Dr.PSRK.Sastry MD, ECMO

Transcription

1 Peripheral blood stem cell transplantation (Haematopoietic stem cell transplantation) Dr.PSRK.Sastry MD, ECMO Consultant, Medical Oncology Kokilaben Dhirubhai Ambani Hospital

2 Normal hematopoiesis

3 Historical Background 1900 s: -Treatment for anemia/leukemia with bone marrow (PO, IM, IV) st recorded use of BM infusion to Rx AplasticAnemia. Osgood et al Modern Transplantation in Leukemia Thomas ED et al 1958: HLAgroups mediate histocompatibility in skin Jean Dausset et al 1985-First peripheral blood stem cell transplantation First Umbilical cord blood transplantation Gluckman et al

4 When is transplant needed? Malignant AML ALL CML JCML NB MDS Nonmalignant Aplastic anemia Hemoglobinopathies Immunodeficiency diseases Metabolic disorders Lymphomas

5 Hematopoietic stem cell sources Bone marrow Autologous Allogenic Peripheral blood stem cells Autologous Allogenic Umbilical cord blood stem cells Autologous Allogenic

6 HLA typing Consent Conditioning Collection Patient Allogenic Transplant procedure Processing Outcome Infusion Reprocessing Cryopreservation

7 Which Donor? (derivative of Murphy s law) FOREMAN S BONE MARROW PRINCIPLE If a patient has 3 siblings, the best match will be the one who: a) Lives farthest away b) has been estranged for years; c) is serving a life-term in prison; or d) all of the above

8 Consent Collection Processing Cryopreservation Patient Autologous Transplant procedure Conditioning Outcome Infusion Reprocessing

9 Quote from GB.Shaw The reasonable man adapts himself to the world:the unreasonable one persists in trying to adapt the world to himself. Therefore all progress depends on the unreasonable man. GEORGEBERNARDSHAW, Maxims for Revolutionists

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11 Circulating blood Thymus Lymph nodes Spleen Bone marrow B lymphocyte To thymus, tonsils, and lymphoid organs From thymus T lymphocyte Hematopoietic stem cell Erythrocytes 1 in blood for every 100 in marrow

12 Neutrophil Production in Bone Marrow

13 Stem cell mobilization Stem cell mobilization PBSC Bone marrow Donors Autologous Allogenic Stem cell collection

14 Stem cell mobilization PBSC mobilization Timing Start GCSF at least 4 days before the first leukapheresis procedure Stop -Continue until the last leukapheresis. Dose G-CSF -10 µg/kg/d PegGCSF 6-12 mg

15 PBSCT mobilization Poor moblilizers Chemo-mobilization AMD 3100 Plerixofor

16 Blood-forming stem cells Whole blood in Stem cells out Whole blood is collected from donor Blood, minus stem cells, is returned to donor

17 PBSCT Central Venous Access Administration of chemotherapy drugs Blood products Total parentral nutrition IV fluids Stem cell collection Repeated blood draws

18 PBSCT Apheresis Machines

19 PBSC Collection Typical collection procedure parameters: Whole blood flow rate = ml / min Blood to anticoagulant ratio = 12:1 to 14:1 Total procedure time = 4 to 5 hrs Product volume = ml Concurrent plasma is usually collected for possible storage of product before processing and the preparation of cryoprotectant

20 PBSC Collection Targets Apheresis is generally continued till the following doses are collected: Parameter Optimal dose MNCs / Kg 4-8 x 10 8 CFU-GM/Kg > 2x10 5 CD34+ Cells / Kg > 2 to 5 x 10 6

21 PBSC Collection Complications Vasovagal reactions Citrate toxicity Allergic reaction Immunosuppression Thrombocytopenia Hemoglobin reduction Plasma protein levels

22 CRYOPRESERVATION Cooled at -80 to 100C

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24 Thawing

25 REINFUSION

26 REINFUSION

27 REINFUSION

28 PBSCT Easier to perform Simple No requirement of anesthesia Can be easily repeated More comfortable to the patient

29 PBSC Engraftment Days

30 PBSCT Graft versus host disease

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32 Liver Skin Conditioning regimen Gut IL1,IL6,TNFα Host APC Graft Versus HostDisease LPS Mo Donor T cell CTL TNFα IL1 Th1 IFNγ IL2 NK Apoptosis

33 PBSC Vs BM

34 PBSC Vs BM

35 PBSC or Bone Marrow Which one is better? Blood stem cells Easier access Larger no of CD34 cells available Donor available for subsequent stem cells Rapid recovery More rapid immune reconstitution Bone marrow Established stem cell source No priming Rx required. Less GVHD

36 Transplant in Lymphomas Allogeneic SCT Disease Autologous SCT Nonmyeloablative Myeloablative chemotherapy DLCL Treatment of choice for first chemosensitive relapse Advanced relapse After failure of auto SCT Refractory disease in young patients FL First chemosensitive relapse Advanced relapse After failure of auto SCT Refractory disease in young patients MCL First remission Relapsed chemosensitive disease Refractory disease in young patients In first remission if no CR after conventional chemotherapy or poor prognostic features (del 17p, ZAP-70, unmutated heavy chain genes) CLL No defined role Relapsed disease Refractory disease in young patients Richter s transformation

37 Autotransplant in Non-Hodgkins lymphoma

38 Transplant in Hodgkins Lymphoma

39 TRANSPLANT IN AML

40 Autotransplant in Multiple Myeloma

41 Autotransplant in Neuroblastoma

42 Conclusions Autologous PBSCT Results in early engraftment Easier to perform Associated with improved outcomes Practically replaces bone marrow Allogeneic peripheral blood stem cell transplantation: May cause excessive GvHD Gives a significantly better mononuclear cell yield, which results in faster hematologic recovery. Early (100-day) mortality is not significantly higher. Bone marrow preferred for Unrelated transplants Aplastic anemia

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