ANEMIA APLÁSTICA- TRANSPLANTE DE MEDULA ÓSSEA

ANEMIA APLÁSTICA- TRANSPLANTE DE MEDULA ÓSSEA Ricardo Pasquini Professor Emérito - UFPR VI BOARD REVIEW CURSO DE REVISÃO EM HEMATOLOGIA E HEMOTERAPIA HOSPITAL ISRAELITA ALBERT EINSTEIN JUNHO - 2012

ANEMIAS APLÁSTICAS ETIOLOGIA HEREDITÁRIAS E ADQUIRIDAS

ANEMIAS APLÁSTICAS HEREDITÁRIAS Anemia de Fanconi Síndrome de Shwachman-Diamond Disceratose congenita Síndrome de Hoyeraal-Hreidarsson Síndrome de Revesz Outras Doenças do Telômero Outras doenças genéticas: Síndrome de Down Síndrome de Dubowitz Síndrome de Seckel Disgenesia Reticular Displasia imuno-óssea de Schimke Outras anemias aplásticas familiares

CITOPENIAS UNILINHAGEM Anemia de Diamond-Blackfan Síndrome de Kostmann (Neutropenia Congênita) Trombocitopenia com ausência de rádio Outras trombocitopenias hereditárias Síndrome de Bart Doença de depósito do glicogênio 1b Anemias diseritropoiéticas congênitas

ANEMIAS APLÁSTICAS ADQUIRIDAS HC-UFPR

TRATAMENTO DA ANEMIA APLASTICA TERAPIA DE SUPORTE TRANSPLANTE DE CTH IMUNOSSUPRESSÃO HC-UFPR

DEFINIÇÃO DA GRAVIDADE DA ANEMIA APLASTICA ANEMIA APLÁSTICA SEVERA: CELULARIDE DA M.O: <25% or 25-50% com <30% e pelo menos 2/3 dos seguintes; neutrófilos <500/ µl, plaquetas <20000/ µl and reticulócitos <20000/µL MUITO SEVERA: Como a forma severe, porém com neutrófilos <200 µl NÃO SEVERA: Pacientes que não preenchem os critérios acima HC-UFPR

APLASTIC ANAEMIA TREATED BY MARROW TRANSPLANTATION E Donnall Thomas, Rainer Storb, Alexander Fefer, SherillJ Slichter, JeanI Bryant, C Dean Buckner, PaulE Neiman, ReginaldA Clift, DonaldD Funk, KennethE Lerner The Lancet, Volume 299, Issue 7745, Pages 284-289, 5 February 1972 Abstract 4 patients with complete marrow failure, 3 due to unknown cause and 1 associated with hepatitis, showed no indication of spontaneous recovery after 7 to 52 weeks of conventional and supportive treatment. They were conditioned for engraftment by the administration of cyclophosphamide, 50 mg. per kg., on each of 4 days, followed in 36 hours by marrow infusion. The marrow donor in each instance was a sibling of opposite sex who matched the recipient with regard to the major human histocompatibility locus (HL-A) as shown by cytotoxicity testing of the family and confirmed by non-reactivity in the mixedleucocyte test. Methotrexate was given for a limited period after grafting as an immunosuppressive agent to modify the graft-versus-host disease. All 4 patients showed prompt engraftment indicated by a return of marrow cellularity and a rise of peripheral blood-counts, confirmed by cytogenetic analysis. 1 patient died of graft-versus-host disease with a cellular marrow 45 days after grafting. Another patient rejected his graft and died 67 days after grafting. 2 patients have excellent-functioning marrow grafts without graft-versus-host disease and are apparently well 138 and 215 days after grafting.

Bone Marrow Graft in Man after Conditioning by Antilymphocytic Serum* G. Mathe, M.D.; J. L. Amiel, M.D.; L. Schwarzenberg, M.D.; J. Choay, M.D.; P. Trolard, M.D.M. Schneider, M.D.; M. Hayat, M.D.; J. R. Schlumberger, M.D.; Cl. Jasmin, M.D. British Medical Journal, 1970, 2, 131-136

Differences (%) in estimated failure free survival, after initial treatment, at 5 years FU Seminars in Hematology 2000; 37: 69 Age PMN 10 yy 20 yy 30 yy 40 yy 50 yy 0 24 20 14 16-2 100 19 200 14 300 16 19 14 8 1-7 14 9 3-4 -11 16 5-1 -7-14 400 6 1-4 -10-16 500 3-2 -7-12 -17 Positive values: BMT has superior (+) survival compared to IS Negative values: BMT has inferior (-) survival compared to IS

Algoritmo no Tratamento da Anemia Aplástica Adquirida Marsh J et al, British Journal of Haematology 2009;147:43-70.

Marsh, JCH. Blood Reviews, 18:143, 2005

Probability of Survival after Allogeneic Transplants for SAA, Worldwide, 2000-20092009 - By Donor Type and Age - 100 100 90 HLA-id sibling, 20y (N=1,191) 90 Probability of Survival, % 80 70 60 50 40 30 20 HLA-id sibling, > 20y (N=1,256) Unrelated donor, 20y (N=574) Unrelated donor, > 20y (N=550) 80 70 60 50 40 30 20 10 0 P < 0.0001 0 1 2 3 4 5 6 10 0 Years Slide 31 SUM-WW11_31.ppt

COX multivariate analysis transplantation P RR Age (<16/=>) 0.0001 1.66 Interval DxTx (< /> 83 dd ) 0.0006 1.56 Locasciulli, Haematologica; 2007;92:11.

Blood 2007; 110:1397 =<20 years(rr 2.4) p=0.02 >20 years(rr 1.2) p=0.1

Overall Experience in Allo HSCT According to the Diagnosis (1979-June/2011) 17% 27% 19% 10% 14% 13% Anemia Aplástica Severa (511) A.Fanconi (239) Leucemia Mielóide Aguda (248) Leucemia Linfóide Aguda (180) Leucemia Mielóide Crônica (345) Outros (308) Unrelated donor 413 Syngeneic 12 SOURCE OF CELLS Bone marrow 1574 Cord blood 180 Peripheral blood 73 bm + (cb or pb) 04 TOTAL: 1831

Aplastic Anemia - Overall Experience BMT Center UFPR Curitiba - Brazil Period: 10/1979 31/08/09 Patients referred 1225 Patients treated at our institution 1034 Types of treatment - Bone Marrow Transp. 478 - Immunosuppression 556

HSCT in SAA Clinical Characteristics Period 1979-Junho 2011 Number of patients 511 Age - range (M) 1-49 (19) Gender (M/F) 319/192 Female donor (%) 40 Previous transf U. - range(m) 0-675 (28) Disease duration (months) 0.5-232 (4) Granulocytes/µL 0-3835 (322) Infused Cells X10 8 /Kg (bm) 0.69 12.9 (3.4) Donor type related 482

HSCT in SAA - UFPR Overall survival Survival (%) 1.1 1.0 0.9 0.8 0.7 0.6 0.5 423 pts 0.4 0.3 0.2 0.1 0.0 0 5 10 15 20 25 Time (years)

HSCT in SAA - UFPR Conditioning Survival (%) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 A) Cy200, <16tr (96) B) Bu+Cy (153) C) Cy200, >15tr (74) P<0.0001 0 5 10 15 20 Time (Years) B X C: p=0.006

HSCT in SAA > 50 transfusions Survival 1.0 B) bucy, >50transf(41) 0.9 C) cy, >50transf (21) 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 A) bu+flu - todos (23) 0.0 0 10 20 30 Time post transplant (Y) A X C: p = 0.03

FACTORS AFFECTING THE OUTCOME OF HSCT FOR SEVERE APLASTIC ANEMIA PATIENTS multivariate analysis SURVIVAL Odds ratio P value Previous transf. 7.01 <0.001 Disease duration 1.5 0.03 Engraftment 69.0 <0.001 agvhd 2.98 <0.001 Bussulfan (cond.) 0.52 <0.013

FACTORS AFFECTING THE OUTCOME OF HSCT FOR SEVERE APLASTIC ANEMIA PATIENTS -multivariate analysis- O.R. p value GRAFT FAILURE Age 0.49 0.018 Bussulfan (cond.) 0,17 <0.001 Previous treat. 0.49 0.017 (<16 transf./pred) agvhd >50 transfusions 0.047 cgvhd Age 2.94 0.001

Causes of Death Cy <16 RBCT n= 10 Cy 16 RBCT n= 46 Bu + Cy 16 RBCT n=23 Graft failure 30% 35% 2% IPN/ARDS* 0% 13% 11% Infection 30% 31% 35% GVHD 0% 0% 4% Organ failure 10% 4% 22% Hemorrhage 20% 4% 13% Other causes 10% 13% 13% *IPN=Interstitial pneumonia; ARDS=Acute respiratory distress syndrome. AAF06_3.ppt

Anemia Aplástica Severa Experiência Brasileira em 6 Centros de TCTH (930 pacientes) HC-UFPR

Centros de TCTH CEMO INCA - RJ Luiz Fernando Bousas H. Amaral Carvalho Jaú - Vergilio Culturato Hospital das Clínicas/USP - Frederico Dulley Hospital de Clínicas UFPR Santa Casa de São Paulo - José Carlos Barros UNICAMP Afonso Vigoritto HC-UFPR

Overall survival All Centers Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 5 10 15 20 25 30 Time (Years) 930 patients HC-UFPR March/2011

Overall Survival Related donor - All Centers Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 C)2000-2010 (381) B)1990-1999(362) A)1980-1989 (133) 0 5 10 15 20 25 30 Time (Years) HC-UFPR A X B: p=0.0001 B X C: p=0.0157 March/2011

Overall Survival Related donor - All Centers Previos transfusion Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 <16 (234) >15 (490) P<0.0001 0 5 10 15 20 25 30 Time (Years) HC-UFPR March/2011

Overall Survival Related donor - All Centers Conditioning Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 A)BusCy (250) B)Cy200 <16tr (150) C)cy200 >15tr(102) P<0.0001 0 5 10 15 20 25 30 Time (Years) HC-UFPR March/2011

Graft failure/rejection All Centers (wo CEMO) Conditioning Rejection C)cy200>15tr(43/102) B)cy200<16tr(64/151) 1.0 A)bucy(36/249) 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 5 10 15 20 25 30 Time (Years) HC-UFPR AXB, AXC: P<0.0001 BXC: p=0.0442 March/2011

Treatment After Rejection Cy <16 RBCT N=36 Cy 16 RBCT N=19 Bu + Cy 16 RBCT N=16 Second Transplant 8 6 6 Cyclosporine 21 8 6 Combination 7 5 4

Survival After Rejection Rejection 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 P=0.0002 Cy<16 (42) Cy>15 (24) Bucy (20 pts) 0 5 10 15 20 Days

Chimerism after 2 yrs/sct for SAA Conditioning CY alone BUS+CY Transf. <16 >15 politransf. Number of patients 52 14 55 Donor cells % <50 16 10 01 51-90 10 01 06 >90 26 (50%) 07 (50%) 48 (87%)

Brazil * 1989-2005 239 20(2-58) 15% 17 20 68% at 7yrs * HCUFPR, UNICAMP e UFMG

Overall Survival All Centers Donor type Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 p=0.2356 Related (878) Unrelated (51) 0 5 10 15 20 25 30 Time (Years) HC-UFPR March/2011

TCTH NAP em pacientes com AAS : 34 pts Período : 1997 a 2012 1997 a 2009 : regime MAC 12.2009 a 05.2012 : regime RIC Idade: 1 a 36 anos ( M: 14 anos) Transfusões: 10 a 350 ( M: 51) Fonte de células: 7 TSCU : Todos morreram 1 PBSC : óbito 26 MO

TMO NAP em pts com AAS 1997 a 06.2009 : 10 pts - Mieloablativo CY(120)+TBI(1440 rads) +/- ATG 12.2009 a 04.2012 : 16pts Intensidade reduzida CY1200mg/m2 + FLU +ATG +/- TBI (200) : 9pts CY60mg/kg + FLU+ ATG + TBI (200): 7pts

TMO NAP em pts com AAS - Mieloablativo: 10 pts 1997 a 06.2009 : 10 pts CY+TBI +/- ATG Todos pegaram ( VNTR 100%) 8 vivos 3 DECH C extenso Nenhuma perda de enxerto tardia 2 óbitos : D+85 ( fungo), D+ 410 ( PI por CMV)

TMO NAP condicionamento RIC CY1200mg/m2 + FLU+ATG+/- TBI: 9 pts 6 vivos Mediana de transfusões ; 101 1 óbito precoce D+ 32 (PI RSV) 3 rejeições Re TMO 2 óbitos Quimerismo misto na maioria.2 pts com pega arrastada;1 pt com AHAI grave CY60mg/kg +FLU+ATG+TBI 200: 7 pts 6 vivos Mediana de transfusões: 101 1 óbito precoce D+39 (FPP ) 6 vivos : 1 rejeição re TMO Haplo 100% do doador. Plaq 30000 (1 ano) 5 pts com 100% de quimerismo

SG após o TMO NAP em pts com AAS 19/25pts vivos com um seguimento 2 anos SG de 76%

Sobrevida Global de acordo com o tipo de condicionamento ( MAC x RIC) 10pts SG de 80% 5 anos 15pts SG de 72% 2 anos

SG de acordo como os 3 tipos de condicionamento MAC 10pts SG: 80%/ 5 anos RIC CY 60: 6pts SG: 83%/1 ano RIC CY 1200/m2: 9pts SG: 66% / 2 anos

Actuarial survival of 100 patients with acquired SAA undergoing an alternative donor transplant (WPSAA 2009) 75% days from transplant

Scheinberg, P. Blood, 2012

Survival 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Immunossupressive treatment X BMT in SAA BMT (243 pat) Immuno (198 pat) 0 1000 2000 3000 4000 5000 6000 Days Sep/2005

Transplante de Medula Óssea HPN UFPR 03/1988-02/2005 14 pacientes Idade mediana 28 anos 12 pancitopenia Condicionamente predominante: bussulfan 12 + ciclofosfamida 120 12 doadores irmãos DECHa= 4 pacientes DECHc= 4 pacientes 2 óbitos relacionados TMO (+10,+11) Sobrevida global 70%

FANCONI ANEMIA CLINIC Hospital de Clínicas Universidade Federal do Paraná Curitiba - Brazil Cortesia da Dra. Carmem M. Bonfim

Introdução Anemia de Fanconi é uma doença rara herdada atravéz de um gene autossômico recessivo e caracterizada por progreessiva falência da medula óssea, anomalias congênitas e evidente predisposição em desenvolver neoplasias malignas. A alta sensibilidade aos agentes clastogênico tais como dietóxibutano( DEB) e mitomicic\na C, é fundamental para o diagnóstico desta entidade. O transplante de medula óssea é o único tratamento capaza de curar as complicaões hematológicas relacionadas à doença.

Fanconi Anemia Clinic (1983-2009) Patients evaluated: 411 (71 new patients over the last five years) Geographic origin: South 121, Southeast 144, Central-west 41, Northeast 84 and North 13. Low social economic class: 68%. Current active patients followed: 183 (110 post HSCT and 73 non-transplanted).

Preliminar panel to set up the screening of common mutations of Brazilian patients MUTATION LOCALIZATION GENE 987-990del (c.987-990 del ) Exon11 FANCA 2535-2536del (c.2535-2536del) Exon27 FANCA IVS29(-19)-1del (c. 2853-19 del 19) Intron29 FANCA 3788-3790del (c.3788-3790del) Exon38 FANCA 1115-1118 del (c.1115-1118del) Exon13 FANCA c.1390c>t (c.1393 C>T) Exon13 FANCC 320G>A (c.65g>a) Exon 1 FANCC IVS4 + 4 A>T (c.711+4 A>T Intron 4 FANCC 322delG (c. 67delG) Exon 1 FANCC IVS8-2A>G (c.1077-2a>g) Exon 8 FANCG IVS11 + 1G>C (c.1480+1g>c) Exon 11 FANCG

HSCT FOR FANCONI ANEMIA Brazilian experience 276 patients o Curitiba PR : HC-Universidade Federal do Paraná 231pts o Rio de Janeiro RJ : Instituto Nacional do Câncer -11pts o Recife - PE : Hospital Real Português -8pts o Belo Horizonte MG: HC-Universidade Federal de MG -7pts o São Paulo SP: Instituto de Oncologia Pediátrico -6 pts o Ribeirão Preto SP: HC-Universidade de São Paulo -3pts o Hospital Albert Eisntein -SP: 4 pts o Jaú SP: Hospital Amaral Carvalho -2pts o Porto Alegre RS: HC-Universidade Federal do RS - 2pts o Porto Alegre RS: Serviço de Oncologia Pediátrica 2 pts

HLA Matched Related Bone Marrow Transplantation in 85 patients with Fanconi Anemia: The Brazilian Experience using Cyclophosphamide 60mg/kg C Bonfim; L Ribeiro; M Bitencourt; J Zanis-Neto,A Seber, R Gouveia, R Florencio, A Souza, L Daudt, A K Vieira, M Ostronoff, L F Bouzas, R Pasquini CIBMTR Tandem Meetings 2012

Patient Selection o Number : 85pts o Period: 07/1999-05/2011 o Graft type: Bone marrow from HLA matched related donors o Transplanted at 6 Brazilian BMT Centers: o Curitiba : Federal University of Parana: 68pts o São Paulo: Pediatric Oncology Institute 6pts o Recife : Hospital Real Português : 4pts o Rio de Janeiro : National Institute of Cancer: 3pts o Belo Horizonte :Federal University of Minas Gerais: 2pts o Porto Alegre : Federal University of R G do Sul: 2pts

Patient Characteristics: 85 pts o Gender 40F/45M o Age - years - M (range) 09 (03-34) < 10 ys old : 48 pts > 15 ys old : 07 pts o Previous transfusions: 0-101 Units ( M: 6 U) o Phase of the disease : o Severe Aplastic Anemia 82pts o MDS 3pts o Type of donor: o Siblings: 74 pts o Other Related HLA identical Donors : 11 pts

Transplant Characteristics o Preparatory Regimen : o Cyclophosphamide 60mg/kg (15mg/kg/day x 4) o GVHD Immune prophylaxis: ocyclosporine 3mg/kg/d + Methotrexate 15mg/m2 on D+ 1 and 10mg/m2 on D+ 3,+6 and + 11 o Prophylactic antibiotics : oacyclovir, Bactrim, Fluconazol or Micafungin, Levofloxacin o Other : Ursodiol and Mesna

Overall Survival after an HLA Matched related donor using CY 60mg/kg 72 pts: 84,5% at 5ys Follow-up: 5m- 12ys (: 5ys)

Overall Survival according to age at BMT 48 pts < 10ys: OS - 96% in 5ys 37pts 10ys: OS - 72% in 5 ys p=0,012

Overall Survival according to type of donor or BMT center ORD 11pts: 91% in 5ys Other BMT Centers: 17pts OS 86.3% at 5ys MSD : 74pts :82,3% in 5 ys Curitiba : 68pts OS 83.7% at 5ys p= 0,48

Unrelated Bone Marrow Transplantation for Children and Adolescents with Fanconi Anemia using Cyclophophamide, Fludarabine and ATG: Analysis of 33 patients transplanted in a single institution. C. Bonfim, L. Ribeiro, G. Loth, M. Bitencourt, S.N. Kanaan, A. Koliski, V. Funke, D. Pilonetto, J. Zanis-Neto and R. Pasquini Bone Marrow Transplantation Unit - Federal University of Parana Curitiba Brasil BMT Tandem Meetings San Diego - 2012

Patients Selection and Inclusion Criteria o Number of patients: 33 o All patients were transplanted at the Federal University of Parana Curitiba - Brazil o Period: 02/2002 to 02/2011 o Graft source: Bone Marrow transplants from unrelated donors, typed at least for low resolution in Class I (A,B,C) and High resolution in Class II (DRB1) o Preparatory regimen : CY+FLU+rATG and GVHD prophylaxis with cyclosporine and methotrexate

Patient Characterisitcs Gender: 17F/16M. Age: 5-18ys(M: 10ys). 70%: < 15 previous transfusions 64% : Previous use of Androgens All patients had Aplastic Anemia and only 4/31 had cytogenetic abnormalities

Transplant Characteristics o Preparatory Regimen : Cyclophosphamide 60mg/kg (15mg/kg/day x 4) Fludarabine 125mg/m2 ( 25mg/m2 x 5) ratg : 4-6mg/kg/ total dose ( 3 days) o GVHD prophylaxis: Cyclosporine 3mg/kg/d + Methotrexate (4 doses) o Prophylactic antibiotics : Acyclovir, Bactrim, Fluconazol or Micafungin, Levofloxacin (2006) o Other : Ursodiol and Mesna

Donor Characteristics Compatibility (retrospective analysis): 29pts: 8/8 compatible (LR class I and HR class II) 4pts: incompatible 7/8 : 3pts 6/8: 1pt REDOME Other Registries 1995 : HR DRB1 typing 2008: HR class I 8 4 9 12 Immunogenetics Lab: Noemi F. Pereira accredited by ASHI Unrelated donor search : Luciane Pangracio and Margareth Kleina Before 2008 After 2008

Overall Survival after UBMT in Fanconi Anemia : CY+FLU+ATG 26/ 33 pts: OS 79% in 3ys Follow up: 26pts are alive between 10m 8 ys ( M: 3ys)

Overall Survival according to age <10ys and compatibility 17 pts < 10ys: OS 94%/3ys 29pts matched 8/8 : OS 86 % in 3 ys 16 pts 10ys: OS 62%/3ys 4pts mismatched: OS 25% in 3 ys p=0,02 p: < 0,001 Gender/ sex mismatch/previous transfusions, previous use of androgens and acute or C-GVHD : NS OS according to compatibility 1995 : HR DRB1 typing 2008: HR class I

Overall Survival according to time of transplant before or after 2008 URD HSCT < 2002: 20 pts OS: 15% in 10ys UBMT 2008: 16 pts OS: 100% UBMT 2002-2008: 17pts OS: 58,8% p: 0,004

Results of unrelated cord blood transplant in fanconi anemia patients: risk factor analysis for engraftment and survival. Gluckman E, Rocha V, Ionescu I, Bierings M, Harris RE, Wagner J, Kurtzberg J, Champagne MA, Bonfim C, Bittencourt M, Darbyshire P, Fernandez MN, Locatelli F, Pasquini R; Eurocord-Netcord and EBMT. Biol Blood Marrow Transplant. 2007 Sep;13(9):1073-82.

Unrelated Cord Blood Transplantation in patients with Fanconi Anemia 100 patients with a minimum 3 months FU: 89 children <16y,11 adults Median age : 8.6 y (1.4-45.4) Median weight : 26.0 kg (9.0-71) Median follow-up time : 22 months (3.3-121.3)

Significant factors improving survival Multivariate analysis HR Number of cord blood cells >4.9 2.44 <0.001 Presence of Fludarabine 2.04 0.012 CMV negative serology 2.78 <0.001 p

Transplante Haplo-idêntico : 8 pts CY 25mg/kg/d Changes for the haplo protocol : CY pre transplant : 5mg/kg/day/2days :first 3 pts CY post transplant: 25mg/kg/day/2days

Protocolo : Haploidêntico do CY pós transplante 8 pts (3ps no protocolo: PI - HP Kiem e Monica Thakar) 1 em Seattle e 7 em Curitiba 6 pts : 1º TMO e 2pts : resgate ( 2º e 3º TMO) Todos tiveram pega completa do enxerto 5/8 pts : GVHD-A grau II-IV ( 3pts grau IV) 3/6*pts : GVHD-C ( extenso e severo) 2 pts óbito: D+37 ( Toxo + sepsis) e D+681 ( GVHD-C + sepsis) 6 pts vivos: 2 pts com GVHD-C (14 meses)

Colaborações internacionais

II Encontro Nacional de pacientes e famílias com Anemia de Fanconi Curitiba 25 e 26 de novembro 2011

Dokal I.Dyskeratosis Congenita. Hematology Am Soc Hematol Educ Program. 2011;2011:480-6.

Disceratose congenita 9 pacientes Período : 04/93 a 11/2011 Idade: 2 a 24 anos ( M: 16) Sexo : 6M/3F 7 DC clássica 1 doença dos telomeros ( AAS + telomeros curtos) 1 síndrome de Revesz

Disceratose congenita Aparentado compatível (todos medula óssea): 5pts Todos receberam apenas CY 200 Nenhum fez GVHD agudo ou crônico 3 quimerismo misto, 2 completo Apenas 1 paciente viva e bem 9 anos pós TMO 3 pts morreram entre 7 e 11 anos pós TMO por progressão da doença pulmonar e hepática 1 paciente perdido de seguimento 7 anos pós TMO. Problemas sociais sérios, uso de drogas ilícitas, internamentos em clínicas para drogados. Na época em que foi perdido o seguimento ele apresentava quimerismo misto, plaquetopenia 34000 e baço palpável

Disceratose congenita Nao aparentado : 4 pts TSCU NAP 4/6 : 1pt. Óbito no D+ 70 por VOD, sepsis, recuperação neutrofilica apenas. Condicionada com BU8 + Fludarabina TMO NAP 9/10 ou 10/10 : 3 pts Todos vivos. Os 3 receberam condicionamento do proposto por Bacigalupo CY+FLU+ATG ( sem TBI) 1 pt com 24 anos e doença dos telomeros, sem manifestações clássicas da DC. Pega completa, sem GVHD, excelente 18 meses pós TMO 1 pt com 2 anos e síndrome de Revesz. VNTR 100% do doador. Plaquetopenia persistente. Sangramento GI grave com necessidades múltiplas de cauterizações. O prognóstico da síndrome é muito reservado (ponto de vista neurológico e GI) 1 pt com 10 anos de idade, forma clássica, no D+46 pós TMO com pega completa e provável DECH de intestino.

Obrigado

Acknowledgements PHYSICIANS Carmem Sales Bonfim Caroline Bonamin Sola Daniela Carinhanha Setubal Elenaide C. Nunes Jefferson Ruiz José Zanis Neto Larissa Medeiros Marco Antonio Bitencourt Michel Mishels de Oliveira Samir Nabhan Vaneuza Moreira Funke Nursing Team Keiko e Denise Social Worker Marlene Dias Immunogenetics Noemi Farah Pereira Data Manager Heliz Neves