摘要:

Forty one patients with acute myeloid leukemia (AML), including 27 at presentation and 14 relapsed or resistant cases, were assessed for laboratory evidence of the MDR phenotype. Leukaemic cells from all 41 cases were studied by immunocytochemistry using the JSB-1 monoclonal antibody and simultaneously by reverse transcription polymerase chain reaction (RT-PCR) to evaluate expression of the mdr 1 gene. Cells from 32/41 cases were also assessed for daunorubicin (DNR) accumulation and retention by flow cytometry (FC). Nineteen of the 41 (46%) patients were positive for MDR by JSB-1 immunocytochemistry (11/27 [41%] at presentation and 8/14 [57%]relapsed or resistant cases). Nine of the 19 (47%) P-gp positive, de novo patients achieved complete remission. 22 patients were negative by JSB-1 immunocytochemistry (16/27 [59%] at presentation and 6/14 [43%]of the relapsed or resistant cases) and 11/22 (50%) P-gp negative patients achieved a complete remission.Of the 32 patients assessed by FC, 7 (22%) were positive for the MDR phenotype with increased DNR accumulation and retention in the presence of the MDR reversing agent verapamil (VPM). 6/7 of the FC positive cases were also JSB-1 positive, and 6 had additional poor risk features. Of the twenty five FC negative patients, 6 had received previous chemotherapy and 15 (60%) achieved complete remission. Mdr 1 mRNA levels were increased in all seven FC positive cases whereas only 7/19 JSB-1 positive cases had raised mdr 1 mRNA levels.These results suggest that the assessment of MDR status by immunocytochemistry using JSB-1 is not predictive of response to chemotherapy. Flow cytometric analysis of blast cells appears to correlate well with mdr 1 mRNA levels and may be a better predictor of treatment outcome.

ISSN:1042-8194    

DOI:10.3109/10428199309087001

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Granulocyte colony-stimulating factor (G-CSF) is a potent stimulator of the growth of normal and malignant hematopoietic cells and synergizes with other factors such as interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The action of G-CSF is mediated through a specific membrane receptor, however it is not clear if all of the effects of G-CSF are direct or indirect. As a step towards addressing this problem, a recombinant diphtheria toxin (DT)-related human G-CSF fusion protein has been constructed and purified fromE. coli.The 70,000 dalton chimeric protein has immunologic determinants characteristic of both DT and G-CSF. At high concentrations, DAB486-G-CSF is cytotoxic towards G-CSF-dependent OCI/AML1 cells, but not factor independent OCI/AML3 cells; colony formation by G-CSF-responsive leukemic blasts from a patient with acute myeloblastic leukemia (AML) was also inhibited. The G-CSF fusion toxin displayed ADP-ribosyltransferase activity in a cell-free system. Genetic conjugation of G-CSF to an enzymatically inactive DT mutant, CRM197, resulted in a 200-fold reduction in the ability of G-CSF to stimulate normal bone marrow colony formation. These results suggest that fusion of G-CSF to DT sequences interferes with some of the activity but not the specificity of the ligand binding domain of the molecule. Nevertheless, DAB486-G-CSF may be included with the increasing number of other toxin-hormone fusion proteins whose toxicity is directed towards specific receptor-bearing cells, and may represent a novel approach towards the study and treatment of leukemia.

ISSN:1042-8194    

DOI:10.3109/10428199309087002

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Human umbilical cord blood cells represent a potential alternative to bone marrow as a source of stem and progenitor cells for allogeneic transplantation. Therefore, many studies are underway to evaluate the number of cord blood stem cells and their amplification potential. We analyze here the amplification potential of CD34+cord blood cells in liquid cultures stimulated with stem cell factor (SCF) in combination with interleukin-3 (IL-3), erythropoietin (Epo) or granulocyte colony-stimulating factor (G-CSF) under serum-deprived conditions. We report that under certain circumstances (stimulation with SCF and IL-3, replacing of the medium and growth factors every 3-4 days, no change of the initial culture flask, 37°C as incubation temperature), CD34+cells give rise to differentiated cells and progenitor cells for more than two months. During this period, more than 1010differentiated cells and 106progenitor cells are generated from 0.25-1×104CD34+cells in the absence of a stromal layer. These data highlight the high proliferative and differentiative potential of cord blood stem cells and, because the culture procedures are relatively simple and do not require a stromal layer, open the way to the clinical use of ex vivo stem cell expansion.

ISSN:1042-8194    

DOI:10.3109/10428199309087003

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Cardiotoxicity is a well recognized side effect of anthracyclines (doxorubicin and epirubicin) or antracenadiones (mitoxantrone) at cumulative or high doses. However the side effects have not been evaluated in adults with Hodgkin's disease who received therapeutic doses of these drugs. We analyzed the cardiac function studying the left ventricular ejection fraction (LVEF) at rest in 136 patients with Hodgkin's disease treated with doxorubicin, epirubicin or mitoxantrone used in combination with vinblastine, bleomycin and decarbazine. No other risk factors, such as radiation therapy to the mediastinum, were considered. The follow-up is 5 to 8 years for patients in complete remission. Forty-five patients received doxorubicin (from 325 to 685 mg/ m2, median 475 mg/m2), 51 patients received epirubicin (from 310 to 610 mg/ m2, median 510 mg/m2) and 40 patients were treated with mitoxantrone (from 70 to 165, median 125 mg/m2). The median time between the end of treatment and the evaluation was 6.7 years. Thirty seven percent of the patients (similar rates in the three groups) showed abnormalities in the LVEF with decreased rates independent of the drug dosage. These were compared with two control groups, 46 patients treated with the MOPP combination (me-chlorethamine, vincristine, prednisone and procarbazine) or LOPP (chlorambucil, for me-chlorethamine) and 35 healthy volunteers. We believe that the use of anthracyclines or an-tracenadione will produce late cardiac effects in a fraction of patients independently of the doses used and that the indications for these drugs be carefully monitoring so as to evaluate the development of late side effects.

ISSN:1042-8194    

DOI:10.3109/10428199309087004

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

To identify factors that might improve the prognosis of adult T-cell leukemia/lymphoma (ATL), we reviewed data on 47 autopsied cases of ATL with reference to the complications and cause of death. The primary cause of death was respiratory insufficiency due to pulmonary infection. Respiratory insufficiency was also attributed to the diffuse alveolar damage and pulmonary fibrosis resulting from chemotherapy given and oxygen. About 90% of the cases had infections with one or more pathogens. Cytomegalovirus (CMV) was the most frequent pathogen involved in 35/47 (74.5%) while fungal infections were also commonly seen in 25 of the 47 cases (53.2%). Of these, 17 (70%) had pulmonary aspergillosis. Other neoplasias were present in 10 of the 47 cases, while hypercalcemia was evident in 21 patients. These findings suggest that the prevention and treatment of nosocomial infections and of drug-induced pulmonary toxicity may improve the prognosis and quality of life of ATL patients.

ISSN:1042-8194    

DOI:10.3109/10428199309087005

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Treatment of a 74 year old patient with chronic myelogenous leukemia (CML) with busulphan resulted in an abrupt and pronounced decrease of the white blood cell (WBC) count with restoration of normal peripheral blood cell morphology and regression of splenomegaly. The Philadelphia positive (Ph+) clone was however still detectable. The alterations in the WBC count and morphology were not preceded by marrow hypoplasia but correlated closely with a marked decrease in the serum levels of Transcobalamin I (TC I), a vitamin B12-binding protein derived from immature myeloid precursors and a reciprocal rise in serum TC III, a vitamin B12-binding protein originating from terminally differentiated mature granulocytes. Studies on the HL-60 cell line showed that busulphan is capable of inducing leukemic cells to differentiate into granulocyte-like cells. These observations, taken together, suggest that in addition to its potent myelosuppressive effects, busulphan may induce apparent clinical remissions in some CML patients by promoting terminal cell differentiation.

ISSN:1042-8194    

DOI:10.3109/10428199309087006

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Permanently established human cell lines can produce several retro viruses. It is important to routinely test such cell lines for human T cell lymphotropic virus (HTLV) type I and II, and for human immunodeficiency virus (HIV) type 1 and 2 in order to exclude any potential biohazard from cell lines producing human retroviruses. Reverse transcriptase assay, polymerase chain reaction,* and dot-blot hybridization of in-vitro amplified DNA with virus-specific probes are used.

ISSN:1042-8194    

DOI:10.3109/10428199309087007

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

A fourteen month old boy presented with hepatosplenomegaly and pancytopenia. An extensive evaluation, including bone marrow aspiration and biopsies of both liver and lymph nodes, revealed a polyclonal B cell proliferation consistent with a reactive process, with no evidence of leukemia. After receiving transfusions of red cells and platelets, his blood counts recovered. Five weeks later, he returned with an elevated white blood count and bone marrow findings diagnostic of acute lymphocytic leukemia. The leukemic blasts contained a novel chromosomal translocation, t(5; 14) (q34;q12). We describe the clinical, immunophenotypic and cytogenetic features of this case, review the literature of acute lymphocytic leukemia associated with a preleukemic phase, and discuss the relationship of this clinical entity to the Sq-abnormality associated with myelodysplasia.

ISSN:1042-8194    

DOI:10.3109/10428199309087008

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We describe a case of acute myeloid leukaemia (Mo) presenting with pericardial and pleural effusions due to a granulocytic sarcoma adherent to the thymus gland situated in the anterior mediastinum. This has not been described previously in the setting of AML Mo.

ISSN:1042-8194    

DOI:10.3109/10428199309087009

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

We present a unique case of crisis type chronic adult T-cell leukemia (ATL), in which the majority of leukemic cells had abundant periodic acid-Schiff (PAS)-positive cytoplasmic inclusions. These inclusions were found to be composed of glycogen because the PAS-positivity completely disappeared after digestion with amylase or human saliva. Electron microscopy also revealed that the inclusions consisted of aggregated beta particles of glycogen. The mechanism of glycogen accumulation in leukemic cells remains unknown; however, the presence of such inclusions in leukemic cells may be helpful diagnostically in T-lymphocyte malignancies.

ISSN:1042-8194    

DOI:10.3109/10428199309087010

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor