Characterization of bone marrow stromal abnormalities in a patient with constitutional trisomy 8 mosaicism and myelodysplastic syndrome

The development of myeloid leukemias and myelodysplastic syndrome (MDS) is common in children with trisomy 8 mosaicism. However, the mechanisms by which the presence of an additional chromosome 8 translates to an increased risk of leukemias and MDS is currently unknown. The authors describe the analysis of stromal cells from a pediatric MDS patient with constitutional trisomy 8. Patient and control marrow stromal cells were analyzed for alterations in cytokine production. Clonogenic assays were used to examine stromal support for hematopoiesis. The interplay between leukemia cells and stroma was studied by co-culture experiments. The results indicate that stromal cell function in this patient was seriously altered in favor of progenitor cell proliferation and expansion. This indicates that constitutional trisomy 8 in stromal cells plays a critical role in the pathogenesis of MDS.     

Value of Routine Bone Marrow Examination for Detection of Bone Marrow Relapse in Children with Standard Risk Acute Lymphoblastic Leukemia

The value of routine bone marrow examination (RBME) in children during and after treatment for standard risk acute lymphoblastic leukemia (SR-ALL) was Investigated. The clinical symptoms and peripheral blood findings at the time of bone marrow relapse of 28 children were reviewed and compared with those of 28 matched controls in continuous complete remission. Five (45%) children with bone marrow relapse during maintenance therapy and six (35%) after cessation of cytostatic treatment were asymptomatic at the time of relapse. Signs indicative of relapse duriny treatment were lymphoblast cells in the peripheral blood, thromhocytopenia, hepatomegaly, anemia, or leukopenia in decreasing order of frequency. Afer cessation of treatment these signs were lymphoblasts in the peripheral blood, hepatomegab, splenomegaly, thrombocytopenia, or leukocytosis. Except for one case with thrombocytopenia, no signs suspicious for relapse were found in the control groups. When each sign was evaluated separately only the presence of lymphoblasts in peripheral blood and hepatomegaly were significant symptoms for relapse after cessation of treatment. The mean percentage of lymphoblasts in the bone marrow at the time of relapse was significant& lower for patients with an unpredicted relapse (46.8%) than patients with clinical and/or laboratory evidence of relapse (79.5 %). When lymphoblasts were present in the peripheral blood the percentage of lymphoblasts in the bone marrow was always more than 40%, both during and after cessation of treatment. These data suggest a relation between clinical and laboratory symptom and progression of the disease. It is concluded that 467% of relapses are detected by RBME in the absence of clinical or laboratory symptoms. This early detection may have a positive prognostic influence with more effective treatment for relapsed ALL.     

The geldanamycin derivative 17-AAG decreases VEGF secretion and leukemia growth support by trisomy 8 myelodysplastic syndrome bone marrow stromal cells

Stromal cells from a child with constitutional trisomy 8 who developed myelodysplastic syndrome (MDS) were found to produce abnormal levels of various cytokines, including VEGF, and supported the growth of leukemic cells in co-culture assays. This study shows that the geldanamycin derivative 17-AAG effectively reduces the VEGF expression by MDS stromal cells. In co-culture experiments this agent also blocks the ability of the MDS stromal cells to stimulate the growth of leukemic cells. These data provide important initial evidence for the effect of 17-AAG on the marrow microenvironment and its potential use in the treatment of MDS and leukemia.     

Listeria Septicemia Complicating Bone Marrow Transplantation for Diamond-Blackfan Syndrome

Infection with Listeria monocytogenes is uncommon in patients receiving cytotoxic chemotherapy, and is even rarer among recipients of bone marrow transplantation. Hemosiderosis, either idiopathic or caused by transfusion, appears to be another risk factor. We report a 3-year-old Chinese girl with transfusion-dependent Diamond-Blackfan syndrome who had L. monocytogenes septicemia when she received an allogeneic bone marrow transplantation. She was treated successfully with intravenous ampicillin. Our case adds to the clinical evidence that patients with iron overload are susceptible to listeriosis, particularly when they are immunocompromised and do not receive iron-chelation treatment.     

Listeria Septicemia Complicating Bone Marrow Transplantation for Diamond-Blackfan Syndrome

Infection with Listeria monocytogenes is uncommon in patients receiving cytotoxic chemotherapy, and is even rarer among recipients of bone marrow transplantation. Hemosiderosis, either idiopathic or caused by transfusion, appears to be another risk factor. We report a 3-year-old Chinese girl with transfusion-dependent Diamond-Blackfan syndrome who had L. monocytogenes septicemia when she received an allogeneic bone marrow transplantation. She was treated successfully with intravenous ampicillin. Our case adds to the clinical evidence that patients with iron overload are susceptible to listeriosis, particularly when they are immunocompromised and do not receive iron-chelation treatment.     

Comparison of Autologous and Allogeneic Bone Marrow Transplantation in Children with Acute Leukemia

Thirty-one patients with acute non-lymphocytic leukemia (18 patients) or with high-risk refractory acute lymphocytic leukemia (13 patients) underwent bone marrow transplantation between March 1980 and March 1990. The high-dose conditioning regimen employed included cyclophosphamide followed by fractionated total body irradiation (12 GY). Fourteen patients who had an HLA-identical sibling donor received allogeneic bone marrow transplantation (ailo-BMT); the other 17 patients received autologous bone marrow transplantation (auto-BMT) purged with 4-hydroperoxycyclophosphamide (4HC). Four of the 14 allo-graft recipients died of leukemic relapse and 2 others died of graft-versus-host disease. Three of the 17 auto-graft recipients died of relapse and 1 suffered relapse in the testes. The actuarial risk of relapse was 29% for the allo-BMT patients and 24% for the auto-BMT patients (P<0.05). The event-free survival rate at five years was 57% and 74% respectively (P<0.05). Although there was no difference between them, a trend toward a higher survival rate and a lower mortality and morbidity was observed in the auto-BMT group. These results suggest that autologous bone marrow transplantation purged with 4HC is an effective and useful treatment for children with acute non-lymphocytic and lymphocytic leukemia who have no HLA-identical donor.     

Hematologic and Bone Marrow Abnormalities in Pediatric Patients with Human Immunodeficiency Virus (HIV) Infection

This study presents the peripheral blood and bone marrow findings in eight children with perinatally acquired HIV infection, ranging in age from 5 months to 3 years. The indications for bone marrow examination were comparable to those for adults with HIV infection and included cytopenia(s), slenome-galy, failure to thrive, and suspected tuberculosis. Thrombocytopenia was the most common indication, and platelet-associated antibodies were elevated in all patients with thrombocytopenia. The peripheral blood morphology was remarkable for the presence of plasmacytosis and eosinophilia in those patients with lymphocytic interstitial pneumonia. Five patients had trephine biopsies, and marrow cellularity was normal with normal or increased megakaryocytes in all cases. Lymphoid aggregates, also described in adult patients with acquired immunodeficiency syndrome (AIDS), were present in three of five trephine biopsies. In contrast to the adult patients, myelodysplasia was not observed in the pediatric age group. None of the eight children had malignancies or opportunistic infections that were diagnosed by bone marrow examination.     

Primary Ocular Recurrence of Leukemia Following Bone Marrow Transplant

A patient with acute lymphoblastic leukemia (ALL) who had undergone an allogeneic bone marrow transplant that included high-dose chemotherapy and total body radiation without eye shielding, sustained an isolated relapse of her disease in the iris. A review of ocular leukemic disease is discussed.     

阿司匹林对免疫性血管炎幼兔骨髓巨核细胞及基质细胞的影响

目的 研究阿司匹林对骨髓巨核细胞及基质细胞的影响,探讨其抗血小板作用是否与抑制骨髓功能有关.方法 建立免疫性血管炎模型,实验共分为模型组、正常对照组和阿司匹林组.检测骨髓巨核细胞集落(CFU-MK)的数量和功能以及骨髓基质成纤维细胞集落形成单位(CFU-F),同时检测其外周血血小板数量,电镜观察其血管病理改变.结果 免疫性血管炎模型组血小板数量、骨髓巨核细胞数、CFU-MK数较正常对照组均显著增加(Pa<0.05).阿司匹林治疗能够显著抑制血小板,阿司匹林组血小板[(523.50±69.70)×109 L-1]较模型组[(931.33±254.19)×109 L-1]显著降低(P<0.05);也能明显抑制骨髓巨核细胞数和CFU-MK,模型组和阿司匹林组巨核细胞分别为(29.17±8.40)个/片和(13.50±10.86)个/片(P<0.05),CFU-MK分别为(33.00±14.27)个/(2×105)和(15.67±9.79)个/(2×105)(P<0.05).阿司匹林同时能够显著抑制骨髓基质细胞,模型组CFU-F数(58.17±14.48)个/(2×106),阿司匹林组为(34.17±17.41)个/(2×106)(P<0.05).相关分析显示:血小板计数与CFU-MK的数目及形成能力呈正相关.病理组织学检查发现阿司匹林能够明显减轻血管炎的病理损害.结论 阿司匹林可能通过抑制骨髓巨核细胞和骨髓基质细胞,抑制血小板生成,从而达到减轻炎症损害的目的.     

低危骨髓增生异常综合征的诊断和治疗

目的探讨小儿低危骨髓增生异常综合征（MDS）的临床诊疗特点,提高小儿低危MDS诊疗水平。方法分析17例低危MDS的辅助检查特点,监测治疗药物环孢素血药质量浓度,评价治疗效果。结果血常规检查示三系减少11例（64.7%）,二系减少5例（29.4%）,一系减少1例（5.9%）;82.4%（14/17）网织红细胞计数增高,3例正常。17例中骨髓增生活跃14例（82.4%）,增生低下3例（17.6%）。其中一系病态造血8例（47.1%）,二系病态造血7例（41.2%）,三系病态造血1例（5.9%）,无病态造血1例（5.9%）。骨髓细胞遗传学检查示染色体正常10例（58.8%）,异常7例（41.2%）。15例CD59阴性细胞比例在正常范围,占88.2%;2例略高。9例于治疗3周测环孢素血药质量浓度95.3-316.5μg/L。10例于治疗3个月时进行疗效评价。其中血液学改善8例,血液学无改善2例,总改善率80%。结论低危MDS患儿多为学龄期儿童,全血细胞减少最多见。泼尼松、环孢素和司坦唑醇的联合治疗对低危型MDS效果较好。环孢素个体吸收差异较大,临床应用时应定期监测血药质量浓度,并随时调整剂量。     

急性白血病患儿浓缩红细胞输注与骨髓复发的关系

目的 回顾性分析近5 a本院收治的急性白血病(AL)患儿临床资料,探讨浓缩红细胞输注量与AL患儿骨髓完全缓解(CR)后出现骨髓幼稚细胞增生、骨髓复发的关系.方法按初次化疗CR后骨髓原始幼稚细胞分布情况将74例AL患儿分为3组:规律无事件完成化疗组(无事件组)、首次骨髓幼稚细胞增生后缓解组(增生组)与首次骨髓复发组(复发组).应用SPSS 17.0统计软件进行单因素方差分析,并对患儿复发及增生后骨髓原始+幼稚细胞比例与患儿平均每次每公斤体质量浓缩红细胞输注量的关系行Pearson相关分析.结果 3组患儿每次每公斤体质量浓缩红细胞输注量比较,差异有统计学意义(F=4.774,P<0.05),复发组、增生组均较无事件组患儿输注浓缩红细胞明显增多,复发组亦较增生组明显增多.复发及增生后骨髓原始+幼稚细胞比例与患儿平均每次每公斤体质量浓缩红细胞输注量呈正相关(r=0.51,P<0.05).结论浓缩红细胞输注可能是促使AL患儿出现骨髓幼稚细胞增生、骨髓复发的重要因素之一.     

Hematologic and Bone Marrow Changes in Children with Protein-Energy Malnutrition

Background: All systems in an organism are affected by protein-energy malnutrition (PEM), but one of the worst affected is the hematopoietic system. Today PEM remains a very serious problem in developing countries. We examined the relationships between clinical features, hematological, and bone marrow changes with severe PEM from Turkey. Method: We evaluated 34 (11 females and 23 males) consecutive cases of severe PEM, with no underlying diseases aged 3–20 months. The clinical nutritional conditions of the patients were determined using the Wellcome-Trust PEM classification. Ten of the patients were in the Marasmic-Kwashiorkor (M-K) group, 10 were in the Kwashiorkor (KW) group, and 14 were in the Marasmic (M) group. Full blood count, protein, albumin, serum iron (SI), iron-binding capacity (TIBC), ferritin, vitamin B12, folic acid, complement-3 (C3), complement-4 (C4), and bone marrow were investigated in all groups. Results: Anemia was detected in 97% of patients. We determined serum iron levels were low in 67.6% of the patients, TS levels were low in 76.4% of the patients and ferritin levels were low in 20.5%. The level of vitamin B12 was normal in all patients. Bone marrow analysis showed erythroid series hypoplasia in 28.5% of patients in the M group, 50% in the KW group, and 30% in the M-K group. Marrow iron was absent in 58.8% of patients. Conclusion: The most common hematologic change in the children with PEM was anemia and major cause of anemia was iron deficiency in this study. Patients with severe PEM have normal Vit B12 and serum folate levels. Most of the patients with severe PEM had normal cellularity with megaloblastic and dysplastic changes in bone marrow due to the inadequate and imbalanced intake of protein and energy.     

Sensory-Motor and Cognitive Functioning in Children Who Have Undergone Bone Marrow Transplantation

ABSTRACT. Sensory-motor and cognitive functioning was investigated in a group of 32 children treated with bone marrow transplantation (BMT), 1–6 years after treatment. Twenty-five of the patients had suffered from leukemia. The BMT procedure had involved a regimen of cytostatic drugs and, for leukemia patients, total body irradiation at a dose of 10 Gy, administered in one session. Cytostatic drugs and irradiation are known to be potentially neurotoxic, particularly when combined. The examination involved four neuropsychological tests of sensory-motor and cognitive functioning, as well as an age-appropriate intelligence test. For control the bone marrow donors (n=32), siblings of the patients, were also investigated. A pronounced delay in motor development was found in four children, who had been treated with BMT including total body irradiation before 3 years of age. Patients between 3 and 11 years of age at BMT were at a slight disadvantage, compared to donors, on tasks involving perceptual and fine motor speed. In older patients no deficits were observed.     

小儿骨髓坏死19例

目的对19例小儿骨髓坏死（BMN）进行总结分析,探讨其临床和实验室特点。方法回顾性分析1996年1月~2005年11月住院治疗19例BMN的临床资料、实验室检查、治疗方法、随访资料,并进行总结。结果引起骨髓坏死的原发病15例为恶性疾病,4例为感染所致。贫血、白细胞减少和血小板减少是最常见实验室检查特点,骨髓涂片可见到典型坏死改变。结论恶性肿瘤是骨髓坏死主要原因,对于疑诊患者应及时行骨髓检查。     

Kidney Function in Long-Term Pediatric Survivors of Acute Lymphoblastic Leukemia Following Allogeneic Bone Marrow Transplantation

Renal dysfunction may occur in survivors of bone marrow transplantation (BMT). The renal function of children who have survived 5 to 10 years after BMT has not been reported. Bone marrow transplantation was performed in 55 children with acute lymphoblastic leukemia less than 18 years of age at the University of Florida between September 1983 and October 1992. All received a uniform conditioning regimen of high-dose cystosine arabinoside and fractionated total body irradiation. Twenty-three are currently surviving. The survival average period following transplantation is 79 ± 6.6 (SD) months. The longest survival is 129 months after BMT. We retrospectively examined data evaluating kidney function prior to transplantation, within 150 days after transplantation, and at each child's most recent clinic visit (1.7 to 10 years after transplantation). We were able to collect follow-up data regarding renal function for 17 survivors. Two children (11 %) have renal dysfunction in the form of hypertension, glucosuria, and hematuria. One of them had acute renal insufficiency during the first 100 days following BMT. An unexpected finding was the presence of hyperfiltration in 10 patients. In conclusion, in this homogeneous group of children, allogeneic BMT did not lead to significant long-term renal dysfunction.     

Bone marrow polyamines in children with acute leukemia as related to remission status,therapy, and cellularity of specimens

Measurements of polyamines have potential practicality as biochemical markers of disease activity in adult cancer patients. On this basis, similar measurements were made in children with leukemia and solid tumors. Fluctuations in blood polyamine concentration were studied in relationship to chemotherapy schematics, cellularity and composition of blood and bone marrow specimens, and remission status of patients. Our results indicate that each of these factors may influence these determinations and consequently their clinical usefulness.     

Incidence of Bone Marrow Involvement in Ewing's Sarcoma: Value of Extensive Investigation of the Bone Marrow

Purpose: Bone marrow (BM) status is a critical matter when intensified chemotherapy with bone marrow rescue is proposed to improve the survival of patients with poor prognosis Ewing's sarcoma (ES): metastatic or relapsing disease. A systematic bone marrow investigation was performed in all the patients with newly diagnosed ES or relapsing ES to assess their BM status. Patients and Methods: From January 1985 to February 1989, 59 untreated patients and five patients at the time of relapse had a bone marrow investigation under general anesthesia: two BM biopsies and two BM aspirates until May 1986, then two BM biopsies and 10 BM aspirates. The classical method of smearing each BM aspirate was compared to cytocentrifugation of the pool of BM samples after gradient density separation. Results: The BM was involved in 13 of 59 untreated patients. BM was the single site of metastatic spread in only one patient but was involved in 52% of the patients with metastatic disease at other sites. This involvement was focal in several patients and frequent discrepancies were noted between the aspirates and biopsies at the various sites explored. The number of positive cases of BM involvement discovered by the two methods is somewhat limited. However preliminary results indicate a superior rate of positive smears with the pool technique which did however fail to detect involvement in some cases. Conclusions: The present study indicates that 1) BM involvement is a frequent event in metastatic ES (52%); 2) is often multifocal and therefore requires extensive BM investigation; and 3) further investigation of the pool technique to facilitate the BM screening is warranted. © 1995 Wi1ey-Liss, Inc.     

Systemic Form of Juvenile Xanthogranuloma: Report of a Case with Liver and Bone Marrow Involvement

Systemic form of juvenile xanthogranuloma with involvement of liver and bone marrow is reported in a 2-month-old female infant who presented with hepatosplenomegaly, severe anemia, and thrombocytopenia. There was no skin lesion, nor bone lesion. The enlarged liver has generalized yellowish spots. The diagnosis of juvenile xanthogranuloma was made by pathologic findings of marrow and portal tract infiltration by S-100 negative, CD1a negative, CD68 positive, and Factor XIIIa positive large pale to foamy histiocytes with Touton giant cells, and lack of Langerhans cell granule by electron microscopic examination. The patient was treated with Vinblastine and Etoposide, and experienced slow and gradual disease regression in one year. To the best of knowledge, this is the first documented case of bone marrow involvement in systemic juvenile xanthogranuloma. published online December 6, 2004     

Immunity to Polioviruses and Tetanus After Bone Marrow Transplantation in Children

Immunity to tetanus toxoid and polioviruses was studied in 34 (27 allografted, 7 autografted) children who underwent bone marrow transplantation (BMT). At a median time of 3 years after BMT, only one recipient was seronegative for tetanus toxoid. On the contrary 73 % of children were seronegative for at least one of the three poliovirus types and 30% for all vim types. Undetectable antibody titers were more frequently found against type 3 than the other two types. We recommend that reimmunizations of children after BMT be based on serologic tests for antibody titers.     

Immunity to Polioviruses and Tetanus After Bone Marrow Transplantation in Children

Immunity to tetanus toxoid and polioviruses was studied in 34 (27 allografted, 7 autografted) children who underwent bone marrow transplantation (BMT). At a median time of 3 years after BMT, only one recipient was seronegative for tetanus toxoid. On the contrary 73 % of children were seronegative for at least one of the three poliovirus types and 30% for all vim types. Undetectable antibody titers were more frequently found against type 3 than the other two types. We recommend that reimmunizations of children after BMT be based on serologic tests for antibody titers.