Reviews in clinical and experimental hematology最新文献

{"title":"Allogeneic stem cell transplantation for multiple myeloma.","authors":"Roberto Bellucci,&nbsp;Jerome Ritz","doi":"10.1046/j.1468-0734.2002.00075.x","DOIUrl":"https://doi.org/10.1046/j.1468-0734.2002.00075.x","url":null,"abstract":"<p><p>The sensitivity of myeloma cells to high dose chemotherapy has led to the use of allogeneic hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disease. In addition to providing more effective chemotherapy, the transplantation of allogeneic stem cells also initiates the development of an allogeneic immune response directed against residual myeloma cells. Direct evidence for a graft vs. myeloma (GVM) effect is provided by the ability of donor lymphocyte infusion (DLI) to induce significant responses in 30-50% of patients with myeloma who have relapsed after allogeneic HSCT. Nevertheless, allogeneic stem cell transplantation is also associated with a high incidence of transplant related toxicities, including regimen-related toxicities, graft vs. host disease (GVHD) and opportunistic infections. DLI has been shown to enhance immune reconstitution after allogeneic HSCT in addition to inducing a GVM response. Current efforts are directed at reducing the toxicities associated with allogeneic HSCT, identification of the target antigens of GVM and the development of new strategies to selectively enhance the immune response to myeloma cells.</p>","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1468-0734.2002.00075.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22271564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal gammopathies of undetermined significance.","authors":"Robert A Kyle,&nbsp;S Vincent Rajkumar","doi":"10.1046/j.1468-0734.2002.00076.x","DOIUrl":"https://doi.org/10.1046/j.1468-0734.2002.00076.x","url":null,"abstract":"<p><p>The term 'monoclonal gammopathy of undetermined significance' denotes the presence of a monoclonal protein in patients without evidence of multiple myeloma, macroglobulinemia, amyloidosis or related plasma cell proliferative disorders. The disorder has been found in approximately 3% of persons older than 70 years and in approximately 1% of persons older than 50 years. A population-based study included 1384 patients from south-eastern Minnesota who had the disorder diagnosed at the Mayo Clinic from 1960 through 1994. Risk of progression was about 1% per year, but patients were at risk of progression even after 25 years or more of stable monoclonal gammopathy of undetermined significance. The risk for development of multiple myeloma was increased 25-fold; the risk of macroglobulinemia, 46-fold; and the risk of primary amyloidosis, 8.4-fold. Concentration and type of monoclonal protein were the only independent predictors of progression. The presence of a urine monoclonal protein and the reduction of one or more uninvolved immunoglobulins were not risk factors for progression. Monoclonal gammopathy of undetermined significance may be associated with various disorders, including lymphoproliferative diseases, leukemia, von Willebrand disease, connective tissue diseases and neurologic disorders.</p>","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1468-0734.2002.00076.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22271565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of multiple myeloma.","authors":"Jean-Luc Harousseau","doi":"10.1046/j.1468-0734.2002.00077.x","DOIUrl":"https://doi.org/10.1046/j.1468-0734.2002.00077.x","url":null,"abstract":"<p><p>There has been no improvement in the treatment of multiple myeloma (MM) during the last decades and two meta-analyses of randomized trials recorded no significant survival benefit for combination chemotherapy compared to the classic melphalan-prednisone combination. However the past 15 years has seen several innovative strategies which have dramatically modified the management of MM. In younger patients, high-dose therapy with autologous stem cell transplantation is considered to be superior to conventional chemotherapy and is used as part of front-line therapy. A number of issues have been addressed in recent trials in order to improve the results of autologous transplantation (source of stem cells, conditioning regimen, impact of double transplants, maintenance therapy). Bisphosphonates reduce the incidence of skeletal-related events and improve the quality of life. Recombinant erythropoietin reduces red blood cell transfusion need and improves the quality of life. Thalidomide has been introduced more recently. Phase II studies with thalidomide alone or combined with dexamethasone have shown impressive response rates and this drug is currently being evaluated as part of front-line therapy. Finally, analysis of prognostic factors such as beta 2 microglobulin and cytogenetics define subgroups of patients with a completely different outcome and help the process of selecting therapeutics strategies.</p>","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1468-0734.2002.00077.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22271566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The biology and cytogenetics of multiple myeloma.","authors":"P Joy Ho,&nbsp;Lynda J Campbell,&nbsp;John Gibson,&nbsp;Ross Brown,&nbsp;Douglas Joshua","doi":"10.1046/j.1468-0734.2002.00081.x","DOIUrl":"https://doi.org/10.1046/j.1468-0734.2002.00081.x","url":null,"abstract":"<p><p>Despite the advances in our knowledge of myeloma cell biology, our understanding of myeloma pathogenesis is still incomplete. In this review, we present a summary of the cellular and molecular aspects of B-cell development and immunoglobulin (lg) gene rearrangement which have been important in defining the characteristics of the myeloma plasma cell (MPC). The PMC has undergone variable gene recombination, somatic hypermutation and isotype switching, and is therefore at a postgerminal center stage of development. The finding of preswitch clonal cells and isotype variants have raised interesting questions about the cell of origin of myeloma, for which no conclusive data is as yet available. However much information has been obtained about the chromosomal and genetic aberrations in myeloma, including monosomy 13, Ig heavy chain (IgH) switch region translocations, numerical abnormalities and a multitude of heterogeneous changes. A variety of techniques have been developed to overcome the insensitivity of conventional karyotyping, utilizing molecular cytogenetic strategies ranging from the delineation of precise loci by fluorescent in situ hybridization, a more \"global\" assessment of the genome by multicolor spectral karyotyping, to the quantitation of chromosomal material of specific origin by comparative genomic hybridization. Whether the abnormalities detected represent oncogenic insults, are involved in disease progression or are simply \"by-products\" of genetic instability is still unclear. For IgH translocations, the role of candidate genes such as Cyclin D1 and FGFR3 has been studied extensively by quantitating their expression and assessment of their oncogenicity (e.g. for FGFR3) in animal models. The significance of other aberrations such as c-myc, ras and p53 has also been investigated. With the advent of oligonucleotide microarrays, the expression of thousands of genes can be efficiently examined. So far, this approach seems promising in defining subgroups of different disease behavior, and may highlight specific genes and molecular mechanisms which are important in myeloma pathogenesis.</p>","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1468-0734.2002.00081.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22270404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Philadelphia chromosome-positive acute lymphoblastic leukemia- current concepts and future perspectives.","authors":"S. Faderl, G. Garcia-Manero, D. Thomas, H. Kantarjian","doi":"10.1046/J.1468-0734.2002.00066.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2002.00066.X","url":null,"abstract":"Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) is diagnosed rarely in children, but constitutes the most frequent cytogenetic abnormality in adults with ALL. In contrast to chronic myeloid leukemia (CML), patients with Ph-positive ALL usually demonstrate expression of a truncated version of the BCR-ABL protein called p190bcr-abl. Irrespective of age and breakpoint location, Ph-positive ALL carries a poor prognosis. Although remission rates are identical to those of Ph-negative ALL, relapse is almost universal and long-term survival remains rare. Given the poor outcome with current chemotherapy consolidation programs, stem cell transplantation is usually recommended for these patients in first remission or as soon as feasible. Even with transplantation the impact on outcome is limited and new therapeutic concepts are urgently needed. One of the most promising developments in recent years has been the introduction of the tyrosine kinase inhibitors such as STI571. An overview of current treatment modalities in Ph-positive ALL will be provided and the rationale for new therapies will be discussed.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2002.00066.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytogenetics and molecular genetics of acute lymphoblastic leukemia.","authors":"C. Harrison, L. Foroni","doi":"10.1046/J.1468-0734.2002.00069.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2002.00069.X","url":null,"abstract":"An important factor in the diagnosis of acute lymphoblastic leukemia (ALL) is that karyotype is an independent prognostic indicator, with an impact on the choice of treatment. Outcome is related to the number of chromosomes. For example, high hyperdiploidy (51-65 chromosomes) is associated with a good prognosis, whereas patients with near haploidy (23-29 chromosomes) have a poor outcome. The discovery of recurring chromosomal abnormalities in the leukemic blasts of patients with ALL has identified a large number of genes involved in leukemogenesis. Certain specific genetic changes are related to prognosis. The ETV6/AML1 fusion arising from the translocation (t12;21) (p13;q22) has been associated with a good outcome; the BCR/ABL fusion of (t9;22)(q34;q11), rearrangements of the MLL gene, and abnormalities of the short arm of chromosomes 9 involving the tumor suppressor genes p16INK4A have a poor prognosis. Unfortunately, the classification of patients into prognostic groups based on cytogenetics is not always as predicted. Even when other clinically based risk factors are taken into account, some patients with good-risk cytogenetic features will relapse. In the search for new measures of prognosis, it has recently emerged that the level of minimal residual disease following induction therapy can be a reliable predictor of outcome in ALL.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2002.00069.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards an integrated classification of adult acute lymphoblastic leukemia.","authors":"R. Foà, A. Vitale","doi":"10.1046/J.1468-0734.2002.00070.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2002.00070.X","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) represents a biologically and clinically heterogeneous group of diseases characterized by the abnormal proliferation and accumulation of immature lymphoid cells within the bone marrow and lymphoid tissues. Following a diagnostic work-up, prognostic data are routinely achieved through physical examination, serum biochemical profiles, peripheral blood count and bone marrow morphology. Over the years, information obtained through karyotype, molecular genetics, extensive immunophenotype, multidrug resistance and, more recently, genomic profiling is progressively contributing to a better understanding of the biology of this complex disease, to the identification of subgroups of patients with a different clinical outcome, to the more precise monitoring of minimal residual disease, to the use of different therapeutic protocols based on prognostic indicators and, recently, also to the design of innovative and specific treatment strategies. In the present review, we will discuss how an integrated approach is now mandatory for the optimal management of adult ALL.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2002.00070.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concluding remarks: Concluding remarks","authors":"R. Foà, A. Hoffbrand","doi":"10.1046/J.1468-0734.2002.00065.X-I2","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2002.00065.X-I2","url":null,"abstract":"","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2002.00065.X-I2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute myeloid leukemia: treatment of adults under 60 years.","authors":"A. Burnett","doi":"10.1046/J.1468-0734.2002.00058.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2002.00058.X","url":null,"abstract":"Current chemotherapy with advanced supportive care will enable 75-80% of acute myeloid leukemia patients aged 60 years or under to enter complete remission. Several regimens achieve broadly similar results. For patients who enter complete remission, the overall relapse risk is now 45-50%, but this is highly variable and is primarily determined by the biology of the disease. Cytogenetics are strongly influential in response to induction and consolidation with t(15:17), t(8:21) and inv(16) either occurring alone or with additional abnormalities having a relapse risk of about 30% and complex changes, abnormal 3q or abnormalities of chromosomes 5 and 7 resulting in a lower remission rate and a rapid relapse cumulating to 80%. FLT3 mutations occur in 25% of patients and are an independent predictor of relapse and, when combined with cytogenetics, adversely influence the prognosis in each cytogenetic risk group. Recent prospective collaborative group trials have endeavored to evaluate allogeneic and autologous bone marrow transplant against or in addition to consolidation chemotherapy. Suboptimal treatment delivery emerged as a problem. When the results were reported on an intention-to-treat basis, no overall survival advantage was consistently seen for either type of transplant. However, a significant reduction in risk of relapse was usually seen overall and within risk groups. Analysis within risk groups suggests that transplant is not indicated in good risk disease and continues to require evaluation in standard or poor risk patients. It is probable that traditional dose intensification has now reached its limits of tolerability, so new approaches will be required for further progress to be made. Modulation of chemoresistance mechanisms or immunologically directed chemotherapy represent immediate prospects for clinical study.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2002.00058.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57744742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell transplantation for leukemias following myelodysplastic syndromes or secondary to cytotoxic therapy.","authors":"T. D. de Witte, M. Oosterveld, Bart Span, P. Muus, A. Schattenberg","doi":"10.1046/J.1468-0734.2002.00057.X","DOIUrl":"https://doi.org/10.1046/J.1468-0734.2002.00057.X","url":null,"abstract":"Two main forms of therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) have been recognized. The most frequent type, occurring after treatment with alkylating agents, is characterized by abnormalities of chromosomes 5 and/or 7 and t-MDS/AML following treatment with topoisomerase II inhibitors and is associated with molecular aberrations of MLL (11q23) and AML-1 (21q22). Individuals with certain polymorphisms associated with impaired detoxification of cytotoxic agents have an increased risk of developing MDS or AML after treatment of unrelated cancers. Multidrug chemotherapy is less effective for patients with MDS, or AML following MDS, or t-MDS/AML when compared with primary AML, and results in lower complete remission (CR) rates and lower long-term survival. Patients with good risk cytogenetic features, such as t(15; 17), t(8; 21) and inversion 16 are an exception as their treatment outcome is comparable with primary AML patients. Patients who attain a polyclonal and/or a cytogenetic CR may be candidates for autologous stem cell transplantation. For the remaining patients, the only curative option is allogeneic stem cell transplantation with stem cells from a histocompatible sibling or an alternative donor. Reduced intensity conditioning regimens may be considered for patients older than 50 years or patients with comorbidities. The advice is to treat patients early after diagnosis and preferably before progression as these patients have the highest chance of a favorable outcome.","PeriodicalId":82483,"journal":{"name":"Reviews in clinical and experimental hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/J.1468-0734.2002.00057.X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57745193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}