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At least 361 records · Page 20Linked to original sources
PubMed2001

The expression of ETV6/CBFA2 (TEL/AML1) is not sufficient for the transformation of hematopoietic cell lines in vitro or the induction of hematologic disease in vivo.

ETV6/CBFA2 (TEL/AML1) is the most frequent genetic abnormality associated with acute lymphoblastic leukemias in children, and is associated with a favorable prognosis. To investigate the influence of ETV6/CBFA2 on cellular transformation, the fusion gene was cloned into a murine ecotropic retroviral vector and transduced into IL-3-dependent Ba/F3 and 32Dcl.3 and IL-7-dependent IxN/2b murine hematopoietic cell lines. Different variants of ETV6/CBFA2, corresponding to CBFA2 alternatively spliced variants, and the reciprocal product CBFA2/ETV6, were stably expressed in each of these cell lines. However, although Western blot analysis demonstrated expression of each variant, none of the stable cell lines expressing CBFA2/ETV6 or the variants conferred factor-independent growth. We further investigated the effect of ETV6/CBFA2 expression in vivo by generating transgenic mice in which expression of the fusion was directed to lymphoid cells using the immunoglobulin heavy chain enhancer/promoter. Four founder mice were identified showing transmission and expression of the chimeric product. The mice were bred for five generations and followed for more than 24 months. The mice did not develop a malignant hematologic disorder, nor did they display histopathologic, morphologic, or immunophenotypic abnormalities, although ETV6/CBFA2 expression was confirmed in each line. We conclude that the expression of ETV6/CBFA2 alone is not sufficient for induction of growth factor independence in hematopoietic cell lines or hematologic disease in transgenic mice.

Animals↗
PubMed2006

Hepatic injury following reduced intensity unrelated cord blood transplantation for adult patients with hematological diseases.

Liver injury is a common complication in allogeneic hematopoietic stem cell transplantation. Its major causes comprise graft-versus-host disease (GVHD), infection, and toxicities of preparative regimens and immunosuppressants; however, we have little information on liver injuries after reduced intensity cord blood transplantation (RICBT). We reviewed medical records of 104 recipients who underwent RICBT between March 2002 and May 2004 at Toranomon Hospital. Preparative regimen and GVHD prophylaxis comprised fludarabine/melphalan/total body irradiation and cyclosporine or tacrolimus. We assessed the etiology of liver injuries based on the clinical presentation, laboratory results, comorbid events, and imaging studies in 85 patients who achieved primary engraftment. The severity of liver dysfunction was assessed according to the National Cancer Institute Common Toxicity Criteria version 2.0. Hyperbilirubinemia was graded according to a report by Hogan et al (Blood. 2004;103:78-84). Moderate to very severe liver injuries were observed in 36 patients. Their causes included cholestatic liver disease (CLD) related to GVHD or sepsis (n = 15), GVHD (n = 7), cholangitis lenta (n = 5), and others (n = 9). Median onsets of CLD, GVHD, and cholangitis lenta were days 37, 40, and 22, respectively. Frequencies of grade 3-4 alanine aminotransferase elevation were comparable across the 3 types of hepatic injuries. Serum gamma-glutamil transpeptidase was not elevated in any patients with cholangitis lenta, whereas 27% and 40% of patients with CLD and GVHD, respectively, developed grade 3-4 gamma-glutamil transpeptidase elevation. Multivariate analysis identified 2 risk factors for hyperbilirubinemia; grade II-IV acute GVHD (relative risk, 2.23; 95% confidential interval, 1.11-4.47; P = .024) and blood stream infection (relative risk, 3.77; 95% confidential interval, 1.91-7.44; P = .00013). In conclusion, the present study has demonstrated that the hepatic injuries are significant problems after RICBT, and that GVHD and blood stream infection contribute to their pathogenesis.

Adolescent↗
PubMedDate not supplied

Double-stranded RNA excess in hematologic diseases: clinical implications.

Evaluation of double-stranded RNA by flow cytometric analysis is an important parameter for discriminating quantitatively between human tumoral and normal cells. We studied double-stranded RNA (ds-RNA) measurements using propidium-iodide after DNase treatment in bone marrow and in peripheral blood cells from patients with acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma. The highest incidence of ds-RNA excess (greater than 30%) was observed in patients with acute leukemia (75%), while those displaying it in complete remission phase were 20-25% and in relapse about 80%. A high incidence was also noted in patients with chronic myeloid leukemia in blastic crisis (100%) and in patients with multiple myeloma with heavy tumor stage myeloma (78%). We never observed an elevated ds-RNA excess in the control group, formed by normal peripheral blood lymphocytes. Indeed the specificity of this tumor marker is attested to not only by its high levels in various hematologic malignancies, but also by its absence in normal cells. Hence the importance of its clinical implications in malignant hematologic diseases is confirmed.

Biomarkers, Tumor↗
PubMed1986

[First results of in vitro cultivation of stem cells from bone marrow and peripheral blood in an autologous test system of patients with hematological diseases].

In 17 patients with haematological diseases an autologous test system was elaborated for determining the percentage of unipotent myeloic stem cells in the bone-marrow and peripheral blood and implemented by experiments. In comparing the results obtained by means of the traditional heterologous culture method, differences (diminutions, increase of aggregate numbers) could be found which allow certain conclusions to be drawn on the patient's real bone marrow function. For reasons of standardization, cultivation in the heterologous system cannot be abandoned. The investigations are continued.

Bone Marrow↗
PubMed2002

Management of mycoses in patients with hematologic disease and cancer -- review of the literature.

During the past years, progress has been made in the treatment of patients with cancer, and the proportion of patients achieving a complete remission and longer survival has increased. However, fungal infections have become one the leading factors contributing to morbidity and mortalitiy in patient with heamatological malignancies and solid tumours. Most opportunistic fungal infections are caused by Candida and Aspergillus species, but a growing number of less frequent fungal pathogens has been observed in recent years. The management of patients consist of a multidisciplinary approach combining radiology, new techniques in laboratory diagnostics such as serology and PCR as well as use of a growing armentarium of antifungal agents. Therapy of invasive mycosis no more rely on amphotericin B, but newer antifungal agents such as voriconazole and caspofungin have the potential to substitute the current standard therapy.

Antifungal Agents↗
PubMed2001

[Laparoscopic splenectomy in pediatric hematologic diseases].

INTRODUCTION: Surgical acceptance of the laparoscopic splenectomy in the pediatric hematological disorders has improved due to safety, to relif postoperative pain, and to reduce the hospital stay. The aim of this study is present our surgical laparoscopic technique performed. MATERIAL AND METHODS: Eight patients, 6 spherocytosis (age ranged: 6-14 years, average age: 9.5 years; 5 girls and 1 boy) and 2 cases of autoimmune hemolytic anemia (both boys of 18 months and 4 years) underwent laparoscopic splenectomy. The Trias-Targarona technique has been performed placing the patient at the right lateral-decubitus position. Four trocars are placed, two of 5 mm in the posterior axillary line and epigastrium and other 2 trocars of 12 mm, in the middle of them. RESULTS: In all these 8 patients a laparoscopic splenectomy was completely performed. We had 2 cases with problems with the sac introduction. Cosmetic results have been excellent and we changed the 7-day antibiotic protocol for 2-day protocol. The surgical time has changed from 3 to 2 hours. CONCLUSIONS: With laparoscopic splenectomy we can give an adequate response to hematological disorders in children with a acceptable surgical time, an excellent cosmetic result with a minimum postoperative time and a very short hospital stay.

Adolescent↗
PubMed1991

[Mesenteric and portal vein thrombosis following splenectomy in hematologic diseases. Apropos of 3 cases].

Mesenterico-portal venous thrombosis following hematological splenectomy is infrequent. We report about three cases successfully treated with heparin. A review of the literature allows identifying three factors acting in the etiopathogenesis of such thrombosis: alteration of blood composition, blood stasis and injuries to the vascular walls. The diagnosis is confirmed by ultrasonography and abdominal CT, and echo-Doppler will play a more important role in the future. The treatment of mesenterico-portal thrombosis is mainly medical, with surgery being indicated only in case of intestinal necrosis. An anticoagulant or platelet-suppressive treatment and the ligation of the splenic vein as close as possible to its junction with the mesenteric vein may be proposed as preventive measures.

Hematologic Diseases↗
PubMed1980

Complications after therapeutic splenectomy for hematologic disease in adults.

221 patients were treated by splenectomy for various hematologic disorders, including immunologic thrombocytopenia (80 cases), hereditary spherocytosis (15 cases), immune hemolytic anemia (25 cases), chronic lymphatic leukemia (27 cases), lymphosarcoma (27 cases), myelofibrosis (11 cases) and pancytopenia/aplastic anemia (14 cases). There were 8 postoperative deaths (3.6%), and 49 patients (22%) had postoperative complications, mainly infections and bleeding. Complications were more frequent in cases of massive splenomegaly (greater than or equal to 1 000 g) (65 cases), severe thrombocytopenia (less than 20 X 10(6)/1) (51 cases), and leukemia. Late postsplenectomy fulminant infection was seen in 8 patients (3.6%) for a mean follow up of 5.3 years. We conclude that splenectomy is sufficiently well tolerated even by severely ill patients to make it applicable as a therapeutic modality in the various hematologic disorders presently studied.

Adolescent↗