摘要:

Abstracts: The term familial and congenital polycythemia encompasses a heterogeneous group of disorders with the common characteristic of an absolute increased red cell mass since birth and/or similar phenotype also present in relatives. In the last 2 decades the differential diagnosis between primary and secondary familial polycythemias became more physiologically relevant as new sensitive techniques, such as accurate measurements of serum erythropoietin (S‐EPO) concentration by radioimmunoassay (RIA) or ELISA, and assessment of growth of erythroid progenitor cellsin vitrobecame available. Consequently, correct classification of many older previous reports of familial polycythemias is difficult. While familial secondary polycythemias due to high oxygen affinity hemoglobin mutants are not infrequent and have been well delineated in terms of molecular pathophysiology and phenotype during the last 3 decades, those secondary familial polycythemias due to 2,3 DPG deficiency are very rare. Familial and congenital polycythemias with increased EPO concentration and normal arterial oxygen saturation and oxygen dissociation kinetics represent an intriguing group of disorders wherein the molecular lesions remain obscure; however, in some instances a possibility of abnormal oxygen sensing pathway involving hypoxia inducible factor –1 (HIF‐1) open an intriguing yet unexplored area of hematology and biology. In contrast the primary familial and congenital polycythemia (PFCP) has been only recently recognized (the first report published in 1977). Various designations have been used in the past to describe PFCP, a rare clinical syndrome, including: benign familial erythrocytosis, polycythemia vera of childhood, primary polycythemia, pure erythrocytosis, etc. Some of these terms stressed the relatively benign, non‐progressive course of the disease with a normal lifespan of affected subjects; however, the apparent benignity of some of these disorders has been questioned. These disorders are familial and/or congenital, and the clinical and laboratory evidence of secondary polycythemias must be excluded. Only about 2 dozen familial and sporadic cases with PFCP have been reported. However, the mutations of erythropoietin receptor (EPOR) found in some of families with PFCP represent the only defined molecular defect of primary polycythemic phenotypes. All reported PFCP associated EPOR mutations result in truncation of its intracytoplasmic C‐terminal domain which negatively regulates the EPO/EPOR signal transduction pathway. Subjects with these mutations have decreased or normal S‐EPO and increased sensitivity of erythroid progenitor cells to low EPO concentrations inin vitroassays. Mutations of other genes involved in post EPOR signaling pathway such as JAK‐2, HCP and STAT 5 may also play a causative role in pathogenesis of some of PFCP families where mutation of EPO

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01376.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: The aim of this study was to investigate if a single apheresis after peripheral blood progenitor cell (PBPC) mobilization can be used to rescue patients receiving high dose chemotherapy (HD.CHE) as treatment for an underlying malignancy. Eighteen consecutive patients who were admitted to the transplant unit for treatment were leukapheresed following mobilization with one of the following protocols: group I: rHuG–CSF alone, group II: conventional chemotherapy (C.CHE)+rHuG–CSF or rHuGM–CSF and group III: high dose Cytoxan (HD.CTX)+rHuG–CSF. The optimal day for leukapheresis was determined by following white blood cell counts (WBC), mononuclear cell counts (MNC) and CD34+cell counts daily. Granulocyte – macrophage colony‐forming cells (GM–CFC) assay was performed at the leukapheresis product and prior to reinfusion. All patients proceeded directly to ablative therapy according to their underlying malignancy. PBPC from single apheresis were reinfused to all patients and cytokines started 24 h after infusion. Hematologic recovery after HD.CHE was the parameter used to ensure successful engraftment. We have been able to recover adequate number of PBPC for transplantation with a single apheresis in all patients. The number of infused cells were for groups I, II and III: (1) median number of MNC 4.7, 3.58 and 2.79 × 108/kg, respectively (2); median number of CD34+cells 4.4, 2.8, 2.7 × 106/kg, respectively. The median apheresis day was 6, 16 and 16, respectively. Recovery times to granulocyte count>0.5 × 109/L was 9 d (range 9–12) and to platelets>20 × 109/L was 12 d (range 1–135); 17/18 patients have engrafted successfully independent of the mobilization method used.These data suggest that sufficient PBPC can be harvested at a single leukapheresis for hemopoietic rescue after myeloablative therapy. Rapid hematologic recovery occurs when cytokines alone after conventional or HD.CHE are used for mobilization. Results of collection products and hematopoietic recovery are independent of the mobi

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01377.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The present study aims at expressing a reporter gene in hematopoietic cellsin vivoby introducing it into primitive hematopoietic cells with a 2‐gene retroviral vector. Various constructs of retroviral vectors containing the human IL‐2 receptor α chain gene (TAC) as the reporter and the neomycin phosphotransferase gene (neo) as a selectable marker were engineered, and the effectiveness of these vectors for expression of the reporter gene was evaluated after transfection into the packaging cell line GP+E86. It was found that the highest levels of reporter gene expression were attained with constructs ordered 5′ long terminal repeat (LTR)‐TAC‐internal promoterneo‐3′ LTR. In experiments investigating the expression of a reporter gene in hematopoietic cells, we used theEscherichia coliβ‐galactosidase gene (lacZ) instead of TAC, because a very sensitive detection method was available for lacZ. For transduction of hematopoietic progenitors, packaging cell lines producing recombinant viruses were cultured in a Transwell hung into a Dexter‐type bone marrow (BM) culture. The BM cells were selected with G418, and transferred into irradiated recipient mice. LacZ enzyme activity was detectable in the peripheral blood lymphocytes (PBL) of recipients taken 8 wk a

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01378.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In order to assess the relative importance of the clinicohematological features most commonly associated with the accelerated phase (AP) of chronic myeloid leukemia (CML) in 175 consecutive patients, 12 variables generally considered as indicating AP were analyzed for their predictive value for blast crisis (BC) appearance in less than 1 yr. At the time of analysis, 118 patients had died and 104 had developed BC. At univariate study, 6 features were associated with a significantly higher BC‐probability: poor performance status (ECOG score>2), unexplained fever/sweats, severe bone pain, progressive splenomegaly despite adequate therapy, blood basophils (>20%) and peripheral blasts (6–12%). At logistic regression, only bone pain and blood blasts (6–12%) retained their prognostic importance; the relative risk of unexplained fever/sweats and progressive splenomegaly was also clinically relevant. One‐year BC‐probability from the appearance of 1 or more of the above features was 77.3% (95% CI: 66–86.6) and 100% since all 4 were observed. Finally, at least 1 of the 4 features was present prior to death in 6 of 7 patients dying from CML‐related causes while not in BC. AP can be defined by the appearance along CML evolution of 1 or more of the 4 above‐mentioned clinicohematol

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01379.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: In a multicentre study of 635 consecutive newly diagnosed patients with B‐CLL, the histological bone marrow (BM) specimens were reviewed independently by each of 3 pathologists and found evaluable for BM infiltration pattern in 575 patients, 404 of whom had a CD5+, mainly FMC7–, faint surface‐membrane immunoglobulin (SIg) fluorescence‐intensity phenotype. In these 404 patients the following BM infiltration patterns were found: mixed nodular‐interstitial (30%), moderate interstitial (44%), heavy interstitial (20%) and diffuse packed (6%). In univariate survival analysis, significant differences were found according to BM pattern (p<0.05), the presence of nodules being a favorable prognostic sign. In multivariate survival analysis in a model including age, clinical stage, BM pattern, BM lymphocytosis, WBC and sex, only age and stage but not BM pattern or BM lymphocytosis had independent prognostic significance. In stage A, progression‐free survival was significantly longer in patients with nodular than in patients with non‐nodular bone‐marrow pattern. The overall survival of these patients, however, did not differ, possibly owing to the prompt and prolonged treatment given to most patients at the time of progression to stage B or C. We conclude that in CD5+, SIgfaint, mainly FMC7–B‐CLL, bone‐marrow histology may predict unstable disease in early clinical stage but is not important for treatment decisions, when these are

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01380.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all‐trans retinoic acid (ATRA) on thein vitroautocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; thein vitrosecretions of IL‐1α, IL‐3, IL‐4, IL‐6, IL‐10, G–CSF, GM–CSF, TNF‐α were tested with and without ATRA addition. After 5 d exposure to ATRA 10−6mAPL‐treated samples showed a significant reduction of IL‐6 (p= 0.008) and GM–CSF (p= 0.03) and a significant increase of IL‐1α (p= 0.01) production, if compared to untreated APL samples. No difference was seen in IL‐3, IL‐10 and IL‐4 productions; G–CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G–CSF‐producing cases did not obtain clinical remission with ATRA; GM–CSF and IL‐6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF‐α was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL‐6 was more than twice as high in ANLL non‐APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the ex

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01381.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: The aim of this study was to compare the clinical effect of transfusion of platelet concentrates (PC) prepared from pooled buffy coats (BC) and PCs collected from a single donor (SD) by an apheresis technique. The influence of storage time and various clinical conditions was also studied. Thirty‐two patients suffering from haematological malignancies were given a total of 326 platelet concentrates; 180 BC‐PCs and 146 SD‐PCs, median 7 transfusions per patient. BC‐PCs contained 312±52×109and SD‐PCs 383 ± 133 × 109platelets/unit (mean ± SD). The mean storage time of BC‐PC was 3 d and that of SD‐PC 1 d. The mean platelet count of the patients before transfusion was 11 ± 8 ×109/L. Regression analysis showed a significant decrease of the post‐transfusion platelet corrected count increment (CCI) during storage of PCs for 1–5 d (BC‐PC:p<0.01; SD‐PC:p<0.05). There was no difference in platelet increment between BC‐PC and SD‐PC. Human leukocyte antigen (HLA) alloimmunization was the major cause of clinical refractoriness to random donor platelet transfusions but splen

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01382.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologous natural killer (NK) cells treated with NK cell‐activating cytokines such as interleukin‐2 (IL‐2) or interferon‐α (IFN‐α). The cytokine‐induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by counterflow centrifugal elutriation. Histamine, at concentrations exceeding 0.1 μM, abrogated the monocyte‐induced inhibition of NK cells; thereby, histamine and IL‐2 or histamine and IFN‐α synergistically induced NK cell‐mediated destruction of AML blasts. The effect of histamine was completely blocked by the histamine H2‐receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the monocyte‐induced inhibition of NK cell‐mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the respiratory burst of monocytes. It is concluded that (i) monocytes inhibit anti‐leukemic properties of NK cells, (ii) the inhibition is conveyed by monocyte‐derived ROM, and (iii) histamine reverses the inhibitory signal and, thereby, synergizes with NK cell‐activating cyto

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01383.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract: ACES (Ara‐C, carboplatin, etoposide, steroids) therapy using granulocyte‐colony stimulating factor (G–CSF) was designed for relapsed or refractory non‐Hodgkin's lymphoma (NHL), and the therapeutic effects and adverse reactions were studied. The subjects were 40 patients, including 19 relapsed cases and 21 refractory cases, subjected to chemotherapy using anthracycline type agents. The ACES therapy consisted of carboplatin at 100 mg/m2and etoposide at 80 mg/m2for 4 d from the first day, Ara‐C at 2 g/m2on the fifth day, solumedrol at 500 mg for 5 d from the first day and G–CSF at 2 μg/kg from the seventh day. This therapy was performed every 3 weeks, in principle. The doses were reduced to 70% of the above values for patients aged 70 yr or older. Among the 40 patients, complete remission (CR) was achieved in 14 (35%) and partial remission (PR) in 14 (35%) for a response of 70%. The 50% survival period was 526 d, and the 2‐yr disease‐free survival rate was 58.3%. Adverse reactions of grade 3 or higher included granulocytopenia in 62.5%, anemia in 17.5% and thrombocytopenia in 50%, but there was no death related to treatment. Four patients underwent transplantation of hematopoietic stem cells and have survived for long periods. This treatment was effective against relapsed NHL and could be performed safely with few

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01384.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1996.tb01385.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY