RESUMEN
The atomic nucleus and its electrons are often thought of as independent systems that are held together in the atom by their mutual attraction. Their interaction, however, leads to other important effects, such as providing an additional decay mode for excited nuclear states, whereby the nucleus releases energy by ejecting an atomic electron instead of by emitting a γ-ray. This 'internal conversion' has been known for about a hundred years and can be used to study nuclei and their interaction with their electrons. In the inverse process-nuclear excitation by electron capture (NEEC)-a free electron is captured into an atomic vacancy and can excite the nucleus to a higher-energy state, provided that the kinetic energy of the free electron plus the magnitude of its binding energy once captured matches the nuclear energy difference between the two states. NEEC was predicted in 1976 and has not hitherto been observed. Here we report evidence of NEEC in molybdenum-93 and determine the probability and cross-section for the process in a beam-based experimental scenario. Our results provide a standard for the assessment of theoretical models relevant to NEEC, which predict cross-sections that span many orders of magnitude. The greatest practical effect of the NEEC process may be on the survival of nuclei in stellar environments, in which it could excite isomers (that is, long-lived nuclear states) to shorter-lived states. Such excitations may reduce the abundance of the isotope after its production. This is an example of 'isomer depletion', which has been investigated previously through other reactions, but is used here to obtain evidence for NEEC.
RESUMEN
Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.
Asunto(s)
Anemia Aplásica/genética , Mutagénesis , Anemia Aplásica/patología , Células Clonales/patología , HumanosRESUMEN
This is the sixth special report that the European Society for Blood and Marrow Transplantation regularly publishes on the current practice and indications for haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred in the field of haematopoietic SCT over the last years. Cord blood units as well as haploidentical donors have been increasingly used as stem cell sources for allo-SCT, thus, augmenting the possibility of finding a suitable donor for a patient. Continuous refinement of conditioning strategies has also expanded not only the number of potential indications but also has permitted consideration of older patients or those with co-morbidity for a transplant. There is accumulating evidence of the role of haematopoietic SCT in non-haematological disorders such as autoimmune diseases. On the other hand, the advent of new drugs and very effective targeted therapy has challenged the role of SCT in some instances or at least, modified its position in the treatment armamentarium of a given patient. An updated report with revised tables and operating definitions is presented.
Asunto(s)
Enfermedades Autoinmunes/terapia , Selección de Donante/métodos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias/terapia , Donantes de Tejidos , Aloinjertos , Autoinjertos , Europa (Continente) , Femenino , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , MasculinoRESUMEN
This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.
Asunto(s)
Anemia Aplásica/terapia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Trasplante de Médula Ósea/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Alemtuzumab , Células de la Médula Ósea/citología , Niño , Preescolar , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped , Humanos , Lactante , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Hermanos , Donantes de Tejidos , Resultado del Tratamiento , Reino Unido , Adulto JovenRESUMEN
Alemtuzumab, a humanized anti-CD52, IgG1 monoclonal antibody, is used to reduce graft-versus- host disease (GVHD) and aid engraftment after allogeneic haemopoietic stem cell transplant (HSCT). Its associated low incidence of GVHD makes it an attractive alternative to anti-thymocyte globulin (ATG) in transplant conditioning regimen for severe aplastic anaemia (SAA). We have reviewed the use of alemtuzumab-based conditioning regimen for HSCT in SAA and show that it results in sustained haematological engraftment, a very low incidence of chronic GVHD without an increase in viral infections. Intriguingly, alemtuzumab appears to induce tolerance post-HSCT with the findings of stable mixed T cell chimerism with full donor myeloid chimerism and the absence of chronic GVHD, and which persist on withdrawal of post-graft immunosuppression. Finally, its low toxicity profile may permit future application of HSCT to older patients with SAA who fail to respond to immunosuppressive therapy.
Asunto(s)
Anemia Aplásica/complicaciones , Anemia Aplásica/terapia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Factores de Edad , Alemtuzumab , Anemia Aplásica/mortalidad , Antígenos CD , Antígenos de Neoplasias , Antígeno CD52 , Glicoproteínas/antagonistas & inhibidores , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunosupresores/uso terapéutico , Infecciones/etiología , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The treatment of aplastic anaemia (AA) in the elderly patient population is not always straightforward, as other factors apart from age per se and disease severity need to be considered in clinical management decisions. The presence of comorbidities needs to be evaluated carefully. In general, elderly patients have an inferior outcome following immunosuppressive therapy and haematopoietic SCT; hence patients need to be evaluated on an individual patient basis and their specific wishes respected, as quality of life is an extremely important outcome measure to consider. In this review we aim to provide some guidance on how to approach the options for treatment in the elderly patient.
Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Factores de Edad , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Currently at least 75% of patients with severe aplastic anaemia can be successfully transplanted using a matched unrelated donor (UD) haematopoietic SCT (HSCT). For children, outcomes are similar to matched sibling donor (MSD) HSCT. This improvement in outcome over time is likely due to improved HLA tissue typing to identify better matched donors, improvements in the conditioning regimen, particularly fludarabine-based regimens, and improved supportive care. Graft rejection occurs in â¼15% of adults, but is less frequent in children. Chronic GVHD remains a concern but may be reduced by using Alemtuzumab instead of ATG. UD HSCT should be considered early after failure to respond to one course of immunosuppressive therapy, but for children who lack a MSD up front matched UD HSCT may be considered.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/administración & dosificación , Adolescente , Adulto , Anemia Aplásica/inmunología , Anemia Aplásica/cirugía , Humanos , Terapia de Inmunosupresión , Donantes de Tejidos , Trasplante Homólogo , Donante no Emparentado , Adulto JovenRESUMEN
INTRODUCTION: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). METHODS AND MATERIALS: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V(100) >or= 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V(100). RESULTS: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V(100) for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5). CONCLUSIONS: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Sistema Límbico/efectos de la radiación , Tomografía Computarizada Espiral/métodos , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagen , Estudios de Factibilidad , Hipocampo/diagnóstico por imagen , Hipocampo/efectos de la radiación , Humanos , Sistema Límbico/diagnóstico por imagen , Órganos en Riesgo , Dosis de RadiaciónRESUMEN
The precise effects of CD34+ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34+ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34+ cell doses. Infusion of less than 2 x 10(6)/kg of CD34+ cells was associated with an increased incidence of graft failures (P=0.03), higher incidence of bacterial infections (P=0.006) and a delay in the engraftment of neutrophils (P=0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34+ count. Other parameters, such as plt engraftment (P=0.63), red cell (P=0.94) and plt (P=0.31) transfusion independence, chimerism, acute and chronic GVHD (P=1.0) and OS (P=0.57), were not significantly influenced by the CD34+ cell dose. These findings are different to the published studies on the relevance of CD34+ cell dose in allogeneic transplantation for haematological cancers.
Asunto(s)
Anemia Aplásica/terapia , Antígenos CD34/inmunología , Trasplante de Células Madre , Adolescente , Adulto , Anemia Aplásica/inmunología , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
We report a series of three patients in whom the diagnoses of aplastic anaemia (AA) and coeliac disease were made concurrently. Haematological manifestations of coeliac disease are well described but this is the first report to suggest an association with aplastic anaemia. 'Silent/atypical coeliac disease', in the absence of gastrointestinal symptoms, is increasingly recognised and patients may present with generalised symptoms, such as malaise and fatigue, which are easily attributable to AA. Immunosuppressive therapy for AA could modulate the course of celiac disease. We recommend clinicians should be vigilant for signs of coeliac disease in patients with AA.
Asunto(s)
Anemia Aplásica/complicaciones , Enfermedad Celíaca/complicaciones , Adulto , Anemia Aplásica/sangre , Anemia Aplásica/cirugía , Trasplante de Médula Ósea , Enfermedad Celíaca/sangre , Enfermedad Celíaca/cirugía , Terapia Combinada , Ciclosporina/uso terapéutico , Fatiga/etiología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Adulto JovenRESUMEN
We describe 11 patients with severe refractory autoimmune cytopenias treated with the anti-CD20 monoclonal antibody rituximab. Six patients had autoimmune neutropenia (AIN), two had pure red cell aplasia (PRCA), one had AIN and autoimmune haemolytic anaemia, one had AIN and immune thrombocytopaenia purpura (ITP) and one had PRCA and ITP. Rituximab was administered at a dose of 375 mg/m(2) as an intravenous infusion weekly for 4 weeks. Six of eight patients with AIN and all three patients with PRCA did not respond. Two patients died: one with resistant AIN and autoimmune haemolytic anaemia died of pneumocytis pneumonia infection, and one with PRCA and ITP died of an acute exacerbation of bronchiectasis. Rituximab in AIN and PRCA appears to be less effective than Campath-1H when compared to historical data from our group. This supports the hypothesis that T cells may be important in the pathophysiology of AIN and PRCA.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neutropenia/tratamiento farmacológico , Aplasia Pura de Células Rojas/tratamiento farmacológico , Adulto , Anciano , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/patología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Bronquiectasia/inducido químicamente , Vías de Administración de Medicamentos , Esquema de Medicación , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Neutropenia/patología , Proyectos Piloto , Neumonía por Pneumocystis/inducido químicamente , Púrpura Trombocitopénica/tratamiento farmacológico , Púrpura Trombocitopénica/patología , Aplasia Pura de Células Rojas/patología , Rituximab , Factores de Tiempo , Resultado del TratamientoRESUMEN
We report 14 older patients with aplastic anaemia (AA) who were treated with 'low dose' antithymocyte globulin (ATG). The aims of the study were to assess the efficacy and safety of reduced dose ATG in patients over the age of 60 years. Median age was 71 years (range 62-74 years). At the study endpoint (response to treatment at 6 months) 12 patients were evaluable. All patients received lymphoglobuline (horse ATG; Genzyme) at a dose of 0.5vials/10kg/day for 5 days (5mg/kg/day, equivalent to one-third of the standard dose). There were no deaths attributed to ATG. Two patients died during follow-up, from sepsis and anaphylaxis following platelet transfusion, respectively. Only one of the 12 evaluable patients responded to treatment and remains transfusion independent at 14 months after ATG. These results suggest that this lower dose of ATG, though well tolerated, had low efficacy in the treatment of AA.
Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/administración & dosificación , Inmunosupresores/administración & dosificación , Anciano , Anemia Aplásica/diagnóstico , Suero Antilinfocítico/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/efectos adversos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
For patients with acquired severe aplastic anemia without a matched sibling donor and not responding to immunosuppressive treatment, bone marrow transplantation from a suitable alternative donor is often attempted. We examined risks of graft failure, graft-versus-host disease and overall survival after 318 alternative donor transplants between 1988 and 1998. Sixty-six patients received allografts from 1-antigen and 20 from >1-antigen mismatched related donors; 181 from matched and 51 from mismatched unrelated donors. Most patients were young, had had multiple red blood cell transfusions and poor performance score at transplantation. We did not observe differences in risks of graft failure and overall mortality by donor type. The probabilities of graft failure at 100 days after 1-antigen mismatched related donor, >1-antigen mismatched related donor, matched unrelated donor and mismatched unrelated donor transplants were 21, 25, 15 and 18%, respectively. Corresponding probabilities of overall survival at 5 years were 49, 30, 39 and 36%, respectively. Although alternative donor transplantation results in long-term survival, mortality rates are high. Poor performance score and older age adversely affect outcomes after transplantation. Therefore, early referral for transplantation should be encouraged for patients who fail immunosuppressive therapy and have a suitable alternative donor.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA/análisis , Humanos , Lactante , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Graft failure, regimen-related toxicity and graft-versus-host disease (GVHD) are the critical barriers to unrelated donor transplants for aplastic anaemia (AA). We investigated the use of a novel conditioning regimen consisting of alemtuzumab (humanized CD52 antibody), fludarabine and cyclophosphamide in seven patients with AA, who underwent bone marrow transplant procedure using matched unrelated donors. The aetiology of AA was acquired (n=3), Fanconi's (n=3) and congenital (n=1). Median age was 13 years (range 8-35). All the donors were fully matched for HLA class I and II antigens using high-resolution typing. All the patients engrafted at a median of 18 days (range 13-35). Two patients died of transplant-related complications: one of adenovirus disease and the other developed extensive chronic GVHD of skin followed by cytomegalovirus (CMV) disease. Three patients developed Grade II acute GVHD disease (GVHD); none had Grade III-IV acute GVHD. Of the six evaluable patients, only one developed chronic GVHD. We conclude that this conditioning regimen for unrelated donor transplants for AA is sufficiently immunosuppressive to allow stable engraftment and appears to have a favourable impact on the incidence and severity of GVHD, warranting further investigation.
Asunto(s)
Anemia Aplásica/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Médula Ósea/métodos , Donantes de Tejidos , Vidarabina/análogos & derivados , Adolescente , Adulto , Alemtuzumab , Anemia Aplásica/complicaciones , Anemia Aplásica/etiología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/administración & dosificación , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/inmunología , Niño , Ciclofosfamida/administración & dosificación , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/patología , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión , Incidencia , Resultado del Tratamiento , Vidarabina/administración & dosificaciónRESUMEN
Thymoma-associated agranulocytosis is a rare but almost universally fatal condition. Reports to date have described several immunosuppressive therapies including steroids, cyclophosphamide and vincristine as adjuvants to thymectomy, in an effort to improve neutropenia. We report the response to the monoclonal antibody Campath-1H of a patient with a thymoma and associated agranulocytosis with complete absence of bone marrow granulocyte precursors, which had failed to respond to thymectomy. Treatment with Campath-1H resulted in complete responses of promising durability sustained with the addition of cyclosporin and mycophenolate mofetil as maintenance therapy.
Asunto(s)
Agranulocitosis/complicaciones , Agranulocitosis/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Timoma/complicaciones , Neoplasias del Timo/complicaciones , Agranulocitosis/patología , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Timectomía , Timoma/tratamiento farmacológico , Timoma/patología , Timoma/terapia , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/patología , Neoplasias del Timo/terapia , Resultado del TratamientoRESUMEN
The clinical association between paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA) has long been recognized. Haemolytic PNH, as confirmed by a positive Ham's test, can occur in the setting of AA, and conversely AA can be a late complication of PNH. With the development of sensitive flow cytometry to quantify the expression of phosphatidylinositolglycan (PIG)-anchored proteins on blood cells, a small PNH clone can now be detected in a large number of patients with AA at diagnosis. PIG-A gene mutations can also be demonstrated in some AA patients. In haemolytic PNH, there is always marrow suppression despite a morphologically cellular marrow. In vitro cultures show markedly diminished proliferative capacity in both short-term and long-term marrow cultures, similar to that seen in AA. A similar autoimmune process, through the T-cell cytotoxic repertoire, is probably responsible for the pathogenesis of both AA and PNH. PIG-deficient cells may be resistant to immunological attack by autoreactive cytotoxic T cells, because they lack PIG. They are also more resistant to apoptosis than the PIG-normal cell population. This results in the selection of the PIG-deficient clone, in contrast to the PIG-normal stem cells which possess the PIG anchor and hence are targeted and depleted by the autoreactive T cells.
Asunto(s)
Anemia Aplásica/patología , Células Madre Hematopoyéticas/patología , Hemoglobinuria Paroxística/patología , Adulto , Anemia Aplásica/inmunología , Apoptosis , Enfermedades Autoinmunes/patología , Médula Ósea/patología , Niño , Células Clonales/patología , Glicosilfosfatidilinositoles/fisiología , Hemoglobinuria Paroxística/genética , Hemoglobinuria Paroxística/inmunología , Humanos , Proteínas de la Membrana/deficiencia , Proteínas de la Membrana/genéticaAsunto(s)
Anemia Aplásica/diagnóstico , Anemia Aplásica/terapia , Adulto , Suero Antilinfocítico/administración & dosificación , Examen de la Médula Ósea , Trasplante de Médula Ósea , Humanos , Terapia de Inmunosupresión/métodos , Persona de Mediana Edad , Acondicionamiento Pretrasplante , Trasplante IsogénicoRESUMEN
Aplastic anaemia seems to be predominantly a defect of the stem cell rather than the stroma, though abnormalities of the microenvironment may co-exist. There is highly suggestive evidence that the stem cell is the target of an immune attack, though the main evidence remains the response to immunosuppression with antilymphocyte globulin and cyclosporin. The stem cell defect remains even after recovery of the peripheral blood counts and the AA marrow is a fertile environment for the emergence of abnormal clones, particularly PNH. However, it has recently become apparent that there is an overlap with the myelodysplastic syndromes and clones of monosomy 7 and trisomy 8 amongst others are not uncommon in aplastic anaemia. Recent work has suggested that the emergence of a clone of monosomy 7 cells carries a poor prognosis, whereas trisomy 8 has a good prognosis particularly in response to cyclosporin. However, the setting in which monosomy 7 arises may affect the phenotypic expression. The immune targeting of stem cells may be associated with increased apoptosis in aplastic anaemia, in part mediated by fas expression, but not exclusively. Understanding the pathophysiology of AA should help to improve and perhaps target therapy.