Download Notes on Bone Marrow Transplant

Immunology: Bone Marrow Transplantation (Abidi)
LECTURE OBJECTIVES:
1. List the most common indications for autologous and allogeneic stem cell/bone marrow transplants.
Hematological malignancies
Metabolic disorders
Childhood immunodeficiency
Inherited disorders
CANNOT BE USED FOR SOLID TUMORS
2. Discuss the normal differentiation process of stem cells into hematopoietic cells.
Pluripotent SC  Lymphoid SC  B and T Cells
Pluripotent SC  Myeloid SC  Macrophage, Neutrophil, RBC etc.
3. Identify different sources of hematopoietic stem cells for bone marrow transplantation.
Allogenic Donor:
o Sibiling
o Unrelated
o Cord blood
o Haplo identical donor
o Syngeneic donor (MZ twin); no chance of GVHD
Autologous: patient donating stem cells for their own transplantation
Stem Cell Sources:
o Peripheral Blood: newer procedure
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Filgrastim (Neupogen) used to mobilize stem cells from bone marrow to peripheral blood
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Collected from central vein using catheter
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Blood is circulated through apheresis machine
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Minimum Requirement: 2.5 million cells/kg of recipients weight
o Bone Marrow Harvest: not as popular any more
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Two BMT physicians aspirate bone marrow from bilateral iliac crest (regional/general
anesthetic) from HLA matched voluntary donors
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No Filgrastim required
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Collection again based on recipients weight (20cc/kg weight; therefore, cannot be done with
small donor and large recipient for fear of harming the donor)
o Cord Blood: readily available; more utilized in pediatric patients (or small adults; under 70kg)
4. Describe a systematic approach in diagnosing and treating cancer patients.
5. Understand the decision making process in offering patients autologous versus allogeneic transplant based on
disease characteristics.
Autologous: can be used if
o The disease does not involved the bone marrow
o You have been able to clear the disease from the bone marrow by chemotherapy (cannot do too much
chemo, however, for fear of harming the cells before harvest)
o Basically, the bone marrow needs to be clean when collected
Autologous Process:
o Patient stem cells collected using chemotherapy/growth factors and are frozen
o Patient undergoes high does chemo/radiation
o Day 0: patient receives their own stem cells
o Supportive care ensues (no risk of GVHD)
Allogeneic: needs to be used if the patient has diseased bone marrow or if you cannot collect the stem cells
Allogeneic Process:
o Donor starts GCSF on day -4 and undergoes collection of day 0 (given to patient immediately)
o Patient undergoes several treatments:
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GVHD prophylaxis (tacrolimus, cellcept)
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Antibiotics
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Transfusions
o Compliance is a major issue (lots of medications)
6. Briefly discuss the HLA typing procedure to identify a donor for allogenic transplant.
7. Explain the role of conditioning regimen/preparative regimen in bone marrow transplant.
Conditioning regimen/preparative regimen: high dose chemotherapy combinations and/or radiation to destroy
cancer cells resistant to conventional chemotherapy without fear of harming stem cells
8.
Discuss the spectrum and pathogenesis of graft versus host disease and its relation to benefit of graft versus tumor
effect.
GVHD can be characterized as acute or chronic
o Acute: can be characterized into 4 grades (1-4); you want your patient to develop 1 and 2 (protective
against relapse), but not 3 and 4 (often fatal)
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Reactivity of new donor against patient tissue
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Occurs in 30-50% of allogenic transplants; 50-70% of those between unrelated people
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Acute if it occurs up to 100 days post BMT
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Organs involved: skin, liver, gut (grades based on symptoms seen in these organ systems)
o Chronic: similar to autoimmune disorders; patients own body starts to react against itself; every time
there is a flare up, it heals with scar tissue
It is important to prevent serious complications of GVHD, but it is also important not to overtreat in order to
keep the graft versus tumor effect viable (being too aggressive with the GVHD can lead to loss of protection and
overall suppression of immune system)
In addition, having some form of GVHD (ie. acute and chronic, grades 1 and 2) has been shown to be protective
against relapse
o Lowest rates of relapse found in people with both acute and chronic GVHD
o Highest rates of relapse found in identical twin transplants (no chance of GVHD)
9. Identify complications associated with autologous and allogeneic transplant as a result of high dose chemotherapy
and immunosuppression.
Organ toxicity (cardiac, liver, pulmonary and renal) from high dose chemotherapy
Opportunistic infections (bacterial; fungal-candida, aspergillus; viral-CMV, adenovirus, VZV) from decreased cell
counts
Decreased cell counts (neutropenia, thrombocytopenia-increased risk for bleeding)
10. Distinguish the non-myeloablative transplant from myeloablative transplant and understand its applicability in
current clinical practice.
Myeloablative: what we have just been describing (high dose chemo/radiation)
Non-Myeloablative: reduced intensity chemotherapy/reduced intensity regimen
o For patients in a high age group and with not so perfect organ functions
o Only use enough chemo/radiation prior to ensure that the immune system does not reject the graft 
start medications to prevent GVHD but taper slowly until it is seen  once seen start on high dose
steroids to stop it
o Less toxic regimen takes advantage of the immune-mediated mechanisms of “graft vs. tumor effect” to
control the disease