Transplante nas Hemoglobinopatias - SBTMO...
Transcript of Transplante nas Hemoglobinopatias - SBTMO...
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Transplante nas Hemoglobinopatias
Revendo o Condicionamento, as
Indicações e os Doadores
Luiz Guilherme Darrigo Junior
USP Ribeirão Preto
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AS HEMOGLOBINOPATIAS
Hemoglobinopatia No. RN/Ano
Anemia Falciforme (SS) 217.331
Doença SC 54.736
S b talassemia 11.074
b talassemia maior 22.989
HbE b talassemia 19.128
Doença HbH 9.568
Hb Barts 5.183
Weatherhall DJ Blood 2010Modell B, Darlison M. Bull World Health Organ. 2008
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AS HEMOGLOBINOPATIAS
Hemoglobinopatia No. RN/Ano
Anemia Falciforme (SS) 217.331
Doença SC 54.736
S b talassemia 11.074
b talassemia maior 22.989
HbE b talassemia 19.128
Doença HbH 9.568
Hb Barts 5.183
Weatherhall DJ Blood 2010Modell B, Darlison M. Bull World Health Organ. 2008
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Anemia Falciforme
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Retardo CrescimentoCrises AplásticasSequestro EsplenicoAutoinfartosDactiliteCrises VasoclusivasSTA
STAHemólise CrônicaImunossupressãoAVCLitíase BiliarNecrose AvascularÚlceras crônicasPriapismoDesenvolvimento Sexual atrasado
CardiomiopatiaInsuficiência cardíacaRetinopatia Hipertensão PulmonarDoença PulmonarSequestro HepáticoSobrecarga de ferroInsuficiência RenalNecrose Óssea
CRIANÇAS ADULTOS
EVOLUÇÃO CLÍNICA
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0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
< 5a 05 a 10 19 a 20 20 a 29 30 a 39 40a 49 50 a 59
AF
Controles
No. Of deaths/ 100.000 people * p<0,001
* *
*
*
*
*
Shankar SM, 2005 Am J Hematology
MORTALIDADE NA ANEMIA FALCIFORME
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TCTH EM ANEMIA FALCIFORME
1 - Tratamento é eficaz e seguro
2 - O transplante de medula óssea alogênico é a única opção
terapêutica curativa para as hemoglobinopatias.
Russell E Ware, et al Lancet 2017
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DOENÇA FALCIFORME vs TMO
Dano TMO Doença Falciforme
Óbito Baixa chance de morrer de complicações do TMO
Risco muito baixo na infância com cuidados adequados de suporte, alto riscode morrer prematuramente quandoadulto
Infecções Pacienes muito imunossuprimidos por longo tempo pós TMO
Função esplenica defeituosa ou ausente
Complicações Agudas
Mucosite, alopecia, SOS, hemorragia cerebral, PRES
CVA, sequestro esplenico, STA, colecistite, priapismo, crise aplástica, AVC
Complicações Crônicas
GVHDc Dor crônica, necrose asséptica, lesões orgânicas (rim, pulmão, retina)
Problemas reprodutivos
Possível por toxicidade do condicionamento
Possível por lesão órgãos (disfunção erétil, problemas na gestação) ou hidroxiurea
Social Problema intenso de curta duração Pela vida toda…. Doença crônica
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EXPERIÊNCIA RIBEIRÃO PRETO
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DADOS RIBEIRÃO PRETO
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DADOS RIBEIRÃO PRETO
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OBSERVAÇÕES
Falha de enxertia secundária
Recuperação autóloga após uma fase de aplasia
Neurotoxicidade
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Revendo o Condicionamento, as
indicações e os doadores
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CONDICIONAMENTO
FLUDARABINA30 mg/m2/dia
ATG 4,5 mg/Kg
BUSULFAN 3,2 mg/Kg/dia
- 5 -4 - 3 - 2 - 1 INFUSÃO
MedulaÓssea
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CONDICIONAMENTO
FLUDARABINA30 mg/m2/DIA
ATG 8 mg/Kg
BUSULFAN 3,2 mg/Kg/dia
- 6 - 5 -4 - 3 - 2 - 1 INFUSÃO
MedulaÓssea
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CONDICIONAMENTO
FLUDARABINA30 mg/m2/DIA
ATG 8 mg/Kg
BUSULFAN 3,2 mg/Kg/dia
- 6 - 5 -4 - 3 - 2 - 1 INFUSÃO
MedulaÓssea
FLUDARABINA30 mg/m2/DIA
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Revendo o Condicionamento, as
indicações e os doadores
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Total number of HSCT for SCD reported: 500-600 patients transplanted
Risk factors for transplant-related complications:
Age, history of cerebral events
Time of transplantation: With HLA-identical sibling: as soon as possible
Stem cell source from MSD: Bone marrow, cord blood
Indication for HSCT from unrelated BM or CB donors:
At least one criteria according Walters et al.Within controlled clinical trials only
Conditioning regimen: Standard: IV Busulfan,cyclophosphamide, ATG Reduced: within controlled clinical trials only
GvHD-prophylaxis for MSD-HSCT Standard: CSA + MTX; Antibodies (ATG,alemtuzumab) as rejection- and GvHD-prophylaxis
Post-transplant evaluation: In cooperation of hematologists and transplant experts
Modified from Angelucci et al, Haematologica, 2014
Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations
from an international expert panel.
Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD, Dalle JH, Di Bartolomeo P, de Heredia CD, Dickerhoff R, Giardini C, Gluckman E, Hussein AA, Kamani N, Minkov M, Locatelli F, Rocha V, Sedlacek P, Smiers F, Thuret I, Yaniv I,
Cavazzana M, Peters C; EBMT Inborn Error and EBMT Paediatric Working Parties.
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Total number of HSCT for SCD reported: 500-600 patients transplanted
Risk factors for transplant-related complications:
Age, history of cerebral events
Time of transplantation: With HLA-identical sibling: as soon as possible
Stem cell source from MSD: Bone marrow, cord blood
Indication for HSCT from unrelated BM or CB donors:
At least one criteria according Walters et al.Within controlled clinical trials only
Conditioning regimen: Standard: IV Busulfan,cyclophosphamide, ATG Reduced: within controlled clinical trials only
GvHD-prophylaxis for MSD-HSCT Standard: CSA + MTX; Antibodies (ATG,alemtuzumab) as rejection- and GvHD-prophylaxis
Post-transplant evaluation: In cooperation of hematologists and transplant experts
Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations
from an international expert panel.
Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD, Dalle JH, Di Bartolomeo P, de Heredia CD, Dickerhoff R, Giardini C, Gluckman E, Hussein AA, Kamani N, Minkov M, Locatelli F, Rocha V, Sedlacek P, Smiers F, Thuret I, Yaniv I,
Cavazzana M, Peters C; EBMT Inborn Error and EBMT Paediatric Working Parties.
Indications for HSCT:• Stroke or CNS event • Acute chest syndrome • Recurrent vaso-occlusive pain • Priapism• Impaired neuropsychological
function with abnormal CNS MRI• Sickle lung disease• Sickle nephropathy• Retinopathy• Osteonecrosis• Red-cell alloimmunization
Modified from Angelucci et al, Haematologica, 2014
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PRÉ
PÓS
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• Vários estudos mostraram que o risco de recidiva do AVC é maior
em pacientes com doença de moyamoya associada à AF
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PROPOSTA DE ESTUDO
Transplante
2 Anos - Avaliação
Acompanhamento Padrão
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Revendo o Condicionamento, as
indicações e os doadores
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17 pts transplantados
43% Falha de Enxertia
Nenhum Óbito
36 pts transplantados
9/31 (29%) Falha de Enxertia
Um Óbitos
EBMT 2018
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Thiotepa 10 mg/kg 400 cGy TBI
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Thiotepa 10 mg/kg 400 cGy TBI
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CENTROS PARTICIPANTES
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ASH Education Book December 4, 2010 vol. 2010 no. 1 456-462
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SUGESTÃO
• Incluir transplante de medula óssea para pacientes com
pesaro 1 ou 2 e doadores não aparentados full match
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CONCLUSÕES
• O TCTH é a única opção terapêutica curativa para as
hemoglobinopatias
• Alterações no condicionamento e nas indicações para o transplante
podem trazer melhores resultados
• Pacientes com Moyamoya podem se beneficiar com o TCTH ?
• TCTH MUD é uma opção eficaz e aceitável para pacientes com
talassemia
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AGRADECIMENTOS
• Hemocentro Ribeirão Preto
– Ana Cristina Pinto– Gil de Santis– Ivan Angulo
• Unidade de TMO
– Ana Beatriz Stracieri– Thalita Costa– Laila Rigolino– Joana – Fabiano Pieroni– Renato Cunha– Maria Carolina de Oliveira– Daniela Moraes– Carlos E. Setanni Grecco– Belinda Simões