Peripheral blood stem cell transplantation (Haematopoietic stem cell transplantation) Dr.PSRK.Sastry MD, ECMO Consultant, Medical Oncology Kokilaben Dhirubhai Ambani Hospital
Normal hematopoiesis
Historical Background 1900 s: -Treatment for anemia/leukemia with bone marrow (PO, IM, IV) 1939-1 st recorded use of BM infusion to Rx AplasticAnemia. Osgood et al. 1957- 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 1988 - First Umbilical cord blood transplantation Gluckman et al
When is transplant needed? Malignant AML ALL CML JCML NB MDS Nonmalignant Aplastic anemia Hemoglobinopathies Immunodeficiency diseases Metabolic disorders Lymphomas
Hematopoietic stem cell sources Bone marrow Autologous Allogenic Peripheral blood stem cells Autologous Allogenic Umbilical cord blood stem cells Autologous Allogenic
HLA typing Consent Conditioning Collection Patient Allogenic Transplant procedure Processing Outcome Infusion Reprocessing Cryopreservation
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
Consent Collection Processing Cryopreservation Patient Autologous Transplant procedure Conditioning Outcome Infusion Reprocessing
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
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
Neutrophil Production in Bone Marrow
Stem cell mobilization Stem cell mobilization PBSC Bone marrow Donors Autologous Allogenic Stem cell collection
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
PBSCT mobilization Poor moblilizers Chemo-mobilization AMD 3100 Plerixofor
Blood-forming stem cells Whole blood in Stem cells out Whole blood is collected from donor Blood, minus stem cells, is returned to donor
PBSCT Central Venous Access Administration of chemotherapy drugs Blood products Total parentral nutrition IV fluids Stem cell collection Repeated blood draws
PBSCT Apheresis Machines
PBSC Collection Typical collection procedure parameters: Whole blood flow rate = 50-80 ml / min Blood to anticoagulant ratio = 12:1 to 14:1 Total procedure time = 4 to 5 hrs Product volume = 50-200 ml Concurrent plasma is usually collected for possible storage of product before processing and the preparation of cryoprotectant
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
PBSC Collection Complications Vasovagal reactions Citrate toxicity Allergic reaction Immunosuppression Thrombocytopenia Hemoglobin reduction Plasma protein levels
CRYOPRESERVATION Cooled at -80 to 100C
Thawing
REINFUSION
REINFUSION
REINFUSION
PBSCT Easier to perform Simple No requirement of anesthesia Can be easily repeated More comfortable to the patient
PBSC Engraftment 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 0-7 0 10 15 20 Days
PBSCT Graft versus host disease
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
PBSC Vs BM
PBSC Vs BM
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
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
Autotransplant in Non-Hodgkins lymphoma
Transplant in Hodgkins Lymphoma
TRANSPLANT IN AML
Autotransplant in Multiple Myeloma
Autotransplant in Neuroblastoma
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