Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas.
Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas.
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DOI：
10.1016/j.bbmt.2011.08.020
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发表时间：
2012-05
影响因子：
4.3
通讯作者：
Mackall, Crystal L.
中科院分区：
文献类型：
--
作者：
Baird, Kristin;Fry, Terry J.;Steinberg, Seth M.;Bishop, Michael R.;Fowler, Daniel H.;Delbrook, Cynthia P.;Humphrey, Jennifer L.;Rager, Alison;Richards, Kelly;Wayne, Alan S.;Mackall, Crystal L.
关键词：
一些儿童肉瘤患者的生存率很低。我们试图确定异基因造血干细胞移植（alloHSCT）在预测总生存率<25%的儿童肉瘤人群中的可行性和有效性。患有超高风险尤文氏肉瘤家族肿瘤（ESFT）、腺泡状横纹肌肉瘤或促结缔组织增生性小圆细胞肿瘤的患者接受EPOCH-氟达拉滨诱导、环磷酰胺/氟达拉滨/美法仑制备方案和HLA匹配的相关外周血干细胞。入组了30例患者; 7例患者因诱导期间疾病进展伴体能状态下降而未接受alloHSCT。所有23例alloHSCT受者均经历了快速的完全供体植入，无围移植期死亡。23例alloHSCT受者中有5例（22%）仍然存活（Kaplan-Meier分析3年时的总生存率为30%），包括7例无明显疾病移植的受者中的3例（42%）（有明显疾病移植的患者从alloHSCT开始的中位生存期分别为14.5个月和29.0个月）。在28名在研究中进展的患者中，7名未接受移植的患者从进展之日起的中位生存期为1.9个月，而21名移植患者为11.4个月（p=0.0003）。我们发现移植后进展的存活时间延长，有几个患者表现出惰性肿瘤生长。我们还观察到几例移植后化疗的抗肿瘤作用增强的患者（移植前EPOCH-F的客观缓解率为24%，移植后EOCH的客观缓解率为67%），但这与毒性增加相关。这一最大规模的alloHSCT治疗肉瘤的报告系列表明，alloHSCT在这一人群中是安全的，并且接受alloHSCT而无明显疾病的患者的生存率高于使用标准疗法的报告。移植后观察到肿瘤和正常组织的化疗和放射敏感性增强。
Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic HSCT (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival. Patients with ultra-high risk Ewing’s sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma or desmoplastic small round cell tumor received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT due to progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full donor engraftment, with no peri-transplant mortality. Five of 23 alloHSCT recipients (22%) remain alive (overall survival of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 vs. 29.0 months from alloHSCT for patients transplanted with vs. without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared to 11.4 months for the 21 transplanted (p=0.0003). We found prolonged survival after post-transplant progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced anti-tumor effects from post-transplant chemotherapy (objective response to pre-transplant EPOCH-F was 24% vs. 67% to post-transplant EOCH), however this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radio-sensitivity of tumors and normal tissues was observed post-transplant.
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DOI：
10.1158/1078-0432.ccr-10-1368
发表时间：
2010-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ahn YO;Weigel B;Verneris MR
通讯作者：
Verneris MR
影响因子：
45.3
作者：
BURDACH, S;JURGENS, H;GOBEL, U
通讯作者：
GOBEL, U
影响因子：
45.3
作者：
HOROWITZ, ME;KINSELLA, TJ;MISER, JS
通讯作者：
MISER, JS
影响因子：
45.3
作者：
Cotterill, SJ;Ahrens, S;Craft, AW
通讯作者：
Craft, AW
影响因子：
45.3
作者：
Boulad, F;Kernan, NA;Ghavimi, F
通讯作者：
Ghavimi, F