{"title":"10 Graft-versus-leukaemia","authors":"MD, FRCPath, MRCP A.J. Barrett (Chief), MD, MRCP, MRCPath Frits van Rhee (Visiting Specialist)","doi":"10.1016/S0950-3536(97)80011-X","DOIUrl":"10.1016/S0950-3536(97)80011-X","url":null,"abstract":"<div><p>The high relapse rate after T-cell depleted bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) and the ability of donor lymphocyte transfusions to induce stable remission in patients relapsing after BMT has emphasized the importance of alloreacting donor T-lymphocytes in the graft-versus-leukaemia (GVL) effect in this disease. The mechanisms underlying the GVL response and its relationship with graft-versus-host disease are becoming better defined. There is accumulating evidence that the CD4<sup>+</sup> T-cell plays a central role in the GVL response. The prominent role of GVL in the cure of CML after BMT may be associated with the fact that CML cells are strongly immunogenic. New transplant strategies are being devised to separate GVL from graft-versus-host reactions. Future developments focus on the identification of leukaemia-specific antigens and the amplification of T-cell responses against them.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 337-355"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80011-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307177","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}
FIMLS Reginald A. Clift (Associate Staff Scientist), MD Claudio Anasetti (Associate Member For the Seattle Marrow Transplant Team)
{"title":"9 Allografting for chronic myeloid leukaemia","authors":"FIMLS Reginald A. Clift (Associate Staff Scientist), MD Claudio Anasetti (Associate Member For the Seattle Marrow Transplant Team)","doi":"10.1016/S0950-3536(97)80010-8","DOIUrl":"10.1016/S0950-3536(97)80010-8","url":null,"abstract":"<div><p>Marrow transplantation from human leukocyte antigen (HLA) matched related donors offers a high probability of prolonged treatment-free survival for patients with chronic myeloid leukaemia in chronic phase. Delay, patient and donor gender, patient age and previous palliation with busulphan predict outcome in this setting. Because of the median age at diagnosis and the genetics of the HLA system, transplants from HLA-matched related donors are available to less than 15% of newly diagnosed patients. Alternative donors include relatives with minor degrees of incompatibility and HLA-compatible unrelated volunteers. The probability of finding suitable unrelated donors has increased with the development of a network of registries now containing more than 3.6 million donors worldwide. Survival prospects will be improved by transplantation earlier in the course of the disease, better-matched donors and the discovery of new approaches for the prevention of graft-versus-host disease and opportunistic infections.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 319-336"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80010-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307176","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":"3 Signal transduction pathways involved in BCR-ABL transformation","authors":"MD Charles L. Sawyers (Assistant Professor)","doi":"10.1016/S0950-3536(97)80004-2","DOIUrl":"10.1016/S0950-3536(97)80004-2","url":null,"abstract":"<div><p><em>BCR-ABL</em> is an oncogenic fusion gene found in patients with chronic myelogenous leukamia (CML) and acute lymphocytic leukaemia whose oncogenic potential has been demonstrated using in vitro and in vivo model systems. Current research efforts are focused on defining the mechanism by which BCR-ABL transforms cells, with a view toward applying insights from these studies to the treatment of CML patients. BCR-ABL contains tyrosine residues, an SH2 domain, an SH3 domain, and proline-rich sequences. The presence of so many protein-protein interaction domains raises the possibility of multiple contacts with cellular signal transduction pathways. Indeed, BCR-ABL is reported to bind and/or phosphorylate more than 20 proteins. Many of these can be directly linked to signal transduction pathways based on defined roles in other systems, but others have no known function. As the list of such proteins grows, it is critical to define the role of each in the leukaemogenic activity of BCR-ABL. This review summarizes current views of the mechanism of BCR-ABL transformation with emphasis on the substrates and signal transduction pathways affected by its tyrosine kinase activity.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 223-231"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80004-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20305405","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":"8 Interferon-α: results from randomized trials","authors":"DPhil, MA S.M. Richards (Senior Research Fellow)","doi":"10.1016/S0950-3536(97)80009-1","DOIUrl":"10.1016/S0950-3536(97)80009-1","url":null,"abstract":"<div><p>Interferon α is effective in the treatment of chronic myeloid leukaemia in terms of disease control. However, it is an expensive treatment compared with conventional chemotherapy and is not without side-effects. Examination of all the available randomized evidence demonstrates an absolute improvement in survival at 5 years of 15%±6% compared with conventional chemotherapy. There is no clear evidence that this benefit is different in any particular subgroup of patients. The size of benefit conferred by continuing interferon α in patients who show no cytogenetic response, the best dose to use, and whether it should be given in combination with chemotherapy all remain uncertain at present.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 307-318"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80009-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307175","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":"11 Donor leukocyte infusions","authors":"MD Stephen Mackinnon (Senior Lecturer)","doi":"10.1016/S0950-3536(97)80012-1","DOIUrl":"10.1016/S0950-3536(97)80012-1","url":null,"abstract":"<div><p>Donor leukocyte therapy has resulted in a remission rate in excess of 70% in patients with relapse of chronic myeloid leukaemia (CML) following allogeneic bone marrow transplantation (BMT). Induction of remission with donor leukocyte infusions has been primarily successful for CML patients who have cytogenetic relapse or those with chronic-phase haematological relapse. Response rates appear to be lower in patients who have advanced-phase CML. The majority of patients with CML who enter remission have no detectable minimal residual disease when analysed for <em>BCR-ABL</em> mRNA transcripts by reverse-transcription polymerase chain reaction. The efficacy of donor leukocyte infusions and the ease of therapy are balanced by the potential for significant toxicity. The reported treatment-related mortality rate is almost 20%. The major toxicities of this treatment are secondary to marrow aplasia and graft-versus-host disease (GVHD) which may occur in up to 50% and 90% of responders respectively. Donor leukocytes with a T-cell content of only 1 × 10<sup>7</sup>/kg, approximately a factor of 10 fewer T cells than used in most early studies, are capable of inducing remissions in some patients. The use of lower doses of T cells or CD8<sup>+</sup> depleted T cells may be associated with less GVHD. The optimal treatment schedule using donor leukocytes has yet to be determined. Factors which might influence outcome include phase of disease, use of interferon α, use of unrelated donors and human leukocyte antigen disparity, T-cell dose, CD8<sup>+</sup> depletion of leukocytes and time from BMT to leukocyte infusion.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 357-367"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80012-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307178","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}
MD Jorge Cortes (Assistant Professor of Medicine) , MD Hagop M. Kantarjian (Professor of Medicine, Chief) , MD Sergio Giralt (Assistant Professor of Medicine) , MD Moshe Talpaz (Professor of Medicine, Chairman)
{"title":"6 Natural history and staging of chronic myelogenous leukaemia","authors":"MD Jorge Cortes (Assistant Professor of Medicine) , MD Hagop M. Kantarjian (Professor of Medicine, Chief) , MD Sergio Giralt (Assistant Professor of Medicine) , MD Moshe Talpaz (Professor of Medicine, Chairman)","doi":"10.1016/S0950-3536(97)80007-8","DOIUrl":"10.1016/S0950-3536(97)80007-8","url":null,"abstract":"<div><p>The natural history of chronic myelogenous leukaemia has changed in recent years, partly as a result of earlier diagnosis but mostly as a consequence of the availability of effective therapies that have the potential to eradicate the Philadelphia-positive clone. The prognostic models designed in the pre-interferon-α (IFN-α) era based on clinical characteristics of the disease are still useful in identifying different risk groups after treatment with IFN-α, but achieving a cytogenetic response with IFN-α is now the most important prognostic factor for survival. The significance of other molecular and biological variables remains to be determined.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 277-290"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80007-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307173","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}
PhD Connie J. Eaves (Deputy Director, Professor of Medical Genetics) , MD, PhD Allen C. Eaves (Director, Professor and Head)
{"title":"4 Stem cell kinetics","authors":"PhD Connie J. Eaves (Deputy Director, Professor of Medical Genetics) , MD, PhD Allen C. Eaves (Director, Professor and Head)","doi":"10.1016/S0950-3536(97)80005-4","DOIUrl":"10.1016/S0950-3536(97)80005-4","url":null,"abstract":"<div><p>Chronic myeloid leukaemia (CML) is a transplantable multi-lineage disease. In its initial chronic phase, the leukaemic clone exhibits a hierarchical structure that closely resembles normal haematopoiesis. Thus assays for in vitro colony-forming cells (CFC) and their more primitive precursors identified as long-term culture-initiating cells (LTC-IC) detect subsets of Ph<sup>+</sup>/BCR-ABL<sup>+</sup> cells which cannot be readily distinguished from their normal counterparts. The use of these assays to examine the numbers, properties, genotype, distribution and regulation of primitive progenitors in patients' blood and marrow samples have revealed a number of unique and unexpected findings. These suggest that the indolent nature of the chronic phase of the disease may be explained by competing effects of the BCR-ABL gene product on the commitment to differentiate, control of cell cycle progression and apoptosis. As a result, the amplification of BCR-ABL<sup>+</sup> stem cells is constrained but the expansion of their progeny is enhanced and, on the granulocyte pathway, this expansion proceeds unchecked to the stage of mature end cell production resulting in the leukaemic picture observed.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 233-257"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80005-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307171","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}
DM, FRCP, FRCPath John M. Goldman (Professor of Leukaemia Biology,Consultant Physician)
{"title":"14 Treatment of chronic myeloid leukaemia: some topical questions","authors":"DM, FRCP, FRCPath John M. Goldman (Professor of Leukaemia Biology,Consultant Physician)","doi":"10.1016/S0950-3536(97)80015-7","DOIUrl":"10.1016/S0950-3536(97)80015-7","url":null,"abstract":"<div><p>The treatment of chronic myeloid leukaemia has become extremely complex in recent years. Busulphan has been displaced by hydroxyurea where rapid control of the leukocyte count is required. It is generally accepted that interferon-α (IFN-α) prolongs life for those who achieve a major or complete cytogenetic response and it may also prolong life for those who achieve only a haematological response. Thus routinely most newly diagnosed patients are started on treatment with IFN-α alone or in combination with other agents and this agent is continued if possible for 2 or more years. Because allografting is the only way of curing patients with CML, those under the age of 50 or 60 years who have HLA-identical siblings should be offered treatment by allogeneic haemopoietic stem cell transplantation; however, the risks of morbidity and mortality remain appreciable. Transplants with stem cells from phenotypically HLA-matched donors should also be considered for younger patients. The role of autografting is not yet clearly established; a series of controlled studies comparing autografting with IFN-α have therefore been activated. Because patients usually retain in their blood and marrow substantial numbers of Ph-negative stem cells a variety of methods designed to favour collection in vivo or isolation in vitro of Ph-negative stem cells are currently under investigation. To integrate these different approaches to treating patients with CML in chronic phase a variety of algorithms or flow charts have been proposed but many of the criteria on which the recommended treatment decisions are based remain controversial or ill-defined.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 405-421"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80015-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307131","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}
BSc(Hons), MRCP, MRCPath Stephen G. O'Brien (Clinical Lecturer, Honorary Senior Registrar)
{"title":"12 Autografting for chronic myeloid leukaemia","authors":"BSc(Hons), MRCP, MRCPath Stephen G. O'Brien (Clinical Lecturer, Honorary Senior Registrar)","doi":"10.1016/S0950-3536(97)80013-3","DOIUrl":"10.1016/S0950-3536(97)80013-3","url":null,"abstract":"<div><p>For most chronic myeloid leukaemia (CML) patients the option of a potentially ‘curative’ allogeneic stem cell transplant is not available because of age or lack of donor. Interferon α appears to extend survival when used in the chronic phase of the disease but probably does not produce long-term disease-free survivors. Autografting is being actively explored as a therapeutic option which may improve on the survival data seen with interferon and numerous different autografting methodologies are being investigated. While it seems reasonable to hope that a suitably robust and safe approach to autografting may improve survival it is unlikely with current technology that long-term disease-free survival will be achieved. To date no compelling trial data are available to confirm the efficacy of autografting but large prospective randomized studies are underway to investigate whether autografting can indeed extend survival for CML patients who do not have the option of an allograft.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 2","pages":"Pages 369-388"},"PeriodicalIF":0.0,"publicationDate":"1997-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80013-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20307179","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}
京公网安备 11010802042870号
求助内容：
应助结果提醒方式：