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20 Cards in this Set
- Front
- Back
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Bone marrow transplant preparative regimen
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Need to empty out the bone marrow to make room for the new graft
-Either chemo or total body irradiation |
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HSCT collection sites
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In the past, all transplants involved marrow harvested from the iliac crest
Now, we harvest stem cells via peripheral blood collection How do we get the stem cells in the peripheral blood for collection? -Give high doses of filgrastim (GCSF) |
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DIfferent types of HSCT
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Autologous:
-Collected from and infused into the same person Syngeneic: -Collected from an identical twin Allogeneic: -Collected from another member of the same species --Related: member of the same family, usually a sibling --Unrelated: from the general population (through NMDP) |
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Autologous HSCT
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To rescue the marrow
We give doses of chemotherapy that are so high, that the marrow cannot recover – so we “rescue” it with an autologous transplant. We use this in patients who have tumors that have steep dose response curves to chemotherapy Increasing the doses of chemotherapy continues to increase the numbers of cancer cells killed Can avoid the dose limiting toxicity of myelosuppression! |
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Autologous HSCT complications
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Shorter term complications related to conditioning regimens:
-GI: nausea/vomiting, mucositis, diarrhea -Pancytopenia -Infection (bacterial, viral, fungal, etc) -Hair loss -Liver (venoocclusive disease of the liver) -Lung (diffuse alveolar hemorrhage, interstitial pneumonitis) -Heart, Renal, Neurotoxicity, etc. Long-term complications related to transplant per se: -DMSO toxicity -Graft failure Transplant-related mortality within 3 months: - <5% |
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Autologous HSCT keys to success
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Have a chemosensitive disease
Be able to harvest a healthy graft -Not contaminated by active tumor (leukemia) -Not “contaminated” by bone marrow failure (aplastic anemia) |
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Benefits of allogeneic HSCT
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Guaranteed a clean graft
Can be used in bone marrow failure states Biggest difference is that this is an immunologic intervention: we want a graft vs. tumor effect Donor lymphocytes in the absence of chemotherapy can induce regression of leukemias Higher rate of relapse in syngeneic than allogeneic HSCT in AML (Less immunologic variance) |
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Downsides to allogeneic HSCT
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Need to find an HLA matched donor (sibling)
Graft vs. host disease (GVHD): -Grafted cells see host as “non-self” and attack -Primarily a T cell mediated process -Acute vs chronic: --Patients need additional immunosuppressive drugs to prevent this, which further increases their risk of infection --Because of this greater risk of infection and GVHD, treatment related mortality is much higher: 10-20% by day +100. |
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Donor identification: HLA typing
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Histocompatibility typing (“tissue typing”)
HLA: human leukocyte antigens -MHC (major histocompatibility complex) in humans -Genes on chromosome 6 -Gene loci are designated as: --A, B, C (Class I) --D (Class II) --C appears to have little role in “compatibility” --6 main antigens expressed (2 copies each of A, B, D); one from each chomosome 6 Look for 6 out of 6 matches -Chances a full sibling has a 6/6 match is 1/4 |
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Allogeneic HSCT: Donors
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Some HLA types are ethnically conserved, which can affect the likelihood of finding a match in the registry
-Harder to find a match if you are a minority, then you go to the international registry |
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Umbilical cord blood transplant upside
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Another potential source of
allogeneic stem cells Utilized more in pediatrics than adults Cells are relative immune incompetent in mounting normal allogeneic response -Less GVHD -Donors are less allo-immunized -Can tolerate wider HLA disparity -Less likely to be CMV (+), therefore hosts have less CMV infection --Cord donors 0.3% vs >40% in adult donors -20% are collected from ethnic minorities |
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Umbilical cord blood downside
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Time to engraftment is
dependent on the cellular dose of stem cells transfused -Calculated on a cells/kg body weight Although cords are rich in stem cells, absolute numbers are still low -And no potential for recollection for subsequent donor lymphocyte infusions (DLI) Adults often need two cords (dual cord transplant) |
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Allogeneic transplant complications
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Complications related to conditioning regimens:
-GI: nausea/vomiting, mucositis, diarrhea -Pancytopenia -Infection (bacterial, viral, fungal, etc) -Hair loss -Liver (venoocclusive disease of the liver [VOD]) -Lung (diffuse alveolar hemorrhage, interstitial pneumonitis) -Heart, Renal, Neurotoxicity, etc. Long term complications related to transplant per se: -Transfusion reaction -Graft rejection -Graft versus host disease Treatment related mortality within 3 months: 10-20% |
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Acute Graft vs. Host Disease
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Defined as GVHD occurring before day +100
Occurs in 10-50% of all allogeneic HSCT recipients Risk factors: -Increasing HLA disparity -Donor and recipient gender disparity -CMV status of donor and host -Intensity of the transplant conditioning regimen -Peripheral blood stem cell (worse) vs. bone marrow transplantation -Acute GVHD prophylactic regimen used |
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GVHD Skin
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Most common site of GVHD
Erythematous maculopapular rash, usually with bullae, that begins at the time of engraftment Can also be seen in chronic GVHD leading to sclerodermatous changes |
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GVHD Liver
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Second most common site
Increasing conjugated bilirubin and alkaline phosphatase (due to damage to bile canaliculi: cholestasis) Differential diagnosis includes: -VOD (venoocclusive disease of the liver), viral hepatitis, drug toxicities Diagnosis best made by biopsy, which is always difficult due to thrombocytopenia |
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GVHD GI tract
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Also very common
Symptoms: diarrhea, abdominal cramping -Can be severe: > 10 liters of stool output per day Differential diagnosis: -Side effect of preparative regimen, antibiotics, C diff Diagnosis: -Requires endoscopy and biopsy: apoptotic bodies in crypts and “popcorn” lesions |
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GVHD Prevention
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Use the best matched donor
T cell depletion -Anti-thymocyte globulin, alemtuzumab Pharmacologic therapy -Methotrexate -Mycophenolate -Cyclosporine -Tacrolimus -Steroids -Anti-thymocyte globulin Plan for gradual reduction in immunosuppression Reduced intensity allografting with gradually increased cellular dose of transplanted cells |
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GVHD Treatment
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Immunosuppression
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HSCT Host Factors
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This is aggressive! Patients need to be healthy.
-This is usually not the first step, but the last step Need to be in a minimal disease state, preferably complete remission Need to have preserved cardiac, pulmonary, liver function, no active infections Current recommendations: -Autologous: up to 70 years old -Allogeneic: up to 65 years old…? |
