Transplant Flashcards
Consequences of HLA mismatch with transplant
1) Decrease in post-HCT survival with each HLA allele mismatch (each mismatch reduces probability of 5 yr OS by 10%)
2) GVHD
3)
plerixafor (mozobil) mechanism
CXCR4 antagonist
Risks of auto - HSCT
- transplanting malignant cells
- ## ***higher risk of treatment related MDS + leukemia long term
Risks of allo - HSCT
- death (transplant related mortality)
- GVHD
- DAH
Chromosome on which MHC is found (Site of HLA antigen)
Chromosome 6
Most import HLA antigens for matching
A, B, C, + DR
9/10 Matched related donor vs. 10/10 matched unrelated donor superior
- matched related donor superior since minor histocompability mismatch superior that isn’t included in HLA screening process
Management of ABO mismatch
- RBCs can be removed from donor infusion or PLEX recipient ABO antibodies prior to transplant
Complications of ABO mismatch in transplant
- immediate or delayed hemolysis
- *delayed RBC recovery
- *pure red blood cell aplasia
Types of stem cell transplants
- bone marrow (need to be infused within 24h)
- peripheral blood (most common since they engraft faster)
- umbilical cord
Transplant with highest and lowest risk of GVHD
peripheral blood is highest
umbilical cord is lowest
Transplant with highest graft vs tumor effect
peripheral blood
Why does there always have to be an MD present during stem cell graft transfusion?
DMSO (preservative) can cause an allergic reaction during infusion
Why we don’t use umbilical cord for stem cell graft
- slow to engraft
- prolonged myelosuppression
- higher infection risk
Busulfan SE’s
- seizures
- veno-occlusive disease
- restrictive lung disease/pulmonary fibrosis
- hyperpigmentation
GVHD RF’s
- gender
- type of transplant
- alloimmunization (woman who had prior pregnancies is donor)
Acute GVHD presentation
- hyperbili
- skin toxicity
- GI tract involvement
- hepatotoxicity
GVHD prophylaxis options
- tacrolimus or cyclosporine w/ MTX
(CONFIRM)
First line for GVHD acute treatment
- steroids
Management of steroid refractory GVHD
ruxolitinib (jakafi)
First line for chronic GVHD
steroids
Infectious risk during transplant phases 1) when pts are at risk for PJP 2) CMV risk
- neutropenic pre engraftment phase – bacterial infections
- PJP around 2 months
- CMV 100 days post
**finish this
CMV prophylaxis for patient with positive PCR post transplant
letermovir
CMV reaction treatment post transplant
ganciclovir
First important component of matching
HLA status
DAH treatment
- steroids
- transfuse platelets + FFP to correct coagulopathy
Drug associated with highest risk of VOD
busulfan
VOD clinical features
fulminant liver failure + painful hepatomegaly + weight gain/edema/ascites + renal/respiratory failure
thrombocytopenia (earliest sign, refractory to transfusion) + elevated serum aminotransferases and/or alkaline phosphatase + hyperbilirubinemia (mostly conjugated bilirubin, develops later)
Bronchiolitis obliterans presentation + 2) timeframe post transplant
- respiratory symptoms (coughing, wheezing, crackles) + bronchiolar dilatation on imaging
- months post transplant
Bronchiolitis obliterans management
supportive care
Post transplant microangiopathy 1) clinical presentation 2) drugs precipitating it
- TTP like syndrome
- post cyclosporine or tacrolimus (inducing podocyte damage)
Management of BK virus hemorrhagic cystitis
- ***decrease immunosuppression
- platelet transfusion
- bladder irrigation
Types of transplant (non-auto_
- Sibling donor
- Mathced unrelated donor (MUD)
- haploidentical (50% HLA match)
- syngeneic (identical twin, which is the same as autologous)
Benefit but downside of peripheral blood for transplant
- faster engraftment but higher risk of chronic GVHD
Preferred donor
1) Matched sibling donor (less GVHD + fast and cost-effective)
2) Fully HLA matched unrelated donor (fully matched has similar survival to matched sibling but takes longer)
3) Alternative donor - haplo or cord blood
4) Mismatched MUD
What is a haploidentical donor?
50% HLA match
IS gender a GVHD RF?
Yes, Y chromosome serves as minor HLA mismatch
Consequences of minor ABO incompatability?
- acute hemolysis
- delayed hemolysis secondary to passenger lymphocyte syndrome
What is passenger lymphocyte syndrome?
Donor B lymphocyte production of antibiodies targeted recipient RBCs
*typically in setting of minor ABO mismatch
Standard conditioning regimens used in AML/MDS
- Busulfan/cyclophosphamide
- Fludarabine/busulfan
Typical conditioning regimen used in ALL
Total body irradiation/cyclophosphamide
Conditioning regimen used for for haplo’s
Flu/cy/TBI
HL conditioning regimen
BEAM - BCNU/etoposide/cytarabine/melphalan
Busulfan SE profile
- VOD
- seizures
- pulmonary fibrosis
- secondary malignancies
Cyclophosphamide SE’s
- hemorrhagic cystitis
*cardiomyopathy
*SIADH - pulmonary
Fludarabine SE to know
- T-cell immunosuppression
Melphalan SE’s
- mucositis
- diarrhea
- secondary malignancies
GVHD RF’s
- HLA mismatch
- Age
- Unrelated vs. sibling donor (sibling preferred)
- female to male
*myeloablative vs. RIC (myeloablative is higher risk due to tissue damage) - peripheral blood is higher risk
Primary means of preventing GVHD now
*post transplant cytoxan
- ATG
- ex-vivo T cell depletion (graft engineering and manipulation)
Lung syndrome associated with chronic GVHD
bronchiolitis obliterans
Second line options for chronic GVHD
- ibrutinib
- ruxolitinib
Third line for chronic GVHD
- KD025/belumosidil (ROCK2 inhibitor)
When to initiate treatment for CMV
- persistent viremia (treat before developing CMV end organ disease)
Most frequent cause of mortality after transplant
Relapse of disease
What to think of in altered patient in peri-transplant period
calcineurin-inhibitor-associated PRES
(tacrolimus and cyclosporin)
Clinical features of idiopathic pneumonia syndrome
- post transplant
- mimics pneumonia but infectious workup (BAL) is negative
Consequences of HLA mismatch
- mortality- progressive decrease in survival for each HLA allele mismatch
- higher rates of GVHD
Drug contraindicated with 6-MP
allopurinol
Clinical benefit of post transplant maintenance rituximab in MCL
OS
Typical cause of hematuria 2 months after post transplant cytoxan
BK virus
Problems with haplo donors
- higher GVHD risk because only half HLA matched
Best CMV status
CMV- recipient and CMV- donor
Ideal donor if recipient is CMV seropositive
seropositive donor (immunity restored faster)
Benefit of ATG in transplant
less GVHD
