Bone  Marrow  Transplanta/on  for    

Thalassemia  

John  K.  Wu,  MBBS,  MSc,  FRCP(C)  Clinical  Professor  

Division  of  Hematology/Oncology/BMT  Department  of  Pediatrics  

UBC  and  BC  Children’s  Hospital,  Vancouver,  BC    

Beta  thalassemia  major  

•  Decrease  beta  globin  produc/on  •  Excess  of  alpha  globin  chains  damage  to  red  blood  cells  in  bone  marrow  –  Severe  anemia    – Massive  overwork  of  bone  marrow  –  bony  changes,  fractures,  osteoporosis  

–  Iron  overload  from  transfusion  and  gut  absorp/on  –  damaging  heart,  liver,  endocrine  glands  

•  Transfusion  transmiNed  diseases  –  hepa//s,  immune  deficiency  

Therapy  

•  Adequate  transfusion  –  op/mal  growth  and  development  

•  Adequate  iron  chela/on  –  achieving  iron  balance  •  Op/mal  comprehensive  care  –  physical,  psychosocial  development  

Thalassemia  has  been  transformed  from  a  lethal  disease  of  childhood  into  a  chronic  condi/on  of  adulthood  -­‐  with  a  drama/c  increase  in  both  life  expectancy  and  quality  

Bone  marrow  transplanta/on  

•  Theore/cally,  ridding  oneself  of  the  abnormal  marrow,  replace  with  a  new  unaffected  marrow-­‐  will  achieve  a  cure!  

43%  failed,  25%  died  !!    

Bone  marrow  •  Immune  system  –  differen/ate  “self”  from  “non-­‐self”    

•  Recognize  and  destroy  foreign  /ssue  –  rejec/on  •  In  order  for  a  new  marrow  to  grow,  the  old  one  has  to  be  wiped  out  –  annihilated  

•  Flip  side  –  when  the  new  marrow  grows  in  the  new  body  environment,  it  recognized  the  minor  difference  between  its  original  host,  and  the  new  body  that  it  resides  in  

•  It  will  start  aNacking  the  new  body  causing  major  and  serious  /ssue  damage  –  gra^  vs.  host  disease  

Bone  marrow  transplanta/on    -­‐  complica/ons  

•  High  dose  chemotherapy  –  very  toxic  medica/ons    •  New  marrow  may  take  2-­‐3  weeks  to  grow  •  Complica/ons:  

–  Chemotherapy  effects  –  nausea,  vomi/ng,  hair  loss,  skin  and  mucous  membrane  break  down,  liver  damage,  other  organ  damage,  long  term  –  endocrine  glands  –  infer/lity  

–  Infec/ons  –  bacteria,  fungi,  viruses  –  Pain  –  Poor  nutri/on    –  Transfusions  of  platelet  and  red  cells  

Bone  marrow  transplanta/on    -­‐  complica/ons  

•  Engra^ment  in  2-­‐3  weeks  –  gra^  versus  host  disease  –  skin  rash,  diarrhea,  liver  damage  

•  A^er  the  first  three  months  –  chronic  GVHD  –  immune  imbalance  –  autoimmune  disorder  – Dry  eyes,  mouth  – Skin  rashes  – Damage  to  lungs,  gut  

•  Mortality  –  5-­‐10%  

Bone  marrow  transplanta/on    -­‐  complica/ons  

•  Best  results  in  – Age:  young  <16  years  – Adherent  to  iron  chela/on  – No  organ  damage  –  liver,  heart,  endocrine  glands  

•  Survival:  >90%,  Event  free  survival:  >80%  

hNp://www.medicaltourismmag.com/ar/cle/bone-­‐marrow-­‐transplanta/on-­‐in-­‐downtown-­‐maka/.html  

Alterna/ve  stem  cell  sources  

•  Cord  blood  –    –  lower  gra^  vs.  host  disease,  limited  number  of  cells,  delayed  engra^ment  

•  Matched  unrelated  donor  –    – Good  results  only  if  high  resolu/on  molecular  match  

– Survival  –  80%,  Event  free  survival  –  65%  •  Par/ally  matched  donors  

–  Inves/ga/onal    

Alterna/ve  transplant  

•  Mini-­‐transplant  (non-­‐myeloabla/ve)  – Less  toxic,  higher  rejec/on  rate  – Higher  chance  of  gra^  vs.  host  disease  

Decision  

•  This  decision  process  is  by  defini/on  highly  individualized  and  pa/ent  specific,  since  it  must  consider  age,  clinical  status,  willingness,  capability  and  compliance  to  adhere  to  the  appropriate  transfusion-­‐chela/on  regimen,  quality  of  life  and  resources.  For  pediatric  pa/ents,  parents  face  an  even  more  difficult  decision  

Gene  therapy  

•  Use  Len/virus  carrying  the  corrected  beta-­‐globin  gene  to  infect  stem  cells  

•  Chemotherapy  to  pa/ent  to  prepare  marrow  •  Infusion  of  engineered  stem  cells  

hNp://singularityhub.com/wp-­‐content/uploads/2009/02/gene_therapy.jpg  

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Karlsson S Blood 2005;106:3333-3333

©2005 by American Society of Hematology

Message    

•  Rapid  medical  advances  •  Cure  around  the  corner  •  Organ  damage  –  hard  to  reverse  

– Adherent  to  chela/on  therapy  and  medica/ons  

•  Physically  healthy    •  Psychologically  and  socially  healthy  

THANK  YOU!  Really  cool!