Simposio Genzyme: Enfermedad de Gaucher y otras enfermedades - Dr. Marco Grajales

Page 1

â–Ş We are still without a trust worthy medicine wich can always be relied upon to control purpura.

Manifestaciones Hematolรณgicas asociadas a Enfermedad de Gaucher Diagnรณstico diferencial y manejo

• Trombocitopenia • Esplenomegalia • Enfermedad ósea • Anemia

Hb < 13 H Hb <12 M

ETIOLOGY

producciรณn

destrucciรณn

HIPER PROLIFERATIVA 25 %

HIPO PROLIFERATIVA 75 %

ANEMIAS CON RETICULOCITOS BAJOS • CARENCIALES • ENFERMEDAD CRONICA / IRC • DE CAUSA DESCONOCIDA

Nutricional Hemรณlisis

Hematolรณgica

Enfermedad Crรณnica

Regenerativa

Arregenerati va

JAMES HOMER WRIGHT (–)

Original Articles. THE ORIGIN AND NATURE OF THE BLOOD PLATES. BY JAMES HOMER

WRIGHT, M.D., S.D.,

jagged or fimbriate outline. There is thus to be distinguished in the blood plate two portions, namely, a central, granular, red to violet staining portion and a marginal, homogeneous, hyaline, blue staining portion. The diameter of the central

portion

portion and

the width of the

marginal

vary, the latter being usually narrower than the diameter of the former. School. The giant cells present the following peculiariA prolonged study of the comparative morwhich are of importance for the subject of ties phology of the blood corpuscles of a wide range this paper: of animals has shown me that all of the many The cytoplasm the central and up making AND NATURE THE ORIGIN OF THE BLOOD theories hitherto proposed concerning the origin the greater portion of the giant cell is usually and nature of the blood plates are untenable andPLATES. crowded more or less

Director of the Pathological Laboratory of the Massachusetts General Hospital; Instructor in Pathology, Harvard University Medical

Original Articles.

jagged disting

namely portion set, densely with closelyblue s the to red violet most for minute, granules, part

erroneous.

In this paper I shall not set forth reasons my centra those of M.D., BY JAMES HOMER the blood like the central of WRIGHT, S.D., portions for coming to this conclusion, but I shall confine at the while it is and Massachusetts Director the the plates, periphery hyaline Pathological Laboratory General Figure 4.3 Tit of of own a statement to brief of opinions my myself stained. blue Pathological Techni This Instructor in Medical portion Harvard Figure 4.2 James Homer Wright, during his later years hyaline Hospital; peripheral Pathology, University and nature of these bodies forms a definite narrow zone of somewhat variable concerning the origin by both than th School. and a summary of the facts and observations upon is narrow as compared with the but width, veiy The Dr. Wright had a He also wrote a chapter on other infections for which my opinions are based. has a smooth cell orexamina diameter of whole the and A ration and morthat work. During his early years in Boston, the prolonged By means of a staining fluid,1 devised by me for finely ragged wh In appearance ties by his book with D Dr. Wrightoralsofimbriate authored a twice-yearly review edge. to use in the staining of blood films the wide a according blood of his 1901The contributio the ofBoston of progress in pathology in the Medical anrange ectosarc it ameba. suggests this the method of Leishman, which gives the sopa nique, in which h andof Surgical Journal. Th is was a multipage sumare the cells of form, majority of giant spherical has shown all of polychrome animalsstaining, that the me called Romanofsky I have many briefly boiling it in mary of published research with a detailed literaThe varied a are but minority of and shape irregular staining. No additi the ture review. Th e series had been initiated by Dr. blood been enabled to stain characteristically theories hitherto the reason of the distortion of their by section technique c Councilman in 1893, but Dr. Wright took it over cytoplasm in sections of fixed tissues and so

portion

phology

of

study of comparative corpuscles

proposed concerning

origin

BLOOD PLATES-WRIGHT.

Origin of the blood plates from

the

giant cells of the bone

marrow.

12

Etiología de las Anemias HIPER PROLIFERATIVA 10 %

HIPO PROLIFERATIVA 90 %

Etiología de la Trombocitopenia BAJA PRODUCCIÓN 10 %

EXCESO DESTRUCCIÓN 90 %

ETIOLOGY •

Medicina Interna (paciente hospitalizado)

•

Consulta Externa (trombocitopenia aislada)

•

Unidad de Cuidados Intensivos y Urgencias.

•

Unidad Coronaria

•

Zonas endémicas

•

Embarazadas

ETIOLOGY

producciรณn secuestro

destrucciรณn

Combo 1: Hemograma Reticulocitos ferritina LDH Haptoglobina Bilirrubinas Creatinina

Combo 1: FROTIS DE SANGRE PERIFÉRICA

Grover S, Barkun A, Sackett D. Does this patient have splenomegaly? En The rational clincal examination. JAMA 2009, Cap 46.

Philipe Gaucher

EpidemiologĂ­a

PatogĂŠnesis

Diagnรณstico Beta Glucosidasa Acida Glucocerebrosidasa

OTROS PAISES 31 % USA 50 %

ISRAEL 19 %

100 94

80

60

40

20 5

0

1

TIPO 1

TIPO 2

TIPO 3

The distribution of ages at diagnosis

Arch Intern Med. 2000;160(18):2835-2843

Curso Clinico Pulmonary involvement

Hepatosplenomegaly

Progressive neurologic symptoms*

Thrombocytopenia and anemia

Skeletal involvement * In neuronopathic subtypes only.

HALLAZGOS AL DIAGNOSTICO % 100.0

86.7

80.0

85.8

80.0

76.3

60.0 45.2 40.0 22.6 20.0 0.0 Esplenomegalia

Anemia

Hepatomegalia

Plaquetopenia

Leucopenia

Dolor รณseo

ADENOMEGALIAS Linfomas

Esplenomegalia

Hepatomegalia

Trombocitopenia

ENFERMEDAD Ã’SEA

• RNM • T1-weighted MRI: marrow infiltration • T2-weighted MRI: bone infarcts. • GAMAGRAFIA • Hot spots: Osteomielitis • Coold spots: Necrosis

• RX • DENSITOMETRIA

PEORAMIENTO DE LA CALIDAD ˜SEA YA QUE EL BAZO ES UN RESERVORIO NATURAL DE C£LULAS DE 'AUCHER "EIGTHON &IGURA )

&IGURA $EFORMIDAD EN MATRAZ DE %RLENMEYER LESIONES QUÓS TICAS NECROSIS ØSEA E INlLTRACIØN MEDULAR COEXISTIENDO EN UNA MISMA LOCALIZACIØN

%L MECANISMO POR EL CUAL LA INlLTRACI˜N DE LA M£DULA ˜SEA LLEVA A LA AFECTACI˜N ˜SEA TODAV¤A ES DESCONOCIDO 5N

DEFORMIDAD EN LO EL GENU VARO ,A OST COMO EL CORTICAL Y P

&IGURA )NlLTRACIØN

,A INlLTRACI˜N D

&IGURA )

EL GENU VARO ,A OSTEOPENIA AFECTA TANTO EL HUESO TRABECULAR COMO EL CORTICAL Y PUEDE SER LOCAL O DIFUSA

MEYER LESIONES QUÓS COEXISTIENDO EN UNA

RACI N DE LA M£DULA ES DESCONOCIDO 5N SEA PODR¤A SER QUE

&IGURA )NlLTRACIØN DE LA MÏDULA ØSEA FÏMUR

,A INlLTRACI N DE LA M£DULA SEA TAMBI£N PRODUCE UNA FALLA DE LA REMODELACI N SEA CARACTERIZADA POR LA DEFORMI

RAL ,A ESPLENECTOM¤A Y EL AUMENTO DEL N¢MERO DE PLAQUE TAS ESTÖN ASOCIADAS A UN MAYOR RIESGO DE OSTEONECROSIS

-0.2 -0.4 -0.6 -0.8 -1 -1.2 -1.4 -1.6 0

&IGURA %NFE SCORE : PARA P A×OS TRATADOS &IGURA .ECROSIS DE CABEZA DE HÞMERO

,AS CRISIS ˜SEAS SON MANIFESTACIONES CL¤NICAS DE UN IN

/TRA ALTER CON PATOLOG¤A &IGURA CA

PUEDEN SER CONFUNDIDAS CON LA PRESENCIA DE INlLTRACI N ME

.ACIMIENTO 2OJA

!MARILLA

años

#ARTÓLAGO

&IGURA #ONVERSIØN DE LA MÏDULA ØSEA ROJA EN MÏDULA ØSEA AMARILLA DURANTE EL DESARROLLO NORMAL DE LOS MIEMBROS INFERIORES 2EIMPRESO CON AUTORIZACIØN

Osteoporosis

Anemia

ETIOLOGY

producciรณn

destrucciรณn

Combo 1: Hemograma Reticulocitos ferritina LDH Haptoglobina Bilirrubinas

Combo 2: * Glucocerebrosidasa *Quitotriosidasa

Valoraciรณn Inicial

BIOMARCADORES

ESTUDIO MOLECULAR

Arch Intern Med. 2000;160(18): 2835-2843

Genotipo • N370S • L444P • 84GG

TRATAMIENTO • Enzyme replacement • Bone marrow transplantation • Sustrate Inhibition Treatment • Splenectomy

Terapia de Reemplazo Enzimatico

Barton NW et al. N Engl J Med 1991;324:1464-1470.

Barton NW et al. N Engl J Med 1991;324:1464-1470.

Barton NW et al. N Engl J Med 1991;324:1464-1470.

Barton NW et al. N Engl J Med 1991;324:1464-1470.

Effect of Macrophage-Targeted Glucocerebrosidase on the Hemoglobin Concentration in Patient 12.

Barton NW et al. N Engl J Med 1991;324:1464-1470.

Barton NW et al. N Engl J Med 1991;324:1464-1470.

Effect of Glucocerebrosidase on Serum Acid Phosphatase Activity in Patient 11:

Barton NW et al. N Engl J

Clin Genet. 2008 May; 73(5): 430–440.

Clin Genet. 2008 May; 73(5): 430–440.

Inhibición de Suatrato • Miglustat Eliglustat •

ELIGLUSTAT • Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4 years of treatment Blood Cells, Molecules, and Diseases Volume 53, Issue 4, December 2014, Pages 274–276

Fig. 1 Improvements in hematologic and organ volume parameters through 4 years of eliglustat treatment. Data are reported as percent change from baseline for platelets, liver and spleen, and change from baseline for hemoglobin in g/dL. All values are mean...

Elena Lukina , Nora Watman , Marta Dragosky , Gregory M. Pastores , Elsa Avila Arreguin , Hanna Rosenbaum , Ari Z... Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4<ce:hsp sp="0.25"/>years of treatment Blood Cells, Molecules, and Diseases, Volume 53, Issue 4, 2014, 274 - 276 http://dx.doi.org/10.1016/j.bcmd.2014.04.002

Fig. 3 Mean lumbar spine bone mineral density improvement from osteopenia to normal range after 4 years of eliglustat treatment. Values for the lumbar spine represent the mean changes in T-score from baseline and the significance of the changes at each ti...

Elena Lukina , Nora Watman , Marta Dragosky , Gregory M. Pastores , Elsa Avila Arreguin , Hanna Rosenbaum , Ari Z... Eliglustat, an investigational oral therapy for Gaucher disease type 1: Phase 2 trial results after 4<ce:hsp sp="0.25"/>years of treatment Blood Cells, Molecules, and Diseases, Volume 53, Issue 4, 2014, 274 - 276 http://dx.doi.org/10.1016/j.bcmd.2014.04.002

Monitoreo / Metas

4ABLA $ATOS CLÓNICOS SOBRE LA RESPUESTA ØSEA A LA TERAPIA DE REEMPLAZO ENZIMÉTICO -ANIFESTACIONES ØSEAS

2ESUMEN DE LOS RESULTADOS

$OLOR ØSEO

s $ISMINUCIØN DEL DOLOR ØSEO s 3E OBSERVA DENTRO DEL PRIMER A×O DE 42%

#RISIS ØSEAS

)NlLTRACIØN MEDULAR /STEOPENIA

s 2EDUCCIØN EN LA FRECUENCIA E INTENSIDAD DE LAS CRISIS ØSEAS CON FRECUENCIA DURANTE EL PRIMER A×O DE 42% s 2ECONVERSIØN EN A×O s 2EMINERALIZACIØN s 2ESPUESTA MÉS RÉPIDA EN NI×OS

!CELERACIØN DEL CRECIMIENTO

s %N LOS NI×OS QUE HAN MOSTRADO RETARDO DEL CRECIMIENTO SE OBSERVA NORMALIZACIØN DEL CRECIMIENTO

&RACTURAS Y OSTEONECROSIS

s 0REVIENE FRACTURAS Y NUEVOS FOCOS DE OSTEONECROSIS

TIAS PUES FRECUEN A LAS PR˜TESIS Y £S

%STABILIZACI

,A ESTABILIZAC %NFERMEDAD DE ' MEDICAMENTO !LG GLUCERASA EN PARA CORREGIR LA D FESTACIONES CL¤NICA

,A PRESCRIPCI˜ ZADA PARA CADA P ENFERMEDAD ESQU PROMISO ESQUEL£T SI˜N DE LAS ALTERA DEBEN SER TENIDOS TRATAMIENTO O UN

Sospechar en ... •

Gaucher is a progressive, debilitating and sometimes life-threatening disease.

Symptoms can include:
 easy bleeding and bruising, fatigue, anemia, weak bones, bone and joint pain, and enlargement of the spleen 
 or liver. Symptoms can appear at any age.

*National Gaucher Foundation (NGF)
 www.gaucherdisease.org *National Organization for Rare Disorders (NORD)
 www.rarediseases.org *National Institutes of Health
 www.rarediseases.info.nih.gov/ Genzyme’s Gaucher disease website
 www.gauchercare.com

*National Gaucher Foundation (NGF)

www.gaucherdisease.org
 *National Organization for Rare Disorders (NORD)
 www.rarediseases.org
 *National Institutes of Health
 www.rarediseases.info.nih.gov/
 Genzyme’s Gaucher disease website
 www.gauchercare.com

#ÏLULAS DE 'AUCHER

/STEOCLASTOS

&IGURA -ODELO DE INTERACCIØN ENTRE CÏLULAS DE 'AUCHER Y OSTEOCLASTOS RESULTANDO EN REABSORCIØN ØSEA 7ENSTRUP 2* #ÏLULAS DE 'AUCHER SE CRETAN FACTORES QUE INmUENCIAN LA DIFERENCIACIØN OSTEOCLÉSTICA Y PROMUEVEN LA REABSORCIØN ØSEA

Bone Marrow Biopsy and Aspirate Specimens.

Larsen EC et al. N Engl J

MRI Scans of the Pelvis and Femurs.

Larsen EC et al. N Engl J Med

Abdomen of Patient 7 before (A) and after (B) Six Months of Enzyme Replacement.

Barton NW et al. N Engl J Med

Gaucher Disease Gaucher disease is inherited (passed from parent to child). Both parents must be either carriers or have the disease for the disease to present in 
 a child.

Abdomen of Patient 7 before (A) and after (B) Six Months of Enzyme Replacement.

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