconi anemia with acute myeloid leukemia
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异基因造血干细胞移植序贯治疗范可尼贫血合并急性髓系白血病
DOI：
10.3324/haematol.2013.098954
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发表时间：
2014
期刊：
影响因子：
10.1
通讯作者：
G. Socié
中科院分区：
文献类型：
--
作者：
A. Talbot;R. D. de Latour;E. Raffoux;N. Buchbinder;S. Vigouroux;N. Milpied;T. Leblanc;J. Soulier;M. Michallet;G. Socié
范可尼贫血是一种罕见的异质性遗传性疾病。FA的自然史的特征是骨髓衰竭和克隆进化的风险。急性髓细胞白血病的演变是过早死亡的主要原因。异基因造血干细胞移植（HSCT）被认为是这种情况下的治疗选择，但HSCT后的进展通常很差（由于治疗相关的死亡率）。从2006年8月至2011年12月，6例连续FA患者在4个不同的法国机构接受化疗和降低强度的克隆进化预处理序贯治疗进行了审查。5例患者表现为AML，1例表现为骨髓增生异常综合征。序贯策略包括移植前化疗，氟达拉滨30 mg/m2/d 5天，阿糖胞苷1 gr/m2x2/d 5天，粒细胞集落刺激因子注射液（FLAG），随后早期进行低强度预处理[4天环磷酰胺10 mg/kg，4天氟达拉滨30 mg/m2，2天抗胸腺细胞球蛋白（3.75 mg/kg）和TBI（2戈伊）]。3例患者的干细胞来源为脐带血（2例为HLA 5/6，1例为4/6），其他患者的干细胞来源为无关供体的骨髓（1例为HLA 9/10，2例为10/10）。移植物抗宿主病预防包括环孢霉素+霉酚酸酯。HSCT患者的中位年龄为20.5岁（5 - 28岁）。移植前化疗和预处理方案耐受良好。化疗和HSCT日期之间的中位时间为30天（当中性粒细胞计数达到低于500/μ L的值时）。所有患者均植入。中性粒细胞植入的中位时间为26天（14、21、25、27、31、35），血小板植入的中位时间为29天（21、25、29、35、42）。5例患者在第100天完成供体嵌合体。分别在HSCT后1个月、3个月和4个月，3名患者（葡萄球菌、肠杆菌和念珠菌）出现败血症。1例患者在HSCT后1个月发生空肠弯曲菌腹泻，另1例患者接受了尿道口切开术。2例患者发生急性GvHD（1例皮肤I级和1例胃肠道II级）。两人都对类固醇治疗有反应。2例患者发生慢性GvHD（累及皮肤）。在中位随访（FU）30个月（5 - 72）后，所有患者仍然存活，克隆演变完全缓解。中位随访时间为30个月，所有患者均存活，且无原发AML或MDS。患者数量很少，但在这种特殊情况下，HSCT后通常进展非常差。因此，我们认为这项研究支持在患有AML或MDS的FA患者中使用序贯策略（FLAG和RIC HSCT）。
Fanconi anemia is a rare and heterogeneous inherited disorder. The natural history of FA is characterized by marrow failure and a risk for clonal evolution. Evolution to acute myeloid leukemia is the main cause of premature mortality. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered the treatment of choice in this situation but the evolution is usually poor post-HSCT (due to treatment-related mortality). From August 2006 to December 2011, 6 consecutive patients with FA who received a sequential treatment with chemotherapy and reduced-intensity conditioning for clonal evolution in four different French institutions were reviewed. Five patients presented an AML and one a myelodysplastic syndrome. The sequential strategy consisted of a pre-transplant chemotherapy by fludarabine 30 mg/m2/d 5 days and cytarabine 1gr/m2x2/d 5 days with granulocyte-colony stimulating factor injections (FLAG) followed early after by a reduced-intensity conditioning [4 days cyclophosphamide 10 mg/kg , 4 days fludarabine 30 mg/m2, 2 days anti-thymocyte globulin (3.75 mg/kg) and TBI (2 Gy)]. The source of stem cells was cord blood for three patients (HLA 5/6 for 2 and 4/6 for one) and bone marrow of unrelated donors for others (HLA 9/1O for one and 10/10 for two). Graft versus host disease prophylaxis consisted in cyclosporine plus MMF. Median age of the patients at HSCT was 20.5 years (5-28). Pre-transplant chemotherapy and conditioning regimen were well tolerated. The median time between chemotherapy and the date of HSCT was 30 days (when neutrophil count reached values below 500/microL). All patients engrafted. Median time to engraftment was 26 days (14,21,25,27,31,35) for neutrophils and 29 days for platelets(21,25,29,29,35,42). Donor chimerism was complete at day 100 for 5 patients. Septicemias were encountered in three patients (Staphylococcus, Enterobacter, and Candida) at 1, 3 and 4 months after HSCT, respectively. One patient developed a diarrhea to Campylobacter jejuni one month after HSCT and another patient underwent meatotomy. Acute GvHD (1 grade I of the skin and 1 grade II in the gastrointestinal tract ) occurred in 2 patients . Both responded to steroid therapy. Chronic GvHD occurred in two patients (involve the skin). After a median follow-up (FU) of 30 months (5-72), all patients are still alive in complete remission from the clonal evolution. With a median FU of 30 months, all patients are alive and free from their original AML or MDS. The number of patients is little but the usual evolution is very poor post-HSCT in this particular situation. We thus believe this study supports the use of a sequential strategy (FLAG and RIC HSCT) in FA patients with AML or MDS.
DOI：
10.1016/j.bbmt.2014.12.001
发表时间：
2015-03
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Jagasia MH;Greinix HT;Arora M;Williams KM;Wolff D;Cowen EW;Palmer J;Weisdorf D;Treister NS;Cheng GS;Kerr H;Stratton P;Duarte RF;McDonald GB;Inamoto Y;Vigorito A;Arai S;Datiles MB;Jacobsohn D;Heller T;Kitko CL;Mitchell SA;Martin PJ;Shulman H;Wu RS;Cutler CS;Vogelsang GB;Lee SJ;Pavletic SZ;Flowers ME
通讯作者：
Flowers ME