Use of the Ommaya reservoir in the prevention and treatment of CNS leukemia—an update

The prophylaxis of the CNS in ALL with intraventricular methotrexate therapy via an Ommaya reservoir in 18 patients resulted in a reduction of the CNS relapse rate to 11% with a 6-10+ year follow-up. This procedure proved to be safe and effective in our hands, but with newer, equally effective and less invasive methods of CNS prophylaxis now available, its use is no longer indicated. Intraventricular therapy via the Ommaya reservoir was also evaluated for its role in improving CNS remission duration after a leukemic recurrence in the CSF. The treatment of CNS relapse with intraventricular chemotherapy and low dose (600r) neuraxis radiation is encouraging. Of the ten patients treated for CNS leukemia, three are long-term (8-11+ years) survivors. Isolated CNS relapse occurred in three. The median CNS disease-free survival and the median relapse-free survival are 39 months and 21 months respectively.     

Juvenile Chronic Myeloid Leukemia: Oncogene Characterization

A 3 1/2-year-old female presented with thrombocytopenia and anemia. The bone marrow showed marked hemophagocytosis with an increase in macrophages. Over the next 2 months, there was a progressive de-differentiation of this monocytic population with the accumulation of blasts in the blood and bone marrow. The blasts had a normal 46XX karyotype and showed no fusion of the bcr and abl genes associated with Philadelphia chromosome positive leukemia. Intensive chemotherapy produced a transient hypoplastic state during which a bone marrow transplant was performed. The bone marrow after transplant again demonstrated a large population of macrophages. These cells continued to de-differentiate over the ensuing year up until the time of the patient's death. The mononuclear blast cell population was inducible toward monocytic maturation in tissue culture by low doses of ARA-c or daunorubicin. These mononuclear blasts expressed c-myc and c-fos mRNA at high levels, a further marker of their proliferative state and monocytic origin.     

Juvenile chronic myelogenous leukemia: In vitro characterization before and after allogeneic bone marrow transplantation

In previously published studies on patients with juvenile chronic myelogenous leukemia (JCML), excessive proliferation of malignant monocyte-macrophage elements and impaired growth of normal hematopoietic progenitors were demonstrated. A selective hypersentivity of granulocytemachrophage progenitors (CFU-GM) to granulocyte-macrophage colony stimulating factor (GM-CSF) seems to represent the main pathogenetic mechanism. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only curative strategy for patients with JCML. In this study, we evaluated the growth of peripheral blood hematopoietic progenitors in semisolid cultures in two children with JCML before and after allogeneic BMT. Serum levels of GM-CSF, interleukin-1 (JCIL-1) and tumor necrosis factor-α (TNF-α) were also assessed. IL-1-β, GM-CSF and TNF-α serum levels of the patients before and after BMT did not differ significantly from those obtained in 45 healthy controls. After marrow transplant, the engraftment of donor hematopoietic stem cell was associated with the disappearance of both pretransplant GM-CSF hypersensitivity and CFU-GM spontaneous growth. The inhibitory effect on the growth of normal hematopoietic progenitors also resolved. This confirms that the substitution of the pathological hematopoietic progenitors represents the basis for the curvative effect of allogeneic BMT in the treatment of JCML, abolishing both the excessive responsiveness of JCML progenitor cells even to very low concentrations of GM-CSF and the growth-inhibitory effect on normal hematopoiesis. © 1995 Wiley-Liss, Inc.     

多重RT-PCR检测儿童急性髓细胞性白血病融合基因的临床与实验研究

目的研究儿童急性髓细胞性白血病(AML)染色体畸变所形成融合基因的临床和实验关系。方法采用多重巢式RT_PCR方法对38例儿童AML的融合基因联合染色体核型分析、免疫表型、临床资料进行研究。结果38例儿童AML中有23例(60.53%)具有4种融合基因:MLLex7/AF9、TLS/ERG、AML1/ETO、PML1RARα。8例患儿有HOX11原癌基因活化,7例为单纯表达HOX11原癌基因活化,1例同时伴有其他融合基因表达。伴AML1-ETO、PML-RARα的20例患儿中接受化疗的11例全部达CR,且无复发。结论基因分型是儿童AL最精确的分型方法,为临床化疗提供方向:AML表达HOX11者预后不良;伴MLL基因重排者预后极差。采用多重RT-PCR方法可快速同时检测儿童急性白血病29种染色体畸变所形成的融合基因,完善白血病的MICM分型、指导临床个体化治疗。     

A comparative trial of daunorubicin,cytosine arabinoside,and thioguanine,and a combination of the three agents for the treatment of acute myelocytic leukemia

In this study 523 previously untreated patients with acute myelocytic leukemia were randomly allocated to induction therapy with daunorubicin 60 mg/M² daily × 3, cytosine arabinoside and thioguanine 100 mg/M² each every 12 hours until marrow hypoplasia was achieved, or a 5-day course of the three drugs with daunorubicin 100 mg/M² given on dav 1 and cvtosine arabinoside plus thioguanine each given at a dose of 100 mg/M² every 12 hours for five days. All patients received cyclophosphamide 600 mg/M² followed in 24 hours by hydroxyurea 500 mg/M² every six hours for four doses monthly for maintenance therapy. Patients were randomized to receive one of three antimetabolite treatments beginning 24 hours after the last dose of hydroxyurea each month for seven days. One such treatment consisted of 6-mercaptopurine 100 mg/M² daily, another group received 6-thioguanine at the same dose daily, and the third group received 50 mg/M² of both antimetabolites daily. There were no significant differences in complete response rate, remission duration, or survival among the various treatment groups.     

无脾肿大体征的儿童慢性粒细胞性白血病早期诊断:附3例报告

慢性粒细胞白血病(CML)是一种获得性造血干细胞恶性克隆增殖性疾病,儿童患者少见,约占同期儿童白血病总数的1.9％、3．2％、3．4％、5．9％左右。典型的CML主要表现为轻度贫血、乏力、低热、脾脏肿大,持续进行性外周血白细胞增高,并出现各阶段的幼稚粒细胞;骨髓增生极度活跃,以粒细胞系增生为主,有原始 早幼粒细胞增多,但 <20％,同时有嗜酸性粒细胞、嗜碱性粒细胞增多,90％以上患者骨髓中有特征性的ph 染色体或BCR／ABL融合基     

幼年类风湿性关节炎并虹膜睫状体炎10例

目的探讨幼年类风湿性关节炎(JRA)并虹膜睫状体炎的临床表现及预后、转归。方法对107例JRA中并虹膜睫状体炎的10例临床表现与JRA各型的发病关系及免疫学特征等方面进行回顾与分析,总结其潜在发病规律。结果幼年类风湿性关节炎少关节型患儿中并虹膜睫状体炎9例(9/48),多关节型1例(1/20)。急性虹膜睫状体炎3例,慢性虹膜睫状体炎7例。其中急性病例均治愈,慢性病例中1例继发青光眼,1例失明。结论虹膜睫状体炎是JRA常见并发症,以少关节型为主。急性虹膜睫状体炎预后好,而慢性虹膜睫状体炎多因白内障、青光眼等多种并发症而预后不良。     

Juvenile chronic arthritis profile in Greek children

Background: Juvenile chronic arthritis (JCA) is the commonest autoimmune rheumatic disease in childhood and presents different clinical subtypes. Juvenile chronic arthritis is considered to be of a polygenic nature and its genetic background is still under investigation. The clinical profile of JCA in the Greek population has not been studied completely. This study retrospectively analyzed the clinical and immunological features of JCA in Greek children presented between 1989 and 1994. Human leukocyte antigen (HLA)-positive or -negative associations in the different clinical subtypes were also detected. The findings of this study were correlated with those reported from other populations. Methods and results: Antinuclear antibodies (ANA) anti-ds DNA and anti-extractable nuclear antigen antibodies were estimated by immunofluorescent and ELISA assays. Human leukocyte antigen typing was performed by microlymphocytotoxicity. using immunobeads. The peak ages of JCA onset were between 2 and 5 years and also between 9 and 12 years. There was a high female predominance in pauciarticular and polyarticular groups. The most common disease was pauciarticular (58.7%) followed by systemic (25%) arthritis. The incidence of eye involvement was 12.5% and presented only in the pauciarticular group. Overall, ANA positivity was 53.7%, increasing to 90% in pauciarticular cases associated with chronic uveitis. In the early-onset (EOPA) pauciarticular subtype, positive-HLA associations with alleles DR11 and DR8 were shown. In the late onset pauciarticular (LOPA) group only B27 allele was increased. Conclusions: The results of this retrospective study did not reveal major differences between JCA in Greek children compared with other Caucasian series.     

Lack of bcr rearrangement in juvenile chronic myeloid leukemia

Juvenile chronic myeloid leukemia (JCML) is an unusual subtype of children's leukemia, characterized by unique clinical presentation. Recent studies revealed several biological features, distinguishing from those observed in adult type chronic myeloid leukemia (ACML). The majority of ACML cases are characterized by the presence of an hybrid bcr-abl rearranged gene. In an effort to elucidate the molecular basis of this unusual leukemia we looked for bcr rearrangement in six JCML cases. No bcr rearrangement was identified in any of the analyzed samples. Together with previous studies from JCML cases, JCML has a different mechanism of leukomogenesis from ACML.     

Juvenile xanthogranuloma and acute leukemia: A case report

Juvenile xanthogranuloma (JXG) is a rare benign disease of the skin. It is seen in combination with juvenile chronic myelo-monocytic leukemia (JCML) and/or neurofibromatosis type 1 (NF1). The association with acute lymphoblastic leukemia is hardly mentioned in the literature. A case report of this rare combination is described and a review of the literature is given. © 1994Wiley-Liss, Inc.     

Leukemic blasts with markers of four cell lineages in Down's syndrome (“megakaryoblastic leukemia”)

Among 16 patients with Down's syndrome (DS) and acute leukemia admitted to our department during a ten year period, 6 were diagnosed as acute megakaryoblastic leukemia (AMkL). The diagnosis was based on clinical and hematologic criteria, confirmed in three patients with the use of monoclonal antibodies (MoAb) specific for megakaryocytic antigens. In these three, and in a fourth patient, the leukemic blasts were positive for other myeloid, lymphoid and erythroid markers in MoAb testing. We suggest that AMkL in DS is a mixed lineage leukemia with blasts presenting a variety of cell surface antigens, indicating origin from an early progenitor cell with the capability of megakaryocytic differentiation. Of the 6 patients with AMkL, 4 treated with standard AML protocols are in complete continuing remission (CCR) with observation periods from 57+ to 148+ months. © 1993 Wiley-Liss, Inc.     

Successful acute lymphoblastic leukemia‐type therapy in two children with mixed‐phenotype acute leukemia

Mixed‐phenotype acute leukemia (MPAL) is a rare type of leukemia expressing both myeloid and lymphoid markers. There is limited information, especially on pediatric cases. Therefore, the optimal therapeutic approach to pediatric MPAL has not been defined. Here, we report two pediatric cases of MPAL. According to the 2008 World Health Organization (WHO) classification and European Group for the Immunological Characterization of Leukemias (EGIL) criteria, patient 1 was diagnosed with overt MPAL positive for the myeloid marker myeloperoxidase (MPO), and B‐lymphoid markers. Patient 2 was diagnosed with T‐cell acute lymphoblastic leukemia (T‐ALL) using EGIL criteria. According to the 2008 WHO classification, however, patient 2 was diagnosed with overt MPAL positive for CD3, T‐lymphoid markers and MPO. We chose an ALL‐type therapy consisting of both lymphoid‐ and myeloid‐directed agents; these patients have maintained complete remission following treatment. Further information on pediatric MPAL is needed to establish an appropriate therapeutic strategy including stem cell transplantation for this rare condition.     

Cardiac Relapses in Myeloid Leukemia: Case Report and Review of the Literature

Granulocytic sarcoma (GS) is a localized destructive tumor mass composed of immature cells of the granulocytic series, occurring before, concomitantly, or after the overt development of acute or chronic myelogenous leukemia. Although this tumor is known to occur in almost every site of the body, cardiac involvement is rare. We report a case of a 12-year-old female previously treated for 28 months with chemotherapy for acute promyelocytic leukemia, who presented with GS in the left mastoid 3 months after discontinuing treatment. The patient was treated with local radiotherapy only. Thirty months later she presented with heart failure, the result of a right-sided intracardiac mass, while in continuous hematological remission of the primary disease and off therapy. The cardiovascular, hematological, and postmortem findings are described and the literature is reviewed. This is the first clinicopathologic report of GS involving the heart in which the echocardiographic and pathologic findings are detailed.     

Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia

The association of neurofibromatosis 1 (NF1), juvenile xanthogranulomas (JXG), and juvenile myelomonocytic leukemia (JMML) has been previously reported. We describe herein this triad in a Caucasian male infant with a pathogenic mutation in the NF1 gene (neurofibromin). The clinical course from initial presentation to final diagnosis is detailed; the physical features and hematologic characteristics are discussed. The patient underwent bone marrow transplantation and is currently in remission. Children with concurrent cutaneous café‐au‐lait and JXG lesions should be evaluated and monitored closely for the possible development of JMML. Pediatr Blood Cancer 2010; 54:173–175. © 2009 Wiley‐Liss, Inc.     

儿童气管幼年性黄色肉芽肿1例报告并文献复习

目的 探讨儿童气管幼年性黄色肉芽肿的临床特征和治疗方法.方法 回顾分析1例气管幼年黄色肉芽肿患儿的临床资料并复习相关文献.结果 患儿,女,1岁10个月,以反复喘息为主要表现,常规抗感染、全身糖皮质激素及支气管舒张剂治疗效果不佳.电子支气管镜提示患儿声门下气管侧壁可见1个直径约0.8 cm的淡黄色肿物,表面光滑,阻塞气管...     

Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†

Relapse‐enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet‐based polymerase chain reaction to establish whether relapse‐enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.