20- HPC Transplant Flashcards
What is the function of bone marrow and what is a great analogy?
organ in the body which makes blood cells (RBCs, WBCs, platelets)
garden!
What is the function of a hematopoietic progenitor cell? analogy
(the old blood stem cell) the cells from which form the foundation that the other cells stem from
HPC= seeds!
What does autologous mean? allogeneic?
autologous- from yourself. High intensity chemo bc you don’t have to wait for bone marrow regeneration
allogenic- from some one else
What is the difference between GVHD and Rejection?
GVHD: donor attacks host
Rejection: Host attacks donor (aka Host vs graft)
How do we interfere in the BMT cycle?
To prevent GVHD: we need a stem cell source.GVHD prevention strategy
To prevent Rejection: Conditioning of host (immune suppression)
How has bone marrow transplant therapy changed over time?
we used to use very aggressive therapy, now we offer reduced intensity transplant
What are the 2 parts of BM transplant
conditioning with chemo and possibly radiation
infusion of the HPC product with a GVHD prevention strategy (bone marrow, cord blood, peropheral blood progenitor cells-natural or manipulated to enrich or deplete cells)
What are the two variables that determine which chemo package will be used to condition for bone marrow transplant? What are the 2 kinds of therapies?
Disease and donor!!!
Myeloablative or reduced intensity therapy (reduced intensity has less collateral damage)
Rank common donor sources in terms of their histoINcompatibillity (tissue typing)? start at the least and go up!
Autologous=self or identical twin
matched sibling
unrelated donor
half matched parent “haplo”
Describe the timing of a BMT
Conditioning phase (1 week)
wait for engraftment (3 weeks)
Initial post engraftment phase (1-3 months) **most complications
long term follow up (late term effects including growth and development issues)
How fast doe the new marrow/immune system development?
ANC 500 by 3 weeks
platelet and RBC independent by 6 weeks (faster with PBPC slower with cord blood)
CD4 count is MUCH slower (6-18 months to get CD4>200) CD4is crucial for fighting virus’. It is as if the patient has HIV AIDS bc their CD4 is so low
Who gets a BMT?
Children with…..
- cancers that start in the bone marrow (leukemia)
- cancers that start elsewere in the body (abdominal tumors, bone tumors)
- bone marrow failure (aplastic anemia) or hemoglobin abnormalities (sickle cell anemia)
- primary mmune deficiency syndromes
- other inborn errors of metabolism (poor man’s gene rx)
Let’s talk about Acute lymphoblastic leukemia (ALL) !
What age population does is affect?
When is ALL considered high risk?
Pediatric disease!
infant at diagnosis
high risk CR1 including:
- philadelphia chromosome
- WBC> 100,000 at diagnosis
- 11q23 rearrangement
When should you consult for transplant in ALL?
First relapse, CR2 and beyond
High risk
primary induction failure
there is presence of minimal residual disease after initial or subsequent therapy
When shoudl you consult for HCT consultation in Acute myeloblastic anemia (AML)? (pediatrics)
Early after initial diagnosis!
when primary induction fails
Monosomy 5 or 7
<2yrs at diagnosis
CR2 and beyond
presence of minimal residual disease
When should you not consult for HCT right away in AML?
t(16;16), inv 16, t(8;21), t(15;17), normal cytogenetics with NM1 or biallelic CEBPA mutation and without FLT3-ITD
List 5 malignant diseases where you should do a HCT consultation? (not including ALL, AML)
Hodgkin Lymphoma
Juvenile myelomonocytic leukemia (JNML)
Neuroblastoma
Ewing family of tumors
medulloblastoma
When should you have a HCT consultation for Hodgkin Lymphoma?
primary induction failure
at first or subsequent relapse
CR2 or subsequent remission
When should you get HCT consultation for Juvenile myelomonocytic leukemia? Neuroblastoma?
JMNL- At diagnosis!
Neuroblastoma- short initial remission or poor initial response or at progression
When should you do a HCT consultation for Ewing family or tumors? Medulloblastoma?
Ewing family of tumors- metastatic disease at diagnosis, first relapse or CR2
Medulloblastoma- firt relapse or CR2
List 5 Non-malignant disorders that may need HCT consultation?
immune deficiency diseases (Severe combined immunodeficiency, WIskott-Aldrich syndrome)
inherited metabolic disroders (Hurler’s syndrome, adenoleukodystrophy, and others)
Hemoglobinopathies
Hemophagoyctic Lymphohistiocytosis (HLH)
Severe aplastic anemia and other failure syndromes
Which 4 non-malignant disorders should you do a HCT consultation at diagnosis?
Immune deficicnecy diseases (newborn screening)
inherited metabolic disorders
hemophagocytic lymphohistiocytes
severe alpastic anemia and other marrow failure syndrome
What are 2 hemoglobinopathies? When should you do a consultation for HCT for these hemoglobinopathies?
transfusion-dependent thalassemias (at diagnosis)
sickle cell (with aggressive course-stroke, end organ complications, frequent pain crisis)
What are some benefits of doing an allogenic cord blood transfsion instead of a well matched unrelated donor?
less GVHD, quick bc you don’t have to wait for a donor!
What kind of transplant is best for an elderly man with mutliple myeloma?
Autologous transplant bc he is older an dmay not be able to handle all of the immunosuppressison of a donor
There are 4 cellular theraies. What are the 3 T cell immunoptherapies and what is the other?
- T cell immunotherapies:
- DLI (post BMT)
- Ex-Vivo expanded CTL (post BMT)
- Chimeric Antigen Receptor modified T cells (CART)
- NK cell immunotherapies ( supposedly no GVHD!)
How do CART Cells work?
allows for MHC independent antigen recognition and incorporates costimulatory signals endowing the transduced T cell with potent cytotoxic activity
**basically I think it doesn’t need 2 co-stimulatory mechanisms like most T cells
What are teh 2 conditioning regimen options?
myeloablative or reduced intensity
What are common BMT side effects in the first month?
Mucocitis (destroyed barrier)
Hair Loss
BM destruction
lung, liver, heart, CNS complications
What are common BMT side effects within 30-365 days?
Bugs (infection)
Drug
GVHD
What are some late side effects for BMT transplant?
infertility and stunted growth
WHat is a common side effect after CARTCell therapy?
Cytokine toxicities! Cytokine Release Syndrome
We treat it with a IL6 inhibitor Tocilizumab
