Comparision of the apoptotic effects on lymphoblasts and on increase of myeloid lineage cells of a short-time, high-dose methylprednisolone and the conventional-dose prednisolone treatments in children with acute lymphoblastic leukemia

The authors compare the apoptotic effect on the lymphoblasts and the proliferative effect on the myeloid lineage cells of a short-course high-dose methylprednisolone (HDMP) and the conventional-dose prednisolone treatments in children with acute lymphoblastic leukemia (ALL). The patients were divided into 2 groups. Group I (n = 10) received HDMP (30 mg/kg/day for 7 days) in a single dose before 6 a.m. perorally. Group II (n = 10) received prednisolone (2 mg/kg/day for 7 days) in 3 doses. The apoptotic percentages of lymphpblasts and the percentages of blasts and myeloid lineage cells were determined after performing the bone marrow aspiration (BMA) at diagnosis on the 0th, 3rd, and 7th days of the treatments in all patients. The mean apoptotic percentages of the lymphoblasts on the 3rd day were significantly higher than those on the 0th and 7th days in both groups (p < .05). The highest apoptosis was determined on the 3rd day in group I. The mean percentages of the blast cells on the 7th day were significantly lower than those on the 0th and the 3rd days in both groups (p < .05). The lowest lymphoblast percentage was determined on the 7th day in group I. The mean percentages of the CD13+ and CD33+ cells on the 7th day were significantly higher than those on the 0th and the 3rd days in both groups (p < .05). The highest percentages of the CD13+ and CD33+ cells were found on the 7th day in group I. Prednisolone and HDMP showed no proliferative effect on the CD14+ cells. These findings indicate that a short-course HDMP treatment shows a more effective apoptosis on the lymphoblasts and on the increase of the myeloid lineage cells when compared to the prednisolone treatment. The authors suggest that HDMP may be used in the treatment of patients with ALL instead of prednisolone.     

The rapid correction of hypercalcemia at presentation of acute lymphoblastic leukemia using high-dose methylprednisolone

Hypercalcemia is a well-recognized complication of neoplastic disorders. Herein, we report a hypercalcemic pediatric acute lymphoblastic leukemia case at presentation refractory to hydration, furosemide, pamidronate and calcitonin. Normal serum calcium levels were achieved with the initiation of chemotherapy protocol including vincristine, daunomycin and high-dose methylprednisolone. The impact of high-dose methylprednisolone in the correction of severe hypercalcemia in steroid-responsive tumors as an initial treatment approach or for cases refractory to other measures may be life-saving.     

The effect of short-course high-dose methylprednisolone on peripheral blood CD34+ progenitor cells of children with acute leukemia during remission induction therapy

This study was undertaken to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on peripheral blood (PB) CD34+ progenitor cells during remission induction treatment in 11 children with newly diagnosed acute leukemia (7 with ALL, 4 with AML) whose bone marrow (BM) cells expressed fewer than 5% CD34 at the time of diagnosis. All children who had no infection were given HDMP as a single daily oral dose of 30 mg/kg for the first four days of induction therapy. The number of CD34+ progenitor cells were determined by flow cytometry before and after four days of HDMP treatment. While the number of PB blast cells significantly decreased after only a four-day course of HDMP treatment, the number of PB CD34+ progenitor cells increased in all patients. In addition, after four days of HDMP treatment polymorphonuclear leukocytes (PMN) and mononuclear cells (MNC) increased significantly (p < 0.05). We suggest that the potential beneficial effects of HDMP in the induction treatment of acute leukemia may occur partly by the stimulation of PB CD34+ hematopoietic progenitor cells in a short period of time.     

Acute lymphoblastic leukemia in patients with Down syndrome with a previous history of acute myeloid leukemia

Patients with Down syndrome (DS) are predisposed to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in early and later childhood, respectively, but rarely experience both. We herein discuss four patients with DS with ALL and a history of AML who were treated with various chemotherapies, one of whom later received a bone marrow transplantation. Three patients survived and remain in remission. One patient died of fulminant hepatitis during therapy. No common cytogenetic abnormalities in AML and ALL besides constitutional +21 were identified, indicating that the two leukemia types were independent events. However, the underlying pathomechanism of these conditions awaits clarification.     

儿童急性淋巴细胞白血病髓系抗原表达的研究

急性淋巴细胞白血病(acute lyInphoblastic leukemia,ALL)是儿童最常见的急性白血病,大多数ALL病人的白血病细胞仅表达淋巴细胞抗原,但也有部分同时表达髓系抗原。在我国已有成人ALL髓系抗原表达的报道,儿童ALL同时表达髓系抗原的重要性一直有争议。我们总结了我科收治的36例儿童ALL髓系抗原的表达,并分析了它们     

大剂量MTX治疗小儿急性淋巴细胞白血病毒副反应分析

目的分析大剂量甲氨蝶呤(MTX)治疗小儿急性淋巴细胞白血病(ALL)的毒副反应及其影响因素。方法回顾性分析2016年1月-2018年1月包头市第四医院儿科100例ALL患儿的临床资料,所有患儿均给予大剂量MTX治疗,分析患儿毒副反应发生情况及其影响因素。结果 100例ALL患儿中共接受328例次大剂量MTX治疗,262例次发生毒副反应,检出率为79. 9%,其中胃肠道反应占20. 7(68/328)、骨髓抑制占20.1%(66/328)、肝功能异常占12. 5%(41/328)、排泄延迟占6.1%(20/328),肾功能异常占11. 6%(38/328)、皮肤黏膜损伤占8.8%(29/328)。毒副反应发生组与未发生组患儿的24h、48h、72h的MTX血药浓度(C24、C48、C72)及24h、48h的尿pH值(pH24、pH48)比较,差异有显著性(P <0. 05);但二组性别、年龄、体质量、体表面积、MTX剂量比较,差异无显著性(P> 0.05)。Logistic回归分析显示,高C24、C48、C72和低pH24、pH48可能是ALL大剂量MTX治疗后毒副反应发生的危险因素(P<0.05)。结论 C24、C48、C72和pH24、pH48与ALL患儿经大剂量MTX治疗后发生毒副反应可能相关,对C24、C48、C72升高和pH24、pH48降低的患儿应提高警惕。     

儿童Pre-B急性淋巴细胞白血病和急性髓系白血病特异遗传亚型

目的总结儿童急性白血病(AL)特异遗传亚型的发生率和特征,为评估预后提供依据。方法对365例AL患儿进行骨髓染色体核型检测分析白血病细胞的遗传学特点,荧光原位杂交(FISH)检测特异基因及相应位点拷贝数变异。结果 175例前体B急性淋巴细胞白血病(Pre-B ALL)和54例急性髓系白血病(AML)存在特异亚型。在Pre-B ALL中,高超二倍体最常见(33%),t(12;21)/ETV6-RUNX1、t(4;11)/MLL重排、t(9;22)、t(1;19)和iAMP21占比分别为22%、5%、3%、7%和1%。在AML中,MLL重排最常见(18%),其中t(9;11)型占56%;BCR/ABL阳性1例,FISH证实是隐匿核型ins(22;9);t(8;21)、t(15;17)和inv(16)分别占12%、15%和8%。倍体水平显示ALL高超二倍体和AML超二倍体获得染色体方式为非随机性。值得注意的是特异亚型中的变异型和不同附加异常,如额外融合,del(9p),del(12p),dup(1q)和非整倍体等畸变。结论儿童Pre-B ALL和AML中特异遗传亚型的发生率与西方儿童相似,揭示遗传异质性可能有助于预后研究。     

The role of short course of high-dose methylprednisolone in children with acute myeloblastic leukemia (FAB M2) presented with myeloid tumor

The authors have previously demonstrated a favorable effect of high-dose methylprednisolone (HDMP), which can induce differentiation and apoptosis of leukemic cells in children with acute myeloblastic leukemia (AML). Here, they evaluate the effect of short-course HDMP in 2 children with acute myeloblastic leukemia (AML-M2) presented with myeloid tumor (MT). Methylprednisolone (20 or 30 mg/kg/day) was given orally, in a single dose, without using other antileukemic agents. Rapid cytoreduction in MT, peripheral blood, and bone marrow blasts was observed in both children following short-course (4 or 7 days) HDMP treatment, possibly due to HDMP-induced differentiation and apoptosis of leukemic cells. The effects of HDMP should be explored in patients with other subtypes of AML who present with MT.     

Hemostatic side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia

The purpose of this study is to investigate the hemostatic side effects of HDMTX. Between 2001 and 2002, 20 children with acute lymphoblastic leukemia at the Dr. Sami Ulus Children's Hospital, Department of Pediatric Hematology and Oncology, treated according to the St. Jude ALL XIII protocol were eligible to this study. Methotrexate at a dose of 2 g/m² was infused over 24 hours. Coagulation screening studies included prothrombin time (PT), APTT, fibrinogen, fibrin degradation product (D-Dimer), factor II, factor V, factor VII, factor VIII, factor IX, factor X, PC, PS, AT-III determinations before HDMTX therapy (PreT), 1 day after (PostT^1D), and 1 week after (PostT^1W) the end of the HDMTX infusion. We found that PT and APTT were prolonged, PC, PS, and AT-III levels were decreased with a slight increase in D-Dimer 1 day after the administration of HDMTX and all of them returned to the normal levels by 7 days. In addition we found that FVII, FIX, FX were significantly decreased 1 day after therapy and normalised by 7 days.     

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目的分析髓系抗原阳性儿童急性淋巴细胞白血病(ALL)的临床特点及预后关系。方法根据国际白血病欧洲协作组(EGIL)标准将1999—2004年上海交通大学医学院附属上海儿童医学中心收治的33例髓系抗原阳性表达的ALL(My+ALL)分为双表型、双系列型给予正规治疗。对其预后进行观察。结果(1)My+ALL患儿,双表型26例(78.8%,26/33),其中B系ALL伴髓系表达17例(65.4%,17/26),T系ALL伴髓系表达6例(23.1%,6/26),T系B系伴髓系表达3例(11.5%,3/26)。双系列ALL患儿7例(21.2%,7/33)。(2)26例双表型ALL患儿治疗35d,缓解率80.7%。7例双系列型ALL仅1例达缓解(14.3%)。(3)生存状态双表型26例中20例处于缓解状态(76.9%),双系列型7例中仅1例(14.3%)。(4)复发情况双表型6例复发(23.1%,6/26),双系列7例中6例复发(85.7%)。结论髓系抗原阳性表达在儿童ALL时不能作为预后不良的因素,但双系列白血病患儿预后差,复发率高,长期生存机会少。     

急性淋巴细胞白血病患儿大剂量静脉滴注门冬酰胺酶治疗后脑脊液门冬酰胺浓度

目的　测定急性淋巴细胞白血病 (ALL)患儿大剂量静注门冬酰胺酶 (ASP)治疗前、后脑脊液 (CSF)中门冬酰胺 (ASN)浓度 ,从临床及药代动力学方面 ,探讨ASP在中枢神经系统 (CNS)白血病治疗中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～ 6周 1次静脉注射 4 0 0 0 0U/m2 )的联合化疗。在静脉注射L ASP前及给药后第1、3、4、5周采集CSF ,用安捷伦高效流相色谱仪检测CSF中ASN浓度 ,并观察临床疗效。结果　CSF中ASN浓度分别为 :给药前 1.894± 0 .5 8μmol/L ;给药后第 1周 0 .0 5 6± 0 .0 13μmol/L ;第 3周 0 .117± 0 .0 0 0 0 8μmol/L ;第 4周 0 .2 12± 0 .0 13μmol/L ;第 5周 0 .897± 0 .0 89μmol/L。ALL患儿应用L ASP后CSF中ASN浓度明显降低 (P <0 .0 5 ) ,同时测定CSF中谷氨酰胺浓度在给药前后均无显著变化。结论　 1次注射 4 0 0 0 0U/m2 ASP后能使CSF中ASN浓度降低并持续至第 5周后回升。这种用药方法有预防或治疗CNS白血病的作用     

Fatigue in survivors of childhood acute lymphoblastic and myeloid leukemia in Japan

Background: Fatigue in cancer survivors is a serious problem in pediatric oncology, but reports on this issue are limited, especially in Asian countries. Methods: Sixty‐three patients with acute lymphoblastic leukemia and 18 patients with acute myeloid leukemia who attended a follow‐up outpatient clinic were enrolled. Participants were required to be >8 years of age, in remission, and without any cancer treatment for at least the previous 1 year. A control group consisted of 243 subjects whose age and gender were matched with the patient group. A questionnaire consisting of 12 items was devised for fatigue measurement. Results: Principal factor analysis identified three dimensions, defined as physical fatigue, decreased function, and altered mood. The mean total and the three fatigue dimension scores tended to be higher in the control group, but significant differences between the scores were seen only in the total and physical fatigue scores. Multiple regression analysis indicated an association of present older age or shorter duration after completion of treatment with total and physical fatigue, and an association of presence of total body irradiation with decreased function. Conclusion: Pediatric leukemia survivors in Japan experience equal or less fatigue compared with that of controls in different fatigue dimensions. Elucidation of underlying mechanisms of cancer‐related fatigue including the differences of cultural background among different countries is necessary for future study of this issue.     

儿童急性B系淋巴细胞性白血病有效抗原组合及其临床应用探讨

目的 探讨使用流式细胞术(FCM)检测儿童急性B系淋巴细胞性白血病(B-lineageacute lymphoblastic leukemia,B-ALL)各有效抗原组合的发生频率及其与临床预后顺素相关性.方法 对289例初发B-ALL患儿的骨髓标本进行每组4个抗原,共9个抗原组合检测,统计各有效抗原组合的发生频率并与国外报告进行比较,分析各抗原组合在临床预后因素分组中的分布差异.结果 (1)327例初发B-ALL患儿中,289例存在至少1组可用于微小残留病(minimal residual disease,MRD)检测的有效抗原组合,其覆盖率为88.4%.(2)不同有效抗原组合的发生频率不同,以TdT组频率最高,为70.59%.(3)部分有效抗原组合与临床表型以及治疗反应相关,CD58组和TdT组与良好预后因素相关,而CD66c组和CD38组与不良预后因素相关.结论 B-ALL不同有效抗原组合的发生频率不同,在中国患儿中的表达与国外报道有差异.TdT组有高表达频率,可作为简化的MRD检测目标组合.发生频率较高的4个抗原组合可以为无初发时MRD记录的患儿的疗效评估和治疗强度调整提供一定的参考依据.部分有效抗原组合对临床预后产生影响,可能为B-ALL的个体化治疗提供参考依据.     

High proportion of leukemic stem cells at diagnosis is correlated with unfavorable prognosis in childhood acute myeloid leukemia

In acute myeloid leukemia (AML), the leukemia-initiating cell is found within the CD34(+)/CD38(-) cell compartment. Over the last years evidence grew that AML is initiated and propagated by leukemic stem cells (LSCs). Conceivably, these most immature leukemia cells are more resistant to therapy and subsequently initiate relapse. The authors studied 17 patients with childhood AML treated according to the AML-BFM 98/04 protocol. At diagnosis, the authors determined the characteristic immunophenotype of the leukemic cells by flow cytometry and investigated the expression of CD34, CD38, and CD45 to define a population of immunophenotypically immature cells (CD34(+)/CD38(-)/CD45(-/low)) enriched for LSCs in many cases of AML. The authors compared the fraction of this population of all myeloid cells at diagnosis with event-free survival. Kaplan-Meier analysis revealed significant higher event free survival of patients with low CD34(+)/CD38(-)/CD45(-/low) cell proportion (<0.68%) compared to patients with high burden of this population (>0.83%; log-rank P < .04). This correlation was not found for the total number of CD34(+) cells. This is the first study to show that a higher proportion of immature CD34(+)/CD38(-)/CD45(-/low) blasts at diagnosis correlates with unfavorable prognosis in childhood AML. The results suggest that a large CD34(+)/CD38(-)/CD45(-/low) population reflects a higher fraction of LSCs, leading to increased chemotherapy resistance and elevated relapse rate. Thus the initial frequency of CD34(+)/CD38(-)/CD45(-/low) cells may serve as a prognostic marker in pediatric AML. Future treatment in childhood AML should specifically target this immature population as well as the mature blast population.     

Intracranial hypertension in pediatric patients with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) remains one of the most common malignancies of childhood. Between April 1999 and August 2004, 9 of 207 patients treated at a Tertiary Oncology Service for ALL presented with Intracranial Hypertension (IH). Seven of the patients met the diagnostic criteria for Idiopathic Intracranial Hypertension (IIH). Four of the patients were treated with cerebrospinal fluid (CSF) drainage alone and four required Acetazolamide. Two of the four patients who were treated with Acetazolamide required subsequently a lumbar‐peritoneal (LP) shunt. One patient succumbed to his disease before receiving any specific treatment. Pediatr Blood Cancer 2009;52:418–420. © 2008 Wiley‐Liss, Inc.