Introduction to Haematopoietic Stem Cell Transplantation (HSCT) Covenant Health System HSCT Program...
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Transcript of Introduction to Haematopoietic Stem Cell Transplantation (HSCT) Covenant Health System HSCT Program...
HSC: Key Definition
• Haematopoietic Stem Cell
Cell produced in bone marrow that gives rise to all other blood cells (white cells, red cells, and platelets)
• Replenishes itself
• Relatively resistant to injury
• But, that can be eliminated with high doses of chemotherapy or radiation therapy
Haematopoietic Stem Cell
HSCT: Key Vocabulary
• Stem Cell Transplant
to re-infuse HSC in patients who have received high doses of chemotherapy and/or radiation therapy
• Allogeneic transplant
uses stem cells from another person (who is a perfect match)
• Autologous transplant
uses stem cells taken from the patient
Types of Transplants
• Autologous
• Allogeneic
• Syngeneic
Concepts of HSC Transplant
• Allows delivery of high dose chemotherapy and/or total body irradiation
Destruction of tumor Creation of marrow space Prevention of *graft rejection
*stem cells from allo donor
Diseases Commonly Treated with HSCT.
Indications for Blood & Marrow Transplantation in North America, 2002
Overall Numbers of Stem Cell Transplant
HSCT
How is it done?
Patients are carefully screened Disease responsive to HSCT(i.e.., AML, NHL) Comorbidities and Performance Status (CHF, COPD, CRI) Infectious diseases Profile (i.e.. HIV, Hepatitis, etc)
Stem cells are collected. From the patient (for autologous HSCT) or the donor (allogeneic)
Stem Cell Graft Collection
• Marrow
• Peripheral Blood
• Patient’s own or from somebody else
Source of Haematopoietic Stem Cells
• Bone Marrow Requires general anesthesia in operating room Traditional method
• Peripheral Blood (drawn from veins) Obtained by apheresis Accomplished as outpatient procedure Currently most commonly utilized method
Number of Stem Cells Circulating in Peripheral Blood
Haematopoietic Stem Cell Graft
HSC: Procurement Concepts
• Amount of stem cells collected based on recipients body weight
• Minimal number
2 x 108/kg nucleated cells 2 x 106/kg CD 34 + cells
• CD-cluster differentiation
• Flow Cytometry
HSC from Peripheral Blood Collection
• Translated on:
Mortality rate for autologous transplantation is expected to be below 5%.
Development of Outpatient Transplantation Programs.
Autologous Stem Cell Sources by Recipient Age, 1996-2002
Trends In Autologous Transplants by Recipient Age, * 1990-2002
HSCT Process: Kill the Cancer, Injure the Patient
• Patients are treated with high-dose chemotherapy and/or radiation.
• Stem Cells are infused (IV) back to the patient.
• Patient supported with antibiotics, blood transfusions, and treatment for other side-effects
Bone Marrow Ablation: High Dose Chemotherapy and TBI Administration
Common Complications after HSCT
Mucositis
Stem Cell Engraftment
• Engraftment of new stem cells generally takes 10-21 days
• Patient heals the mucositis
• Resolves the infectious process
• Hope the Cancer was Eliminated
Transplantation: Long-Term Outcomes
Types of Transplants: Why Allogeneic
Autologous versus allogeneic
Marrow and Blood “contaminated” with malignant cells.
Stem cells affected by the disease.
No Stem cells available for collection
Bone Marrow Ablation: High Dose Chemotherapy and TBI Administration
Allogeneic HSCT
When stem cells come from a healthy donor, stem cells are “clean” of Malignant Disease,
(Donor has to be carefully screened about Infectious diseases too)
Grafts, from Donors other than the Patient (sibling or unrelated), bring another weapon to kill the Disease:
Graft versus Tumor (GVT) effect
Graft versus Tumor, is the condition where donor T-Cells recognize recipients tumor (i.e., Leukemia) and builds an immune reaction to systematically destroy the tumor
Allogeneic Transplantation with Full or Reduced-Intensity Preparative Regimens
Allogeneic HSCT
• Allogeneic Stem cells will eventually completely eradicate the patient bone marrow (blood making) and immune system
• A new bone marrow and immune system is built all with cells from the allo donor
• This process allows the elimination of the tumor, Graft versus Tumor, at a cost of an enormous immunosupression and Graft vs. Host Disease
Copelan, E. A. N Engl J Med 2006;354:1813-1826
Graft-versus-Leukemia Effect from a Minor Histocompatibility Antigen.
Postulated Mechanism of Acute GVHD.
Graft versus TumorGraft Versus Patient
Limitations of Allogeneic HSCT
• Scarcity of suitable donors
25% sibling match, not everybody has a donor
• Graft versus Host Disease
• Infections
Complications after HSCT
Graft Versus Host Disease
• Condition where donor T-Cells recognize recipient as foreign and attacks the patient skin, bowel, liver, and other tissues
• This graft-versus-host reaction leads to GVHD signs and symptoms
HLA TypingHuman Leukocyte Antigen
• HLA are proteins found on short arm of chromosome 6
• 3-antigens important in HSCT,
HLA-A HLA-B HLA-DR
one set of 3 from each parent
• Brings to a total of six antigens to match
• A full match is “6/6” or “perfect” match
HLA TypingHuman Leukocyte Antigen
Mother Father
25 % chance that each sibling will match
HLA or Tissue Typing
• Rate of GVHD
Donor Incidence
6/6 40%
5/6 50%
4/6 80%
3/6 90%
GVHD Prophylaxis
Graft vs. Host Disease GVHD
• AcuteUp to Day +100
• Skin
• Liver
• Gut
• ChronicAfter Day +100
• Skin
• Mucous Membranes
• Gut
• Liver
• Scleroderma
Acute GVHD Grading
Acute GVHD Grading
Acute GVHD: Skin
Lichenoid Lesions of Chronic Graft-versus-Host Disease.
Antin, J. H. N Engl J Med 2002;347:36-42
Graft-versus-Host Disease of the Skin
Acute and Chronic GVHD Therapy
• Steroids and Cyclosporine / Tacrolimus
• Other modalities of immunosupression
Late Complications of Allogeneic HSCT
• 50-60% may develop chronic GVHD
• Chronic GVHD GVHD after day +100, single major determinant of
patients outcome and quality of life after HSCT.
• Immunosupression and InfectionsFungal Infections (Aspergillum), viral reactivation (CMV,
HS)
Outcomes of Haematopoietic Stem-Cell Transplantation: Allogeneic
Copelan, E. A. N Engl J Med 2006;354:1813-1826
Outcomes of Haematopoietic Stem-Cell Transplantation in Selected Diseases
Potential/Future Applications
• Autoimmune Disorders Rheumatoid Arthritis Lupus Multiple Sclerosis
• Other Disorders Congestive Heart Failure
CHS-HSCT Program
LS CMC 5th Floor