BMT Flashcards
What is an ommaya reservoir?
Plastic device that’s implanted under your scalp. It’s used to deliver medication to your cerebrospinal fluid (CSF),
Chemo that may be administered intrathecally
methotrexate
cytarabine (Ara-C)
hydrocortisone
What does DLI stand for?
Donor leukocyte infusion
What is DLI? When given?
Patients who have received a blood and marrow transplant (BMT) from a related or unrelated donor could still experience a relapse of their underlying disease/cancer. A donor leukocyte infusion (DLI) is a possible strategy for managing a patient in relapse. In this procedure, the patient receives a boost of immune cells from the original donor’s blood. In certain circumstances, it may be extremely effective in controlling recurrent cancer in a patient.
Indications for CAR T cell therapy
- In general–aggressive, relapsed or refractory NHL
1) DLBCL
2) Primary mediastinal B-cell lymphoma
3) high grade B-cell lymphoma
4) transformed follicular lymphoma
5) mantle cell lymphoma.
For how long are you at risk of invasive fungal infection following transplant?
Risk remains elevated for first few months, even after recovery of neutrophil counts (so you need to continue anti fungal prophylaxis during this time)
Vyxeos is
daunorubicin and cytarabine
Haploidentical means
- half- matched donor to replace the unhealthy ones.
- donor is typically a family member
Cell line that is first to recover
monocytes
How DA-EPOCH-R is referred to
Dose adjusted EPOCH-R
DA-EPOCH-R contains
Etoposide, prednisone, oncovin (vincristine), doxorubicin hhydrochloride, cyclophosphamide, rituximab
DA-EPOCH-R used for
NHL + b-cell lymphoma
Use of VDT PACE
RRMM
VDT PACE is
Bortezomib Dexamethasone Thalidomide Doxorubicin Cyclophosphamide Etoposide
To know about MTX use
order level 24h after last dose (typically by pharmacy as part of orderset)
Repeat MTX level daily (often a send out)
IF high → uptitrate leucovorin
Give leucovorin until MTX level >0.1
Discharge when level is >0.1
Leucovorin dosing with MTX
q6h
Common etiology of fevers post transplant
Engraftment
HCT means
hematopoietic cell transplantation
Transfusion goals
Hgb <7
Plt <10
Ppx during leukemia induction
(bacterial + HSV)
Acyclovir 400 mg PO BID
IF high risk (expected ANC<500 for 7 days (induction for AML or HCT)) → Start levoquin 500 mg PO daily on first day of start of cytotoxic chemo
TBI stands for
total body irradiation
VOD prophylaxis
ursodiol
Hepatic SOS (veno-occlusive disease) timing + context
Occurs days or weeks after HCT
Hepatic SOS or VOD clinical features
Thrombocytopenia + hepatomegaly + ascites + jaundice
- can rapidly progress to multiorgan dysfunction and death
Age cutoff for myeloablative transplant
65 (in europe, 77 in us)
Treatment of EBV post transplant
Rituxan
Order of recovery of cell lines after engraftment
neutrophils, then T cells, RBC’s, platelets
Clinical features of primary graft failure
cell lines continue downtrending and don’t respond (no engraftment)
management of primary graft failure
do bx → then usually have to repeat graft
Transplant referred to as
infusion
Presentation of CMV
- mono like syndrome + organ specific involvement (hepatitis, colitis, pneumonitis)
When CMV typically occurs after solid organ transplantation
- within first few months
Explanation for why CMV-positive recipients may still develop CMV from CMV-positive donors
- several strains of CMV don’t confer cross-immunity
1st and second best CMV status
1) seronegative donor and recipient
2) seropositive donor and seronegative recipient (a seropositive donor has immunity that can be transferred to recipient and recipient does not have dormant CMV that can be reactivated)
Preferred conditioning regimens at UMass for allo’s
1) Flu/cy + TBI
2) Bu/Flu + TBI
Flu/cy is
Fludarabine + high dose cytoxan
Bu/Flu is
busulfan + fludarabine
Preferred prophylaxis for GVHD at UMass + other 2 medications used for GVHD prophylaxis
- Cytoxan
- Mycophenolate + tacrolimus
When cytoxan is given after transplant for GVHD prophylaxis
D+3/4
tacro level goal, generally speaking
5-10
first and second line for chronic GVHD
1 mg/kg prednisone
- ???
“death from transplant” term in malignant heme
Relapse free mortality
mortality rate of allo transplant
Around 10%
Percentage of allo transplant recipients who get GVHD
50%!
Conditioning regimen for autos + dose
melphalan 200 mg/m2
Indications for auto transplants
1) Multiple myeloma
2) MCL
3) RR lymphoma (DLBCL and t cell)
4) Refractory HL
conditioning regimen typically used in auto transplants for RR lymphoma
BEAM
when myeloma patients are taken for transplant typically
CR1
beta d glucan tests for
candida
test for aspergillus
galactomanan
fluconazole covers and does not cover
candida, does not cover molds
Standard of care antifungal prophylaxis for leukemics + patients with long duration of neutropenia
- posaconazole
- cresemba (broader coverage)
Problem with voriconazole
side effect profile + need to check levels frequently
Most common transplant donor + recipient for CMV infection
D+/R-
Medication used to prevent CMV reactivation
Letermovir
Common viral infections in post-transplant
- CMV
- HHV8
HHV8 clinical presentation
meningoencephalitis
BK virus presentation
Hemorrhagic cystitis
Treatment of BK viremia at UMass
Cedofovir
Induction regimen at UMass for AML
Mitoxantrone + cytarabine
Consolidation therapy for AML
IF moderate or high risk – allo transplant
All others – High dose ara C (HIDAC)
HiDAC stands for
High dose cytarabine
Most common precipitants of CRS
1) CAR-T
2) Bispecifics
Drugs commonly implicated in differentiation syndrome
1) ATRA+arsenic for APL patients
2) IDH inhibitors
Medications for post transplant TMA
1) Narsoplumab
2) Eculizumab
clinical presentation of engraftment syndrome
- around D10
- inflammatory syndrome that looks like mild HLH (effusions, edema, fevers, dyspnea, LFT bump)
management of engraftment syndrome
High dose steroids for 3-7 days
when VOD happens
allo transplants D1-20
first line for VOD
defibrotide
key pieces of information to know about every transplant patient
1) transplant type
2) graft source
3) HLA typing
What are the aggressive b cell lymphomas?
1) DLBCL
2) Primary mediastinal B-cell lymphoma
3) high grade B-cell lymphoma
4) transformed follicular lymphoma
5) mantle cell lymphoma.
Immunophenotype of stem cells
CD34+
When risk of infection increases dramatically
ANC below 500
basic process for auto transplant
- patient gets chemo and goes into remission – get chemo and GSCF to mobilize stem cells into peripheral blood – cells are frozen – patient gets admitted a week or two later for transplant – patient gets chemo followed by autologous stem cell infusion
Best choices for HLA matched donor AND why
1) Young matched sibling (least transplant related mortality)
2) Matched unrelated donor (high number of cells compared to cord blood and hence quicker engraftment and less risk of viral infection)
3) Cord blood donor (less GVHD but high risk of viral infection)
Types of HLA matching
1) Matched sibling
2) Matched unrelated donor
3) Cord blood
4) Haplo identical donor
Top two choices for CMV status
1) CMV + and +
2) CMV - and -
Donor features associated with less risk of GVHD
- younger age
- male
- nulliparous female donor
Allo transplant indications
- AML (intermediate or high risk)
- ALL
- MDS
- Myelofibrosis or CMML
- CML not responding to TKI
- Lymphoma (relapse after an auto)
- MM (high risk and young)
- AA (age less than 40)
- Beta thalassemia major
What is allogenic effect?
Graft vs. leukemia affect
Point of a conditioning regimen
Even when a patient is in clinical remission, leukemia cells might be present below the threshold of detection. Myeloablation eradicates both normal and abnormal stem cells
When does post transplant TMA happen?
A long ways out (day 100+)
Mucositis peak after myeloablative regimen
Day 7-15
Diarrhea distinguishing feature in terms of timeframe
Typically non-infectious before day 15
Concept of reduced intensity conditioning
- Less intense regimen to improve post-transplant immune suppression
- DLI used to eliminate residual disease (instead of conditioning regimen)
Indications for reduced intensity preparative regimen
- age over 60
- CR
- Slow growing disease (follicular NHL)
- heavily treated with chemo
- borderline PS
RIC stands for
Reduced intensity conditioning
Timeframe of when patient is at increased risk of infection post transplant for viruses, fungi, and bacteria
Bacteria = hours to days Fungal = days to weeks Viral = weeks to months
T cell depletion methods
- Campath
- ATG
Prophylaxis after allo transplant at UMass and dosing
Acyclovir 400 mg PO TID OR valacyclovir 500 mg BID
Levoquin 500 mg PO daily on first day of start of cytotoxic chemo
DC when ANC>500
Posaconazole 300 mg PO daily OR cresemba (until immunosuppression discontinued)
Start Bactrim DS BID on Saturday or Sunday only 30 days after transplant for 6 months
Prophylaxis after auto transplant at UMass
Acyclovir 800 mg PO BID (400 mg BID if renal insufficiency)
Levoquin 500 mg PO daily (renally dosed) on first day of start of cytotoxic chemo
Fluconazole 400 mg PO daily for 1 month
Bactrim 1 DS tablet 3x/week for 1 year
NRM stands for? Means?
non-relapse mortality, refers to death after transplant from disease unrelated cause (eg conditioning regimen)
Types of conditioning regimens
1) myeloablative conditioning (MAC)
2) nonmyeloablative (NMA)
3) reduced intensity conditioning (RIC)
Caveats about hydrea dosing (onset, effect after stopping)
- onset is 3-5 days
- effect is short lived after HU is stopped, thus shouldn’t make dose adjustments more often than once per month to prevent fluctuations in platelet count
campath generic name
alemtuzumab
cresemba generic name
Isavuconazole
what is a haplo SCT?
- type of allotransplant
— Uses stem cells from a half-matched donor (typically a family member)
Duration of increased infectious risk after transplant
- up to 2 years after a transplant
when can live vaccines be used in transplant patients
2 years after transplant (risk of infection is highest 2 years after transplant, even if they’ve been weaned off immunosuppression)
Problems with using cord blood
- limited number of stem cells in a single cord-blood unit so you can’t use in recipients with larger body mass
- studies have shown superiority, however, over single cord-blood unit transplants over double cord blood unit transplants
benefits of using single cord blood unit allo transplant
- improved platelet recovery
- lower incidences of grade III and IV GVHD
clinical features of Cryptogenic organizing pneumonia after transplant
- bilateral GGO’s
- PFTs with restrictive pattern + reduced DLCO
- rapid improvement with steroids
clinical features of bronchiolitis obliterans after transplant
- airflow obstruction (due to bronchiectasis from small airway inflammation and narrowing due to fibrous scar tissue formation)
antifungals with invasive mold coverage
posaconazole (not fluconazole)
- others…
T cell markers
CD2 *CD3 CD5 CD7 CD30
B cell antigens
CD19, CD20, CD22, CD79a, CD22, PAX5
Significance of MPO+
Myeloid marker, excludes B-ALL
blast markers
CD34+
CD117+
CD123+
HLA-DR
Myeloid lineage (AML) markers
CD13
CD33
MPO+
CD11b+
Manifestations of CMV reactivation
- hepatitis
- pneumonia
- retinitis
- encephalitis
Definition of preengraftment period
less than 30 days following transplant
most common infections during preengraftment period
- bacterial + HSV + candida and aspergillus (due to neutropenia)
How is postengraftment period defined?
30-100 days post transplant
most common infections during postengraftment period
- CMV, PJP, aspergillus
late phase of engraftment period refers to
100 days following HSCT
most common infections during late phase
- aspergillus, PCP, encapsulated bacteria, VZV
Drugs that can cause TMA’s
- cyclosporine (transplant-associated TMA)
- tacrolimus
- gemcitabine
unique management of drug-induced TMA
- unclear if plasma exchange is helpful
transplant periods in which autotransplant recipients are at increased risk of infection
pre- and immediate postengraftment periods
common pathogen in oral mucositis in transplant patients
strep viridans
when to start + duration of PJP prophylaxis in allos
Start Bactrim DS BID on Saturday or Sunday only 30 days after transplant for 6 months or completion of immunosuppressive regimen (whichever comes first)
difference in azoles in fungal coverage
- fluconazole = yeast/candida
- posa and vori = cover molds
infection common with iron overload
gram negative bacteria
Inqovi includes
Decitabine/cedazuridine
cedazuridine mechanism
cytidine deaminase inhibitor
Engraftment syndrome clinical features
fever + skin rash + pulmonary symptoms
Management of engraftment syndrome
Observation or steroids depending on severity
Differentiation syndrome occurs with which drugs?
1) IDH inhibitors
2) FL3 inhibitors
3) ATRA
Drug interaction to know with posaconazole + management
1) venetoclax
2) dose reduce venetoclax
Standard of care drug used for CMV prophylaxis
Letermovir
RF’s for VOD/SOS
- High dose myeloablative conditioning regimens (particularly busulfan)
- Certain drugs in induction, consolidation, and salvage (gemtuzumab, inotozumab)