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Does Lymphocyte Count Impact Dosing of Anti-Thymocyte Globulin in Unrelated Donor Stem Cell Transplantation?
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2020-03-09 , DOI: 10.1016/j.bbmt.2020.02.026
Francine Heelan 1 , Ranjeeta Mallick 2 , Adam Bryant 3 , Osman Radhwi 3 , Harold Atkins 3 , Lothar Huebsch 3 , Chris Bredeson 3 , David Allan 3 , Natasha Kekre 3
Affiliation  

Anti­thymocyte globulin (ATG) is used to reduce the incidence and severity of graft-versus-host disease (GVHD) with hematopoietic cell transplantation, yet optimum dosing has yet to be determined. We have previously demonstrated that 2.5 mg/kg ATG in conditioning can reduce the incidence of GVHD in unrelated donor transplants. Recent literature has suggested that ATG dosing based on absolute lymphocyte count (ALC) could lead to more optimum exposure of the drug. We sought to determine if ALC at the time of transplant could impact clinical outcomes. We conducted a retrospective single-center study analyzing all consecutive patients at The Ottawa Hospital who received a matched unrelated donor stem cell transplant with ATG between 2009 and 2014. Patients received rabbit ATG (thymoglobulin) at 0.5 mg/kg on day –2 and 2.0 mg/kg on day –1. Univariate and multivariate analyses were used to determine if any patient- or transplant-related factors, including weight, ALC, and total ATG dose given, impacted GVHD, relapse, or mortality. In total, 111 patients met inclusion, with a median age of 50 years (range, 19 to 70). The most common diagnoses were acute myelogenous leukemia (43%), Myelodysplasia/myeloproliferative neoplasms (13%), and lymphoma (12%). The median weight at time of conditioning was 80.3 kg (range, 45 to 216). The median ALC on the first day of ATG administration was 0.1 × 109/L (range, 0 to 190). The median total dose of ATG received was 201 mg (range, 112 to 540 mg). The incidence of acute and chronic GVHD was 35.1% and 21.6%, respectively. In the multivariate model, the actual dose of ATG given to patients was not associated with GVHD (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.99 to 1.25; P = .07), relapse (HR, 1.13; 95% CI, 0.98 to 1.30; P = .1), or mortality (HR, 1.09; 95% CI, 0.92 to 1.28; P = .32). Similarly, the pretransplant ALC was not associated with GVHD (HR, 1; P = .82), relapse (HR, 1; P = .90), or mortality (HR, 1; P = .39). If patients had received ALC-based dosing according to previously published work (Admiraal et al., Lancet Haematol 2017), the mean total dose of ATG received would have been 1205 mg, more than 5 times the mean dose that was actually given based on weight. With GVHD outcomes being similar to that published by Admiraal et al. and ALC not independently associated with outcomes in our study, further studies are still needed to compare standard weight-based dosing to ALC-based dosing of ATG in matched unrelated donor stem cell transplant.



中文翻译:

无关的供体干细胞移植中淋巴细胞计数是否影响抗胸腺细胞球蛋白的剂量?

抗胸腺细胞球蛋白(ATG)用于降低造血细胞移植后移植物抗宿主病(GVHD)的发生率和严重程度,但最佳剂量尚待确定。先前我们已经证明,调节条件下2.5 mg / kg ATG可以减少无关的供体移植物中GVHD的发生。最近的文献表明,基于绝对淋巴细胞计数(ALC)的ATG剂量可能导致药物的最佳暴露。我们试图确定移植时的ALC是否会影响临床结果。我们进行了一项回顾性单中心研究,分析了2009年至2014年期间在渥太华医院接受匹配的无关供体干细胞移植的所有连续患者,他们在第2天和第2天接受了0.5 mg / kg兔ATG(胸腺球蛋白)第–1天的mg / kg。使用单变量和多变量分析来确定是否有任何患者或移植相关因素,包括体重,ALC和给定的总ATG剂量是否影响了GVHD,复发或死亡率。共有111例患者符合纳入标准,中位年龄为50岁(范围为19至70)。最常见的诊断是急性骨髓性白血病(43%),骨髓增生异常/骨髓增生性肿瘤(13%)和淋巴瘤(12%)。调理时的体重中位数为80.3千克(45至216)。ATG给药第一天的ALC中位数为0.1×10 最常见的诊断是急性骨髓性白血病(43%),骨髓增生异常/骨髓增生性肿瘤(13%)和淋巴瘤(12%)。调理时的体重中位数为80.3千克(45至216)。ATG给药第一天的ALC中位数为0.1×10 最常见的诊断是急性骨髓性白血病(43%),骨髓增生异常/骨髓增生性肿瘤(13%)和淋巴瘤(12%)。调理时的体重中位数为80.3千克(45至216)。ATG给药第一天的ALC中位数为0.1×109 / L(范围从0到190)。接受的ATG的中位总剂量为201毫克(112至540毫克)。急性和慢性GVHD的发生率分别为35.1%和21.6%。在多变量模型中,给予患者的ATG实际剂量与GVHD不相关(危险比[HR]为1.11; 95%置信区间[CI]为0.99至1.25;P  = .07),复发(HR为1.13) ; 95%CI,0.98至1.30;P  = 0.1),或死亡率(HR,1.09; 95%CI,0.92至1.28;P  = 0.32)。同样,移植前ALC与GVHD(HR,1; P  = .82),复发(HR,1; P  = .90)或死亡率(HR,1; P)不相关。 = 0.39)。如果根据先前发表的工作(Admiraal等人,Lancet Haematol 2017),患者接受了基于ALC的剂量,则接受的ATG的平均总剂量应为1205 mg,是实际基于ALC的平均剂量的5倍重量。GVHD结果与Admiraal等人发表的结果相似。并且ALC与我们的研究结果并不独立相关,在匹配的无关供体干细胞移植中,仍需要进一步研究以将基于体重的标准剂量与ATG的基于ALC的剂量进行比较。

更新日期:2020-03-09
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