Wake Stem Cell Transplantation

Front 1

Diseases that are treatable by HSCT

Back 1

1. Leukemias and lymphomas
2. myelodysplastic/myeloproliferative disorders
3. Bone marrow failure syndromes
4. Immunodeficiency States
5. Hemoglobinopathies
6. Inborn metabolic disorders
7. Other malignancies

Front 2

HSCT

Back 2

hematopoietic stem cell transplatation

Front 3

Different type of HSCT

Back 3

1. Autologous
2. Synergenic
3. Allogenic

Front 4

Autologous

Back 4

collected from and infused into the same person

Front 5

Syngenic

Back 5

collected from an identical twin

Front 6

Allogeneic

Back 6

collected from another member of the same species
- Related - member of same family, usually a sibling
- Unrelated - general population (NMDP)

Front 7

What is the collection site for HSCT?

Back 7

bone marrow, peripheral blood after granulocyte colony stimulating factor “priming or mobilization”, umbilical blood

Front 8

In the past, how did we obtain HSC’s?

Back 8

- all bone marrow transplants utilized bone marrow from an iliac crest harvest
- Bone marrow contains cells at various stages of maturation

Front 9

A harvest is...

Back 9

a larger volume (500-1500 ccs)
performed on general anesthetic

Front 10

Peripheral HSCT collection

Back 10

- After GCSF priming (+/- preceding chemotherapy) the peripheral blood WBC is monitored. After it increases an outpatient procedure called APHERESIS is performed

Front 11

How does the apheresis machine know which cells to take?

Back 11

takes CD34 cells

Front 12

What is the point of autologous HSCT?

Back 12

- The cells are not the cure. The cells are the “rescue” from the cure.
- Autologous HSCT is nothing more than glorified high dose chemotherapy, or chemotherapy with a cellular rescue.

Front 13

Which tumors do you consider using HSCT?

Back 13

- tumors with steep dose response curves to chemotherapy
- allows higher dosages of chemotherapy to kill more cancer cells because you can rescue the bone marrow with your own healthy bone marrow

Front 14

AutoHSCT

Back 14

mechanism to get around the dose limiting toxicity (which is myelosuppression)

Front 15

How long after autologous SCT until you have count recovery?

Back 15

14 days

Front 16

what things exclude you from being able to harvest healthy graft?

Back 16

active tumor contamination
bone marrow failure states (aplastic anemia, myelofibrosis)

Front 17

Common indications for autoHSCT

Back 17

- Multiple myeloma
- Large cell lymphoma in first relapse
- Hodgkins disease in relapse
- AML with high risk cytogenetics in first CR if not a candidate for allogeneic HSCT due to lack of donor or underlying patient status
- High risk peripheral T cell lymphomas in first CR

Front 18

Is multiple myeloma cured with autoHSCT?

Back 18

No, but it improves prognosis

Front 19

What diseases are the most common for Autologous transplants?

Back 19

1. Multiple Myeloma
2. NHL
3. Hodgkin's Dz
4. AML

Front 20

Benefits: Allogeneic vs AutoHSCT

Back 20

- Guarantee of a clean graft
- Can be used in marrow failure states
- Largest difference is this is an immunologic intervention, hoping to harness a graft versus tumor effect

Front 21

graft versus tumor effect

Back 21

a.k.a. graft vs. leukemia
- Much of our immunity is based on our blood cells (we think of this in infection). - Cellular immunity also is involved in cancer surveillance
- Donor lymphocytes in absence of chemotherapy can induce regression of leukemias
- Higher rate of relapse in syngeneic than allogeneic HSCT in AML 52 vs 16% at three yrs

Front 22

Negatives Allo vs AutoHSCT

Back 22

- Need to find an HLA matched donor, most often a sibling.
- Graft versus host disease

Front 23

Graft versus host disease

Back 23

- essentially grafted cells recognizing patient as “non-self” and attacking
- Primarily a T cell mediated process
- Acute vs chronic. Need to give additional immunosuppressive drugs to prevent this, which further increases risk of infection
- Largely due to GVHD and increased infections, TRM is much higher- 10-20% by day 100.

Front 24

Who is a compatible donor?

Back 24

Immunology and HLA Typing

Front 25

Class I HLA

Back 25

Gene Loci A, B, C

Front 26

Class II HLA

Back 26

Gene Loci D

Front 27

human leukocyte antigens

Back 27

- Chromosome 6 has the genes that determine the compatibility antigens ( Class I and Class II)
- C appears to have little role in “compatibility”
- 6 main antigens expressed ( 2 copies of each A, B, D) one from each chromosome 6

Front 28

What is the proportional chance that your sibling will have an identical HLA match?

Back 28

1/4

Front 29

Where can you find donors if you have no siblings?

Back 29

- find a donor from the NMDP or international registries
- Over 4,000,000 people in the registry
- Some HLA types are ethnically conserved, and this can affect likelihood of finding a match in the registry

Front 30

Umbilical Cord Blood

Back 30

relatively immune incompetent in mounting normal allogeneic response

Front 31

UCBT...

Back 31

- has been shown to have less GVHD
- donors are less allo-immunized
- can tolerate wider HLA disparity
- is less likely to be CMV+
- 20% of the registery UCB is collected from minorities (higher chance of minority match)

Front 32

Is UCB used more in peds or adults?

Back 32

pediatrics

Front 33

What is the time to engraftment dependent on?

Back 33

- cellular dose of stem cells transfused
- this is based on body weight
- pt has to wait until the cells grow up to the concentation you need

Front 34

What are limitations in UCB?

Back 34

- time to engraftment
- low absolute numbers (an no potential for recollection form subsequent DLI
- adults often need 2 cords - dual cord transplants

Front 35

What are complications related to allogenic transplant?

Back 35

Transfusion reaction
Graft rejection
Graft versus host disease

Front 36

Risk factors for acute GVHD

Back 36

- Increasing age of host
- Prior exposure of donor to other blood groups (including pregnancy)
- Donor and recipient gender disparity
- CMV status of donor and host
- Intensity of the transplant conditioning regimen
- Peripheral blood stem cell versus bone marrow transplantation
- Acute GVHD prophylactic regimen used

Front 37

What is the incidence of GVHD in allogenic stem cell transplant?

Back 37

10-50%

Front 38

GVHD most common sign

Back 38

- Most common site is skin, often manifesting as an erythematous maculopapular rash at the time of engraftment (can lead to complete skin desquamation)
- Can also be involved in chronic GVHD leading to sclerodermatous changes

Front 39

What do you do when there is a skin reaction and a patient received an allogenic SCT?

Back 39

You suspect GVHD
MUST GET A BIOPSY of rash

Front 40

What is the second most common site of GVHD?

Back 40

The liver
- Often first increased serum levels of conjugated bilirubin and alkaline phosphatase resulting from damage to the bile canaliculi, leading to cholestasis

Front 41

What is the DDX for acute GVHD with symptoms in the liver?

Back 41

VOD, viral hepatitis, drug toxicities

Front 42

How is acute GVHD - liver complication made?

Back 42

Diagnosis best made by biopsy, which is technically difficult due thrombocytopenia. Often done via transjugular biopsy to minimize blood loss

Front 43

GVHD symptoms

Back 43

- GI tract involvement
- manifests as diarrhea and abdominal cramping. Often very severe and can cause over 10L stool output per day

Front 44

DDx of GVHD GI symptoms

Back 44

- reaction to preparative regimen
- antibiotics
- infection –c.diff

Front 45

Dx of GVHD GI symptoms

Back 45

reguires endoscopy and biopsy

Front 46

Prevention of GVHD

Back 46

- Use the best matched donor
- T cell depletion: ATG, alemtuzumab
- Chemotherapy with planned gradual reduction of immunosuppression
- Reduced intensity allografting with gradually increased cellular dose of transplanted cells

Front 47

What chemotherapies are given during GVHD prevention?

Back 47

Methotrexate
mmunosuppressants :Steroids, cyclosporine, mycophenylate

Front 48

Treatment of GVHD

Back 48

Additional immunosuppression:
- First step is pulsed steroids
- Increased immune suppression
- Cyclosporine, tactolimus, mycophenylate
- ATG
- Other experimental measures

Front 49

HSCT Host factors

Back 49

a very aggressive therapy, and patients have to be fairly healthy (problem: this is the last step of the therapy)

Front 50

To be considered as a HSCT host, pt must be screened for...

Back 50

- Preserved cardiac (EF>=40%), pulmoary, liver function
- Chemosensitive disease at a minimum, perferable disease in remssion
- ECOG level of 2, which means they can do daily functions
- No substantial ongoing infections

Front 51

On GVHD colon biopsy what do you see?

Back 51

- apoptotic bodies in the crypts and "popcorm lesions"

Front 52

Autologous HSCT most common cause of death...

Back 52

relapse (70%)

Front 53

What are the age cutoffs for autologous and allogenic HSCT recipients?

Back 53

- Autologous <= 70 year old
- Allogenic <=65 year old

Front 54

Allogenic outcome related issues
(acute toxicity?, relapse?)

Back 54

increase acute toxicity
decrease relapse

Front 55

Autologous outcome related issues
(acute toxicity?, relapse?)

Back 55

decrease acute toxicity
increase relapse in bone marrow disease

Front 56

40 year old woman presents with pancytopenia. Bone marrow biopsy reveals AML. She undergoes induction chemotherapy. Cytogenetics reveal a very high risk phenotype: del5,7, and a translocation involving 11q23.
What do you do?

Back 56

With this type of cytogenetics, her likely hood of survival is very low.
If she has a sibling, you can do allogeneic.

Front 57

20 year old woman presents to her university health services due to fatigue. She is found to be pancytopenic. WBC 0.5/ ul, HB 4.5g/dl, plt 20,000. Bone marrow biopsy reveals profoundly hypocellular marrow with cellularity at 5%. Diagnosis of very severe aplastic anemia.

Back 57

Immediately give allogenic HSCT.

Front 58

35 yr old patient with history of Stage III diffuse large B cell lymphoma treated with R-CHOP x 6 cycles. She was in a remission x 3 months, then had recurrence with mediastinal lymph nodes. She has 3 sibs. What would you do?

Back 58

We would give her salvage chemo
Get her to a second chemo
Standard of care is to give her an allogenic transplant

Front 59

What is VOD?

Back 59

Veno-oclusive diease of the liver

Front 60

What is present in characteristic histoloy of skin in graft-versus-host disease?

Back 60

- apoptotic keratinocytes accompanied by lymphocytes
- exocytosis of some lympocytes into the epidermis
- basal vacuolar change
- sparse lymphocytic infiltration of the dermis

Front 61

Complications related to transplant in Autologous stem cell transplant

Back 61

- DMSO toxicity
- graft failure

Front 62

Complications related to conditioning regimens

Back 62

- GI: nausea/vomiting, mucositis, diarrhea
- Pancytopenia
- Infection (bacterial, viral, fungal, etc)
- Hair loss
- Liver (venoocclusive disease of the liver VOD)
- Lung (diffuse alveolar hemorrhage DAH, interstitial pneumonitis)
- Heart, Renal, Neurotoxicity, etc.
- Long term complications