门冬酰胺酶治疗成人和儿童急性淋巴细胞白血病时不良反应比较及处理

目的:研究以门冬酰胺酶(ASP)为主的联合化疗方案治疗儿童和成人急性淋巴细胞白血病(ALL)/淋巴母细胞淋巴瘤(LBL)时的不良反应及处理。方法:25例儿童和45例成人ALL/LBL共接受118疗程含ASP的联合化疗方案治疗。监测治疗前后的凝血指标、肝功能、血脂和血糖。临床或血液检查怀疑胰腺炎时行超声或CT检查。怀疑血栓形成时进行相应血管超声检查。结果:ASP相关的临床不良反应包括过敏反应、静脉血栓和急性胰腺炎,发生率分别为1.7%、1.7%和2.5%。这些并发症均导致治疗中断或原计划的治疗方案推迟2周-3周。另有因脑出血致死亡一例。实验室检查肝功能异常、低纤维蛋白原血症、高甘油三酯血症和高血糖的发生率分别为38.99%、41.5%、5.6%和6.1%。比较儿童和成人各种不良反应的发生率和严重程度均无明显差别。结论:ASP治疗过程中可产生多种不良反应,少数可致死,需密切监测,早期采取措施进行干预。     

门冬酰胺酶在急性淋巴细胞白血病治疗中的副作用及其对策

门冬酰胺酶(L-ASP)是治疗成人和儿童急性淋巴细胞白血病的有效药物,几乎包含在所有的ALL治疗方案中。尽管该药耗竭天冬氨酸的独特作用机理使其对肿瘤细胞具有相对物异性,但部分病人仍在治疗过程中出现各种副反应。L-ASP治疗的严重并发症主要有过敏反应、急性胰腺炎和血栓形成。为预防和早期诊断各种并发症,在L-ASP治疗过程中或治疗后需进行密切的临床和相关实验指标如抗凝血酶和血清淀粉酶观察。     

门冬酰胺酶诱导缓解治疗急性非淋巴细胞白血病16例

目的探讨门冬酰胺酶(Aase)对急非淋巴细胞白血病(ANLL)诱导缓解的影响.方法用Aase联合常规HA(三尖杉酯碱、阿糖胞苷)、DA(柔红霉素、阿糖胞苷)、维甲酸和砷剂等方案治疗了16例ANLL患者.结果16例中有14例CR,总CR率87.5%.结论①Aase对无论是初治、复发还是耐药ANLL都有着明显的疗效;②Aase对CNSL具有防治作用.     

门冬酰胺酶治疗血液肿瘤致高甘油三酯血症的临床研究

为了研究门冬酰胺酶(ASP)治疗血液肿瘤时致高甘油三酯血症(HTG)的发生率、临床特点和治疗,以引起临床对该副反应的重视,对24例儿童和成人急性淋巴细胞白血病(ALL)、淋巴母细胞淋巴瘤和NK/T细胞淋巴瘤患者接受了含ASP的联合化疗方案治疗,测定治疗前后的血胆固醇和甘油三酯(TG)水平,确定血脂异常的发生率和特点。24例患者共接受36个周期含ASP的联合方案化疗,2例次出现HTG,发生率为5.6%。2例均为成人ALL,均在初次缓解后4和5个月,再次使用ASP进行巩固治疗时出现HTG,峰值TG分别为32.57和15.77 mmol/L。1例同时伴有下肢剧烈疼痛。停用ASP并加用胰岛素静脉滴入治疗,9~11 d后血脂均恢复正常。初步研究结果提示,接受ASP治疗的血液肿瘤患者有发生HTG的危险,尽管此种HTG在停药多后多可恢复,但可继发胰腺炎、高黏滞综合征或血栓。因而ASP治疗时应常规监测血TG水平。     

急性淋巴细胞白血病患儿大剂量门冬酰胺酶治疗后脑脊液门冬酰胺浓度测定

目的:从临床及药代动力学方面,探讨ASP在CNS白血病的药理作用及最佳给药方式。方法:10例ALL患儿分别4次接受了德国小儿白血病协作组多中心协作治疗方案(COALL-97)中的主要药物ASP(每隔4周~ 6周1次静脉注射4×104 U/m2日本协和发酵工业株式会社生产的L-ASP)的联合化疗。检测静脉注射L-ASP前及给药后第1周,第3周,第4周,第5周CSF中的ASN浓度。结果:CSF中ASN浓度均值分别为:给药前1.894 μmol/L,给药后第1周0.056 μmol/L,第3周0.117 μmol/L,第4周0.212 μmol/L,第5周0.897 μmol/L;每例患儿应用L-ASP后CSF中ASN浓度明显降低(P <0.05),同时测定CSF中谷氨酰胺浓度在给药前及给药后均无显著变化。结论:1次注射4×104 U/m2 ASP后能使CSF中ASN浓度降低并持续至第5周后回升。有预防或治疗CNS白血病的作用。     

左旋门冬酰胺酶治疗儿童急性淋巴细胞白血病的不良反应及防治

 目的　探讨左旋门冬酰胺酶（L-ASP）治疗儿童急性淋巴细胞白血病（ALL）的不良反应及可行的防治方法。方法　对50例ALL患儿应用L-ASP治疗的171个疗程进行回顾分析。结果　171个疗程中有77个疗程中出现1 种或1 种以上不良反应： 过敏反应6例次（12 %）（维持期）、凝血功能障碍13例次（26 %）（诱导缓解期20 %,维持期6 %）、胰腺炎4例次（8 %）（诱导缓解期）、药物性肝炎23例次（46 %）（诱导缓解期16 %,维持期30 %）、胃肠反应40例次（80 %）（诱导缓解期60 %,维持期20 %）,高血糖症9例次（18 %）（诱导缓解期6 %,维持期12 %）,经及时正确防治无一例死亡。结论　积极预防可减少L-ASP 的不良反应,保证化疗顺利进行; 及时诊断和处理可减少严重并发症的发生,提高ALL患儿的无病生存率。     

左旋门冬酰胺酶治疗儿童急性淋巴细胞性白血病的胰腺毒副作用观察

目的：观察用左旋门冬酰胺酶(L-ASP)治疗儿童急性淋巴细胞性白血病时引起的胰腺毒副作用及转归。方法：用VDLP方案治疗128例，定期做血尿淀粉酶及血尿糖(尿酮)检测。结果：8例(6.03％)出现胰腺毒副作用，年龄9岁～13岁，均发生在诱导缓解治疗期，急性胰腺炎5例，继发糖尿病7例(3例伴酮症酸中毒)；4例上述两者并存。结论：L-ASP引起的胰腺毒副作用与患儿年龄及个体敏感差异有关，与药物累积剂量及性别无关。急性胰腺炎和继发糖尿病可分别发生，也可在同一个体中出现。     

儿童急性淋巴细胞白血病并发急性胰腺炎的临床特点分析

目的:分析儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)并发急性胰腺炎(acute pancreatitis,AP)患儿的临床特点。方法:收集2013年2月至2020年2月天津市儿童医院收治的ALL并发AP患儿11例,均采用中国儿童白血病协作组-急性淋巴细胞白血病-2008(CCLG-ALL 2008)方案联合化疗,总结患儿的危险度分层、主要临床表现、发生胰腺炎的所处治疗阶段、发病原因、培门冬酶(polyethylene glycol conjugated asparaginase,PEG-ASP)的累积用量,整理患儿的胰酶指标、影像学检查、血常规、肝肾功能、血脂血糖、凝血功能等化验结果,对比患儿治疗效果及转归,分析其临床特点。结果:全组11例患儿中,男性7例,女性4例,年龄范围1～14岁,中位年龄6岁;急性B淋巴细胞白血病(type B acute lymphoblastic leukemia,B-ALL)10例,急性T细胞型淋巴母细胞白血病(type T acute lymphoblastic leukemia,T-ALL)1例;初始联合...     

两种门冬酰胺酶治疗儿童急性淋巴细胞白血病的近期效果及对患儿血清LDH、SF和ESR的影响

目的 比较左旋门冬酰胺酶、培门冬酶治疗儿童急性淋巴细胞白血病的近期效果及对患儿血清乳酸脱氢酶(LDH)、铁蛋白(SF)和血沉(ESR)的影响.方法 将急性淋巴细胞白血病患儿86例随机均分为2组,对照组43例应用左旋门冬酰胺酶治疗,观察组43例应用培门冬酶治疗.比较2组的近期疗效,血常规,血清LDH、SF和ESR,住院时...     

儿童及少年急性淋巴细胞白血病的治疗策略

 阐述了儿童急性淋巴细胞白血病患者不同年龄组的特点、遗传学特点、早期治疗效应的评估、治疗耐药以及一些重要的治疗。     

L‐asparaginase treatment in acute lymphoblastic leukemia

Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG‐asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG‐asparaginase for first‐line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second‐ or third‐line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL. Cancer 2011. © 2010 American Cancer Society.     

l-Asparagine depletion levels and l-asparaginase activity in plasma of children with acute lymphoblastic leukemia under asparaginase treatment

Purpose To determine the minimum levels of l-asparaginase (ASNase) activity necessary to maintain l-asparagine (Asn) depletion under ASNase treatment in acute lymphoblastic leukemia (ALL).Methods We measured ASNase activity using an enzyme coupling method with a limit of detection of 2 U/l and examined the relationship between ASNase activity and Asn levels in blood samples from 14 children with ALL.Results In all but one patient showing high ASNase antibody titers, minimum ASNase activity to maintain Asn depletion levels below the limit of detection (40 ng/ml) ranged from 6 to 180 U/l with a median value of 16 U/l. In 11 patients, the enzyme activity corresponding to minimum detectable Asn levels ranged from 2 to 32 U/l with a median value of 6.5 U/l. Patients with an ASNase activity of 2 U/l or an undetectable activity (<2 U/l) had nearly normal Asn levels: 4140±1161 ng/ml at 2 U/l and 7235±3107 ng/ml at <2 U/l (mean±SD). Statistical analysis showed that ASNase activity in the range of 2–32 U/l was inversely correlated with Asn levels (r=–0.803, P=0.001).Conclusion These results show that Asn levels are strongly correlated with plasma ASNase activity even at low enzyme activities (<50 U/l) and that this sensitive ASNase assay can be used to estimate plasma Asn depletion levels.Abbreviations ALL Acute lymphoblastic leukemia - Asn Asparagine - ASNase Asparaginase - SSA Sulfosalicylic acid     

Improved treatment outcome in adult acute lymphoblastic leukemia using the intensive German protocol,a preliminary report

Thirty-nine consecutive patients with acute lymphoblastic leukemia were treated with an intensive chemotherapy protocol. There were 23 males and 16 females with a median age of 37 years (range: 15–65). Eighteen patients had common ALL, seven had pre-B ALL, three earlyprecursor B ALL, seven T-ALL and four had aberrant expression of myeloid antigens (c-ALL in three and pre-B ALL in one). The median initial leukocyte count was 11.8×10⁹/l (range: 0.65–295). Cytogenetic result of the marrow was available in 16 of 39 patients (41 per cent) and showed Philadelphia positivity in six, a normal result in six and one each of t(4,11), t(1,19), hyperdiploidy and del 12p. Hepatosplenomegaly was present in about 20 per cent of the patients. l-Asparaginase-related hepatic toxicity was the commonest toxicity (48.7 per cent) during phase I of induction. Prolonged pancytopenia and hypoplastic death were common during phase II. With the use of growth factors during the neutropenic period of phase II induction, the rate of hypoplastic death was reduced from 40 per cent to 3 per cent. Common causes of treatment failure included early hypoplastic death (27.8 per cent) and leukemia relapses (50 per cent) while primary refractory leukemia, hepatic failure and perforated peptic ulcer contributed to 11.1, 5.5 and 5.5 per cent of the other deaths. A high complete remission (CR) rate (87·4 per cent) was achieved after phase I induction. The median event-free survival (EFS) was 8 months and the 3-year event-free survival was 43 per cent. This result compared favourably to the other regimens previously employed in our institution. In conclusion, satisfactory survival can be achieved with this intensive regimen. Good supportive care was however, essential to minimize toxicities. © 1997 John Wiley & Sons, Ltd.     

New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia

Significant advances have been made in the last decade toward a better understanding of the disease pathogenesis and the development of novel therapies that target specific subsets of adult acute lymphoblastic leukemia (ALL). Risk‐adapted strategies are transforming the disease treatment and prognosis. With current treatment regimens, long‐term survival is achieved by approximately 50% of patients with B‐cell ALL, 50% to 60% of patients with Philadelphia chromosome–positive ALL, and approximately 80% of patients with Burkitt's leukemia. Genomic profiling in ALL has identified new prognostic markers, new therapeutic targets, and novel ALL subtypes. These may be amenable to future targeted therapies that can further improve outcomes. The early recognition of early precursor T‐cell ALL, a distinct pathobiological entity with a poor prognosis, is essential for the development of an effective clinical management strategy. The role of monoclonal antibodies and cytotoxic T‐cell therapies continues to be defined. Many of the approaches are currently being evaluated for ALL salvage. Their incorporation into frontline adult ALL therapy, in concomitant or sequential strategies, may increase the cure rates to levels achieved in pediatric ALL and may reduce the need for prolonged intensive and maintenance chemotherapy. Cancer 2015;121:2517–2528 . © 2015 American Cancer Society.     

成人急性淋巴细胞白血病的诊疗进展

急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL) 是一种常见的恶性血液疾病。虽然成人ALL患者在诱导缓解治疗后完全缓解率可达80%以上,但大多数患者最终出现复发,长期生存率低。本研究对近年来成人ALL诊疗的进展进行综述,为成人ALL患者的诊疗提供参考和依据,以进一步改善该类患者的生存质量。     

大剂量甲氨蝶呤治疗成人急性淋巴细胞白血病的临床观察

探讨使用大剂量甲氨蝶呤(HD -MTX)在成人急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)维持强化治疗过程中的疗效和毒副反应,采用甲氨蝶呤(MTX)1~3 g/m2,24 h持续静脉滴入,用来成人ALL的强化治疗,并用四氢叶酸钙(CF)解救。结果呈缓解状态86 .0%(49/57),骨髓复发7 0%(4/57),中枢神经系统白血病(CNS L)1 .8%(1/57),死亡5. 2%(3/57)。初步研究结果提示,HD- MTX治疗成人ALL疗效肯定,相对骨髓抑制较轻,黏膜皮肤损害较突出,毒副反应可以耐受。     

Obesity and hypertension among children after treatment for acute lymphoblastic leukemia

BACKGROUND: The purpose was to determine the prevalence and treatment-related risk factors for obesity and hypertension among childhood acute lymphoblastic leukemia (ALL) survivors treated with contemporary therapy. METHODS: In a single-center longitudinal study, serial body mass indices (BMI) and blood pressure (BP) measurements of children ages 2-20 at time of ALL diagnosis and enrolled on pediatric cooperative group trials from 1993-2003 were abstracted from medical records and converted to population-referenced z-scores. RESULTS: Among 165 study participants, BMI z-scores increased significantly between diagnosis (median age 4.8 years) and therapy completion. At the end of therapy, 17.0% of survivors were overweight (BMI of 25-29, or 85-94% for age), 21.2% were obese (BMI >or=30, or >or=95% for age), and 15.3% had BP meeting stage 1+ hypertension thresholds (systolic or diastolic BP >or=140/90 mm Hg, or 95% for age and height plus 5 mm Hg). These proportions were found to be unchanged 2-3 years later. In multivariate analysis, the highest level of corticosteroid exposure was associated with both obesity (odds ratio [OR] 6.0; 95% confidence interval [95% CI], 1.2-28.5) as well as stage 1+ hypertension (OR 2.4; 95% CI, 1.2-5.1) compared with the lowest level. Females also were more likely to have increased BMI and elevated BP compared with males. Treatment intensity and cranial radiotherapy were not found to be associated with BMI or BP changes. CONCLUSIONS: Despite reductions in the use of cranial radiotherapy, contemporary childhood survivors of ALL remain at an increased risk of obesity and hypertension at least several years after the completion of treatment, with those exposed to higher doses of corticosteroids at greater risk.