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.     

Bone marrow relapse occurring as first relapse in children with acute lymphoblastic leukemia

In a retrospective review which covered the whole Dutch childhood population of approximately 3 million children we studied the prognosis in 164 children with acute lymphoblastic leukemia (ALL) who were initially treated between 1973 and 1983, and who had an isolated bone marrow relapse occurring as first relapse. Until their first relapse, the patients were initially treated according to standard protocols, while treatment for relapse was heterogeneous, and not intensive. Second complete remission (CR) was attained by 78% of the patients. The median duration of second CR was 9 months, the median survival 13 months. Multivariate analysis showed that the duration of the first CR was the most significant variable with regard to prognosis. None of the patients who developed their bone marrow relapse during initial treatment, i.e., within 24 months from diagnosis, survived. Among the 73 patients who relapsed after cessation of the initial treatment there were 19 long-term disease-free survivors, 14 of whom had not developed subsequent relapses after 48+-125+ months. From this study we conclude that treatment in children with first bone marrow relapse has to be intensified.     

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。     

Detection of Minimal Disease in Bone Marrow of Neuroblastoma Patients by Immunofluorescence

Indirect immunofluorescence studies were compared with conventional smear cytology in 82 paired bone marrow samples from children with neuroblastoma using monoclonal antibodies (MAbs) BW 575 (neuroblastoma-associated 95 kD glycoprotein) and BW 625 (ganglioside GD₂) and tetanus toxin labeling. Congruent results were obtained in 70 of 82, or 85% (positive/positive; negative/negative). In 12 of 82 (15%) patients, bone marrow infiltration was demonstrated by immunofluorescence but not by conventional cytology. As few as 0.01% neuroblastoma cells were reliably detected—in some cases even fewer. Because of antigen heterogeneity, false negative results were obtained in five cases with MAb BW 625, in two cases with MAb BW 575, and in no case with tetanus toxin. No antibodies showed any cross-reactivity to hematopoietic cells in either bone marrow of infants or during regeneration after chemotherapy. We conclude that this panel of antibodies is highly sensitive and specific to detect minimal disease in bone marrow of neuroblastoma patients, which has major implications for the staging procedure, monitoring treatment, early detection of relapse, and assessment of bone marrow status before autologous bone marrow transplantation.     

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.     

Phagocytic Macrophages in the Bone Marrow Biopsies of Children with Hodgkin's Disease

Phagocytic macrophages in bone marrow aspirates have been described as normal and are frequently observed in autoimmune disorders. They are rarely seen in bone marrow biopsies. We observed phagocytosis of leukocytes and nuclear debris by macrophages in the bone marrow biopsies in 20 of 26 children with Hodgkin's disease before therapy.

In contrast, phagocytic activity was present in only 1 of 16 children with solid tumors and 4 of 17 children receiving chemotherapy for neoplasia other than Hodgkin 's disease. In all groups the marrow was not directly involved by tumor. The presence of macrophage activity did not correlate with clinical stage or histological type of Hodgkin's disease or with the peripheral blood count. Its increased frequency in patients with Hodgkin's disease may reflect abnormal macrophage function in those patients.     

Incubation Of Autolocous Bone Marrow Graft with Asta Z 7557: Comparative Studies of Hematological Reconstitution After Purged or Nonpurged Bone Marrow Transplantation

Thirty-three patients with advanced solid tumors were treated by high-dose chemotherapy (combined high-dose melphalan), followed by cryopreserved autologous bone marrow transplantation (ABMT). Thirteen of them had bone marrow (BM) tumor involvement at diagnosis, and BM harvest was purged with 50 μglml ASTA Z 7557 before cryopreservation. Following incubation, in vitro growth of granulomonocytic colony-forming cells (GM-CFC) was regularly inhibited (>99%). Hemopoietic reconstitution after purged and nonpurged ABMT was studied. All patients experienced engraftment. However, peripheral leukocyte and granulocyte recoveries were delayed significantly in patients receiving purged BM (mean 27 and 26 days) compared with those observed in patients receiving nonpurged BM (mean 18 and 18 days). These results confirm that purged BM, despite GM-CFC depletion after in vitro treatment, ensures engraftment after high-dose chemotherapy, but prolonged pancytopenia is observed and postgraft hemopoietic recovery is delayed. A clinical trial is necessary to evaluate the efficiency of the purging technique in eradicating residual tumor cells.     

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.     

The Immunophenotype of Bone Marrow Lymphocytes in Children with Immune Thrombocytopenic Purpura

Purpose: Primary immune thrombocytopenic purpura (ITP), caused by immune system dysfunction, is recognized as the leading cause of thrombocytopenia in pediatric population. Nonetheless, inadequate studies have been performed on bone marrow immunophenotyping of children with ITP. In this study, we aimed to investigate the immunophenotype of bone marrow lymphocytes in these children. Patients and methods: Between 2008 and 2012, 35 children with ITP and 26 age and sex matched healthy controls were recruited. All participants underwent bone marrow aspiration. Appropriate B-cell, T-cell, and myeloid lineage monoclonal antibodies were employed to determine the immunophenotype of these patients. Results: CD10, CD19, and CD20, all indicative of premature B-cell markers, were significantly greater in children with ITP. CD22, mainly expressed on mature B cells was slightly, but not significantly reduced in the patients’ group (P = .42). On the other hand, T cell markers including CD2, CD3, CD5, and CD7 were underexpressed. CD33, a specific marker for myeloid lineage, was underexpressed in the patients’ group (5.6 ± 4.7 vs. 12.9 ± 7.3, P < .001). Noteworthy, the immunophenotype did not significantly differ between acute and persistent cases. Conclusion: Overall, a phenotype characterized by increased pre-B-cell markers along with decreased T cell immunophenotypic markers was observed in bone marrow lymphocytes of children with ITP in the present study. Further larger scale studies are recommended to confirm our findings, as precise mapping of the immunophenotype of lymphocytes in these patients would pave the road to improved diagnosis and treatment.     

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.     

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.     

Allogeneic Bone Marrow Transplantation in Childhood Leukemia

Allogeneic bone marrow transplantation was performed in 94 patients with hematologic malignancies or other various diseases during the period between March 1982 and November 1990 at Tokai University Hospital. Projected disease-free survival rates of HLA genotypically identical marrow recipients were 88.9% for chronic myeloid leukemia transplanted in the first chronic phase (N = 9), 90.9% for acute leukemia in the first complete remission (N = 15), 54.5% for acute leukemia in later remissions (N = 14), 62.5% for solid tumors (N = 8) and 0% for patients transplanted in relapse (N = 7). The rate for HI A-mismatched marrow recipients with leukemia was 27.8% (N = 16). For patients with non-neoplastic diseases it was 100% regardless of HLA-compatibility (N = 26). The quality of life in long-term surviving pediatric marrow recipients has been acceptable. Common abnormalities among survivors are long-lasting hypogonadism due to radiation and subclinical impairment of lung function in the first year post-BMT. About two-thirds of children experienced a transient decrease in growth velocity in the immediate posttransplant period.     

Cryopreservation of Pluripotent and Committed Hemopoietic Progenitor Cells from Human Bone Marrow and Cord Blood

As one of the studies on autologous bone marrow transplantation for childhood cancer, the viabilities of several kinds of hemopoietic progenitor cells after cryopreservation was assayed using bone marrow and cord blood samples. The mean recovery rates of granulocyte-macrophage colony forming units (CFU-GM), erythroid burst forming units (BFU-E) and erythroid colony forming units (CFU-E) from bone marrow cells were 47.9%, 31.3% and 10.5%, respectively. The mean recovery rates of CFU-GM, BFU-E and CFU-E from cord blood cells were 46.7%, 39.1% and 22.4%, respectively. The ratio of primitive to mature BFU-E did not change after cryopreservation. The mean recovery rate of mixed colony forming units (CFU-mix) from marrow cells was 30.2%, and that from cord blood cells was 58.9%, demonstrating their sufficient proliferative activity after cryopreservation. These results demonstrate that CFU-mix, primitive BFU-E as well as CFU-GM, mature BFU-E can be well cryopreserved, supporting the usefulness of autologous marrow transplantation for the rescue of the ruined hemopoiesis after intensive cancer therapy.     

Infantile Hemangioendothelioma Associated with Bone Marrow Dysfunction

A 5-month-old-girl had hepatomegaly and severe anemia. Based on the multiple imaging studies, hemangioendothelioma was suspected. Wedge resection of the liver and hepatic artery ligation were performed. The peripheral blood film showed pancytopenia, and the myelogram showed markedly reduced erythroid series and myeloid predominance with shift to the left. The correlation between hemangioenothelioma and bone marrow dysfunction is unknown. As far as we know, this is the first report of infantile hemangioendothelioma associated with bone marrow dysfunction.     

Prevention of Gram-Positive Infections in Patients Treated with High-Dose Chemotherapy and Bone Marrow Transplantation: A Randomized Controlled Trial of Vancomycin

Between January 1986 and June 1988, 155 patients (73 children and 82 adults), who were candidates for bone marrow transplantation, were included in a randomized controlled trial (75 patients in vancomycin group and 80 patients in the group without vancomycin) to evaluate the efficiency of a short course of vancomycin (10 mg/kg IV every 6 hours, day -5 to + 1) in decreasing the incidence of Gram-positive infections during aplasia after high-dose chemotherapy and bone marrow transplantation. There was no statistical difference in the occurrence of documented septicemia, documented coccus Gram-positive infections, or fever of unknown origins during aplasia in the 2 groups. Thus, short prophylactic treatment with vancomycin proved inefficient in reducing morbidity due to infection after high-dose chemotherapy and bone marrow transplantation.     

Diarrhea and Weight Loss After Bone Marrow Transplantation in Children

To define the determinants of diarrhea after bone marrow transplantation (BMT) and its nutritional sequelae, the medical records of 20 consecutive children (median age, 9 years; 13 boys and 7 girls) undergoing BMT at Children's Hospital in Birmingham, UK were surveyed. All patients who received total body irradiation (TBI) required parenteral nutrition (PN). Seventy-eight percent of TBI patients and 73% of children who received allografts developed diarrhea compared with only 27% of non-TBI patients and 22% of those who received auto grafts (P < 0.05). Ninety percent of children with diarrhea required PN. Duration of PN in these children was longer than in those without diarrhea who requested PN (P < 0.05). Despite PN, weight loss at discharge was still greater in the study group (P < 0.05). Diarrhea was associated with a significant fall in serum albumin (P < 0.005). Diarrhea and weight loss occur in children after BMT despite active PN support. Pretransplant TBI and the we of all grafts are important determinants of these complications.     

Eosinophilic Meningitis Preceding Meningeal Relapse in a Child with Acute Lymphoblastic Leukemia: Abnormal Nucleotide Content of Eosinophils

A case of eosinophilk meningitis 2 months before the appearance of lymphoblasts in the cerebrospinal fluid is described in a child with acute lymphoblastic leukemia (ALL). The peripheral blood showed no simultaneous eosinophilia. The child was successfully treated for her CNS relapse, and complete remission was easily obtained. The eosinophils and lymphoblasts disappeared quickly after the administration of intrathecal methotrexate. However, 3¹/₂ years later hypereosinophilia developed in the blood and bone marrow, heralding bone marrow relapse. Simultaneously, meningeal relapse was diagnosed and this time the cerebrospinal fluid showed a mixture of lymphoblasts and eosinophils. Treatment was reinstituted and complete remission was again obtained. Analysis of the blood eosinophils showed abnormal nucleotide patterns. Similar patterns were previously found in the lymphoblasts from other ALL patients.