Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- Preface -- Part I Pathophysiology of acquired aplastic anemia -- 1 Stem cell defect in aplastic anemia -- Abbreviations -- Normal stem cells -- Definition -- Regulation -- The experimental study of primitive hemopoietic cells -- Selection of primitive cells by phenotype -- How many stem cells get to express themselves? -- Aplastic anemia stem cells -- Functional assessment of AA hemopoietic progenitor cells -- Phenotypic quantitation of AA hemopoietic (CD34+) cells -- Assessment of the long-term marrow-repopulating ability of AA hemopoietic cells -- Mobilizing potential of AA progenitor cells -- Apoptotic properties of AA CD34+ cells -- Analysis of telomeric DNA length in AA -- Conclusion -- References -- 2 Cytokine abnormalities in aplastic anemia -- Introduction -- Erythropoietin (EPO) -- Granulocyte colony-stimulating factor (G-CSF) -- Thrombopoietin (TPO) -- Stem cell factor (SCF) -- Granulocyte-macrophage colony-stimulating factor (GM-CSF) -- Flt-3 ligand (Flt-3L) -- Interleukin-1 (IL-1) -- Production of cytokines by marrow stromal cells -- Rationale for the therapeutic use of cytokines -- Conclusion -- References -- 3 Role of T-lymphocytes in the pathophysiology of aplastic anemia -- Introduction -- Immunophenotyping data on T-cells and natural killer cells in bone marrow and peripheral blood -- CD4 and CD8 T-cells -- Activated T-cell subpopulation -- T-cell receptor VBeta subfamily -- Natural killer cells -- Markers of T-cell activation -- Activation antigens -- Cytokine production -- Stress proteins -- Production of myelosuppressive cytokines by T-lymphocytes -- Reactivity of T-lymphocytes against hemopoietic progenitor cells -- Evidence of the involvement of an antigen-driven response in the development of AA.

Hemopoietic progenitor cells as a target of T-cell attack -- Association of certain HLA alleles with a susceptibility to AA -- Clonal predominance in T-cell subsets defined by T-cell receptor VBeta expression -- Establishment of a T-cell clone reactive to hemopoietic cells from AA patients -- Conclusion -- References -- 4 Role of apoptosis in the pathophysiology of aplastic anemia -- Introduction -- Features of apoptotic cells -- Control of apoptosis -- Apoptosis: role in immune regulation -- Methods of detecting apoptotic cells -- Apoptosis in progenitor cells in the bone marrow of those with aplastic anemia -- Expression of Fas on normal hemopoietic progenitor cells -- Expression of Fas on progenitor cells in aplastic anemia -- Modulation of apoptosis by therapeutic intervention -- Conclusion -- References -- 5 The interrelation between aplastic anemia and paroxysmal nocturnal hemoglobinuria -- Introduction -- AA-PNH syndrome - clinical observations -- The deficiency of GPI-anchored proteins in AA-PNH syndrome -- The GPI anchor and its biosynthesis (reviewed in Rosse, 1997 -- Socié, 1997) -- The most widely studied GPI-anchored proteins (reviewed in Rosse, 1997 -- Socié, 1997) -- The GPI-anchored protein deficiency (reviewed in Rosse, 1997 -- Socié, 1997) -- The GPI-anchored protein deficiency in AA-PNH syndrome -- Mutations of the PIG-A gene in AA-PNH syndrome -- Molecular biology of the PIG-A gene -- Abnormalities of the PIG-A gene in PNH -- Abnormalities of the PIG-A gene in AA-PNH syndrome -- Conclusion: the mutations of the PIG-A gene as a common genetic basis for PNH and AA-PNH syndrome -- References -- 6 Aplastic anemia and other clonal disorders -- Introduction -- Clinical observations: the evolution of AA to myelodysplastic syndrome and acute myelogenous leukemia.

Studies on clonal hemopoiesis in AA patients using X-linked DNA polymorphisms -- Cytogenetic abnormalities in patients with severe aplastic anemia -- Conclusion -- References -- Part II Epidemiology and clinical features of acquired aplastic anemia -- 7 Epidemiology and etiology of aplastic anemia -- Introduction -- The role of medical drugs: a good old theory revisited -- Environmental and industrial chemicals -- Viruses -- Risk factors others than exposure -- Conclusion -- References -- 8 Clinical presentation, natural course, and prognostic factors -- Clinical manifestations -- Complementary investigations -- Peripheral blood cell counts -- Other analytical data -- The cytology and histopathology of medullary aplasia -- Isotopic investigations of hemopoiesis -- Proton magnetic resonance imaging and spectroscopy -- Follow-up and survival -- Prognosis identification -- The prognostic value of symptoms -- The prognostic value of peripheral blood cell counts -- The prognostic value of the cytology and histopathology of medullary aplasia -- The prognostic value of isotope examinations -- Statistical prediction models -- International criteria -- Conclusion -- References -- Part III Treatment of acquired aplastic anemia -- 9 Supportive treatment of patients with severe aplastic anemia -- Introduction -- Prevention and treatment of infections -- Risk of infections -- Types of infections in SAA patients -- Prevention of infections -- Antibacterial chemoprophylaxis -- Antiviral prophylaxis -- Diagnosis of infection -- Investigation of fever -- Investigation of patients with pulmonary infiltrates -- Treatment of infection -- Treatment of bacterial infections -- Treatment of fungal infections -- Treatment of viral infections -- Transfusion support -- Transfusions and risk for graft rejection after BMT -- Alloimmunization after transfusion.

Transmission of infectious agents -- Transfusion-associated GVHD -- Iron overload -- Conclusion -- References -- 10 Immunosuppressive treatment of aplastic anemia -- Introduction -- Lessons from the clinical trials -- Effectiveness of ALG -- The impact of severity of disease -- Cyclosporin -- Intensification of immunosuppression -- Adjuncts to immunosuppression -- Splenectomy -- Timing and quality of response -- Mechanism of action of ALG and cyclosporin -- Treatment schedules -- Adverse events of ALG -- Immunosuppression in elderly patients -- Relapses and nonresponses -- New approaches to immunosuppressive treatment -- Conclusion -- Acknowledgements -- References -- 11 Role of cytokines in the treatment of aplastic anemia -- The rationale and potential aims of growth factor treatment in aplastic anemia -- Serum/plasma levels and production of endogenous growth factors in aplastic anemia -- Clinical trials of hemopoietic growth factors in aplastic anemia -- Granulocyte colony-stimulating factor -- Granulocyte/macrophage colony-stimulating factor (GM-CSF) -- Erythropoietin -- Interleukin-3 (IL-3) -- Interleukin-1 (IL-1) -- Interleukin-6 (IL-6) -- Stem-cell factor (SCF) -- Conclusion -- References -- 12 HLA-identical sibling bone marrow transplantation to treat severe aplastic anemia -- Introduction -- HLA-identical sibling transplants -- Survival, current results, and trends over time -- Engraftment -- Hemopoietic chimerism -- Acute GVHD -- Chronic GVHD -- Interstitial pneumonitis -- Late complications -- The influence of SAA etiology on outcome -- Syngeneic transplants -- HLA-phenotypically identical donors -- Conclusion -- References -- 13 Alternative donor bone marrow transplantation for severe acquired aplastic anemia -- Introduction -- Prognostic factors for HLA-identical sibling BMT -- Partially matched family donor BMT: early experience.

HLA-matched unrelated donor BMT: early experience -- Analysis of factors affecting outcome of alternative donor BMT -- Patients and methods -- Patient population -- Donor population and HLA matching -- Transplant data -- Outcomes analyzed -- Statistical methods -- Results -- Survival -- Engraftment -- Acute GVHD -- Chronic GVHD -- Cause of death -- Discussion -- Future directions -- Transfusion policy in patients with SAA -- HLA molecular epitope analysis -- Conclusion -- References -- 14 Treatment of children with acquired aplastic anemia -- Introduction -- BMT from HLA-identical siblings -- BMT from alternative donors -- Immunosuppressive treatment -- Hemopoietic growth factors -- Late effects on children -- Treatment results obtained in the last 5 years in Europe -- Conclusion -- References -- 15 Long-term follow-up of patients with aplastic anemia: clonal malignant and nonmalignant complications -- Introduction -- Historical background -- Secondary MDS or leukemia -- New solid cancers -- Paroxysmal nocturnal hemoglobinuria -- Conclusion -- References -- 16 Guidelines for treating aplastic anemia -- Decision making: immunosuppressive treatment versus allogeneic bone marrow transplantation as first-line treatment of… -- Bone marrow transplantation -- HLA-matched sibling transplantation -- Unrelated and family-mismatched donor transplants -- Immunosuppressive treatment -- Failures to respond to first-line treatment/relapse -- Failures to respond to second-line treatment -- Age limit for immunosuppressive treatment -- Myelodysplastic syndrome/leukemia after treatment -- Conclusion -- Part IV Fanconi's anemia -- 17 Clinical features and diagnosis of Fanconi's anemia -- Clinical suspicion of Fanconi's anemia -- Diagnosis of FA -- Hematological manifestations -- Leukemia -- Myelodysplastic syndrome -- Cancer -- Liver disease -- Reproduction -- Prognosis.

Conclusion.