PHARM 444: myelosuppression, febrile neutropenia & cancer related infections

what is Myelosuppression?

a condition where bone marrow activity is reduced, leading to fewer red blood cells, white blood cells, and platelets.

Myelosuppression is a common side effect and ________ toxicity of chemotherapy (cytotoxic drugs).

dose limiting

________ is a term used for SEVERE myelosuppression that is difficult to recover from without a stem cell infusion

Myeloablation

neutrophil

a) lifespan

b) purpose

c) implications if low in number

a) 8 hrs

b) kill bacteria using enzyme rich granules & endocytosis or phagocytosis

c) increased risk of severe infections

erythrocytes

a) lifespan

b) purpose

c) implications if low in number

a) 120 days

b) cary O2 to tissues

c) fatigue, SOB

thrombocytes (platelets)

a) lifespan

b) purpose

c) implications if low in number

a) 5-10 days

b) essential for normal blood clotting

c) bleeding & bruising

depending on the antineoplastic regimen, treatment delay or dosing may be adjusted if platelets are ___________

if platelets are critically low ______ patient may be given a platelet transfusion

• < 50-100 X 109/L

• <10 X 109/L

Thrombocytopenia pt education

- easier bruising

- use a soft toothbrush

- blow nose gently

- avoid constipation & straining on the toilet

- avoid use of medications that increase risk of bleeding (i.e. NSAIDs or ASA)

- medical attention is required in uncontrolled bleeding

Neutrophil count will begin to fall occurs approximately___days after chemo

5-12

When neutrophils are at their lowest number in the circulating blood this is referred to as the ______

"NADIR"

where do 80% of infections in cancer pts come from?

pts own flora

is gram negative or positive more common in Bacteremias?

gram positive

does gram positive or negative bacteremias have a higher mortality?

gram negative

Neutropenic patients with bacteremia might exhibit NO signs or symptoms

of infection other than ....

FEVER

what is considered a fever?

- temperature of 38.3˙C or greater OR

- sustained temperature of ≥38.0˙C lasting more than 1 hour.

what does an absolute neutrophil count include (2)

sum of neutrophils + bands (immature neutrophils)

what is Febrile Neutropenia defined as

- Single oral temperature ≥38.3˙C OR sustained oral temperature ≥38.0˙C for more than 1 hour

- ANC < 0.5 X 109/L or expected to fall to < 0.5 X 109/L within the next 48 hours

Features of patients with HIGH RISK of complications or death

- prolonged (> 7 days) or profound (< 0.1 x 109/L) neutropenia

- hemodynamically unstable = Hypotension, neurologic changes, new onset abdominal symptoms, high fever

- significant medical/ comorbid conditions

- worsening infection

- difficult access to urgent care

Features of patients with LOW RISK of complications or death

- no focal findings of infection

- hemodynamically * clinically stable

- brief neutropenic period (< 7 days)

- no or few comorbidities

- easy access to urget care & able to take po meds

in the MASCC risk assessment what score is needed to be considered

a) Low risk

b) High risk

a) ≥ 21

b) < 21

what empiric broad spectrum antibiotics should be initiated in febrile neutropenia

Monotherapy with anti-pseudomonal beta lactam such as:

- Piperacillin+Tazobactam

- Cefepime

- Carbapenem (meropenem or imipenem+cilastatin)

when might we considered adding on additional gram (+) coverage with _______ ?

VANCOMYCIN >>>> IF risk of MRSA:

- Catheter related infections

- Skin or Soft Tissue Infections (SSTI)

- Pneumonia

- Hemodynamic Instability

- Known colonization with MRSA

what is a good oral antibiotic option for treating febrile neutropenia if pt is low risk; able to be discharged and continued therapy at home?

Ciprofloxacin + Amoxicillin/Clavulanate

** avoid Ciprofloxacin if receiving quinolone prophylaxis

what to do if cultures are negative and no source of fever identified:

a) Fever persists

b) fever resolves & clinically well

a) continue antibacterials until neutrophils ≥ 0.5 for 2 consecutive days and trending up

b) discontinue antibacterials after 72 hours (regardless of neutrophil count)

what are good pt education examples to encourage infection prevention?

- Good hygiene

- skin protection (i.e. clean wounds, sun protection, lotions)

- reduce exposures to illness

- good mouth care

- care of medical devices (i.e. IV line, catheter care etc.)

what should you tell pts about fever monitoring?

- if experiencing a fever should seek urgent assessment

- if fever occurs outside clinic hours go to emergency department

- be aware antipyretics (acetaminophen) can mask a fever

- avoid acetaminophen if possible & ibuprofen/ASA due to increased bleed risk

what 2 thermometers are good choices for measuring fever

1. tympanic

2. oral

*** AVOID rectal***

Granulocyte-Colony Stimulating Factors (G-CSF)

hematopoietic growth factor -- Regulates production & function of neutrophils. Can also accelerate neutrophil recovery after chemotherapy

EX: Filgrastim or PEG-filgrastim

Filgrastim or PEG-filgrastim

a) PROS

b) CONS

a)

- Reduced risk of febrile neutropenia

- Reduction in infection related and all cause mortality

- Improved relative dose intensity of chemotherapy delivered

b)

- costly

- AE

- Subcutaneous administration

when is primary prophylaxis with Filgrastim or PEG-filgrastim indicated?

Prevention of FN starting with the first cycle of treatment and continuing through subsequent cycle

- generally when pts ≥20% risk of FN (high incidences with docetaxel for breast cancer)

when is secondary prophylaxis with Filgrastim or PEG-filgrastim indicated?

• subsequent cycles of chemotherapy after an episode of FN

• pts who experienced a neutropenic complication from a previous cycle of chemotherapy AND

• Dose reduction or treatment delay may compromise important outcome (disease free or overall survival outcome)

Filgrastim regimen

daily starting 1-5 days post chemo and continue 3-7 days

Peg-filgrastim regimen

One single 6 mg injection administered 1-3 days post chemo

what is the common adverse effect associated with G-CSF? how can it be managed?

bone pain >>> managed with acetaminophen

what is typically given as a FN Antimicrobial Prophylaxis of Infections

Quinolone (Ciprofloxacin or Levofloxacin)

what is a risk to using FN Antimicrobial Prophylaxis

increased resistance & C.difficle colitis

when should cancer pts receive influenza vaccination if any?

- Immunosuppressed pts avoid intranasal (live) influenza vaccine

- Allow patient opportunity for best antibody response, administer 2 weeks before chemo starts. If already receiving chemotherapy, administer between cycles once blood counts have recovered.

Which cancer patients should NOT receive flu vaccine?

- Rituximab or other B-cell depleting antibodies should have most immunizations postponed until at least 6 months after the last dose of rituximab

- Patients on high dose systemic steroids (prednisone ≥ 20mg/day for ≥14 days) should wait 4 weeks after discontinuation

how long might someone who has under went a stem cell transplant wait to get influenza vaccine?

Generally administered six months post transplant

how long might someone who has under went a stem cell transplant wait to get non-live vaccines?

encouraged to start immunization as per public health guidelines at 6 months after transplant

how long might someone who has under went a stem cell transplant wait to get live vaccines?

Contraindicated for at least 2 years

what are the guidelines on COVID-19 vaccinations and pts receiving cancer treatment?

Should be vaccinated for COVID-19

** Only one EXCEPTION - stem cell transplant in the past 4 months

what prophylaxis might be considered for the following opportunistic infections? And what populations are at risk?

a) PJP (pneumocystis jirovecii pneumonia)

b) HSV/VZV (Herpes Simplex/Varicella Zoster)

c) Yeast, Fungal, Mold Infections

d) Hepatitis B Reactivation

a) At risk = bone marrow transplant, chronic corticosteroids, highly immunosuppressive agents (fludarabine, alemtuzumab)

PROPHYLAXIS: Septra or Dapsone in sulfa allergic

b) At risk = bortezomib, bone marrow transplant

PROPHYLAXIS: Acyclovir or Valacyclovir

c) At risk = bone marrow transplant, AML

PROPHYLAXIS: Fluconazole (Candida), Voriconazole or Posaconazole (Aspergillus)

d) At risk = HPV surface antigen positive and receiving rituximab

PROPHYLAXIS: Lamivudine or Entecavir