小儿急性淋巴细胞性白血病伴继发骨髓纤维化及疗效观察

对１９９１年１０月至１９９６年２月收治的７４例小儿急性淋巴细胞性白血病（ＡＬＬ）同时作骨髓（ＢＭ）涂片与切片（活检）检查，发现１１例伴有继发骨髓纤维化（ＳＭＦ）。其中５例ＢＭ涂片与切片增生度不相符，涂片增生度减低或极度减低，切片示增生活跃至极度活跃（相差２￣５个级别）；４例ＢＭ涂片未达ＡＬＬ诊断标准，原淋＋幼淋〈０．３（０．０８￣０．２５），切片见大量幼稚细胞浸润；６例外周血白细胞〈３×１０＾９／     

小儿再生障碍性贫血的诊断及鉴别诊断

目的提高对小儿再生障碍性贫血（AA）诊断及鉴别诊断的认识。方法对30例CAA、17例骨髓增生异常综合征（MDS）及4例小儿急性淋巴细胞白血病前期（pre - ALL）做血象、骨髓象及骨髓活检分析。结果CAA组与MDS组血象单核细胞及血小板计数间比较（P〈0．05），有显著性差异。CAA组骨髓增生低下，原始 ＋ 早幼粒细胞、原始 ＋ 早幼红细胞、巨核细胞明显少于MDS，各组间比较（P〈0．01），有显著差异性，并见MDS各系病态造血。骨髓活检CAA组96％以上造血组织明显减少、脂肪组织明显增多，巨核细胞缺如或减少（均〈2个／片），检出率9．7％，纤维组织增生检出率16．3％。MDS组70％增生良好，近60％检出红系同一阶段发育幼红细胞岛，近90％检出幼稚前体细胞异常定位（ALIP），全部病例见纤维组织增生和小巨核细胞等异常。4例pre - ALL示三系细胞减少，骨髓增生减低，巨核细胞0 ～ 6个／片，活检示脂肪组织增多，造血组织明显减少，亦可见病态造血，1 ～ 4周内转变为急性淋巴细胞白血病（ALL）。结论CAA患儿外周血细胞减少，骨髓造血功能衰竭，无病态造血。MDS外周血单核细胞增多，骨髓增生良好，具有多系病态造血；ALIP、巨核细胞形态异常及红系同一阶段发育幼红细胞岛伴纤维组织增生是其特征。pre - ALL具有CAA和MDS的临床及实验室特点，但在短期内转变为ALL又与之不同。     

小儿白血病继发骨髓纤维化16例报告

总结分析了１６例继发骨髓纤维化（ＳＭＦ）的小儿白血生白血病（ＡＬＬ）１２例;８例外周血白细胞〈３．０×１０＾９／Ｌ;肝肿大１０例,肋下≥３ｃｍ（３～１４ｃｍ）;脾肿大１０例,肋下≥２ｃｍ（２～１１ｃｍ）;５有髓涂片与切片增生度不相符（相差２～５个级别）;４例骨髓涂片未达白血病诊断标准;早期用不同药物化疗后骨髓变化相差较大。提示：小儿白血病伴ＳＭＦ以ＡＬＬ多见;肝脾肿大明显而外周血白细胞少要注意伴Ｓ     

骨髓增生异常综合征诊断治疗探讨──附25例报告

本文对25例骨髓异常增生综合征（MDS）的诊断治疗探讨。均具有中度贫血，发热，出血症状及浅表淋巴结轻──中度肿大，肝脾轻──中度种中，外周血象血红蛋白平均50g／L，＜90g／L者占89％；红细胞增均1．78×10(12)／L，白细胞＜4×109／L者占52．3％，血小板平均62×109／L，骨髓表现增生活跃或明显活跃者占88％，增生减低者占12％，粒：红≤1者占65％，红系增生活跃占68％，减低占32％，并且大多数表现为成熟红细胞大小不等。巨幼样变及核的畸形，粒系统增生活跃者28％，减低者72％，多表现为核的不规则，核浆发育不平衡，多见双核粒细胞，巨核系统大部分受抑制，出现小淋巴样巨核细胞，部分表现为巨核细胞，血小板罕见。其中，难治性贫血（RA）16例；环状铁粒幼细胞性贫血（RA—S）1例；原始细胞过多难治性贫血（RAEB）6例；转化中难治性贫血伴有原始细胞增多（RAEB-T）1例；急性淋巴细胞性白血病（ALL）1例。提示：本组病例骨髓原始淋巴细胞增多占相当比例，MDS一旦转化为急性白血病，则病情迅速恶化，存活期明显缩短。我们体会到MDS应与再障相鉴别：其关键是MDS具有各种代表DNA复制紊乱的现象和骨髓中原始细胞增多之特点而再障则不具备。     

rhG-CSF在小儿ANLL强烈化疗中的应用

为探讨rhG-CSF对小儿ANLL强烈化疗后粒细胞缺乏的疗效，采用AAE方案（ADM、Ara-C、VP(16)或VM(26)），化疗后当WBC＜1×109/L或ANC＜0．5×109/L时，给予rhG-CSF200μg/m2·d（5～10μg/kg·d），皮下注射，一般连续5～10天。本文15例ANLL，用rhG-CSF30例次。用rhG-CSF前，WBC平均0．78×109/L、ANC0．15×109/L。用rhG-CSF后，平均6．5天WBC升至＞3×109/L、ANC升至＞1×109/L。粒细胞恢复时间与对照组相比明显缩短（P＜0．01）。骨髓复查未见原始细胞增多或复发。rhG-CSF有促进强烈化疗所致骨髓抑制和粒细胞缺乏的恢复，但未见骨髓原始细胞增多和白血病复发。     

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目的提高对小儿急性淋巴细胞白血病前期(Pre-ALL)的认识。方法对西安市儿童医院1997—2004收治的6例Pre-ALL患儿的临床经过及实验室的特点进行分析,并复习相关文献。结果男4例,女2例,年龄2岁3个月至8岁7个月,6例均有发热、贫血、出血。初诊为再生障碍性贫血(AA)5例、骨髓异常增生综合征(MDS)1例。4例出现肝、脾、淋巴结肿大(非同时),三系细胞减少,骨髓穿刺涂片示:增生减低4例,重度减低2例;骨髓病理活检:4例均示脂肪组织增多,造血组织减少;2例出现干抽的患儿伴有纤维组织增生,2例出现病态造血。经或不经糖皮质激素治疗,在1~9个月内均转变为急性淋巴细胞白血病(ALL)。3例接受VDLP方案治疗获完全缓解。结论6例转变为ALL,对化疗敏感,部分Pre-ALL有形态学异常。     

急性白血病患儿血清铁指标的变化

目的 探讨白血患儿血清铁指标变化，了解白血病患儿铁代谢状况。方法 血清铁蛋白（SF）测定采用化学发光法；转铁蛋白（Tf）测定采用比浊法；血清铁（SI）测定采用火焰法。结果 1．SF在急性淋巴细胞白血病（ALL）、急性髓性白血病（AML）初治组显著地正常对照组（P＜0．01）；经4周化疗完全缓解组ALL、AML与初治组无显著差异（P＞0．05）；ALL长期缓解组接受正常（P＞0．05），AML缓解前后SF高于ALL（P＜0．05）。2．ALL、AML初始组Tf显著低于正常对照组（P＜0．01），ALL与AML间无显著差异（P＞0．05），经4周化疗完全缓解组ALL、AML与初治组无显著差异（P＞0．05）；ALL长期缓解与正常对照组无差别（P＞0．05）。3．ALL、AML及缓解前后SI均无明显变化。4．上述各项指标与患者血红蛋白之间无显著相关关系。结论 白血病患儿存在体铁代谢紊乱，而不存在铁缺乏。     

巢式PCR追踪检测急性淋巴细胞白血病微小残留病

为探讨联合追踪急性淋巴细胞白血病（ALL）患儿骨髓（BM）、外周血（PB）、脑脊液（CSF）等多种微小残留病（MRD）的临床意义。采用巢式PCR法检测28例ALL患儿，对其中14例联合追踪完全缓解（CR）后BM、PB、CSF多种标本MRD的消长。结果BM、PB、CSF标本在CR后一段时间有MRD存在，但分布不均，随访14例中，8例CR后BM、PB、CSFMRD渐少者呈持续缓解，而4例BM的MRD持续阳性或由阴转归者骨髓复发，CSF的MRD1例持续阳性，另1例由阴转阳性，发生中枢神经系统自血病（CNSL）。提示多标本联合追踪急淋缓解期MRD对指导治疗、预测复发有重要意义。     

VP-VDLP方案治疗儿童高白细胞急淋白血病18例

外周血白细胞计数≥100×109／L的急性白血病称高白细胞急性白血病。此型白血病极易发生颅内出血及呼吸窘迫综合症，早期死亡率高，缓解率低。本文报导我院1989年1月至1996年6月采用VP-VDCP方案治疗儿童高白细胞急淋白血病18例，目的在于探讨降低早期死亡率，提高长期缓解率的方法。18例中男，14例，女4例，年龄6个月至13岁，确诊时外周血白细胞计数100～200×109／L8例、200～300×109／L6例，＞200×109／L4例。ALL113例、ALL24例、ALL31例。确诊后先给以小剂量VP方案（VCRlmg／m2、Prcl40mg／m2／天），辅以扩容、抗凝〈低分子右旋糖酐〉，碱化尿液（5％碳酸氢钠、别嘌呤醇）等综合治疗。外周白血细胞数第3天开始下降，一般3～5天，最迟10天降至50×109／L以下，此后再给以VDLP方案强化疗，同时鞘内注射MTX．Ara－cDXM每周1次。用此方案使早期死亡率由文献报导的60％降至16．7％；缓解率由20％提高到83．3％，其中2例完全缓解已达7年。然而此型白血病髓外浸润严重，中枢神经系统及睾丸白血病发生率高，极易导致复发，本文复发率33．3％。所以如何加强髓外白血病的防治，是降低复发率，提高长期缓解率的关键，也是急待解决的问题。     

小儿急性淋巴细胞白血病长期生存(附4例报告)

我院儿科从1987年5月～1990年5月共收初治小儿急性淋巴细胞白血病（ALL）10例，经化疗及辅助治疗获完全缓解（CR）者7例（70．0％），其中4例（占CR者57·1％）存活M3年，4例中有1例（占CR者14．3％）存活＞5年，现就该4例临床特征，治疗及随诊情况报告如下：资料和方法一、临床资料该4例患儿根据临床表现，血象与骨髓细胞形态结果，按1986年杭州会议“小儿急性白血病诊疗建议（修订案）”标准“‘确诊，其中男1例，女3例，年龄1十岁～10岁，骨髓片报告示原淋十幼淋数为68％～85％，血片均可见幼稚细胞，白细胞数3．5X10’八。～32X10…     

小儿血液病骨髓活检的临床意义

小儿血液病骨髓活检的临床意义屠立明，沈亦逵，王若洁广东省人民医院儿科ＣＬＩＮＩＣＳＩＧＮＩＦＩＣＡＮＣＥＯＦＢＯＮＥＭＡＲＲＯＷＢＩＯＰＳＹＩＮＣＨＬＬＤＲＥＮＨＥＭＡＴＯＬＯＧＩＣＤＩＳＥＡＳＥＳ￥ＴｕＬｉｍｉｎｇ，ｅｔａｌ．（ＧｕａｎｇｄｏｎｇＰ...     

Immunodiagnosis of childhood all: Problems associated with the use of peripheral blood alone

The immunologic classification of acute lymphoblastic leukemia (ALL) based solely on peripheral blood (PB) cell phenotypes may lead to conflicting results. This was demonstrated by the simultaneous assay of five immunologic markers on PB and bone marrow (BM) cells from 13 children with untreated ALL. We assayed erythrocyte (E) rosettes at 4°C and 37°C, presence of membrane Ig(mIg), and binding of antisera raised against thymus (T), and E^? ALL blasts, respectively. At diagnosis, the PB of these children contained > 90% lymphoid cells with 0–48% E rosettes and 1-84% cells with T antigen(s). Of 7 children with WBC < 10,000/cu mm there were 4 who had 20% or more E rosettes and T-antigen-positive cells. Of 6 children with WBC > 10,000/cu mm there were only 2 who had more than 20% E rosettes and T-antigen-positive cells. Based on examination of PB alone, six children may have been classified as having T-like ALL. However, these results were due to the presence of circulating normal T lymphocytes, and assay of BM cells established that only one of the 13 children had T-like ALL and none had B-cell ALL. Bone marrow blasts from 12 patients did not form rosettes at 37°C, did not have mIg, and did not react with anti-T serum. A high proportion of BM blasts from these 12 patients (39-96%) did react with antiserum against E^? ALL blasts. Of these 12 patients 11 had a higher proportion of E^? ALL antiserum-positive blasts in the BM than PB. Thus, immunologic classification of ALL should be based on the study of BM blasts, or both PB and BM cells.     

Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: A 10-year follow-up study

The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1–86 mo) and followed over 10 years (median 60 mo; range 1–232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy. © 1995 Wiley-Liss, Inc.     

Proliferation of myeloid lineage cells and apoptosis of lymphoblastic leukemic cells induced by short-course high-dose methylprednisolone in patients with acute lymphoblastic leukemia

In this paper, we investigated the effects of short-course high-dose methylprednisolone (HDMP) treatment on the proliferation of myeloid lineage cells and on apoptosis of blast cells in eight children with acute lymphoblastic leukemia (ALL). The patients were given the HDMP treatment (30 mg/kg/d, perorally) before 9:00 a.m. for seven days. Bone marrow (BM) aspiration was done at days 0 and 3 of the HDMP treatment in all patients and at the 7th day of the HDMP treatment in six patients. Bone marrow blast cells had gradually decreased after the HDMP treatment by the 7th day. There were statistically significant differences between the mean percentages of BM blast cells at days 0 and 3, days 0 and 7, and at days 3 and 7 (p<0.05). The mean percentages of blast cell apoptosis at the 3rd day was significantly higher than at days 0 and 7, and apoptosis at day 0 was significantly lower than at the 7th day (p<0.05). The mean percentages of BM myeloid lineage cells at the 7th day was significantly higher than at days 0 and 3 (p<0.05), and the mean percentage at day 0 was significantly lower than at the 3rd day (p<0.05). These findings indicate that short-course HDMP treatment causes apoptosis on lymphoblasts and increases the proliferation of myeloid lineage cells in children with ALL.     

Hematologic involvement in mitochondrial cytopathies in childhood: a retrospective study of bone marrow smears.

We retrospectively analyzed the bone marrow (BM) smears of 10 children with mitochondrial cytopathies. Light microscopic examination showed large and coalescent cytoplasmic vacuolization of some BM precursors in nine cases, including two children with normal peripheral blood counts and four with sideroblastic anemia. BM ultrastructural study showed abnormal mitochondria in the erythroid lineage in all three children studied. Ultrastructural studies in two cases revealed a population of giant mitochondria with abnormal ultrastructure coexisting with a population of normal mitochondria in proerythroblasts, basophil erythroblasts, and less commonly in more mature erythroblasts. In a third child, mitochondria were normal in size with cristae either absent or exhibiting abnormal longitudinal orientation. Heteroplasmic segregation of mitochondria during cell division could account for the finding of a double population of cells on ultrastructural examination. These features suggest that cytologic and ultrastructural BM examination could be useful for the diagnosis of mitochondrial disorders. That is, when large and coalescent cytoplasmic vacuoles of BM precursor cells are present, the clinician should search for mitochondrial cytopathy in a child with unexplained cytopenia(s).     

急性淋巴细胞白血病并EB病毒感染的临床分析

目的 探讨EB病毒(EBV)在急性淋巴细胞白血病(ALL)儿童中的感染及其临床意义.方法采用荧光定量聚合酶链反应(FQ-PCR)技术检测EBV DNA,ELISA法检测EB病毒衣壳抗原IgM抗体(EBV-CA-IgM),共检测47例.其中新发45例,复发2例;年龄0～14岁[(8.06±3.71)岁].另取14例健康儿童作为健康对照组.男9例,女5例;年龄2～10岁[(7.24±2.54)岁].结合临床表现、诱导治疗骨髓完全缓解(CR)率、形态学CR状态下的微小残留病(MRD)、复发率及无事件生存(EFS)率等分析ALL患儿中EBV感染情况及其临床意义.结果 47例ALL患儿中检出EBV感染15例(31.9%),其中11例(23.40%)检出EBV DNA,EBV DNA水平为(3.28±5.95)×108copy·L-1;14例健康对照组外周血未检测到EBV DNA及EBV-CA-IgM.ALL中EBV感染组与非EBV感染组白细胞数分别为(78.00±58.38)×109 L-1、(27.46±60.10)×109 L-1(t=2.70,P=0.01),诱导治疗CR率分别为 46.7%、87.5%(P<0.01),MRD>10-3分别为90.0%、26.1%(P<0.01),复发率分别为53.8%、13.8%(P<0.01),EFS率分别为 23.1%、82.8%(P<0.01).结论 ALL并EBV感染具有高白细胞数、低诱导治疗CR率、高复发率、低EFS率,提示EBV感染可能参与儿童ALL的发生发展过程,亟待改善EBV感染ALL的治疗方法.     

Computed tomography scans of the brain in acute leukemia and lymphoblastic lymphoma. Follow-up of children receiving prophylactic central nervous system irradiation

Twenty-seven long-term survivors diagnosed between 1971 and 1977 as having acute lymphoblastic leukemia (23 children), acute myeloblastic leukemia (1 child), and lymphoblastic lymphoma (3 children) have been studied using CT scans of the brain. None of the children had ever had symptoms or signs of CNS involvement. CT scanning was performed in 19 cases at the cessation of therapy; in the other eight cases, CT scanning was performed 24 to 49 months after the end of therapy. In all children, CNS prophylaxis included cranial irradiation with 24 Gy. Six children were also given spinaJ radiation, while in the remaining 21 cases intrathecal Methotrexate was given 5-6 times. CT scans of the brain showed slight abnormalities with increased ventricular size in only two cases. No differences in attenuation or intracranial calcifications were found. (CT = Computed Tomography, ALL = Acute Lymphoblastic Leukemia, AML = Acute Myeloblastic Leukemia, CNS = Central Nervous System). Acute leukemia, brain, children, CT scan, lymphoma.     

Hepatotoxicity in the treatment of acute lymphoblastic leukaemia.

Serial liver function tests and percutaneous liver biopsies were performed on 21 children receiving treatment for acute lymphoblastic leukaemia (ALL). The patients received continuing chemotherapy either with daily 6-mercaptopurine and weekly methotrexate or with five-day pulses of these drugs every three weeks. Liver function tests were transiently abnormal in the majority of children, but the abnormalities bore no relationship to the histology of the liver biopsy. Mild inflammatory and fatty changes were commonly seen, and early portal fibrosis was found in three out of 16 patients biopsied at between 108-130 weeks on treatment. There was no correlation between treatment regime and results of biopsy. Three patients showed possible progression of abnormalities on repeat biopsy. The risk of development of portal fibrosis appears low after 2-3 years of continuing chemotherapy, but examination of liver histology may be indicated if more prolonged therapy is contemplated.     

CRANIAL COMPUTED TOMOGRAPHY DURING TREATMENT OF CHILDHOOD LYMPHOCYTIC LEUKEMIA

ABSTRACT. Twenty-three children with acute lymphocytic leukemia (ALL) were examined by computed tomography (CT) of the head on two occasions more than 11 months apart. The first CT was performed at the time of diagnosis in 11 children, who were re-examined while still in their first complete remission. They had received prophylactic central nervous system (CNS) treatment consisting of intrathecal methotrexate supplemented by irradiation in 7 cases and intermediate dose methotrexate in 4 cases. Twelve children were receiving treatment for CNS relapse. This included therapeutic irradiation and intrathecal methotrexate. Abnormal CT developed in 7 children. Three CT scans demonstrated areas of decreased attenuation coefficient, one with intracerebral calcifications. In 5 patients, dilatation of the ventricles and cortical sulci had developed. AU CT abnormalities occurred in children in remission after CNS relapse. These results indicate that prophylactic treatment including cranial irradiation with 24 Gy and low cumulative doses of methotrexate is a safe procedure. Patients with CNS leukemia are at risk of developing CNS abnormalities, when they receive treatment with cranial irradiation and methotrexate. The risk is not correlated with age or sex of the child, the duration of the disease, the dose of irradiation or the cumulative dose of methotrexate.     

Value of flow cytometric analysis of peripheral blood samples in children diagnosed with acute lymphoblastic leukemia

Diagnostic procedures in children with acute lymphoblastic leukemia (ALL) are typically performed under general anesthesia. Anticipation of the diagnosis based on findings in peripheral blood allows scheduling of the first dose of intrathecal chemotherapy and diagnostic bone marrow (BM) aspirate during a single anesthetic. We retrospectively compared paired results of peripheral blood (PB) flow cytometric analysis and BM evaluation in 383 children with ALL diagnosed consecutively at a single center and found very high concordance of results between both tests. We conclude that PB flow cytometry may help streamline planning of procedure‐related anesthetics during diagnosis and early treatment of childhood ALL.