Experience with a Reduced Toxicity Allogeneic Transplant Regimen for Non-CGD Primary Immune Deficiencies Requiring Myeloablation.
Experience with a Reduced Toxicity Allogeneic Transplant Regimen for Non-CGD Primary Immune Deficiencies Requiring Myeloablation.
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DOI：
10.1007/s10875-020-00888-2
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发表时间：
2021-01
影响因子：
9.1
通讯作者：
Marsh RA
中科院分区：
文献类型：
--
作者：
Chandra S;Chandrakasan S;Dávila Saldaña BJ;Bleesing JJ;Jordan MB;Kumar AR;Grimley MS;Krupski C;Davies SM;Khandelwal P;Marsh RA
需要降低毒性的预处理方案，其在维持骨髓消融的同时提供较少的毒性，特别是对于需要骨髓消融或高供体骨髓嵌合以实现治愈的原发性免疫缺陷。我们采用了Gungor等人的白消安和氟达拉滨方案，用于因需要骨髓消融或高供体髓系嵌合体的非CGD原发性免疫缺陷而接受同种异体HCT的儿童和年轻人，并在此报告我们的经验。我们回顾性分析了41例连续患者的记录，这些患者接受了同种异体HCT治疗Wiskott-Aldrich综合征（n = 12），原发性HLH/XLP（n = 10），CD 40 L缺乏症（n = 7），或其他（n = 12）原发性免疫缺陷，采用含有药代动力学指导的白消安给药的预处理方案，累积AUC为57 - 74 mg/L × h（常规清髓性暴露的65-80%），沿着氟达拉滨和阿仑单抗或抗胸腺细胞球蛋白，在2014年至2019年期间在3家移植中心进行。41例患者接受了第一次（n = 33）或第二次（n = 8）同种异体HCT。中位年龄为2.3岁（范围：0.3 -19.8岁）。除1例患者（97.5%）外，所有患者均在中位14天（范围：11-34天）时实现中性粒细胞恢复。1例患者出现窦阻塞综合征，2例患者出现弥漫性肺泡出血。四名患者出现II-IV级急性GVHD。三名患者出现慢性GVHD。1年总生存率为90%（95%置信区间[CI] 81-99%），无事件生存率为83%（95% CI 71-94%）。我们的经验表明，降低毒性的白消安-氟达拉滨方案提供低毒性、2-4级GVHD的低发生率、持久的骨髓移植和优异的存活率，并且可以考虑用于需要清髓性HCT的各种原发性免疫缺陷。
A need exists for reduced toxicity conditioning regimens that offer less toxicity while maintaining myeloablation, especially for primary immune deficiencies where myeloablation or high donor myeloid chimerism is required to achieve cure. We adapted a busulfan and fludarabine regimen by Gungor et al. for children and young adults undergoing allogeneic HCT for non-CGD primary immune deficiencies requiring myeloablation or high donor myeloid chimerism, and herein report our experience. We retrospectively reviewed records of 41 consecutive patients who underwent allogeneic HCT for Wiskott-Aldrich syndrome (n = 12), primary HLH/XLP (n = 10), CD40L deficiency (n = 7), or other (n = 12) primary immune deficiencies with a conditioning regimen containing pharmacokinetic-guided busulfan dosing which achieved a cumulative AUC between 57 and 74 mg/L × h (65–80% of conventional myeloablative exposure), along with fludarabine and alemtuzumab or anti-thymocyte globulin at 3 transplant centers between 2014 and 2019. Forty-one patients underwent a first (n = 33) or second (n = 8) allogeneic HCT. Median age was 2.3 years (range, 0.3 years–19.8 years). All but one patient (97.5%) achieved neutrophil recovery at a median of 14 days (range, 11–34 days). One patient developed sinusoidal obstruction syndrome and two patients developed diffuse alveolar hemorrhage. Four patients developed grades II–IV acute GVHD. Three patients developed chronic GVHD. One-year overall survival was 90% (95% confidence interval [CI] 81–99%) and event-free survival was 83% (95% CI 71–94%). Our experience suggests that a reduced toxicity busulfan-fludarabine regimen offers low toxicity, low incidence of grades 2–4 GVHD, durable myeloid engraftment, and excellent survival, and may be considered for a variety of primary immune deficiencies where myeloablative HCT is desired.
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影响因子：
4.3
作者：
Bacigalupo, Andrea;Ballen, Karen;Rizzo, Doug;Giralt, Sergio;Lazarus, Hillard;Ho, Vincent;Apperley, Jane;Slavin, Shimon;Pasquini, Marcelo;Sandmaier, Brenda M.;Barrett, John;Blaise, Didier;Lowski, Robert;Horowitz, Mary
通讯作者：
Horowitz, Mary
DOI：
10.1016/j.bbmt.2015.04.009
发表时间：
2015-08
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Marsh RA;Rao MB;Gefen A;Bellman D;Mehta PA;Khandelwal P;Chandra S;Jodele S;Myers KC;Grimley M;Dandoy C;El-Bietar J;Kumar AR;Leemhuis T;Zhang K;Bleesing JJ;Jordan MB;Filipovich AH;Davies SM
通讯作者：
Davies SM
影响因子：
9.1
作者：
Marsh, Rebecca A.;Leiding, Jennifer W.;Kang, Elizabeth M.
通讯作者：
Kang, Elizabeth M.
DOI：
10.1016/j.bbmt.2015.02.025
发表时间：
2015-06
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Lee SJ;Wolff D;Kitko C;Koreth J;Inamoto Y;Jagasia M;Pidala J;Olivieri A;Martin PJ;Przepiorka D;Pusic I;Dignan F;Mitchell SA;Lawitschka A;Jacobsohn D;Hall AM;Flowers ME;Schultz KR;Vogelsang G;Pavletic S
通讯作者：
Pavletic S
影响因子：
6.2
作者：
GLUCKSBERG, H;STORB, R;THOMAS, ED
通讯作者：
THOMAS, ED