Intro to Transplant

Question 1

preparative regimen for a bone marrow transplant

Answer 1

*for any transplant, need to empty out the bone marrow to make room for the new graft
*give high dose chemotherapy and/or radiation to empty out the bone marrow and make room for the new cells
*disease burden needs to be minimized (debulk the cancer) prior to transplant

Question 2

hematopoietic stem cell transplant (HSCT) collection sites

Answer 2

*past: all transplants involved marrow harvested from iliac crest
*now: we harvest stem cells via peripheral blood collection
-to get peripheral cells into peripheral blood, we use G-CSF priming (growth factor)
-filter out the cells via pheresis

Question 3

autologous hematopoietic stem cell transplant (HSCT) - what is it?

Answer 3

collected from and infused into the SAME person (getting your own bone marrow back)

Question 4

allogeneic hematopoietic stem cell transplant (HSCT) - what is it?

Answer 4

*bone marrow collected from another member of the same species

*related = usually a full sibling
-matched donor (10/10 match)
-mismatched donor (<10/10 match)
-haploidentical donor (half-match)
-syngeneic (from an identical twin)

*unrelated = from general population (bone marrow donors in the donor pool)

Question 5

autologous transplants - indications

Answer 5

*most common due to diseases we use this for & relative low side effect profile
*indications:
-multiple myeloma & other plasma cell dyscrasias
-Non-Hodgkin’s Lymphoma
-Hodgkin’s Lymphoma
-other malignancies

Question 6

autologous transplants - why do we do it?

Answer 6

*to rescue the marrow
*we give doses of chemo that are so high, the marrow cannot recover - so we “rescue” it with an autologous transplant
*we collect the stem cells BEFORE chemo, and then give the cells back after the chemo therapy to rescue the marrow

*autologous transplant = stem cell rescue (give back ONLY stem cells)

Question 7

autologous & allogeneic transplants - short term complications

Answer 7

*related to the preparative regimen:
-GI: N/V, mucositis, diarrhea
-pancytopenia
-infection
-hair loss

Question 8

autologous transplants - long term complications

Answer 8

*related to transplant:
-DMSA toxicity
-graft failure -> aplasia

Question 9

autologous transplants - mortality & survival

Answer 9

*transplant-related mortality within 3 months: <5%

*overall survival at 3 years:
-for multiple myeloma = 85%
-for DLBCL = 74%

Question 10

autologous transplants - keys to success

Answer 10

1. have a chemosensitive disease
2. be able to harvest a healthy graft:
   -not contaminated by active tumor (leukemia)
   -not “contaminated” by bone marrow failure (aplastic anemia)

Question 11

allogeneic transplants - indications

Answer 11

*AML (acute myeloid leukemia)
*MDS/MPN (myelodysplastic syndrome / myeloproliferative neoplasms)
*ALL (acute lymphoblastic leukemia)
*aplastic anemia
*some non-malignant diseases

Question 12

allogeneic transplants - benefits

Answer 12

*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

Question 13

allogeneic transplants - graft vs. tumor effect

Answer 13

*donor lymphocytes (T cells especially) in the absence of chemotherapy can induce regression of leukemias in the recipient
*ie. the donor T cells kill the tumor cells (in addition to other non-donor-self cells - graft vs. host)

Question 14

allogeneic transplants - downsides

Answer 14

*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

Question 15

donor identification - HLA typing

Answer 15

*histocompatibility typing (“tissue typing”)
-completely different from blood typing
-there are 6 HLA antigens (each with 2 alleles), but one of them is irrelevant, so we go for a 10/10 match

Question 16

donor identification: HLA typing - chances of a full sibling matches?

Answer 16

1 in 4

Question 17

umbilical cord blood transplants

Answer 17

*another potential source of allogeneic stem cells
*utilized more in peds than adults
*cells are relative immune incompetent in mounting normal allogeneic response:
-less GVHD
-can tolerate wider HLA disparity
*time to engraftment is dependent on the cellular dose of stem cells transfused
*although cords are rich in stem cells, absolute numbers are still low
*adults often need 2 cords

Question 18

allogeneic transplants - long term complications

Answer 18

*complications related to transplant:
-transfusion reaction
-graft rejection
-graft vs. host disease

Question 19

acute graft vs. host disease

Answer 19

*defined as GVHD occurring before day +100
*occurs in 30-70% of all allogeneic transplant recipients
*risk factors:
-increasing HLA disparity

Question 20

graft vs. host disease - 3 most common sites affected

Answer 20

1. skin
2. liver
3. GI tract

Question 21

graft vs. host disease - skin complications

Answer 21

*skin is most common site of GVHD:
-erythematous maculopapular rash, usually with bullae, that begins at the time of engraftment
-in chronic GVHD, can lead to sclerodermatous changes

Question 22

graft vs. host disease - liver complications

Answer 22

*increasing conjugated bilirubin and alkaline phosphatase (due to damage to bile canaliculi -> cholestasis)
*dx best made by biopsy

Question 23

graft vs. host disease - GI tract

Answer 23

*s/s: diarrhea, abdominal cramping
*dx requires endoscopy & biopsy (apoptotic bodies in crypts and popcorn lesions)

Question 24

graft vs. host disease - treatment

Answer 24

*add on immunosuppression (note - comes at the cost of the graft vs. leukemia effect)