Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study
Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study
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DOI：
10.3324/haematol.12948
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发表时间：
2008-10-01
期刊：
影响因子：
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通讯作者：
Gruel, Yves
中科院分区：
文献类型：
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作者：
Hunault-Berger, Mathilde;Chevallier, Patrice;Gruel, Yves
背景与儿童相比，L-天冬酰胺酶对成人诱导化疗期间止血的影响不太明确。因此，我们研究了 L-天冬酰胺酶对成人患者的作用。设计和方法这是对 214 名接受 L-天冬酰胺酶 (7500 IU/m(2)x 6) 治疗的急性淋巴细胞白血病或淋巴母细胞淋巴瘤患者的回顾性分析。在诱导过程的第 1 天和出院之间，对临床事件以及生物学和治疗修改进行了审查。结果 71% 和 73% 的患者的抗凝血酶和纤维蛋白原水平分别低于 60% 和 1 g/L。 9.3%的患者出现20次血栓；这些患者在事件发生时的中位抗凝血酶水平为 53%（范围为 21-111）。 31 名患者发生 42 次出血，中位纤维蛋白原水平为 1.3 g/L。由于纤维蛋白原和/或抗凝血酶水平较低，64% 的患者减少或延迟了 L-天冬酰胺酶的输注。分别有 31%、41% 和 52% 的患者输注了新鲜冰冻血浆、抗凝血酶和纤维蛋白原。输注抗凝血酶或纤维蛋白原后，平均抗凝血酶和纤维蛋白原水平分别从 61% 增加至 88%，从 1 g/L 增加至 1.4 g/L，而输注新鲜冰冻血浆后，这两个水平保持不变。在接受抗凝血酶浓缩物的患者中，L-天冬酰胺酶注射被省略或延迟的情况较少（53% vs. 72%，p=0.005），血栓形成率较低（4.8% vs. 12.2%，p=0.04），并且无病生存期也降低（p=0.05）。结论这项回顾性研究表明，抗凝血酶浓缩物可能对以下患者产生有益影响： 用 L-天冬酰胺酶治疗急性淋巴细胞白血病成人的结果；前瞻性研究对于证实这一假设至关重要。
BackgroundThe effects of L-asparaginase on hemostasis during induction chemotherapy are less defined in adults than in children. We, therefore, studied the effects of L-asparaginase in adult patients.Design and MethodsThis was a retrospective analysis of 214 patients treated with L-asparaginase (7500 IU/m(2)x 6) for acute lymphoblastic leukemia or lymphoblastic lymphoma. Between day 1 of the induction course and discharge, clinical events, and biological and therapeutic modifications were reviewed.ResultsAntithrombin and fibrinogen levels were lower than 60% and 1 g/L in 71% and 73% of patients, respectively. Twenty thromboses occurred in 9.3% of the patients; these patients had a median antithrombin level of 53% (range, 21-111) at the time of the event. Forty-two episodes of bleeding occurred in 31 patients with a median fibrinogen level of 1.3 g/L. Infusions of L-asparaginase were reduced or delayed in 64% of patients due to low fibrinogen and/or antithrombin levels. Fresh-frozen plasma, antithrombin and fibrinogen were infused in 31%, 41% and 52% of patients, respectively. The mean antithrombin and fibrinogen levels increased from 61% to 88% and from 1 to 1.4 g/L after infusion of antithrombin or fibrinogen respectively, while both levels remained unchanged after the infusion of fresh-frozen plasma. In patients who received antithrombin concentrates L-asparaginase injections were less frequently omitted or delayed (53% vs. 72%, p=0.005), the rate of thrombosis was lower (4.8% vs. 12.2%, p=0.04) and the disease-free survival was also reduced (p=0.05).ConclusionsThis retrospective study suggests that antithrombin concentrates may have a beneficial effect on the outcome of adults treated for acute lymphoblastic leukemia with L-asparaginase; prospective studies are essential to confirm this hypothesis.