Neutropenia, SOT, HSCT Flashcards
Intensity of therapeutic immunosuppression
Induction therapy - highest
Maintenance therapy - less, +/- GVHD Tx
Lymphocyte-depleting agents increase risk . . .
cytomegalovirus (CMV),
polyoma BK virus,
Pneumocystis species,
and other fungi.
EBV–associated posttransplant lymphoproliferative disease (PTLD)
higher risk in patients taking . . .
lymphocyte-depleting agents and
in those receiving sirolimus and tacrolimus
Timeline and risk for infection SOT
Early Period (<1 Month ): surgical site and other nosocomial infections, IFI, and site specific related to the transplanted organ
Middle Period (1-6 Months ): viruses, opportunistic pathogens, IFI, Tb
Late Period (>6 Months )a: community accuired infections (more severe presentations) + infections associated to middle period
Immune risks for infection BMT timeline . . .
– Neutropenia (early)
- Bacterial infections
- Fungal infections
– Impaired cellular and humoral immunity (late)
- Bacterial infections
- Fungal infections
- Viral infections
Approach for the boards SOT, BMT, neutropenia
– Patient’s age, disease, history impact risks after BMT
– What kind of BMT did the patient have?
– Is the patient early vs. late after BMT?
Type of BMT and timeline impacts immunity, drugs and exposures
Pulmonary Complications BMT
– Aspiration events with severe mucositis early after BMT
– Encapsulated sinopulmonary pathogens late after BMT
- Filamentous fungi early and late (A. fumigatus)
- Respiratory virus infection follows seasonal epidemiology
Adenovirus: reactivation and acute infection (particular issue with kids)
– HSV classically described with prior airway manipulation
Early non‐infectious lung injury
- Diffuse alveolar hemorrhage: Vasculitis, drug‐induced injury, cancer‐chemotherapy / thrombocytopenia
- Idiopathic pneumonia syndrome
Think Fusarium spp if . . .
Positive BCx and skin lesions (also PNA?)
DDx of Late pulmonary syndromes
– CMV disease
– Respiratory virus infections
– PCP
• Non‐infectious – Bronchiolitis obliterans syndromes
CMV Infection after BMT
– Highest risk group
- Reactivation: Highest risk group for viral disease: D‐ / R+
- Primary infection: D+ / R‐ or blood products (rare)
• Pneumonitis • Gastrointestinal disease • Encephalitis, retinitis less frequent
CMV Tx after BMT
– Pre‐emptive with ganciclovir driven by PCR
• Not prophylaxis (SOT) with ganciclovir;
– Induction therapy with maintenance GCV
– Resistance to GCV is rare (as opposed to SOT)
Pneumocystis Pneumonia Prophylaxis in BMT
– Bactrim
• Dapsone, atovaquone, aerosolized pentamidine
– Less effective, other infections occur**
Pneumonia + encephalitis + fever in patient w/o BACTRIM prophylaxis, THINK . . .
Toxoplasmosis
Bronchiolitis Obliterans
Chronic GVHD of lung; late s/p BMT
GVHD: Acute (early after HSCT)
– Fever
– Rash
– GI: hepatic, colon
GVHD: Chronic (later after HSCT)
– Skin changes (lichen planus, sceroderma)
– Hepatic (cholestatic)
– Ocular (keratoconjunctivitis)
– GI (oral, dysphagia)
– Pulmonary syndromes
Chronic diarrhea mimicking GVHD
Norovirus
Adenovirus Infection after BMT
- More common in children, high risk BMT
- Enteritis, cystitis, upper respiratory infection, pneumonia, encephalitis, hepatitis
DDx of Hemorrhagic Cystitis
- Conditioning related (early) – Cyclophosphamide
- BK virus (later)
- Adenovirus (later)
Selected DDx of Neurologic Syndromes
– HHV6*
– West nile virus
– JCV – PML (especially with T‐depleting Abs)
– Pulmonary + CNS lesions: • Invasive fungal infections • Nocardia • Toxoplasmosis
• carbapenems, cefepime, PRES*
HHV‐6 after BMT
Meningoencephalitis
ACV‐resistant. Treat with ganciclovir, foscarnet, cidofovir
Posterior reversible encephalopathy (PRES), associated with . . .
Calcineurin inhibitors: Cyclosporin*, tacrolimus
PLAY THE ODDS
- Patient completing valganciclovir prophylaxis 6 weeks prior presenting with fatigue, low grade fever and leukopenia • CMV Syndrome
- Donor died from skiing accident in fresh water lake in Florida and recipient presents 3 weeks post transplant with encephalitis • ACANTHAMOEBA
- Renal transplant recipient on valganciclovir prophylaxis presents with asymptomatic renal dysfunction • BK Virus
- Lung transplant recipient planted vegetable garden 2 weeks prior while on posaconazole prophylaxis and presents with productive cough and cavitary lung lesion • NOCARDIA
Listeria monocytogenes in SOT
• Bacteremia with or without meningitis
Nocardia in SOT
- Most often pulmonary nodules, CNS (15-20%), skin (15%), or bone (2-5%)
- Nocardia is Neurotropic; r/o asymptomatic brain abscess
Branching, Gram positive rods • Partially acid-fast by modified Kinyoun stain
• TMP-SMX considered drug of choice
CMV Syndrome
- CMV blood PCR postive and
- Fever and
- One or more of the following - Malaise, leukopenia, atypical lymphocytosis, thrombocytopenia, elevated hepatic enzymes
Greatest risk for CMV disease after SOT
D+/R-
and
ALA Therapy (R+)
CMV prophylaxis s/p SOT
Bottomline:
- D+/R- or ALA for rejection → Universal
- R+ → Universal or Preemptive
GI CMV disease after SOT
CMV disease of GI tract may not have detectable viremia; diagnosis often requires tissue biopsy
Viral load may continue to rise during first 2 wks of Rx
EBV - PTLD risk factors
- Primary EBV infection • (D+ / R-)
- Antilymphocytic antibody therapy
- Organ transplanted • (intestine > lung > heart > liver > kidney)
EBV - PTLD
- Clinical manifestation
- Diagnosis
- Tx
- Clinical manifestation: Febrile mono-like illness + lymphadenopathy • Solid tumors
- Diagnosis: biopsy
- Tx: Reduce Immunosuppression • Rituximab - anti-CD20 monoclonal antibody
BK virus nephropathy pearls
- Cause of nephropathy post renal transplant • Up to 15% of patients
- Manifests as unexplained renal dysfunction (as does rejection)
- Renal Bx - “Gold Standard” for diagnosis
- Blood PCR as indicator for biopsy
- Detection in Low PPV but High NPV
- Tx: Reduce immunosuppression
SOT: Toxoplasmosis Risk factors and Tx
• Acquired from donor, reactivation, blood transfusion or ingestion
• D+ / R-
- HEART > LIVER > KIDNEY TRANSPLANT
- TREATMENT: sulfadiazine-pyrimethamine-leucovorin
Selected Unexpected D+ derived infections in SOT
- Lymphocytic choriomeningitis virus (LCMV): Hamsters and rodents
- Rabies virus
- Chagas’ Disease (Trypanosoma cruzi)
- HIV, HCV, HBV, West Nile Virus (WNV)
- Remember the “Window” prior to development of antibodies
OTHER PEARLS FOR BOARDS… SOT
- If you’re thinking PCP but its not think TOXO
- Patient presenting atypically during first month post transplant think donor transmitted infection
- Remember drug interactions and syndromes • TTP and PRESS (RPLS) induced by calcineurin inhibitors • Sirolimus-induced pneumonitis
- Remember Strongyloides hyperinfection syndrome
- TB- Don’t miss a case!
- BK, CMV and EBV/PTLD – know how to diagnose and manage
Immune suppression drug associations
Rituximab (anti‐CD20)
Alemtuzimab (anti‐CD52)
BCR – ABL Tyrosine – kinase inhibitors – (ex. imatinib, dasatinib, nilotinib, more)
- Rituximab (anti‐CD20) • Hepatitis B reactivation, PML
- Alemtuzimab (anti-CD52): Herpes viruses (esp. CMV), fungal infections (PJP, Aspergillus)
- Imatinib, dasatinib, nilotinib, etc: • (VZV reactivation, Hep B reactivation).
- JAK/STAT inhibitors (ex. tofacitinib, ruxolitinib): VZV, CMV, PCP, M. Tb
Neutropenic “syndromes”
Viridans Streptococci
- Key points: neutropenia, mucositis, high‐dose cytosine arabinoside, fluoroquinolone
- Can present with fever, flushing, chills, stomatitis, pharyngitis • VGS shock syndrome
- Endocarditis unusual (<10%)
- S. mitis, S. oralis
- Typical patient‐ neutropenic, progressive sepsis
- Recognize holes in protection, specific syndromes
- – ARDS, rash, quinolones, mucositis ⇒ viridans Streptococci
- – Sepsis with β‐lactams ⇒ Stenotrophomonas, ESBL
- – Sepsis with carbepenems ⇒ KPC
- – Lung and skin lesions ⇒ P. aeruginosa, Fungi
- – Skin lesions, gram + ⇒ Corynebacterium jeikeium
- – Mucositis (upper, lower tract) ⇒ Fusobacterium spp., Clostridium spp., Stomatococcus mucilaginosis
Neutropenia and Skin Lesions
- Candidiasis – Small, tender papules
- Aspergillus – ulcerative, necrotic, minimal erythema
- Other filamentous fungi (Fusarium, P. boydii) – Multiple, erythematous, different stages
- P. aeruginosa – Ecthyma gangrenosum
Neutropenia and Fusarium
Invasive pulmonary disease with skin lesions
Neutropenic Enterocolitis
• Neutropenic enterocolitis (typhlitis) – Can be accompanied by bacteremia • Hint: mixed, anaerobic (C. septicum, C. tertium, B. cereus)
Hepatosplenic Candidiasis
Fungi invaded by portal vasculature
• Presentation after engraftment: abdominal pain, increased LFTs (alk phosph), fever, leg / flank pain
Alemtuzumab
• Anti‐CD52 Ab (Campath)
- Reactivation of CMV is the most common infectious complication
- Other risks: PCP, IFI (T cell)
