摘要:

The relative scarcity of Hodgkin (H) and Reed-Sternberg (RS) cells within biopsies from cases with Hodgkin's disease (HD) is an impediment to the analysis of the nature and function of these cells. Continuous cell lines as uniform and permanently available sources of cells provide a valid alternative. Development of HD cell lines has proven to be rather difficult when compared with the results on leukemia and Non-Hodgkin lymphoma cells. Only a few cell lines containing cells that resemble in-vivo H-RS cells have been established. Because the in-vitro culture conditions favor the self-propagation of residual normal cells, e.g. Epstein-Barr virus transformed B-lymphoblastoid cells or monocyte/macrophage monolayers, early attempts at culturing HD tissue resulted mainly in the generation of such cell lines. Even for the bona fide HD cell lines it is difficult to prove that the immortalized cells originated from an H-RS cell. These 13 HD cell lines have been extensively characterized in a large variety of aspects. These data have resulted in widely varying conclusions about the nature of the cell lines. It is apparent that all HD cell lines are unique among hematopoietic cell lines and are also different from one another. No conclusive evidence towards the origin of the cells has been obtained for some cell lines, while others could be operationally, albeit not always unequivocally, assigned to the T- or B-cell or monocyte-macrophage lineages. The overall phenotypes are often not concordant with those of normal hematopoietic cells; some cell lines show clearly mixed lineage attributes. The artifactual expansion of non-HRS cells in culture and the acquisition or loss of certain properties during the adaptation to culture systems cannot be excluded. There was also a bias for the establishment of cell lines from cases with advanced clinical stages, nodular sclerosing subtype and pleural effusions. The extensive analysis of a few cell lines has provided a wealth of information useful for the understanding of the biology of H-RS cells. The striking heterogeneity could be reflective of a biologically heterogeneous disease.

ISSN:1042-8194    

DOI:10.3109/10428199309148499

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

An historical appraisal of the clinical, hematological and biological features of erythroleukemia and myelodysplastic syndromes is presented in view of the current morphological and numeric FAB-criteria for myelodysplastic syndromes and acute leukemias.

ISSN:1042-8194    

DOI:10.3109/10428199309148500

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Chronic myelomonocytic leukaemia (CMML), a disorder belonging to the group of myelodysplastic syndromes, has a number of peculiar features which raise the question as to whether it should be considered a distinct entity in its own right. The problems associated with its classification and diagnosis are discussed in this report using all currently available tools from clinical data to molecular genetics, including morphology, histology, cellular biology and cytogenetics. Three groups of patients can be identified (isolated monocytosis with a mild degree of dysplasia, severe cytopenia and the most frequent type with proliferative symptoms dominating the clinical picture). The latter group is close to atypical chronic myeloid leukaemia and perhaps these two entities should be regarded as a single one. Classification of the disease is further complicated by the possibility of evolution from one subgroup into another one and by the finding that CMML can also arise as a disorder secondary to other myeloproliferative (MPS) or myelodysplastic (MDS) syndromes. No specific marker of the disease has been identified by cytogenetics or molecular biology. Due to all these facts, we believe that CMML should perhaps be viewed more pragmatically by considering the use of prognostic factors that could at least help to define different groups of patients who may require different therapeutic strategies. We conclude that CMML is a heterogeneous syndrome with features of both MPS and MDS, encompassing primary and secondary stem cell disorders and varying widely in its clinical presentation. This heterogeneity should stimulate the search for reliable predictors of evolution which would allow a better definition of CMML subtypes based on prognostic factors.

ISSN:1042-8194    

DOI:10.3109/10428199309148501

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Current understanding of molecular genetics enables the establishment of new categories based on pathogenesis. Philadelphia (Ph) chromosome-positive leukemia has been reclassified into two molecularly distinct subsets, and the leukemogenesis at the cell level might be linked to the molecular changes. Therefore, treatment for leukemia patients with Ph chromosome could be based on the molecular characteristics. In this review, we discuss the strategy of treating patients with Ph-positive acute lymphoblastic leukemia and the benefit of the combined modality of interferon and chemotherapy.

ISSN:1042-8194    

DOI:10.3109/10428199309148502

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

A cutaneous or systemic vasculitis occurs in myelodysplasia as well as in myeloproliferative and lymphoproliferative disorders. The most common lesion is a leucocytoclastic vasculitis, with neurological or joint involvement occurring less often. The vasculitis may appear contemporaneously with or precede the clinical onset of the blood dyscrasia. Occasionally the lesions respond dramatically to the use of steroids but in general, patients with vasculitis have a worse prognosis than those with uncomplicated myelodysplasia. Vasculitis and myelodysplasia appear together too often for the association to be coincidental and the vasculitis in most cases cannot be attributed to intercurrent infections, therapeutic agents or a pre-existing rheumatological disorder. While autoantibodies are frequently present in myelodysplasia, and ANA and anti-neutrophil cytoplasm antibodies (ANCA) are found in other vasculitides, neither of these antibodies is associated with the vasculitis of myelodysplasia. There has however been one report of ANCA in Sweet's syndrome a non-vasculitic skin condition that also occurs in the myelodysplastic syndromes.

ISSN:1042-8194    

DOI:10.3109/10428199309148503

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The megakaryocytic ploidy was microfluorometrically measured in 12 normal controls and 15 myelodysplastic syndrome (MDS) patients using DAPI (4′,6-diamidino-2-phenylindole) staining after destaining of the Wright-Giemsa (WG) stain. MDS patients had slightly more immature megakaryocytes when compared with normal controls. The megakaryocytic ploidy distribution had a peak at 16N in normal controls, at 8N in the 11 of the 15 MDS patients, and at 4N in the remaining 4 patients, which is suggestive of impaired polyploidization in MDS patients. In MDS, micromegakaryocytes were shown not to be immature but much more impaired in polyploidization than non-micromegakaryocytes. However, there was no difference in the megakaryocytic ploidy pattern among the type of the modification of Feinendegen' classification in each case for both the normal controls and the MDS patients, suggesting that the megakaryocytic ploidy is probably determined at the maturation level of the megakaryoblasts or the precursor cells. The study of megakaryocytic ploidy before and after therapy in the case of refractory anemia with excess of blasts might suggest that the remission of MDS patients might be qualitatively different from that seen in acute leukemia patients. Furthermore, the DNA histogram of the megakaryocytes from one of the two MDS patients obtained by the new method, which is able to determine the amount of DNA in the immunologically identified megakaryocytes microfluorometrically, using the monoclonal anti-glycoproteins IIb/IIIa antibody on bone marrow smears, showed a shift towards small ploidy compared with those defined on the basis of WG staining. This finding indicates that the micromegakaryocytes or the megakaryoblasts which could not be identified morphologically can be identified immunologically. This method may be useful, especially in the cases with pathological megakaryocytes and megakaryocytic precursor cells such as in MDS.

ISSN:1042-8194    

DOI:10.3109/10428199309148504

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

In order to evaluate the role of Mitoxantrone in the therapy of non-Hodgkin's lymphoma (NHL) (intermediate-high grade malignancy) a series of successive phase II-III studies were performed in a multicenter cooperative group. The first phase II study consisted of Mitoxantrone alone administered at 14 mg/m2i.v. on day 1 and repeated every 3 weeks for six times. Fifteen refractory or relapsed patients (pts) entered the study, and an overall response of 54% (CR 4 pts, PR 4 pts) was obtained. 7 pts progressed or remained stable disease (NR).The second phase II consisted of Mitoxantrone in combination with Etoposide and Prednisone (VeMP). Twenty pts were treated and a complete remission (CR) of 50% with 1 partial remission (PR) were obtained with an overall response of 55%. The third phase II study consisted of 13 pts with refractory or relapsed disease treated with Mitoxantrone, Cis-platinum, Etoposide and Prednisone (CEMP); an overall response of 62% was obtained with an acceptable toxicity. This was not superior to other conventional salvage regimens.On this background a phase III study with VEMP (Etoposide, Cyclophosphamide, Mitoxantrone, Prednisone) was started as first line therapy for pts presenting one or more of following criteria: Performance Status (P.S.) 2–3, aggressive histology at stage I-IIE or advanced stage in old pts, low grade histology with B-symptoms stage in III-IV, age over 65 years.Until now 64 pts entered this study. At present 61 pts areévaluable for response: CR was obtained in 43 pts (70%), PR in 9 pts (15%), progression disease (PD) in 9 pts (15%) 4 pts relapsed within one year after the CR.These data suggest that the VEMP combination (VEMP) is safe and as effective as other more aggressive regimens. Moreover the low hematological and general toxicity indicate this regimen as useful especially for pts not eligible for anthracycline-including protocols, and old aging pts.

ISSN:1042-8194    

DOI:10.3109/10428199309148505

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The use of high-dose cyclophosphamide, carmustine, and etoposide (CBV) with autologous bone marrow transplantation (ABMT) results in long-term disease-free survival of about 30% in patients with relapsed Hodgkin's disease. Laboratory and clinical data show that cisplatin is synergistic with etoposide and carmustine, with non-overlapping extramedullary toxicity. Twenty-one patients with relapsed Hodgkin's disease that had progressed after both MOPP-like and ABVD-like regimens were treated with CBV plus cisplatin (90 mg/m2) and ABMT. The CR rate was 55%; the three-year disease-free and overall survival were 29% and 38% respectively; these results are comparable to prior experience with CBV. Performance status was strongly correlated with achievement of CR, survival, and time to treatment failure. Nephrotoxicity was seen in 3 patients, and ototoxicity in 1 patient. Although cisplatin could be added to CBV with minimal additional toxicity, the results obtained in this small patient population were not better than those of the earlier regimen. A larger trial in patients not previously exposed to cisplatin may better define the role of its addition to CBV.

ISSN:1042-8194    

DOI:10.3109/10428199309148506

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

It has been recently demonstrated that erythropoietin increases the haemoglobin levels in anemia secondary to chronic renal failure. Moreover some recent experiences also suggested a possible role in the treatment of MDS. From April 1990 to April 1992, 23 patients (16 males and 7 females, median age 63.S years) affected with low risk myelodysplastic syndrome (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and transfusional requirement. All patients received high doses of rHuEPO (800 U/Kg weekly s.c. in 2–3 divided doses, for 3 months). A complete remission, defined as stable normalization of Hb level, was achieved in 1/23 patients. This patient had refractory anemia, by FAB criteria. A partial response, defined as stable increase of Hb levels≥lg/dl and/or reduction of transfusional requirement≥50% lasting at least 3 months, was achieved in 7/23 patients. Patients with a partial response received rHuEPO at increased dosages (1200 U/Kg weekly s.c. 2–3 times): 1/7 achieved a complete response, 4/7 remained stable and 2/7 decreased to pre-therapy Hb value. These results suggest that rHuEPO may be a promising therapeutic tool for some MDS patients.

ISSN:1042-8194    

DOI:10.3109/10428199309148507

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Tumor-infiltrating T lymphocytes (TIL-T) were quantitated by three color flow cytometry in cell suspensions from excisional biopsy specimens of 43 B cell non-Hodgkin's lymphomas (NHL) and 8 benign lymphoid hyperplasias (BLH) to identify potential differences in host T cell responses. We quantitated three TIL-T subsets: CD3 + CD4 + CD8- (helper-inducer), CD3 + CD4-CD8 + (suppressor-cytotoxic) and CD3 + CD25-HLADr+ (long term activated TIL-T) and compared them in three diagnostic groups: BLH, low grade B cell NHL (LG NHL) and intermediate-high grade B cell NHL (IG-HG NHL). The following results were obtained: Mean percentage±s.e. of activated TIL-T for BLH, LG-NHL and IG-HG NHL: 10.3±1.9, 23.2±4.6 and 38.8±9.5, respectively. Mean percentage±s.e. of suppressor-cytotoxic TIL-T for same groups: 13.9±1.5, 14.9±1.9 and 34.4±4.5, respectively. Mean percentage±s.e. of helper-inducer TIL-T cells for the same groups was 38.2±12.7, 32.1±7.2 and 22.5±4.6, respectively. Helper/suppressor ratio±s.e. for same groups was 3.0±1.1, 2.4±0.6 and 1.3±0.4, respectively. Activated and suppressor-cytotoxic TIL-T percentage progressively increased from BLH toward IG-HG NHL. The percentage of these two TIL-T subsets were significantly higher in IG-HG NHL than in BLH and LG-NHL (P<0.0007, 0.0002, 0.0001 and 0.0260 for the comparisons TIL-T in BLH vs IG-HG NHL and LG-NHL vs IG-HG respectively). These results suggest the possibility that activated-cytotoxic TIL-T represent a host cellular immune response versus neoplastic NHL B cells and encourage future in vitro functional studies.

ISSN:1042-8194    

DOI:10.3109/10428199309148508

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor