Transplant Flashcards
Define neutropenia?
<500 cells/mm3 or <1000 cells/mm3 with anticipated drop to less than 500
why is it important to focus on neutropenia ?
<500 cells/mm3 + prolonged (>10 days) associated with high risks of severe bacterial and fungal infections (bacteremia, pneumonia, candidemia, aspergillosis)
what is bendamustine?
nitrogen based alkylating agent and antimetabolite used for indolent NHL with higher risk for infections (bacterial, CMV, PCP, histoplasmosis)
what drugs (common) that impact B and T cells?
Rituximab (anti - CD20) and Alemtuzimab (anti - CD52)
what is rituximab used for and infectious complications?
Used in CLL and lymphoma. See PML, encapsulated bacteria, Hep B reactivation, loss of vaccine response.
What is alemtuzimab used for and infectious complications?
lymphoma, luekeimia, BMT (gVH); see herpes virus (CMV), fungal infections (PJP, aspergillosus)
what is the MOA of imatinib? infection complications?
inhibits signal transduction through BCR-ABL oncogene. Used for CML. Think T and B cells (VZV reactivation, Hep B reactivation) or unrelated to drug.
what does AML and MDS predispose patients to?
qualitative and quantitative neutropenia
what does lymphoma predipose patient to?
functional asplenia
what does CLL and MM predipose patients to?
hypogammaglobulinemia (recurrent chronic/atypical infections)
what does aplastic anemia predispose patients to?
- severe, prolonged neutropenia.
- aplastic anemia is autoimmune disease in which the body fails to produce blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there
Key words for viridans streptococci cause in transplant patients?
ARDS, rash, quinolones, mucositis, high dose cytosine, arabinoside
neutropenic patient with sepsis with b-lactams?
think stenotrophomonas, ESBL
neutropenic patient with lung and skin lesions?
P.aeruginosa, fungi
neutropenic patient with skin lesion, gram stian positive?
corynebacterium jeikeium
neutropenic patient with mucositis?
FUsobacterium, clostridium, stomatococcus mucilaginosis
neutropenic, septic patient while on carbapenems?
KPC-producing organism
pneumonia in patient nodular lung lesion with AML after induction therapy. Tx?
Voriconazole for suspected aspergillus
neutropenic patient with pneumonia. ddx?
- aspergillus most common.
- Fusarium, mucormycosis, Scedosporium
candidiasis skin lesion in neutropenic patient description?
small, tender papules
Vesicular skin lesion in neutropenic patient description?
Herpes
Filamentous fungi (fusarium) skin lesion in neutropenic patient description?
multiple, erythematous, different stages. Would also have invasive pulmonary disease too.
Aspergillus skin lesion in neutropenic patient description?
ulcerative, necrotic
P.aeruginosa skin lesion in neutropenic patient description?
Ecthyma gangrenosum
Early risks in stem cell transplant patients?
mucositis, neutropenia
late risks in stem cell transplant recipeints?
GVHD (steroids, asplenia, T-cell dysfunction)
early pulmonary syndromes in stem cell transplant patients?
- bacterial, fungia pneumonia.
- Noninfectious: alveolar hemorrhage, IPS
late pulmonary syndromes associated with stem cell transplant patients?
- CMV, respiratory viruses, invasive fungal infections
- Non-infectious: BOOP
GI syndromes associated with stem cell transplant patients?
- diarrhea, colitis, hepatitis.
- Herpes viruses
- noninfectious: GVHD
GU complications associated with stem cell transplant recipeints?
BK virus, noninfectious: conditioning
Neurologic syndromes associated with stem cell transplant recipients?
- Infectious: HHV6, WNV, toxoplasmosis, PML
- Noninfectious: PRES, antibiotics
what are the 3 types of allogenic donors?
- Related, HLA - Matched (MR)
- Related, HLA - matched (MUD) or mismatched (haploidentical)
- UNrelated, HLA - mismatched (MM-URD)
what are the types of stem cells transplanted?
- bone marrow
- peripheral blood
- cord blood
what are the types of conditioning regimens in stem cell transplant patients?
- myeloablative
- nonmyeloablative
what bacterial pathogens do you suspect in pulmonary complications s/p stem cell transplant patient?
- P.aeruginosa, streptococci, legionella, S.aureus
- aspiration events with severe mucositis early after BMT
- encapsulated sinopulmonary pathogens after BMT
what fungal pulmonary complication would you expect to see and timing?
filamentous fungi early and late - aspergillus fumigatus
what respiratory virus would you expect to see?
- LTI involvement
- Influenza, RSV, parainfluenza 3, human metapneumovirus, adenovirus (H-PAIR)
DDx of late pulmonary syndromes?
- Infectious: CMV, respiratory virus (seasonality), PCP
- Non-infectious: bronchiolitis obliterans syndromes
what is the biggest risk for CMV infection after BMT?
D-/R+
when does re-activation occur in CMV infection patient?
- late stage finding, occurring in R+ patients, triggering cytokine storm, GVHD.
- Primary infection in R- from D+ or blood products rare
how does CMV disease present?
pneumonitis, GI (esophagitis, colitis)
how do you prevent CMV disease after BMT?
prophylaxis with ganciclovir
prevention and timing of pneumocystis pneumonia in BMT?
common late after BMT with risk factors of steroids, T-cell depletion
prophylaxis with bactrim at least 6 months
ddx of hepatitis in BMT?
- GVHD
- Herpes virus (CMV, VZV)
- Hep B virus
ddx of diarrhea in BMT?
- GVHD
- CMV
- C.Diff
- norovirus (chronic diarrhea mimicking GVHD)
- Adenovirus
Ddx of hemorrhagic cystitis in BMT?
- Conditioning related (early) - cyclophosphamide
- BK (later)
- Adenovirus (later)
Ddx of neurologic syndromes - infectious?
- Herpes viruses (CMV, HSV, HHV6**)
- WNV
- JCV-PML
- Pulmonary-CNS (IFI, nocardia, toxoplasmosis)
Ddx of neurologic syndromes - drugs?
carapenems, cefepime, PRES**
when should you suspect HHV 6 after BMT?
- Meningoencephalitis - early within 60 days of BMT with risk factors of MM/URD or UCB SCT, anti- T cell
- correlation with rash, marrow suppression, idiopathic pneumonitis
When do you typically see PRES in HSCT? symptoms?
- early - within the first 3 months
- See: seizures, visual changes, MS changes
- Associated with calcinuerin inhibitors: cyclosporin, tacrolimus
what is suggestive of VZV infection after BMT?
- multidermatomal lesions
- viral pneumonia
- encephalitis
- Hepatitis: abdominal pain, with late transaminitis
Illness script for CMV syndrome in SOT patient?
Patient completing valganciclovir prophylaxis 6 weeks prior presenting
with fatigue, low grade fever and leukopenia
Illness script for acanthamoeba in SOT patient?
Donor died from skiing accident in fresh water lake in Florida and
recipient presents 3 weeks post transplant with encephalitis
Illness script for BK virus in SOT patient?
Renal transplant recipient on valganciclovir prophylaxis presents with
asymptomatic renal dysfunction
Illness script for nocardia in SOT patient?
Lung transplant recipient planted vegetable garden 2 weeks prior while
on posaconazole prophylaxis and presents with productive cough and
cavitary lung lesion
what bacterial infections do you need to worry about in SOT? Tx?
- Late findings
- Strep pneumo
- LIsteria monocytogenes - tx with ampicillin x 3 weeks
- Nocardiosis - Tx with Bactrim
how would you diagnose CMV syndrome after SOT?
CMV viremia + fever+ clinical supiscion
what are the most common findings of CMV disease after SOT?
hepatitis, colitis, pneumonitis
risk of CMV disease is highest in what CMV serologic status/ALA therapy?
D+/R- - high
ALA R+ - rejection
how long do you receive CMV prophylaxis after SOT?
universal approach: D=/R- or ALA for rejection:
- 3-6 months post transplant
- at least 1 month post - ALA for rejection
when does CMV disease occur post SOT?
typically occurs 1-3 months post transplant
How long do you treat CMV disease?
2-3 weeks, until viremia clears
when do you suspect ganciclovir resistance CMV disease after SOT?
Suspect resistance if prolonged (> 6 weeks)
ganciclovir exposure AND:
• No reduction in viral load after 14 days of treatment
• No clinical improvement after 14 days of treatment
how would you manage suspected ganciclovir resistance?
- Reduce immunosuppression
- • Switch to foscarnet ( CMV hyperimmune globulin)
what mutations are associated with CMV resistance?
- UL97 CMV Phosphotransferase gene mutations (most common)- Imply ganciclovir resistance
- UL54 CMV DNA Polymerase gene mutations- May confer resistance to ganciclovir, foscarnet, & cidofovir
what is EBV post-transplant lymphoproliferative disorder (PTLD) and risk factors?
EBV transformed B -cells in the recipient.
RIsk factors include
- primary EBV infection (D+/R-),
- ALA therapy,
- organ transplantation (Intestine>lung>heart>liver>kidney)
- Febrile mononucleosis with lymphadenopathy
What ist he treatment for EBV PTLD?
- reduce immunosuppression
- Rituximab (anti-CD 20 MAB)
- antivirals - not effective
- little effect on latently infected lymphocytes
what is the treatment of toxoplasmosis?
sulfadiazine-pyrimethamine-leucovorin
how is toxoplasmosis acquired and what are the risk factors in SOT?
- • Acquired from donor, reactivation, blood transfusion or ingestion of
- contaminated food or water
- • Donor seropositive/Recipient seronegative at high risk
- • HEART > LIVER > KIDNEY TRANSPLANT
how would you diagnose toxoplasmosis?
DIAGNOSIS:
- • PCR
- • Giemsa smear of BAL
- • Brain aspirate for tachyzoites
- • Immunoperoxidase stain of endocardial biopsy or other tissue
what are the “expected” donor-derved infections?
Expected = known before tx or for which there are
recognized standard prevention guidelines
- • Cytomegalovirus (CMV)
- • Epstein–Barr virus (EBV)
- • Toxoplasmosis
what are the “unexpected” donor-derived infections?
- • Lymphocytic choriomeningitis virus (LCMV)- • Hamsters and rodents
- • Rabies virus - bats
- • Chagas’ Disease (Trypanosoma cruzi) - • Reduviid bug (Latin America)
- • HIV, HCV, HBV, West Nile Virus (WNV)
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipeint FOR LCMV?
Encephalitis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipeint FOR rabies?
encephalitis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR toxoplasmosis?
- diffuse pneumonia myocarditis
- retinitis
- encephalitis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR WNV?
- meningitis
- encephalitis
- poliomyelitis-like flaccid paralysis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR chagas disease?
- Fever
- myocarditis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR acanthamoeba?
- skin lesion
- encephalitis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR balamuthia mandrillaris?
encephalitis
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR visceral leishmaniasis?
pancytopenia
hepatosplenomegaly
TYPICAL PRESENTATIONS OF UNEXPECTED
DONOR DERIVED INFECTIONS in recipient FOR malaria?
fever
what are the vaccine recommendations pre - SOT?
Hepatitis A, Hepatitis B, Flu, TDaP,
Pneumococcal & Varicella vaccines
what vaccinations are recommended post - SOT?
- •Pneumococcal
- •Tetanus-diphtheria toxoid
- •Inactivated Influenza
which vaccines are not recommended after SOT?
live virus vaccines
- Measles Mumps Rubella
- •Varicella
- •Inhaled influenza
- •Oral polio
- •Yellow fever
- •BCG
- •Small pox
- •Salmonella typhi (oral)
SOT travel risk location for babesia microti?
Northeast & Upper Midwest U.S.
SOT travel risk location for malaria?
the tropics
SOT travel risk location for visceral leishmaniasis?
spain and Mediterranean basin