Abu-Ghosh A, Goldman S, Slone V, van de Ven C, Suen Y, Murphy L, Sender L, Cairo M
Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Bone Marrow Transplant. 1999 Sep;24(5):535-44. doi: 10.1038/sj.bmt.1701921.
We investigated early immunological reconstitution and the production of circulating inflammatory mediators and their relationship to aGVHD in children during the first 100 days following unrelated UCBT. Nine patients had an underlying malignant disease (ALL, ANLL), and two, non-malignant diseases (SAA, ALD). The median age was 10 years (range: 1.25-21). Seven of 11 patients were alive by day 100, two died from regimen-related toxicity, and two died from severe aGVHD (grade >/=III). Myeloid engraftment (ANC >/=500/mm3 x 2 days) occurred at a median of 24 days (range: 14-55), while platelet engraftment (platelet count >/=20 000/mm3 untransfused x 7 days) was delayed and occurred at a median of 52 days (range: 33-95). The mean cell dose of CD34+ cells was 3.3 +/- 3.51 x 10(5)/kg, and of CD34+/CD41+ cells was 3.94 +/- 3.99 x 10(4)/kg. Acute GVHD (grade II-IV) developed in seven patients (77%), and severe aGVHD (grade III-IV) developed in five patients (55%). Serum levels of IL-2Ralpha, IL-2, IL-4, IL-7, IL-12, and IFNgamma were not significantly different between patients with grades 0-I aGVHD and patients with grades II-IV aGVHD. Evaluation of immunological reconstitution on day 90 post UCBT demonstrated an early recovery of the absolute numbers of B cells (CD19+) and NK cells (CD3-/CD56+). Immunoglobulin levels for IgG, IgM and IgA remained normal throughout the study period. PMN functional studies demonstrated normal superoxide generation, bacterial killing (BK), and chemotaxis (CTX). However, both helper (CD3+/CD4+) and suppressor (CD3+/CD8+) T cell subsets remained low during the first 100 days post UCBT with mean +/- s.e.m. values of 120 +/- 29/mm3 and 10 +/- 50/mm3, respectively (normal = 900-2860/mm3 (CD3/CD4), normal = 630-1910/mm3 (CD3/CD8)). Mitogen response studies showed low blastogenesis to PHA and PWM, with a mean c.p.m. +/- s.e.m. value of 1.7 +/- 0.67 x 10(4) for PHA (NL >/= 75 x 10(3)) and 8.42 +/- 4.1 x 10(3) for PWM (NL >/=25 x 10(3)). In conclusion, serum levels of inflammatory mediators were not predictive nor did they correlate with the severity of aGVHD. Recovery of NK cells, B cells, and PMN functions occurred within the first 90 days post transplant. However, T cell subsets, CD3+/CD4+ and CD3+/CD8+, and T cell functional activity remained significantly decreased and may account for the high incidence of infectious morbidity seen during this immediate post UCBT period.
我们研究了无关脐血移植后100天内儿童的早期免疫重建、循环炎症介质的产生及其与急性移植物抗宿主病（aGVHD）的关系。9例患者患有潜在恶性疾病（急性淋巴细胞白血病、急性非淋巴细胞白血病），2例患有非恶性疾病（重型再生障碍性贫血、肾上腺脑白质营养不良）。中位年龄为10岁（范围：1.25 - 21岁）。11例患者中有7例在第100天时存活，2例死于与治疗方案相关的毒性反应，2例死于严重aGVHD（≥III级）。髓系造血重建（中性粒细胞绝对值≥500/mm³×2天）中位时间为24天（范围：14 - 55天），而血小板造血重建（血小板计数≥20000/mm³且未输血×7天）延迟，中位时间为52天（范围：33 - 95天）。CD34⁺细胞的平均细胞剂量为3.3±3.51×10⁵/kg，CD34⁺/CD41⁺细胞的平均细胞剂量为3.94±3.99×10⁴/kg。7例患者（77%）发生了急性移植物抗宿主病（II - IV级），5例患者（55%）发生了严重aGVHD（III - IV级）。0 - I级aGVHD患者与II - IV级aGVHD患者血清中IL - 2Rα、IL - 2、IL - 4、IL - 7、IL - 12和IFNγ水平无显著差异。脐血移植后第90天的免疫重建评估显示B细胞（CD19⁺）和自然杀伤细胞（CD3⁻/CD56⁺）的绝对数量早期恢复。在整个研究期间，IgG、IgM和IgA的免疫球蛋白水平保持正常。多形核白细胞功能研究显示超氧化物生成、细菌杀伤（BK）和趋化性（CTX）正常。然而，在脐血移植后的前100天内，辅助性（CD3⁺/CD4⁺）和抑制性（CD3⁺/CD8⁺）T细胞亚群数量仍然较低，平均±标准误分别为120±29/mm³和10±50/mm³（正常范围：900 - 2860/mm³（CD3/CD4），正常范围：630 - 1910/mm³（CD3/CD8））。丝裂原反应研究显示对PHA和PWM的增殖反应较低，PHA的平均每分钟脉冲数±标准误为1.7±0.67×10⁴（正常≥75×10³），PWM的平均每分钟脉冲数±标准误为8.42±4.1×10³（正常≥25×10³）。总之，炎症介质的血清水平不能预测aGVHD的严重程度，也与之无相关性。自然杀伤细胞、B细胞和多形核白细胞功能在移植后90天内恢复。然而，T细胞亚群CD3⁺/CD4⁺和CD3⁺/CD8⁺以及T细胞功能活性仍然显著降低，这可能是脐血移植后早期感染发病率高的原因。
Zotero 插件