ANEMIA APLASICA

ANEMIA APLSICADr. Ramn RosalResidente de 2do ao

Universidad de OrienteNcleo BolvarC.H.U. Ruz y PezPostgrado de Medicina Interna

ANEMIA APLASICATrastorno hematopoytico raro

PANCITOPENIA

HIPOCELULARIDAD EN MDULA SEADisminucin o ausencia de precursores hematopoyticos

Adquirido o heredadoBrodsky, R., Jones, R. 2005. Aplastic anaemia. Lancet. 365: 164756Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

ANEMIA APLASICAMas frec dao a la clula madre pluripotencial

1er caso descrito por Ehrlich en 1888

Incidencia estimada 2-4 casos/millon hab.Brodsky, R., Jones, R. 2005. Aplastic anaemia. Lancet. 365: 164756Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

EPIDEMIOLOGAPresentacin entre 15 25 aosSegundo pico > 60 aos

Ciertos locus especficos de histocompatibilidad (HLA DR2) asociados con predisposicin

Incidencia estimada 2-4 casos/millon hab.

Sin diferencias entre edad o sexoBrodsky, R., Jones, R. 2005. Aplastic anaemia. Lancet. 365: 164756Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

The incidence of acquired aplastic anemia in Europe and Israel is two cases per million persons annually. In Thailand and China, rates of five to seven per million have been established. In general, men and women are affected with equal frequency, but the age distribution is biphasic, with the major peak in the teens and twenties and a second rise in older adults.4

Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

FISIOPATOLOGACELULA MADRE PLURIPOTENCIAL

Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

FISIOPATOLOGA

Young, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

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FISIOPATOLOGARADIACINToxicidad directa a clulas madre y clulas precursoras

Dosis dependiente

DL50 alrededor de 4.5 Gy.

Altas dosis (1.5 Gy) al cuerpo pancitopenia severa en 2 4 semanas

> 10 Gy mortalidad 100%Brodsky, R. 2013. Acquired Aplastic Anemia. In Wintrobe's Clinical Hematology. 13th ed. Lippincott Williams & Wilkins

RadiationIonizing radiation is directly toxic to bone marrow stem/progenitor cells, and high doses (>1.5 Gy to the whole body) can lead to severe pancytopenia within 2 to 4 weeks after exposure; the LD50 has been estimated at about 4.5 Gy, and a dose of 10 Gy or greater is thought to have 100% mortality (26,27). While pancytopenia is common after a single high dose of radiation, an increased risk of aplastic anemia is not well documented as a delayed event from atomic bomb survivors

11

FISIOPATOLOGARADIACINToxicidad directa a clulas madre y clulas precursoras

Dosis dependiente

DL50 alrededor de 4.5 Gy.

Altas dosis (1.5 Gy) al cuerpo pancitopenia severa en 2 4 semanas

> 10 Gy mortalidad 100%Brodsky, R. 2013. Acquired Aplastic Anemia. In Wintrobe's Clinical Hematology. 13th ed. Lippincott Williams & Wilkins

RadiationIonizing radiation is directly toxic to bone marrow stem/progenitor cells, and high doses (>1.5 Gy to the whole body) can lead to severe pancytopenia within 2 to 4 weeks after exposure; the LD50 has been estimated at about 4.5 Gy, and a dose of 10 Gy or greater is thought to have 100% mortality (26,27). While pancytopenia is common after a single high dose of radiation, an increased risk of aplastic anemia is not well documented as a delayed event from atomic bomb survivors

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FISIOPATOLOGADROGASRespuesta inmune idiosincrsica directa contra clulas madre hematopoyticas

Terapia citotxica, deficiencia de Tiopurina Metiltransferasa (TPMT)

Cloramfenicol toxicidad directa a precursores eritroides en MO

Schirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDate

Chloramphenicolwas a common cause of aplasia when it was widely prescribed in the United States between 1948 and 1967. It causes bone marrow suppression by two mechanisms [2]:Chloramphenicolhas a direct toxic effect on erythroid precursors in the bone marrow, which can be morphologically identified by vacuoles forming a ring about the proerythroblast nucleus. This occurs in virtually all patients and is dose-related. Because iron is no longer being utilized for hemoglobin synthesis, there is a rise in the serum iron concentration with a concomitant increase in the ratio of serum iron to total iron-binding capacity. These changes are usually reversible with cessation of chloramphenicol therapy.

When drugs are implicated in causing aplastic anemia, it is important to recognize that unlike agranulocytosis and drug-induced thrombocytopenia, stopping the putative drug does not usually lead to hematopoietic recoveryBone marrow aplasia occurs as an idiosyncratic reaction to treatment withchloramphenicol, with a sudden onset after several months of therapy. It occurs in one of every 20,000 patients exposed to the drug and is usually irreversible.

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FISIOPATOLOGABENZENO Y TXICOS AMBIENTALESToxicidad mediada por productos solubles y metabolitosFenoles, hidroquinonas, catecoles

Unin covalente e irreversible a MOInhiben sntesis de ADN, ruptura de cadenas

Mutgeno, Veneno mittico

Young, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

Water-soluble products of benzene metabolism such as phenols,hydroquinones, and catechols mediate the toxicity to the BM.Benzene and its intermediate metabolites covalently and irreversiblybind to BM DNA, inhibit DNA synthesis, and introduce DNAstrand breaks. Benzene acts as a mitotic poison and as a mutagen.Acutely, the more mature, actively cycling BM precursor cells arepreferentially damaged over the more primitive progenitors. Intermittentexposure may be more damaging to the stem cell compartmentthan is continuous exposure. BM stroma can also be damaged bybenzene.14

FISIOPATOLOGAVIRUSInfeccin y citolisis directa de clulas hematopoyticasElaboracin de citoquinas inhibitorias

Respuesta inmune idiosincrsica

Parvovirus B19Mas documentadoClula hospedera natural Progenitor eritroide humanoHepatitis seronegativa 3 5% casosBrodsky, R. 2013. Acquired Aplastic Anemia. In Wintrobe's Clinical Hematology. 13th ed. Lippincott Williams & Wilkins

The only known natural host cell of parvovirus B19 is the human erythroid progenitor (36). The receptor for the virus is a neutral glycolipid, globoside, also known as the erythrocyte P antigen (37). Globoside is expressed on erythroid progenitors, erythrocytes, fetal myocardium, placenta, some megakaryocytes, and endothelial cells; it is not present on hematopoietic stem cells. Other viruses, including a variety of herpesviruses and the human immunodeficiency virus, have been implicated in triggering aplastic anemia, but convincing causal data are lacking. Spontaneous recovery, response to immunosuppression, and response to antiviral therapy have all been described; however, for those with severe disease, conventional therapy (immunosuppression or bone marrow transplantation) should be initiated early.

Seronegative (non-A through non-G) hepatitis precedes the diagnosis of aplastic anemia in 3 to 5% of cases and is recognized as hepatitis-associated aplastic anemia (38). After orthotopic liver transplantation for fulminant seronegative hepatitis, up to 30% of patients will develop aplastic anemia (39,40). In most cases, the hepatitis resolves spontaneously; however, when severe aplastic anemia (SAA) follows, it is often fatal and presents within a few months after the onset of hepatitis (41). The pathophysiology of hepatitis-associated aplastic anemia (HAA) is unknown, but is thought to be immune mediated since it responds to immunosuppressive therapy (41). Furthermore, patients with HAA have a skewed T-cell repertoire, and liver biopsies from these patients show lymphocytic infiltration (42).15

FISIOPATOLOGAEMBARAZOInicio durante el embarazo o poco despus del postpartoInfrecuente

Remisiones espontneas

Asociacin poco comprendidaBrodsky, R. 2013. Acquired Aplastic Anemia. In Wintrobe's Clinical Hematology. 13th ed. Lippincott Williams & Wilkins

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FISIOPATOLOGAORO Y METALES PESADOSSales de oro Inhibicin de formacin de colonias hematopoyticas (in vitro)

Alta frec de reacciones adversas fatales1,6 casos/10000 prescripciones

Leucopenia dosis dependiente

Tratamiento con clulas madres o terapia inmunosupresoraYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

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FISIOPATOLOGAAUTOINMUNIDADActivacin linfocitaria citotxicaNumero y funcin alterada de clulas T CD4+/CD25+/FOXP3+

Produccin de citoquinasINF-TNF

Eliminacin de clulas diana especificas

RESPUESTA HEMATOPOYTICA INHIBITORIAYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

Immune system destruction of BM occurs in animal models ofgraft-versus-host disease (GVHD) and in humans with transfusionassociatedGVHD, in which AA is the invariable cause of death. Verysmall numbers of effector cells, which have been conveyed by residuallymphocytes contained within the transfusion product or with solidorgan transplants, are sufficient to mediate GVHD under these conditions.AA is associated with rheumatologic syndromes, such aseosinophilic fasciitis, and with systemic lupus erythematosus (SLE).AA occasionally occurs in individuals with hypogammaglobulinemiaor congenital immunodeficiency syndrome, thymoma, thymic hyperplasia,and thymic carcinoma.

Laboratory support for the immune hypothesis first came fromcoculture experiments in which mononuclear cells from AA patientsblood or BM were shown to suppress in vitro colony formation byhematopoietic progenitor cells. Removal of T cells from the patientsamples sometimes improved colony formation in vitro. Peripheralblood and BM samples from patients were shown to produce asoluble factor that inhibited hematopoiesis, ultimately identified asIFN-. Patients T cells overproduce IFN- and TNF, two cytokinesthat inhibit hematopoietic proliferation. Tbet, a transcriptional regulatorthat is critical to Th1 polarization, is constitutionally expressedin a majority of AA patients. AA blood and BM also contains elevatednumbers of activated cytotoxic lymphocytes, and activity and levelsof these cytotoxic cells decreased appropriately with antithymocyteglobulin (ATG) therapy.

IFN- and TNFcan suppress hematopoiesis by effects on cell proliferation, but theyalso induce cell death by induction of Fas-mediated apoptosis.Immune-mediated cell cycle blockade and apoptosis can lead to thedramatic elimination of hematopoietic progenitor and stem cells inpatients with AA.

Immune hypothesisThe above observations have led to a hypothesis for immune suppression as the underlying cause in at least some patients with idiopathic aplastic anemia. It has been postulated that damage induced by chemicals, drugs, viruses, or antigens leads to lymphocyte activation. Unregulated lymphocyte activation, perhaps akin to that seen with mutations of perforin in hemophagocytic lymphohistiocytosis [47], or an autoimmune state due to impaired numbers and/or function of CD4+/CD25+/FOXP3+ T regulatory cells, perhaps secondary to the actions of Th17 cells (see below), results in a hematopoietic inhibitory response

This inhibition may be mediated by IFN-gamma or the cytokine cascade released by IFN-gamma [52,53], ultimately leading to apoptotic death of hematopoietic stem cells in the bone marrow [54-58]. IFN-gamma may also lead to increased expression of the Fas receptor and antigen [59]. This receptor is involved in induction of apoptosis and in T cell mediated killing. Indeed, Fas antigen is found in increased concentration in CD34+ bone marrow cells in patients with aplastic anemia18

MANIFESTACIONES CLNICASYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

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MANIFESTACIONES CLNICASPresentacin abrupta o insidiosa (semanas a mesesDisnea de esfuerzo, fatiga

Petequias, epistaxis, gingivorragia

Hipermenorrea

Cefalea, fiebreBrodsky, R. 2013. Acquired Aplastic Anemia. In Wintrobe's Clinical Hematology. 13th ed. Lippincott Williams & Wilkins

20

Young, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

DIAGNSTICO

DIAGNSTICOHEMATOLOGA COMPLETA SANGRE PERIFRICA

BIOPSIA DE MDULA SEAYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

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DIAGNSTICOHEMATOLOGA COMPLETA SANGRE PERIFRICAPancitopeniaMorfologa de GR normalMacrocitosisPlaquetas de tamao normalYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

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DIAGNSTICOMDULA SEAEvaluacin cuantitativa y cualitativa morfologa de clulas residuales.

HIPOCELULARIDADClulas adiposas estroma medular

Ausencia de infiltracin celular maligna o fibrosis

Clulas hematopoyticas residuales morfolgicamente normalesHematopoyesis no megaloblsticaSchirier, S. 2014. Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis. UpToDateYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

The BM must be assessed quantitatively and qualitatively for cellularityand the morphology of residual cells (Fig. 28-8 and see Fig. 28-1).BM aspiration and biopsy should always be performed, and the corespecimen should be at least 1 cm long. There should be no compromisein obtaining adequate specimens and no hesitation in performinga second procedure if required.Bone marrow cellularity is estimated25

Young, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

Guinan, E. 2011. Diagnosis and Management of Aplastic Anemia. Hematology Am Soc Hematol Educ Program;2011:76-81

Young, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

DIAGNSTICO DIFERENCIAL

Guinan, E. 2011. Diagnosis and Management of Aplastic Anemia. Hematology Am Soc Hematol Educ Program;2011:76-81

DIAGNSTICO DIFERENCIAL

DIAGNSTICO DIFERENCIAL

DIAGNSTICO DIFERENCIAL

Young, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

TRATAMIENTO

TRATAMIENTOEmergencia mdica

Tratamiento conservador puede comprometer la vida del paciente e incrementar la morbilidad

Tratamiento de soporte requiere atencin meticulosaYoung, N., Maciejewski, J. 2013. Aplastic anemia. In Hematology. Basic Principles and Practice. 6th Ed. ELSEVIER.

TRATAMIENTORetiro de farmacos posiblemente causales

Tratamiento de soporteTransfusiones, ATB

Tratamiento definitivoTransplante de MOInmunosupresinSchirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Treatment of aplastic anemia (AA) should include a combination of the following: withdrawal of potentially offending agents (table 1); supportive care (eg, transfusion, antibiotics); and some form of definitive therapy (eg, hematopoietic cell transplantation [HCT], immunosuppressive regimens) for patients with severe AA (SAA) or very severe AA (vSAA) [9-11]. Blood and platelet transfusions should be used selectively in patients who are candidates for HCT in order to avoid sensitization.35

TRATAMIENTORetiro de frmacos posiblemente causales

Tratamiento de soporteTransfusiones, ATB

Tratamiento definitivoTransplante de MOInmunosupresinSchirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

36

TRATAMIENTO< 20 aosTransplante Alognico de MOCompatibilidad HLAMinimizar transfusiones

Imposibilidad de transplante inmunosupresionSchirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)37

TRATAMIENTO20 - 50 aosEnfoque variable

Transplante alognico de MO

Ciclofosmamida/globulina antitimoctica previo transplante

Ciclofosfamida + metotrexateReducir incidencia de Enfermedad Injerto vs HospederoSchirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)38

TRATAMIENTO> 50 aosMayor riesgo de enfermedad injerto vs hospedero

TERAPIA INMUNOSUPRESORA

Schirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)39

TRATAMIENTO> 60 aosPeor respuesta a terapia inmunosupresoraTratamiento basado en:ComorbilidadesRiesgo de infeccionesTolerancia a Globulina AntitimocticaConsentimiento del paciente

Schirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)40

REGIMENES INMUNOSUPRESORESGlobulina antitimoctica (ATG)

ATG + CiclosporinaPremedicacinPrednisona o metilprednisolonaProfilaxis enfermedad del sueroAdicin de G-CSF

Ciclofosfamida a altas dosis

Schirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)41

REGIMENES INMUNOSUPRESORESOTROS AGENTES

Anticuerpos anti receptor de IL-2Anemia aplsica moderadaDaclizumab

Schirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)42

PRONSTICODEPENDE DE :

SEVERIDAD DE LA ENFERMEDAD

EDAD

Schirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Under age 20For patients under age 20, allogeneic HCT is the treatment of choice and should be performed promptly if a fully HLA-matched sibling donor is available. (See"Hematopoietic cell transplantation for idiopathic severe aplastic anemia and Fanconi anemia in children and adolescents", section on 'Idiopathic severe aplastic anemia'.)Transfusion of platelets and red cells should be minimized and family blood donors should be scrupulously avoided to minimize sensitization. Approximately 60 to 70 percent of such patients may be cured despite complications such as graft-versus-host disease (GVHD) [18,19]. Patient survival following HCT has improved over time, due primarily to reduced mortality in the first three months post-transplantation; the use ofcyclosporineto prevent severe GVHD accounts for most of the improved outcome [19]. In a review of 1305 HLA-identical sibling transplants performed in 179 centers, patient survival improved from 48 percent in the 1976 to 1980 cohort to 66 percent in the 1988 to 1992 cohort [19]. (See"Prevention of acute graft-versus-host disease".)43

PRONSTICOMortalidad 70% en pxs con enfermedad severa y muy severa sin tratamiento

Riesgo relativo de desenlace adverso posterior a terapia inmunosupresora3,4 % (vSAA)1,5% (SAA)

Schirier, S. 2014. Aplastic anemia: Prognosis and treatment. UpToDate

Unless patients with SAA or vSAA are successfully treated, over 70 percent will be dead within one year [1]. In a retrospective review from the European Group for Blood and Marrow Transplantation (EBMT), the relative risk for a poor outcome following immunosuppressive treatment was 3.4 for patients with an ANC