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Multisystems > Micro- Infections in Recipients of Hematopoeitic Cell Transplantation > Flashcards

Micro- Infections in Recipients of Hematopoeitic Cell Transplantation Flashcards

1
Q

What is a conditioning regimen for hematopoeitic stem cell transplantation?

A

It is what prepares the recipient for stem cell transplantation.

  1. chemo
  2. radiation
  3. monoclonal antibodies
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2
Q

What is GVHD?

A

when cells from a donated stem cell graft attack the normal tissue in the transplant patient

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3
Q

What is myeloablative chemotherapy?

A

high dose chemo that kills cells in the bone marrow including:

  1. cancer cells
  2. normal blood-forming cells
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4
Q

What value is given to “severe neutropenia”?

A

an absolute neutrophil count below 500/mm3

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5
Q

What 7 factors affect the development of infection in HCT?

A
  1. underlying disease process
  2. conditioning regimen
  3. autologous v. allogeneic donor source; peripheral stem cell v. umbilical cord blood
  4. presence of GVHD
  5. pre-transplant exposure history
  6. time period after transplantation [intensity of immunosuppression]
  7. prophylactic measures
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6
Q

What 5 groups of people is HCT an option for?

Of these 5 HCT eligible groups, which have the highest risk of infection?

A
  1. malignancies
  2. solid tumors
  3. autoimmune diseases [limited number]
  4. severe immunodeficiencies
  5. bone marrow failure

Immunodeficiency > leukemia/lymphoma/chronic granulomatous disease > solid tumors

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7
Q

What are the 5 types of HCT transplant?

A
  1. umbilical cord blood [UCB]
  2. peripheral blood stem cell transplant [PBSC]
  3. autologous -previously harvested from the recipient
  4. allogeneic - from a donor [related or matched-unrelated]
  5. syngeneic - from an identical twin
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8
Q

What risk of infection is associated with an UBC HCT?

A
  1. prolonged neutropenia [low dose stem cells]
    - bacterial and fungal infections
  2. lack of antigen-specific memory T cells
    - viral and opportunistic infections
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9
Q

What is the risk of infection with PBSC HCT?

A
  1. shorter neutropenia than UCB

2. more chronic GVHD

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10
Q

When getting allogeneic HCT, what does matching refer to?
What problems are associated with higher degrees of mismatch?
What 3 infections specifically are allogeneic HCT recipients at increased risk for?

A

Matching = HLA matching between donor and recipient

more mismatch –> more immunosuppression required so the transplant doesn’t reject–> delayed immune reconstitution and prolonged engraftment which:
1. increases risk of GVHD
2, increases risk of infection with T-cell immunodeficiency
-PCP
- CMV
-EBV post-transplant proliferative disorder

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11
Q

What are the 3 reasons to give conditioning regimens [immunosuppressive and chemo +/- radiation]?

A
  1. eradicate patient disease [malignancy, abnormal cells]
  2. make space in the marrow for transplant
  3. prevent rejection of new stem cells [by killing old immune cells]
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12
Q

What are the 2 forms of conditioning regimens?

A
  1. myeloablative

2. reduced intensity

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13
Q

Myeloablative regimens lead to most infections ________ but a similar risk of infections ______________ due to presence of GVHD.

A

most infections early after transplantation but similar risk late after transplantation

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14
Q

During the conditioning regimen, what does total body irradiation cause?

A

mucositis which is bacterial translocation across the gut wall

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15
Q

What is the recovery time of the following cells after HCT?

  1. B cells
  2. CD4 T cells
  3. CD8 T cells
  4. monocytes
  5. NK cells
A
  1. months to years with abnormal IgG and IgA production for 1-2 years [lower Ab response to vaccinations]
  2. 1-3 months
  3. 2-3 months
  4. one month, but impaired function for a year
  5. recover quickly
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16
Q

GVHD is when the donor T cells attack the recipients cells [immune, skin, liver, intestinal tract].
What percent of patients with allogeneic HCT will experience this?

A

40-80%

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17
Q

What are the 5 ways GVHD predispose to infection?

A
  1. attack GI which leads to mucositis–> bacterial translocation across the gut
  2. alterations of humoral/cellular immunity
  3. functional hyposplenism and poor response to vaccines
    - pneumococcal
    - fungal
    - CMV reactivation
  4. prophylaxis for GVHD is immunosuppression [cylosporine, methotrexate, steroids, MMF, tacrolimus] for a year
  5. acute GVHD is treated with corticosteroids and immunosuppression
    - fungal
    - viral reactivation
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18
Q

What 9 tests are routinely done to test pre-transplant exposure history?
What protection will prior immunization provide post-transplant?

A
  1. CMV
  2. HSV
  3. VZV
  4. EBV
  5. HIV1/2
  6. T. gondii
  7. Hep B
  8. Hep C
  9. TB PPD or Quantiferon

Prior immunization provides LIMITED protection post-transplant

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19
Q

What are the 3 risk-periods after transplantation based on differential immune recovery that predispose to certain infections?

A
  1. Pre-engraftment = immediately post transplant until day 20-40
  2. Early post-engraftment = until day 100
  3. Late post -engraftment = after day 100
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20
Q

What type of infection predominates pre-engraftment stage?

A

Pre-engraftment stage is characterized by:

  1. neutropenia
  2. lymphopenia
  3. mucositis

Therefore, bacterial infections predominate

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21
Q

What are the 2 major causes of bacterial infection during the pre-engraftment stage?
Which bacteria predominate?

A
  1. Central Venous Catheter for chemo, blood transfusion, stem cell infusion leads to bacteremia with:
    - skin flora
    - gram positives such as coag. neg staph [epidermitis]
  2. Mucositis
    - gram negative enteric bacteria [enterobacteria, pseudomonas]
    - gram positive [viridians strep or enterococci]
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22
Q

What is prophylactic treatment for the pre-engraftment stage after HCT?
When should treatment be given until?

A

Fluoroquinolones are given when absolute neutrophils are below 500.
Give them until neutrophils recover

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23
Q

In addition to bacterial infections from mucositis and central line bacteremia, what other 2 infections are likely to occur during the pre-engraftment period?

A
  1. reactivation of HSV [80% of patients]

2. cadidemia and early aspergillosis [rarely]

24
Q

What is prophylaxis for reactivation of HSV during pre-engraftment phase?

A

acyclovir/valacyclovir

25
Q

Candidemia and early aspergillosis are RARE [5%] infections that occur during pre-engraftment after HCT.
What 2 things increase the risk?
What is prophylaxis?

A

Risk is increased by:

  1. prolonged neutropenia PRIOR to transplant
  2. delayed engraftment

Prophylaxis: fluconazole

26
Q

Describe what part of the immune system is recovering during engraftment stage.
What type of HCT has the highest risk of infection?

A

Engraftment is until day 100 after HCT.
It occurs after neutrophil recovery.
During this stage, B and T lymphocyte functional recovery occurs.

Allogeneic transplant is at highest risk for infection because they have to be the most immunosuppressed leading to increased risk of GVHD and CMV reactivation.

27
Q

What specific infections are people in the engraftment stage most at risk for?

A
  1. bacterial
    - GVHD leading to mucositis and enteric G-
    - CVC leading to coagulase neg G+ staph, enterococci
  2. CMV reactivation
  3. late onset fungal or aspergillosis
    - GVHD, CMV infection
  4. PCP
28
Q

What drug prophylaxis is given for aspergillosis/fungal infection and PCP during engraftment stage?

A

Fungal = voriconazole, posaconazole

PCP = TMP-SMX

29
Q

When does late post-engraftment stage occur?
What delays full immune recovery?
What infections occur during this stage as a result of the delayed recovery?

A

Day 100 until full immune recovery [18-36 months]
cGVHD delays immune recovery because you must use immunosuppression leading to abnormal lymphocytes/macrophages and abnormal Ab function.

  1. Respiratory infection predominates
    - encapsulated [h. flu, S. pneumo]
    - viruses
  2. Filamentous bacteria like Nocardia
  3. VZV, CMV
  4. aspergillosis and other mold infections
30
Q

Do gram positives or gram negatives cause the majority of bacteremias after HCT?
What are the risk factors?

A 
G+
Risks:
1. mucositis
2. GVHD
3. indwelling CVC
4. prolonged or severe neutropenia
31
Q

What G+ bacteria are most commonly associated with the following:

  1. bloodstream infections esp with CVC
  2. poor dentition, mucositis, HSV-oral ulcers
  3. catheter-related bacteremia in neutropenic patients
A
  1. coagulase negative staph
  2. S. pyogenes [GABHS], strep mitis, enterococcus
  3. MRSA
32
Q

What G- cause the most problems in neutropenic patients with HCT?
What is prophylaxis?
Which 3 G- have developed drug-resistance?
What are the risk factors for infection with these G-?

A
  1. Enterobacteriaciae and non-lactose fermentors
  2. prophylaxis = fluoroquinolones
  3. pseudomonas, acinetobacter, stenotrophomonas
  4. mucositis, GVHD, neutropenia, CVC
33
Q

What is likely to lead to infection by encapsulated bacteria?
Which bacteria are most common?
What is prevention for this?

A

cGVHD–> functional asplenia leading to infection by:

  1. strep pneumo
  2. haemophilus influenza
  3. nisseria meningitidis

Prevention: pneumococcal vaccination, penicillin, macrolides, fluoroquinolones

34
Q

What diseases can rare legionella infections cause in patients after HCT?
How is diagnosis made?

A
  1. Pneumonia, pulmonary nodules
  2. legionella monocytogenes –> meningitis, bacteremia

Diagnosis is with direct fluorescence Ab, but it can lead to false neg because it doesn’t have all serotypes

35
Q

What disease presentation is associated with Nocardia in patients after HCT?
What is prophylaxis?
What is treatment?

A
  1. pneumonia, pulmonary nodules
  2. brain abscesses

Prophylaxis: TMP-SMX

Treatment: surgical debridement and antibiotics [sulfonamide]

36
Q

What are the 3 modes of acquiring rapidly growing mycobacterial infections post-HCT?

What 2 techniques can be used for diagnosis?

A
  1. CVC exit site wound
  2. bacteremia
  3. pneumonia

Diagnose with:

  1. AFB culture
  2. mycobacterial DNA probes
37
Q

What is prophylaxis for TB?

How long is treatment?

A

Prophylaxis: isoniazid, pyridoxine
Treatment: 6 to 12 months depending on species and site/severity of infection

38
Q

What percent of patients have reactivation of HSV1/2 after HCT?
What does it cause?
How is diagnosis made?
What is prophylaxis?

A

80%
Causes: oropharyngeal, esophageal, perianal ulcers

Dx: DFA, PCR, culture

Prophylaxis: acyclovir

39
Q

Reactivation of CMV depends on the serocompatability of the donor and recipient. Which combo has the highest rate of reactivation?

A

D-/R+ > D+/R+&raquo_space; D+R->D-R-

40
Q

What are the 2 main risk factors for CMV reactivation post-HCT?

A
  1. GVHD

2. lymphopenia

41
Q

What diseases are caused by CMV post -HCT?

What does it also predispose to?

A

CMV predisposes to other bacterial/fungal infections.

It presents with :

  1. pneumonitis [different from HIV]
  2. enteritis
  3. bone marrow suppression
  4. retinitis [rare. but most common in HIV]
42
Q

How is CMV diagnosed?
What is prevention?
What is treatment?

A

Dx: CMV pp65 leukocyte antigen assay [cannot be performed with neutropenia], PCR

Prevention:
1. if seronegative–> CMV safe blood products [leukoreduced]

Tx: ganciclovir/valanciclovir with CMV Ig

43
Q

What are the 5 main risk factors for a EBV reactivation?

A
  1. GVHD
  2. treated with anti-thymocyte globulin
  3. given T cell depleted graft
  4. mismatched transplant recipient
  5. UCB
44
Q

What type of transplant predisposes to HHV6?
What is the presentation?
How is it diagnosed?
Treatment?

A
  1. UCB
  2. most cases are asymptomatic but can present with:
    - meningoencephalitis
    - interstitial pneumonitis
    - bone marrow suppression
  3. PCR
  4. ganciclovir or foscarnet
45
Q

What are the risk factors for adenovirus post HCT?
What is clinical presentation?
What is dx? tx?

A
  1. GVHD, lymphopenia, recipient of UCB or unrelated
  2. hemorrhagic cystitis, pneumonitis, enteritis, hepatitis, nephritis
  3. Dx: PCR, viral culture, DFA
  4. Tx: no effective therapy
46
Q

What viral family is BK virus?
How does an infection present?
Dx? Tx?

A

Polyomavirus [same as JC]
It causes hemorrhagic cystitis, but NOT BK-induced nephropathy like with renal transplants

Dx: PCR

Tx: reduce immunosuppression, cidofovir

47
Q

When after HCT are infections by respiratory viruses most common?
What is the seasonal preference?
How does clinical syndrome progress? Why?

What are 2 techniques to prevent this?

A

Within the first 3 months esp in the winter [except parainfluenza which is year round]

URI–> pneumonia–>respiratory failure and death because of lymphopenia

Prevention:

  1. proper hand hygiene and covering coughs/sneezes
  2. vaccination of family and close contacts
48
Q

What drugs used as prophylaxis have drastically decreased the rate of candida and aspergillosis post-HCT?
What is the drawback of these drugs as prophylaxis?

A

fluconazole/voriconazole

drawback: increases rise of non-aspergillus filamentous molds

49
Q

What is the clinical presentation of candida infection post-HCT?
What are the 3 major risk factors?
What is Dx?

A

Hepatosplenic candidiasis with multiple liver and spleen microabscesses.

Risks:

  1. neutropenia
  2. broad spectrum antibiotics and steroids allow for overgrowth
  3. CVC, GVHD, mucositis

Dx:
- culture, biopsy w/ histology, b-d-glucan assay

50
Q

Describe how aspergillus causes infection post HCT. What time frame?

A

Aspergillus spores are inhaled in the respiratory tract–>pulmonary and sinus infections [fungal ball] –> dissemination–> skin nodules/brain abscesses

Peak 1 at 2-3 wks
Peak 2 at 3-4 months
Peak 3 late during cGVHD

51
Q

What are the risk factors for aspergillosis?

A
  1. older patient
  2. construction near hospital
  3. lymphopenia
  4. CMV, respiratory viruses
  5. mult. myeloma
52
Q

What is treatment for aspergillosis?

A

Amphotericin

or

voriconazole +/- echinocandin

53
Q

What increases the risk of non-aspergillus mold infections?

A

empiric fluconazole/voriconazole prophylaxis in HCT

54
Q

What does PCP cause?

Dx? Tx?

A

Pneumonia
Dx: DFA
prophylaxis and Tx: TMP-SMX

55
Q

What is the most common parasite infection post HCT [although only 2-7% get it]?
When is the highest risk period?
Dx? Tx?

A

T. gondii mostly due to reactivation disease

Highest risk: 2-8wks

Dx: tissue culture, PCR

Tx: TMP-SMX

Multisystems (29 decks)

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