Hematopoietic Stem Cell Transplants

Question 1

What are the types of stem cells and how are they identified/generated?

Answer 1

• Stem cells account for 0.1% of all marrow cells and what makes them significant is the ability of self renewal (stemness)
  
  • Able to mature to all blood elements and also to other immune cells
• The identification of these cells is trough expression of antigens in the surface of the cell such as CD 34 and CD 133
  
  • Negative for some other antigens present on mature or maturing cells such as CD30, CD3, CD19 etc.
• These cells also have the ability to sustain long term culture
• There is a big difference between totipotential stem cells and pluripotent stem cells
  
  • Totipotential is capable of producing all cell types in the body by their exposure to different cytokines
  • Pluripotened is focused on a certain type of differentiation such as the hematopoietic system
• The cells that are primarily used for stem cell transplantation are the pluripotent cells in the hematopoietic system
  
  • Can be collected directly from the bone marrow or trough mobilization with G-CSF into the peripheral blood and collect them with a pheresis machine

Question 2

Describe the autologous use of patient progenitor cells.

Answer 2

• The different types and sources of Tem cells are:
  
  • Autologous the use of patient own progenitor cells used primarily for the treatment of cancer as consolidation therapy in those patients who have a sensitive cancer that still responds to chemotherapy
  • Some examples are for adults Lymphomas and multiple myeloma and for pediatric patients Neuroblastoma and some Brain tumors as well as some lymphomas and Hodgkin’s disease
• The main purpose of this technique is to rescue patients of high dose chemotherapy that will overcome drug resistance, but because of the ability to ablate the rapidly dividing cells in the marrow by re-infusing these cells that have been protected from the effects of chemotherapy the patient will recover their hematopoietic function

Question 3

Describe the allogenic transplant. Define syngeneic transplant.

Answer 3

• The allogeneic transplant is when we use hematopoietic donor cells from an HLA compatible related or unrelated donor for the transplant
  
  • The main indication for this type of transplant is to treat:
    
    • Leukemias
    • Lymphomas
    • multiple myeloma
    • non-malignant diseases such as Aplastic anemia, sickle cell anemia, thalassemia’s, qualitative and quantitative defects of abnormal hematopoiesis, metabolic diseases such as inborn errors of metabolis, Immune deficiencies etc.
• When we use cells from an identical sibling for transplantation the transplant is called a syngeneic transplant
• The source of the hematopoietic cells is from:
  
  • bone marrow
  • mobilized peripheral blood
  • umbilical cord blood cells

Question 4

How are patients conditioned for stem cell transplant?

Answer 4

• Once we have selected the donor and the type of transplant to be performed we will condition the patients to get him/her ready for the transplant
• The decision to be made is based on the type of disease we are treating , the type of donor we are going to use and the purpose of the transplant
  
  • For example a patient with aplastic anemia is already aplastic and we only need to immune ablate him before we give him his cells so we can use a less intense conditioning regimen before we give him his allogeneic cells
  • On the other hand if we are treating a patient with leukemia the intensity of the conditioning regimen will be with either TBI ( total Body Irradiation) with or without high dose chemotherapy

Question 5

What are the major toxicities that accompany stem cell transplant?

Answer 5

• The toxicities that we will encounter will depend on:
  
  • the primary disease
  • the type of donor
  • the conditioning regimen
  • the prophylactic treatment of Graft vs. Host Disease
• Other toxicities:
  
  • Sepsis (bacterial, fungal etc)
  • Viral infections or viral reactivation (CMV, EBV, Adeno)
  • Toxicity from the ablative regimen and GVHD prophylaxis.
  • Metabolic abnormalities
  • Graft vs.. Host Disease acute and Chronic
  • Sinusoidal Obstructive syndrome (SOS) former VOD of the liver
  • Interstitial pneumonitis ( CMV,PCP, etc)
  • Engraftment syndrome
  • Cytokine storm

Question 6

How are stem cell transplants monitored?

Answer 6

• Done by assessing chimerism after the cells are infused and this is done weekly after the cells are infused in
  
  • An example is chimerism using Variable Tandem Repeats (VNTRs)
• There are other techniques to assess chimerism such are small tandem repeats (STR), RT-PCR, FISH etc. and what we are looking is at a percentage of donor cells in the recipient

Question 7

What is graft vs. host disease and what are the major manifestations?

Answer 7

• One of the most important issues in transplantation is the development of GVHD both acute and chronic
• GVHS is when we transplant a new immune system into an immune incompetent subject that is we want to achieve with the conditioning regimen the the immune system rejects that subject is the opposite of what happens in the solid organ transplant where the immune incompetent organ is given to an immune competent subject and the subject rejects the graft
• The main manifestations in acute Graft vs. host disease are:
  
  • skin rash
  • jaundice and diarrhea
  • depending of the severity of this symptom will be how serious the problem is
• We stage each one of the symptomas and then we come up wit a grade that has significance in the prognosis of the patients

Question 8

What are the differences between acute and chronic GVHD?

Answer 8

• Chronic GVHD is a different disease than acute is more likely to a collagen vascular disease
• There are 3 pattern’s for developing cGVHD

Question 9

What are the predisposing factors for GVHD?

Answer 9

• T cell depletion decrease acute but not chronic GVHD
• CGVHD is by itself immune-suppressive
• The mortality is due to infection
• Can be very debilitating
• No specific or effective treatment is available
• Multi-agent immune-suppression is the norm

Question 10

What are the outcomes of stem cell transplantation?

Answer 10

• The outcome of transplantation will be dependent on:
  
  • the disease for which the transplant is performed
  • the donor
  • the conditioning regimen
  • the source of stem cells
• Example for a patient with Aplastic Anemia who receives a reduced toxicity regimen and the donor is a matched sibling
• Event and Overall survival are about 90% while for a relapse child with ALL in second remission using an unrelated donor and a myeloablative regimen maybe 40%

Question 11

What are the long term effects of stem cell transplantation?

Answer 11

• Endocrinopathies (hypothyroidism, hypogonadism, growth hormone deficiency)
• Growth retardation
• Secondary malignancies
• Sterility
• Cataracts
• Learning disabilities
• Psychological disorders