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Jeffrey Schriber, M.D. FRCP (c) Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center Everything You Ever Wanted to Know About Transplant.

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Presentation on theme: "Jeffrey Schriber, M.D. FRCP (c) Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center Everything You Ever Wanted to Know About Transplant."— Presentation transcript:

1 Jeffrey Schriber, M.D. FRCP (c) Medical Director Cancer Transplant Institute Virginia G. Piper Cancer Center Everything You Ever Wanted to Know About Transplant But Were Afraid to Ask

2 Suddenly, Dr. Schriber realized he had left his brain in Toronto

3 Objectives  Understand Basic Principles of Transplantation  Understand Differences between Autologous and Allogeneic Transplants  Understand which Diseases are best treated by each type of Transplant  Understand Major Complications of each type of Transplant

4 Stem Cell Transplant Principles  Dose Intensity  Stem Cell Rescue  Immune System



7 Dose Intensity  Active Agents at Conventional Doses  Avoid Overlapping Nonhematologic Toxicity  Non Cross Resistant Agents  Immunosuppressive* *Allo only

8 Dose Intensity  Increase dose intensity of Cytotoxic Chemotherapy  Up to 10-fold over conventional therapy  Up to 2.5 times MTD without stem cell support TBI Busulfan ThioTEPA

9 Dose Limiting Toxicities  BCNU  Busulfan  Carboplatinum  Cyclophosphamide  Etoposide  Thiotepa  Pulmonary  Gastrointestinal  Renal  Cardiac  Mucosal  CNS

10 Stem Cell Properties  Capable of Producing all Blood cell lines  Capable of Self Renewal  Rare in Resting Peripheral Blood  Has Marker called CD 34


12 Steps in Stem Cell Transplant  Prior therapy to decrease tumor burden  Disease and Functional Testing  Choose Donor (auto vs. allo)  Transplant Regimen  Cytoreductive  Immunosuppressive  Period of Neutropenia  Count Recovery

13 Autologous Stem Cell Transplant  “Trick” to give high doses of chemotherapy  Use Stem Cells to Recover  Cytopenic Phase (Need for transfusions, antibiotics, pain control)  Late Complications Rare  Most Common Cancer Treated is Myeloma

14 HSCT: Choice of Stem Cells: Autologous  Advantages Available for most patients No graft vs. host disease Regimen can be optimized for antitumor activity Low morbidity & mortality Few long-term complications

15 HSCT: Choice of Stem Cells: Autologous  Disadvantages Contamination with tumor Stem cell damage from prior cytotoxic therapy No graft vs. tumor reaction

16 Changes in Autologous Transplant: Myeloma 19962014 Stem Cell SourceBone MarrowPBPC TypeInpatientOutpatient Median Age5770 ANC Recovery18 Days11 Days Plt Recovery22 Days14 Days Length of Stay3-4 weeks6 days Mortality2-5 %< 1%

17 Multiple Myeloma Outcomes NAdmitted > 1 Day %TX Solely Outpatient LOS (Median Range) All Myeloma Patients 24867%7.5 Days (4-24) Myeloma < 70 Years of Age 15473%5 Days (4-7) Myeloma >70 Years of Age 9456%9 Days (8-24)

18 Allogeneic Stem Cell Transplant  True Transplant of the Immune System  Need to Find a Donor Sibling Unrelated Cord Blood  Cytopenic Phase  Immunosuppressive therapy early and late

19 HSCT: Choice of Stem Cells: Allogeneic  Advantages No contamination with tumor Graft vs. tumor reaction No exposure to prior therapy


21 HSCT: Choice of Stem Cells: Allogeneic  Disadvantages Lack of compatible donors Graft vs. Host Disease Prolonged immunosuppression necessary Higher morbidity & mortality

22 HSCT: Complications  Toxicity of Preparative Regimen Mucosal, Liver, Lung, (Heart)  Myelosuppression, Immunosuppression Infection, Hemorrhage  Graft vs. Host Disease (allo only) Acute80% (20-40% severe) Chronic30%  Overall Mortality Allogeneic:10-40% Autologous: 1-5%


24 Acute GVHD  Typically first 100 days  Skin Rash (from minimal to desquamation)  Liver Hyperbilirunemia, Elevated ALP  Gut Diarrhea Persistent Nausea

25 GVHD of the Skin Recurrence of GVHD

26 Chronic GVHD  Later appearing  More like autoimmune disease  Skin  Mucous membranes Mouth Eyes Vagina  Lung, Liver, Joint Involvement Bronchilitis



29 Prevention of GVHD  Remove T Cells Eliminates GVHD High Relapse Rate with lose of GVL Add Backs at later date  Selective Removal of T subsets Remains under investigation

30 Prevention of GVHD  Calcineurin inhibitors (Cyclosporine and Prograf) Inhibit Ca + dependent signaling protein for IL 2 transcription (via TCR)  Rapamycin Inhibits protein kinase required for protein synthesis and cell cycle progression (cytokines and growth factors)  MMF Inhibits enzyme responsible fro Nucleotide synthesizes in B and T lymphocytes

31 Prevention of GVHD  Prednisone  ATG  Rituxan  Methotrexate  Cyclophosphamide post Transplant  Antibodies to IL2, TNF

32 Autologous vs. Allogeneic Transplant  Donors Easily Available  Regimen Tailored  Potential Tumor Contamination  Low Morbidity / Mortality  No GVHD/GVT  Few Long Term Complications  Major Risk Relapse  Must Find Donor  Regimen must be Immunosuppressive  Higher Morbidity/ Mortality  GVHD both Acute and Chronic as Major Complication  GVT Effect  Lower Risk of Relapse

33 Diseases Commonly Treated with Transplant  Acute Myeloid Leukemia  Acute Lymphoid Leukemia  Chronic Leukemia (CML, CLL)  Myelodysplastic Disorders  Congenital Disorders  Non Hodgkin’s Lymphoma (low or high grade)  Hodgkin’s Disease  Myeloma  Germ Cell

34 Nonmyeloablative Transplant  Less intense chemotherapy  Older patients now feasible  Decreased mucositis  Shift to outpatient therapy  Less transfusion requirements  No change in Chronic GVHD/GVL

35 Nonmyeloablative Transplant  Increase Patient Eligibility Age to 70 Allows for Cardiac Pulmonary function Hepatic Renal  Infection not absolute contraindication

36 Changes in Allogeneic Transplant: 19962011 Stem Cell SourceBone MarrowPBPC TypeInpatientInpatient/ Mix Median Age40 (20-55)60 (20-75) ANC Recovery25 Days14 Days Plt Recovery35 Days30 Days Length of Stay8-12 weeks6 -8 weeks Mortality30-40 %20-30 %



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