两种不同剂型门冬酰胺酶治疗急性淋巴细胞白血病的不良反应比较及其对策

Comparisons of Side-Effects and Countermeasures for Two Different Preparations of Asparaginase in Treatment of Acute Lymphoblastic Leukemia

目的比较门冬酰胺酶(L-ASP)和培门冬酶(PEG-ASP)治疗儿童ALL过程中的不良反应,以便及时有效地监测与防范,提高化疗安全。方法回顾性观察诱导缓解和早期巩固治疗期,随机接受ASP或PEG-ASP治疗的135例ALL患儿的临床表现及实验室检查,采用χ2检验及t检验进行分析。结果 ASP、PEG-ASP对ALL患儿的骨髓增殖均有抑制作用,白细胞、中性粒细胞、Hb、血小板及骨髓抑制恢复时间诱导缓解治疗期:ASP组分别为(18.00±5.91)d、(19.70±6.00)d、(21.74±6.97)d、(18.51±8.66)d、(24.04±6.02)d;PEG-ASP组分别为(26.80±6.23)d、(26.40±6.06)d、(30.40±7.31)d、(17.50±8.30)d、(30.30±5.52)d。早期巩固治疗期:ASP组分别为(15.55±3.32)d、(16.68±6.00)d、(2.84±6.58)d、(6.73±8.89)d、(16.61±5.02)d;PEG-ASP组分别为(23.13±13.65)d、(23.78±10.95)d、(11.82±12.61)d、(2.82±7.30)d、(28.12±6.47)d。纤维蛋白原、活化部分凝血活酶时间、抗凝血酶Ⅲ恢复时间,诱导缓解治疗期:ASP组分别为(14.57±7.13)d、(12.15±7.91)d、(12.38±8.15)d。PEG-ASP组分别为(29.70±5.36)d、(24.60±11.37)d、(29.30±8.41)d。早期巩固治疗期:ASP组分别为(11.24±2.90)d、(11.64±2.01)d、(7.13±3.71)d;PEG-ASP组分别为(29.46±7.25)d、(19.05±9.26)d、(30.26±8.56)d。变态反应、总蛋白降低、清蛋白降低发生率,诱导缓解治疗期:ASP组分别为3.77%、56.60%、22.64%;PEG-ASP组分别为0.00%、100.00%、60.00%;早期巩固治疗期:ASP组分别为21.21%、57.58%、30.30%;PEG-ASP组分别为2.56%、84.61%、64.10%。结论 ASP、PEG-ASP均对ALL患儿的骨髓增殖具有抑制作用,其抑制的程度临床相似;PEG-ASP治疗时,骨髓抑制、血常规、血凝恢复正常时间长,蛋白质抑制作用强,变态反应发生率低,余不良反应发生率与ASP相似。

Objective To compare side -effects of 2 different preparations of asparaginase （ASP） and polyethylene glycol conjugated asparaginase（ PEG - ASP） in treatment of childhood acute lymphoblastie leukemia（ALL）, in order to detect and avoid them in time so as to improve the chemotherapy＇s safety. Methods One hundred and thirty - five cases of ALL adopted in Qingdao University Medical College Affiliated Hospital from Apr. 2009 to Jul. 2011 were retrospectively analyzed. Two different preparations of asparaginase were randomly given to ALL children during the remission induction and early consolidation therapy phases, and the clinical manifestations and relevant laboratory re- ports were observed and analyzed byx2 test and t - test. Results Both of the ASP and PEG - ASP could inhibit the bone marrow proliferation and the degree of depressant effect was of no statistical significance. The recovery time of leukocyte, granulocyte, hemoglobin, platelet and bone marrow proliferation inhibition during remission induction phases in ASP group were （ 18.00 ±5.91 ） d, （ 19.70 ±6.00） d, （21.74 ± 6.97） d,（18.51±8.66） d,（24.04±6.02） d,respectively;In PEG-ASP group they were （26.80±6.23） d,（26.40±6.06） d, （30.40 ± 7.31 ） d, （ 17.50 ± 8.30） d, （30.30 ± 5.52） d, respectively. During early consolidation therapy phases in ASP group they were （15.55±3.32） d, （16.68_＋6.00） d, （2.84_＋6.58） d, （6.73 ±8.89） d, （16.61 _＋5.02） d,respeetively; In PEG-ASP group they were （23.13 ± 13.65 ） d, （23.78 ± 10.95 ） d, （ 11.82 ＋ 12.61 ） d, （2.82 ± 7.30） d, （28.12 ＋ 6.47 ） d, respectively. Fibrinogen, activated partial thromboplastin time and antithrombin HI recovery time, remission induction phases： ASP group were （14.57 ± 7.13） d, （12.15 ± 7.91 ） d, （ 12.38 ± 8.15 ） d,respeetively;PEG - ASP group were （29.70 ± 5.36） d, （24.60 ± 11. 37） d, （29.30 ± 8.41 ） d,respectively. Early consolidation therapy phases ： ASP group were （ 1 1.24 ＋ 2.90） d, （ 11.64 ± 2.01 ） d, （ 7.13 ± 3.71 ） d, respectively ; PEG - ASP group were （29.46 ± 7.25 ） d, （ 19.05 ± 9.26 ） d, （30.26 ＋ 8.56） d, respectively ; they were statistically signific.ant, which indicated that PEG - ASP had a longer inhibition in blood clotting routine. The allergy incidence, the low total protein and hypoalbuminemia, during remission induction phases in ASP group were 3.77% ,56.6% ,22.64% ,respectively, while in PEG - ASP group they were 0.00% , 100. 00% , 60.00% , respectively ;durign early consolidation therapy phases in ASP group were 21.21% , 57.58% , 30.30% , respectively,while in PEG - ASP group they were 2.56% , 84.61% , 64.10% respectively. Conclusions Both of the ASP and PEG - ASP can inhibit the bone marrow proliferation and the degree of depressant effect is of no statistical significance ; The protein synthesis inhibition is bigger in PEG - ASP group thau in ASP group, the recovery time of blood routtine, blood clotting routine and bone marrow proliferation inhibition in PEG - ASP group is longer than those in ASP group, which indicates that PEG - ASP can play a longer role in vivo than ASP; the allergy incidence of ASP is higher than that of PEG - ASP, the other side - effects about 2 different preparations of asparaginase are similar.