Introduction to Haematopoietic Stem Cell Transplantation (HSCT)

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Introduction to Haematopoietic Stem Cell
Transplantation (HSCT)

• Covenant Health System HSCT Program
• Lubbock, Texas
• April 4, 2007

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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

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Key Vocabulary

• Bone marrow
• tissue found predominately in spaces of the
  bones of the hips, legs, arms and spines.
• Stem Cells
• produced in the bone marrow and found in
  circulating blood.

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Haematopoietic Stem Cell
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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

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Types of Transplants

• Autologous
• Allogeneic
• Syngeneic

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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

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Diseases Commonly Treated with HSCT.
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Indications for Blood Marrow Transplantation in
North America, 2002
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Overall Numbers of Stem Cell Transplant
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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)

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Stem Cell Graft Collection

• Marrow
• Peripheral Blood
• Patients own or from somebody else

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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

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Number of Stem Cells Circulating in Peripheral
Blood
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Haematopoietic Stem Cell Graft
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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

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HSC from Peripheral Blood Collection

• Translated on
• Mortality rate for autologous transplantation
  is expected to be below 5.
• Development of Outpatient Transplantation
  Programs.

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Autologous Stem Cell Sources by Recipient Age,
1996-2002
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Trends In Autologous Transplants by Recipient
Age, 1990-2002
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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

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Bone Marrow Ablation High Dose Chemotherapy and
TBI Administration
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Common Complications after HSCT
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Mucositis
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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

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Transplantation Long-Term Outcomes
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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

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Bone Marrow Ablation High Dose Chemotherapy and
TBI Administration
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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

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Allogeneic Transplantation with Full or
Reduced-Intensity Preparative Regimens
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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

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Graft-versus-Leukemia Effect from a Minor
Histocompatibility Antigen.
Copelan, E. A. N Engl J Med 20063541813-1826
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Postulated Mechanism of Acute GVHD.
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Graft versus Tumor Graft Versus Patient
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Limitations of Allogeneic HSCT

• Scarcity of suitable donors
• 25 sibling match, not everybody has a donor
• Graft versus Host Disease
• Infections

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Complications after HSCT
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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

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HLA Typing Human 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

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HLA Typing Human Leukocyte Antigen
Mother Father
25 chance that each sibling will
match
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HLA or Tissue Typing

• Rate of GVHD
• Donor Incidence
• 6/6 40
• 5/6 50
• 4/6 80
• 3/6 90

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GVHD Prophylaxis
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Graft vs. Host Disease GVHD

• Acute
• Up to Day 100
• Skin
• Liver
• Gut

• Chronic
• After Day 100
• Skin
• Mucous Membranes
• Gut
• Liver
• Scleroderma

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Acute GVHD Grading
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Acute GVHD Grading
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Acute GVHD Skin
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Lichenoid Lesions of Chronic Graft-versus-Host
Disease.
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Graft-versus-Host Disease of the Skin
Antin, J. H. N Engl J Med 200234736-42
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Acute and Chronic GVHD Therapy

• Steroids and Cyclosporine / Tacrolimus
• Other modalities of immunosupression

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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 Infections
• Fungal Infections (Aspergillum), viral
  reactivation (CMV, HS)

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Outcomes of Haematopoietic Stem-Cell
Transplantation Allogeneic
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Outcomes of Haematopoietic Stem-Cell
Transplantation in Selected Diseases
Copelan, E. A. N Engl J Med 20063541813-1826
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Trends in Allogeneic BMT Recipient Age, 1984 -
2002
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Potential/Future Applications

• Autoimmune Disorders
• Rheumatoid Arthritis
• Lupus
• Multiple Sclerosis
• Other Disorders
• Congestive Heart Failure

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CHS-HSCT Program
LS CMC 5th Floor
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