Blood and Marrow Transplantation

1. Blood and Marrow Transplantation Francisco F. Lopez, MD Hematology and Medical Oncology Bone Marrow Transplantation

2. 1st BMT Reunion (January 2004)

3. Outline • History • Definition • Rationale • Procedure • Indications • Our data • Summary

4. History of Blood and Marrow Transplantation in the Philippines 1990 1st marrow transplant at the NKTI 2001 1st peripheral blood stem cell transplant at NKTI 2002 St Luke’s Medical Center (SLMC) • Asian Hospital Medical Center (AHMC) 2005 1st autologous stem cell transplant at AHMC 2005 1st cord blood transplant at SLMC

5. The transfusion of the immature progenitor stem cells derived from a donor to the recipient (allogeneic); OR stem cells previously harvested from the patient (autologous). It is NOT an operation / surgical procedure.

6. “Let’s crack your bones wide open!”

7. Stem cells • Young immature cells that make up 0.5% to 5% of the marrow cells. • Express CD34+ • Progenitor cells: self-renew and divide to become red and white cells, and platelets.

9. Stem cells Bone marrow 2 to 5 x 108 TNC/kg weight of recipient with the maximum volume dictated by the weight of the donor (20ml BM aspirate/kg) can be stored at room temperature for up to 24hrs until infusion into the recipient or cryopreserved Peripheral blood 2.0 to 5.0 x 106 CD34+ cells/kg for auto/allo transplants can be stored at 4 C overnight or cryopreserved with dimethyl sulfoxide (DSMO) Umbilical cord 3.7 x 106 TNC/kg recipient body weight can be stored at 4 C or 25 C for up to three days or cryopreserved with DSMO

10. Rationale

11. Two kinds • Allogeneic: Donor • Matched or partially mismatched sibling • Unrelated • Cord blood • Autologous: No donor • Stem cells are harvested from patient

12. involves the transfer of stem cells from donor to recipient to permanently replace all hematopoietic cells eradicate malignant cells with high dose chemotherapy +/- radiotherapy sufficient immunosuppression of the host to allow growth of the allograft immune mediated graft vs leukemia/lymphoma or graft vs tumor effect Allogeneic transplant

13. Human Leukocyte Antigen (HLA) typing

14. Autologous transplant • Increasing the dose of some chemotherapeutic agents may result in large increase in tumor cell kill • Transfusing previously harvested stem cells of the patient will guarantee bone marrow recovery

16. ProcedureAllogeneic transplant

20. Schema -8 admit to hospital -7 Total body Irradiation -6 Total body Irradiation -5 Total body Irradiation -4 Total body Irradiation; Donor starts GCSF -3 Cytoxan (60mg/kg) -2 Cytoxan (60mg/kg) -1 Rest day and start cyclosporine IV 0 Harvest and infusion of stem cells +1 Methotrexate 15mg/mm +3 Methotrexate 10mg/mm +6 Methotrexate 10mg/mm +11 Methotrexate 10mg/mm

23. WBC from day of transplant to recovery

24. ProcedureAutologous transplant

25. Procedure: The Harvest D –10 Cyclophosphamide 1.5gm/mm D – 7 Start GCSF 10mcg/kg D – 6 D – 5 D – 4 D – 3 D – 2 D – 1 D 0 Harvest using apheresis machine (collect 2.5 x 106 / kgBW CD 34+ cells)

28. The transplant • Day -8 admit • Day -7 Total body irradiation • Day -6 Total Body irradiation • Day -5 Total body irradiation • Day -4 etoposide 60mg/kg IV • Day -3 rest • Day -2 cytoxan 100mg/kg IV • Day -1 rest • Day 0 infusion of stem cells • Day +5 begin GSCF 5mg/kg/day • Day +10 marrow recovery or engraftment

29. Transfusion of stem cells

30. Indications and Timing of Transplant

31. Allogeneic TransplantMalignant • Acute and chronic leukemias • AML, ALL, CML • Myelodysplastic syndrome (MDS) • Lymphomas (failed chemotherapy) • Multiple myeloma • Myeloproliferative diseases

32. Allogeneic TransplantNon malignant • Aplastic anemia • Thalassemia • Immune disorders • Paroxysmal nocturnal hemoglobinuria (PNH)

33. Autologous Transplant • Multiple Myeloma • Non-Hodgkins Lymphoma • Hodgkins Disease • Solid Tumors • Autoimmune diseases (multiple sclerosis)

34. Allogeneic BMT in Pediatric AML Indications: All except Down’s syndrome t(8;21) t(15;17) inv 16

35. Allogneic BMT in Pediatric ALL Indications: t(9;22) t(4,11) 3rd CR or higher relapse on therapy or w/in 12 months of end of therapy May be offered: > 28 days to achieve CR 2nd CR, relapse > 12 months of end of therapy

36. Severe Aplastic Anemia

37. Allogneic BMT in adult ALL Poor risk features • WBC > 25,000 • T(9;22) t(8;14) t(4;11) • Age > 30y/o • Extramedullary disease • Requiring more than 4 weeks to achieve a CR

38. Allogeneic BMT in adult AML Prognostic indicators that predict outcome of standard chemotherapy based on cytogenetic abnormalities. favorable: t(8;21) t(15;17) inv 16 Intermediate: del y; normal karyotype; 11q23 Poor: all others

39. 2nd BMT Reunion (January 2005)

40. Complications During BMT

41. Nausea and Vomiting • Nutrition • Mouth Sores • Diarrhea • Infection • Renal complications • Veno-Occlusive disease of the liver (VOD) • Pancytopenia • Graft Rejection • Acute Graft vs Host Disease • Rash • Pulmonary complications • Death

42. Nausea and Vomiting • More common during the early part of transplant • Round the clock anti emetic medications • During the recovery phase, nausea / vomiting / abdominal pain (cramps) / diarrhea, the patient may have graft vs host disease (GVHD).

43. Nutrition • Low bacteria diet: no fresh fruit and vegetables; served hot; no left over; tray should be clean; • Appetite diminishes after chemotherapy • Total parenteral nutrition until patient can eat.

44. Mouth Sores • Mouth wash (nystatin and biotene) • Morphine pushes or drip when severe (face will be swollen) • Thrush

45. Diarrhea • Chemotherapy induced (Cuclophosphamide) • Infection: Clostridium Defficile • GVHD (graft vs host disease) • Food induced (avoid creamy, milk, oily food)

46. Bacterial Infections • Gram negative • Gram positive (central line or skin); patient should shower or sponge bath daily. • Antibiotics: third generation cephalosporin and vancomycin • Fungal • Pulmonary (aspergillus) • Yeast • Amphoteric B prophylaxis • Viral • Herpes zoster • Acyclovir IV

47. Prevention • Isolation room : positive pressure • Strict hand washing • Mask • No need for gown or gloves unless patient is positive for clostridum defficile

48. Renal Complications • Renal insufficiency • Drugs: cyclosporine, vancomycin, amphotericin B) • Monitor I & 0 accurately every 12 hours. Balance fluid I & 0. lasix IV given prn.

49. Liver Complications • Veno-Occlusive disease of the liver (VOD) • Water retention • Tender liver • Elevated bilirubin • Elevation in bilirubin and SGPT and SGOT • Medications: cyclosporine, TPN • GVHD

50. Pancytopenia • Blood and platelet transfusion • Platelet apheresis is always used • Blood and platelets should always be available, filtered and irradiated.