摘要:

Poor prognosis AML consists of 3 clinically definable groups of patients whose response to therapy is substantially worse than that of standard prognosis patients. The response rate is lowest for those patients who have more than a single risk factor and for the patients who have low platelet and serum albumin levels at diagnosis. The treatment associated mortality of the latter patients is quite high. Even if one avoids the high mortality rate by carefully selecting patients the likelihood that drug resistant disease is present is very high. Since the basis for resistance is multifactorial, a variety of strategies will have to be explored as means to improve treatment outcome. At the present time, the greatest chance for long term survival is found in relatively young patients whose AML is induced into complete remission and who then receive a matched allogeneic bone marrow transplant.

ISSN:1042-8194    

DOI:10.3109/10428199309148524

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Cytogenetic patterns in correlation with cytologic, biomolecular and clinical findings were studied in 45 adult patients with AML expressing at least one of the following lymphoid associated markers (LM): CD2, CD7, CD10, CD19, CD22, TdT. Four cytogenetic groups were recognized: group I, including 8 patients with 11q23 rearrangements; group II including S patients with the Ph chromosome; group III, with 19 patients and aberrations of the“myeloid type”including 4 cases with aberrations of chromosome 13, 3 cases with lq and 7q anomalies, 2 cases with trisomy 1 lq; group IV, including 13 patients with normal karyotype.Patients showing extensive lineage infidelity were encountered more frequently in cytogenetic groups I and II than in groups III and IV. Two of 4 cases with aberrations of chromosome 13 showed two or more lymphoid features either at immunophenotyping or at biomolecular analysis of the configuration of lg and TCR genes. Patients with 1 Iq23 rearrangements and with the Ph chromosome were generally young, presented with high WBC count and had low complete remission rate. Survival in Ph chromosome positive patients was uniformly short. We conclude that, although there is no cytogenetic anomaly specific for AML with LM, chromosome findings may be clinically relevant in AML with LM. A morphologic, immunologic and cytogenetic classification of AML with LM may constitute a working basis for future studies aimed at a better definiton of clinicopathological features and optimal treatment strategy for these leukemias.

ISSN:1042-8194    

DOI:10.3109/10428199309148525

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The use of chemotherapeutic drugs in combination with bone marrow transplantation to treat cancer patients has markedly improved the disease-free survival and cure rate. Part of the tumor cells, however, can escape from therapy due to resistance. Tumor-specific delivery of toxins that do not interfere with conventional drugs and are not cell cycle dependent seems to be a reasonable approach to overcome this problem. Natural ribosome-inhibiting-proteins (RIPs) from plants, bacteria and fungi which are extremely toxic inhibitors of protein synthesis are isolated and coupled to monoclonal antibodies (MoAbs) and receptor-specific ligands, immunotoxins (ITs), to fulfil this purpose. ITs are very suitable to eliminate malignant cells in vitro and in vivo.RIPs contain two or three active sites: a binding site which can be absent in a part of the RIPs and can be replaced by the MoAb; a translocation site that facilitates transport into the cytosol after internalization, and a cytotoxic site that enzymatically inhibits protein synthesis. Binding site containing toxins induce strong nonspecific cytotoxicity when coupled to MoAbs. Recent developments in recombinant DNA techniques enable genetic elimination of the binding site to reduce nonspecific cytotoxicity of these toxins.In this review the structures and mechanisms of action of RIPs as well as factors that influence cytotoxicity of immunotoxins are discussed. Moreover the problems dealing with in vivo application of ITs such as blood clearance by instability of the IT and hepatic entrapment, and production of antibodies directed against MoAb and toxin are reviewed.

ISSN:1042-8194    

DOI:10.3109/10428199309148526

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Current concepts of immunotherapeutic approaches in Ieukemias and lymphomas using activated cytotoxic lymphocytes and macrophages are briefly reviewed. Defective cellular immunocytotoxic activities and effects of interleukins and chemotherapeutic drugs thereupon are discussed. In vitro assays to measure lymphokine-activated killer (LAK) and natural killer (NK) cell activities suffer from various problems, depending on the quality of the endpoints. Our clonogenic microassay for LAK cell activity, using agar-containing glass capillaries, avoids some of the potential artifacts and offers several advantages that are discussed. As an example the stimulatory effect of low mafosfamide concentrations on the LAK cell activity versus K562 human myeloid Leukemia cells is demonstrated. Thus, our clonogenic LAK microassay provides a valid tool for preclinical screening of immunomodulatory agents.

ISSN:1042-8194    

DOI:10.3109/10428199309148527

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Tissues containing Hodgkin's disease tumors of the nodular sclerosis and mixed cellularity subtypes are frequently infiltrated by numerous degranulating eosinophils that release granule proteins such as eosinophil peroxidase and major basic protein. Until recently, the causes of the eosinophil infiltration and degranulation in Hodgkin's disease tumors were unknown. Analysis of Hodgkin's disease tissues by a sensitive and specific immunoperoxidase technique has now demonstrated the extensive presence of IgE in the Reed-Sternberg cells and adjacent cells of Hodgkin's disease tumors. Because eosinophils express a cell-surface receptor (CD23) for IgE and degranulate in the presence of IgE deposits, the extensive eosinophilia that is frequently present in Hodgkin's disease tumors is, at least in part, attributable to the IgE deposits within the tumor. In this review, we discuss the possible mechanisms and biological significance of IgE-related eosinophilia in Hodgkin's disease.

ISSN:1042-8194    

DOI:10.3109/10428199309148528

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

CD30+anaplastic large cell lymphoma (ALCL) represents a novel lymphoma entity at the borderline between Hodgkin's disease and non-Hodgkin's lymphomas. Phenotypic, genotypic, and karyotypic analyses have shown that ALCL are heterogeneous in cellular origin, and may be conceived as malignancies derived from activated, mainly T–or B-lymphoid cells, in some instances with an immature genotype. Epstein-Barr virus genomes and gene products, most notably the transformation-associated latent membrane protein (LMP), have been detected in a proportion of cases, and some cutaneous ALCL proved to harbor complete or incomplete HTLV-1 proviruses. These findings suggest that both EBV and HTLV-I, which are powerful inducers of CD30 expression in lymphoid cellsin vitro, may contribute to the pathoetiology of ALCL.

ISSN:1042-8194    

DOI:10.3109/10428199309148529

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Hematopoietic growth factors stimulate proliferation and enhance functional activity of hematopoietic cells. Erythropoietin, recombinant human (rh) granulocyte colony stimulating factor (CSF), rh granulocyte macrophage CSF and rh interferon have been proven to be a clinically useful therapy. Several other cytokines with other unique effects are being developed for possible clinical usage. The purpose of this manuscript is to review novel uses of current approved cytokines and potential application of experimental growth factors.

ISSN:1042-8194    

DOI:10.3109/10428199309148530

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Second malignancies represent an important iatrogenic complication of the treatment of hematologic and other neoplasms. In this review we summarize the literature relating specifically to malignancies developing in the wake of treated non-Hodgkin's lymphoma (NHL). In these patients, the risk of myelodysplastic syndrome (MDS) and acute non lymphocytic Leukemia (ANLL) is reported to be increased 10–105 fold over that of the general population. Factors in the development of MDS and ANLL include basic defects in cellular immunity in NHL patients as well as treatment with alkylating agents and low dose total body irradiation. Biologically these secondary MDS and ANLLs are characterized by specific cytogenetic abnormalities and results of treatment are poor. Currently bone marrow transplantation offers the only potential cure.There is no clear statistical evidence that solid tumors occur more frequently after NHL. However, bladder carcinoma, in cyclophosphamide treated patients, and lung cancer have been reported by some to occur with an increased incidence. Further investigation of the molecular events leading to the occurrence of second malignancies in NHL patients and the role played by oncogenes and tumor suppressor genes in this process is still needed.

ISSN:1042-8194    

DOI:10.3109/10428199309148531

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

There is a strong association between ability of Leukemia blasts to accumulate ara–CTP, the active metabolite of ara-C, and response to ara-C in patients with relapsed or refractory AML. Ara-C dose rates in excess of 0.5 g/m2/h do not produce further ara-CTP formation. In contrast, when given 4 h prior to ara-C at this dose rate, fludarabine, at doses that are free of neurotoxicity in CLL, enhances ara-CTP accumulation. This led us to administer fludarabine and ara-C to 59 patients with AML in relapse or unresponsive to initial therapy. Fludarabine was given at 30 mg/m2once daily for 5 doses and ara-C at 0.5 g/m2/h for 2–6 h daily for 6 doses. Doses of fludarabine preceded those of ara-C by 4 h. Results with fludarabine and ara-C (FA) were compared with those of patients treated at M.D. Anderson with high-dose ara-C (HDAC) or intermediate-dose ara-C (IDAC). The complete remission rate with FA was 21/59 (36%) and the actuarial median CR duration 39 weeks. FA produced significantly higher remission rates than HDAC or IDAC in patients with initial remissions>1 yr (14/20 vs 9/23 vs 6/18, p<0.05). Response rates were similar for all three treatments in patients with initial remissions<1 yr or with primary refractory disease. The regimen was well tolerated; one patient developed peripheral neuropathy. This low level of toxicity encourages combination with other antiLeukemia agents.

ISSN:1042-8194    

DOI:10.3109/10428199309148532

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Cerebrospinal fluid (CSF) neopterin levels were determined by high-pressure liquid chromatography in 48 normal children and in 15 children with meningeal relapse of hematologic malignancies (13 acute lymphoblastic leukemia and 2 high-grade lymphomas). When meningeal relapse was diagnosed, all patients had CSF neopterin levels higher than mean normal value + 2 standard deviations. No significant correlation between the blast count in the CSF and neopterin levels was observed. CSF data before relapse were available in 10 children: the neopterin values at relapse were significantly higher than values observed at diagnosis. In 3 patients, elevated neopterin levels preceeded the occurrence of neurologic signs and the detection of blast cells in CSF by 15 to 30 days. In the absence of infection, the rise of CSF neopterin levels in patients with hematologic malignancies indicates an active phase of the disease. This could reflect a cell-mediated immunologic process induced by malignant cells. The measurement of CSF neopterin should be helpful in the monitoring of patients to detect early meningeal relapse.

ISSN:1042-8194    

DOI:10.3109/10428199309148533

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor