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Transplantation

Transplantation. Principle of Hematopoietic stem cell transplantation 24 th January, 2018 Kleebsabai Sanpakit, MD Division of Hematology/Oncology Department of Pediatrics, Siriraj hospital Mahidol University. Topic outline. Overview and source of HSC

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Transplantation

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  1. Transplantation Principle of Hematopoietic stem cell transplantation 24th January, 2018 Kleebsabai Sanpakit, MD Division of Hematology/Oncology Department of Pediatrics, Siriraj hospital Mahidol University

  2. Topic outline • Overview and source of HSC • Type of HSCT and Matching donor / patient • Indication of HSCT in Pediatrics • Complications post HSCT : GVHD • Outcome of HSCT

  3. Stem cells (SC) Developmental properties Fertilised egg • Totipotent • Unrestricted differentiation potential • Gives rise to all cells necessary for • development of fetal and adult organs Embryonal SC • Pluripotent • Give rise to a variety of specialised cell types • Cannot support the development of a fetus Adult somatic SC (tissue specific SC) i.e.Hematopoietic SC, neural , hepatic SC) • Multipotent • Limited to specific tissues Type of stem cells

  4. Advantages - adequate SC content - low T cell content - adequate SC - rapid hematopoietic recovery - naive SC - very low T cell content (immature) - low transmission of viral infection Disadvantages - collect in OR, under GA - use growth factor - high T cell content - only adequate wt. donor - low SC content - one-time collection only - delay hematopoietic recovery Sources of stem cells BM PB CB

  5. Type of HSCT 1.

  6. Type of HSCT 2. Allogenic SCT 2.1 Related allogenic SCT 2.2 Syngenic SCT 2.3 Unrelated allogenic SCT

  7. Father Mother A B DR A B DR A B DR A B DR c d a b A B DR A B DR A B DR A B DR A B DR A B DR A B DR A B DR a c c a d b b d 25 % 25 % 25 % 25 % Child Prob of matched siblings: 1 sibling 25 % 2 siblings 43.7 % 3 siblings 57.8 %

  8. Principle of HSCT • Nonmalignant diseases: replacement of abnormal hematopoietic system after myeloablative Rx with the normal HSC • Malignant diseases: allow higher and more effective doses of chemoRx to eradicate the malignant cells before rescue the BM fn. with normal HSC : offer immunotherapy (GVT) that can eradicate chemoresistant malignant cells

  9. Indications for HSCT in Pediatrics Autologous HSCT • Hematologic malignancies: Relapsed NHL/HL • Solid tumors: - Neuroblastoma stage IV - High risk or recurrent solid tumors: medulloblastoma, rhabdomyosarcoma, Ewing’s sarcoma, primitive neuroectodermal tumor etc. • Autoimmune diseases

  10. Indications for HSCT in Pediatrics AllogeneicHSCT: Malignancies • ALL: 1st remission in high risk case (Ph+ve ALL, MLL rearrangement with slow early response, etc.) 2nd or subsequent CR • AML: 1st CR in high risk case (ie. preceding MDS, high risk cytogenetics) 2nd or subsequent CR • CML in chronic or early accelerated phase • JMMoL • MDS - RAEB or RAEB-t • NHL/HL: 2nd or subsequent CR or PR

  11. Indications for HSCT in Pediatrics Allogeneic HSCT: Non malignancies • Hematologic disorders: - Hemoglobinopathies: severe thalassemia - Bone marrow failure: severe AA, FA, cong. pure red cell anemia etc. - Red cell enzymopathies: PK def. etc. • Immunodeficiencies: SCID, WAS, CGD etc. • Lysosomal storage diseases: Gaucher’s disease etc. • Infantile osteopetrosis • Familial hemophagocyticlymphohistiocytosis • myelofibrosis Major obstacle: no HLA-matched related donor

  12. Unrelated HSCT • Aim:expand donor pools  increased possibility to find matched unrelated donor ( 1 : 25,000 – 50,000 ) • Important points : improve HLA matching system expand donor pools financial support • Thai National SC donor registry and Thai National CB bank

  13. Patient preparation - infectious screening : CMV, Hepatitis B, C, HIV - dental check up - clear intestinal parasite, stool exam - PPD skin test, CXR - insertion of Hickman’s cath. (double lumens) - sterile bowel with nonabsorbable antibiotic - conditioning regimen - postgraftingimmunosuppression for GVHD prevention

  14. Conditioning regimens Aims1. Eradication of the abnormal hemopoietic system : Busulfan, Total body irradiation 2. Suppression of the immune system : Cyclophosphamide, Fludarabine Postgrafting immunosuppression for GVHD prevention: 1.Corticosteroids: prednisolone, methylprednisolone 2.T-cell signaling blockade: CSA, FK506 3.Antiproliferatives: MTX, MMF

  15. Supportive treatment 1. Reverse isolation (sterile room, laminar air flow) 2. PRC transfusion, keep Hb >10 g/dL 3. Plt conc. transfusion, keep plt > 20,000/m3 PRC and platelet – irradiated , prestoraged or Wbc filtered 4. G-CSF 10 g/kg/day until WC > 10,000/mm3 x 2 days when ANC > 1,000/mm3 x 2 days → off isolation 5. Antibiotics for febrile neutropenia and early Rx for any sign of infection 6. parenteral nutrition 7. psychological support

  16. Engraftment • Evidence- DNA analysis (Chimerism study) - donor’s sex chromosome - donor’s blood group • In thal pt - normalization of Hb, Hct, reticulocyte count - donor’s Hb type • In malignant pt - no evidence of disease • In immunodeficincy pt - normal or near normal immune function

  17. Complications post HSCT Graft rejection, graft failure Nausea/vomiting

  18. Graft versus host disease • Classification Acute GVHD – consisting of dermatitis-enteritis and hepatitis following a BMT (usually within 30 – 40 days) Chronic GVHD – autoimmune like syndrome consisting of impairment of multiple organs or organ systems (collagen vascular disease)

  19. Factors that influence outcome of HSCT • Underlying diseases • Type of HSCT • Dedree of HLA matched • Sources and cell doses of viable HSC • Conditioning regimen • Pre-HSCT condition of the pt: organ dysfunction • Supportive care post-HSCT

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