transplantation
Terms
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- two types of transplant
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1. autologous-- allowed high dose therapy
2. allogeneic-- intentive chemo permitted and discovery of graft v host and graft v leukemia - HSCs
- can recontstitute host hematopoiesis entirely; gnerally occur in bonemarrow; just a few can repopulate an individual; occur in bone marrow; CD34+; lineage negative, not in cell cycle (Go phase); give rise to determined progenitor cells
- allogeneic transplant
- sibling; unrelated; haploidentical (rarely done)
- types of hematopoeitic transplant
- autologous; allogeneic; BMT; peripheral blood stem cell transplantation (PBSCT); cord blood transplantation
- advantages of allogenous transplant
- stem cells are inherently healthy; chance of cure due to graft vs leukemia effect
- disadvantages of allogenous transplants
- limited by HLA identity; acute complications are most often caused by GVHD; chronic complications may be due to protracted immunosuppression and chronic GVHD; mortality 5-25%
- advantages of autologous transplant
- patients' own stem cells are harvested; mortality 0-3%
- disadvantages of autologous transplant
- stem cells may be damaged by previous chemo or contaminated with tumor cells; main negative outcome is tumor recurrence
- complications of stem cell transplantation-1
- infections; bleeding; transplant failure; GVH reactions; microangiopathy; veno-occlusive disease
- infections
- treatment of pneumonias; PCP prophylaxis; treatment of CMV infections; tx and prophylaxis of other herpes virus infxns
- transplant failure
- definition: pancytopenia following SCT with hypocellular marrow following 21 d after SCT or 28 d after BMT;
- risk factors for autologous transplant failure
- heavy pretreatment with cytostatic drugs, purging
- risk factors for allogeneic transplant failure
- T cell depletion, low numbers of progenitor cells, HLA incompatibility
- GVHD- acute
- 0-100 d post SCT skin- erythema; gut: diarrhea; liver- increased liver enzymes. prophylaxis: CSA, MTX; tx: steroids and anti T cell antibodies
- chronic GVHD
- >100 d; skin- scleroderma like changes; liver- fibrosis; gut- chronic diarrhea; tx: immunosuppression, supportive measures
- veno-occlusive disease of the liver
- sudden appearance of ascites, hepatomegaly, increased bilirubin; damage to endothelial cells caused by chemo and/or radiation; risk factors: previous hepatic disease; tx: mainly supportive, thrombolysis (experimental)
- thrombotic microangiopathy
- realted to hemolytic-uremic syndrome; signs: new anemia, thrombocytopenia, increased LDH occuring 1-6 mo after SCT; tx: plasma infusions or plasma exchange
- indication for SCT (1)
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leukemias, myelodysplastic syndromes
autologous is under study for all leukemias; allogeneic is mostly used for high risk patients in first or second remission; used for younger patients in MDS. only used in certain circumstances for CML b/c of imatiunib. - indication for SCT (2)
- lymphomas: hodkin's: use autologous in 2nd remission; NHL (low grade): use autologous in 2nd remission/experimental; allogeneic is experimental; NHL (high grade): autologous in second remission
- indications for SCT (3)
- aplastic anemias: allogeneic for young pts with severe dz; congenital immunodeficiencies: allogeneic; MM: NHL high grade--autologous in 2nd remission and allogeneic in young with matched donor; solid tumors: autologous only in studies
- cord blood transplantation
- adv: less stringent matching required, speedy, reduced GVHD, lower viral transmission; Disadv: paucity of progenitors; prolonged time for neutrophil and platelet engraftment, higher rate of failure, concern ab reduced antitumor or antiinfectious activity, inability to get additional cells, and concerns about quality
- cord blood transplant in kids
- good reconstitution
- CBT in adults:
- consierable early transplant related mortality (57% in 3 mo in one study)
- how to improve results of CBT?
- pooling of 2 units; reduced intensity conditioning, validate procedures
- new development in allogeneic SCT
- metastatic renal cell carcinoma
- article conclusions
- - allogeneic HSCT for metastatic RCC is feasible; overall survival around 30% at 2 yrs; factors assoc with tumor response/survival are :chronic GVHD, DLI, less than 3 metastatic sites.