Typically, these regimens are tailored to these complex patients and guidelines serve as a starting point. Practitioners must consider current meds, immunosuppression, and individual patient risks. These practices also vary by site and individual practitioner.
Kedia, S., Acharya, P.S., Mohammad, F., Nguyen, H., Asti, D., Mehta, S., Pant, M., & Mobarakai, N. (2013). Infectious Complications of Hematopoietic Stem Cell Transplantation. Journal of Stem Cell Research & Therapy, 2013.
- The single most important risk factor for infection following chemotherapy is neutropenia.
- Many early gram + infections are complications from therapy since patients can’t clear transient bacteria so PICC lines and catheters become more problematic.
- If patients have anticipated prolonged and profound neutropenia ( (i.e., absolute neutrophil count [ANC] <100 cells/mm3 for >7 days – usually does not include solid-transplant recipients), three guidelines (National Comprehensive Cancer Network® (NCCN®), Infectious Diseases Society of America (IDSA), and the American Society for Blood and Marrow) all recommend levofloxacin for broad-spectrum prophylaxis.
- Patients who present with neutropenic fever should receive an anti-pseudomonal B-lactam, since Pseudomonas is not regularly covered by prophylaxis.
- Usually Zosyn or cefepime monotherapy, but meropenem monotherapy can be used if concerns for ESBL.
- If neutropenic enterocolitis, a.k.a. typhlitis, is suspected may add metronidazole.
- https://twitter.com/1min_idconsult/status/1589685626299121665
Immunosuppression and Cancer/Transplants
- Most transplant patients are on corticosteroids, and risk of immunosuppression increases with dose and duration of corticosteroids
- Corticosteroids blunt fever and signs of infection and cause lymphopenia (predominantly T-cell)
- Some cancers are associated with immunodeficiencies of their own (leukemia)
- Purine analogs (i.e., fludarabine) are Lymphotoxic, especially to CD4+ lymphocytes
- Tacrolimus/cyclosporine causes depressed T-cell response
- Mycophenolate causes lymphopenia, depressed B-cell response
- Ibrutinib, acalabrutinib causes Depressed B-cell response
- Rituximab, ocrelizumab, obinutuzumab causes B-cell apoptosis
- Alemtuzumab causes profound lymphopenia
- Antithymocyte causes globulin profound T-cell lymphopenia
- Conventional chemotherapy causes significant leukopenia
Molds and Yeast
- Most antifungals cause QT prolongation and have CYP effects.
- Almost everyone gets yeast prophylaxis, but mold becomes a higher consideration in patients receiving more immunosuppressive drugs
- Graft-versus-host disease (GVHD) is a systemic disorder that occurs when a donor’s immune cells attack a recipient’s body cells after a transplant. “Graft” refers to the transplanted tissue, and “host” refers to the recipient’s tissues. These patients will usually need mold prophylaxis too (specifically against aspergillosis). Posaconazola is firt line.
- Acute myeloid leukemia patients need posaconazole for aspergillosis prophylactic too.
- Some patients will need Trimethoprim-sulfamethoxazole or other Pneumocystis jirovecii prophylaxis while on immunosuppression. Allogeneic HCT and Acute lymphoblastic leukemia patients are two such groups.
- Mucur is a rare, but devastating invasive mold that crosses tissue planes and causes rapid destruction of tissue. They’re usually less susceptible to antifungals. Usually only found in immunocompromised patients. Usually found in the sinus cavity. The mainstay of therapy is amphotericin B. The most important treatment is surgical debridement and removing the tissue.
Aspergilliosis
- Galactomannan is a very specific fungal test that looks for a component of Aspergillus cell wall. If a patient is galactomannan positive, they have aspergillus, but it’s not recommended as a screening lab.
- Aspergillus is usually found in the pulmonary cavity.
- -β-D-glucan is another fungal marker, but it’s for all fungi and some yeast, not just aspergillosis.
- IDSA recommends voriconazole as the first-line agent for aspergillosis, but amphotericin B is often used clinically.
Viral Prophylaxis
- Consider prophylaxis for HSV and VZV in intermediate-risk groups (e.g., lymphoma, autologous HCT, multiple myeloma, chronic lymphocytic leukemia, purine analog therapy) with acyclovir, famciclovir or valacyclovir.
- It’s assumed that everyone is at risk of HSV and VZV and patients should receive prophylaxis.
- HSV and therefore will receive prophylaxis (same assumption is made for VZV)
- CMV should be monitored in CMV-seropositive allogeneic HCT recipients.
- All CMV seropositive (i.e., donor and/or recipient with evidence of past CMV infection) allogeneic HCT recipients should receive anti-CMV prophylaxis with letermovir through 100 days post-HCT
- Recommendations are slightly different for solid organ transplant patients. Still want to prophylaxis against HSV. Those at high risk for CMV should receive prophylaxis.
- For treatment of CMV: foscarnet or ganciclovir: ganciclovir causes myelosuppression, foscarnet causes renal toxicity and electrolyte abnormalities. Practitioners must weigh the pros and cons when choosing an agent.
Vaccines in Immunocompromised Patients
Cancer, radiation therapy, chemotherapy, and immunosuppressive drugs used during and after a transplant can destroy many or all of a patient’s antibody-producing cells, which provide immunity. This means their immunity for many vaccine-preventable diseases will essentially reset. Vaccination should ideally precede any planned cancer treatment by 2-4 weeks. However, nonlive vaccines can be administered during or after chemotherapy or immunotherapy, hormonal treatment, radiation, or surgery.
Complete revaccination starting 6-12 months after hematopoietic stem-cell transplant should be offered in order to restore vaccine-induced immunity. Live and live attenuated vaccines should be delayed for at least 2 years and only given in the absence of active GVHD or immunosuppression. COVID-19, influenza, and pneumococcal vaccines can be administered as early as 3 months after transplant.
Adults with hematopoietic malignancies receiving CAR-T therapy directed against B-cell antigens (CD19, BCMA) should receive influenza and COVID-19 vaccine no sooner than 3 months after the completion of therapy. Nonlive vaccines should be administered no sooner than 6 months after completion of therapy
Adults who receive B-cell–depleting therapy should be revaccinated for COVID-19 only, no sooner than 6 months after completion of treatment
Long-term survivors of hematologic malignancy with or without active disease or those who have long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines even though the response may be attenuated
Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination
Note. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe
Einarsson J, Wilkinson AN. Vaccination considerations for patients receiving cancer therapy. Canadian Family Physician Medecin de Famille Canadien. 2022 Oct;68(10):751-752. DOI: 10.46747/cfp.6810751. PMID: 36241417; PMCID: PMC9833152. **Note: Canadian Vaccines schedules and products aren’t the same as US ones, but the live vs non-live is the same).
The AASCO Guidelines were updated in 2024 and are the definitive guidelines. These tables are from those guidelines.
| Vaccine | Recommended Age | Schedule |
|---|---|---|
| Influenza | All ages | Annually |
| RSV | 60 years and older | Once |
| COVID-19 | All ages | As per the latest CDC schedule for immunocompromised |
| Tdap or Td | 19 years and older | One dose of Tdap, followed by Td or Tdap booster every 10 years |
| Hepatitis B | 19-59 years: eligible 60 years and older: immunize those with other risk factors | For adults 20 years and older, use high antigen (40 µg) and administer as a three-dose Recombivax HB series (0, 1, 6 months) or four-dose Engerix-B series (0, 1, 2, 6 months) |
| Recombinant zoster vaccine | 19 years and older | Two doses at least 4 weeks apart |
| Pneumococcal vaccine | 19 years and older | One dose PCV15 followed by PPSV23 8 weeks later OR One dose PCV20d |
| HPV | 19-26 years: eligible 27-45 years: shared decision making | Three doses, 0, 1–2, 6-months |
Table 3. Recommendations for Other Vaccines That May be Indicated for Adults With Cancer and Coexisting Health Conditions
| Vaccine | Type | Other Risk Factor | Recommendation |
|---|---|---|---|
| Haemophilus influenzae type b vaccination (Hib) | Nonlive | Anatomic asplenia | For elective splenectomy: one dose at least 14 days before splenectomy (preferred) |
| Functional asplenia | One dose if previously did not receive Hib | ||
| Hepatitis A vaccination | Nonlive | Chronic liver disease, HIV, MSM, homelessness, injection or noninjection drug use, occupational exposure, travel | Two-dose series HepA or three-dose series HepA-HepB |
| Meningococcal vaccination | Men ACWY (nonlive) | Anatomic or functional asplenia, complement component deficiency, complement inhibitor (eg, eculizumab, ravulizumab), Travel, Occupational, Military recruits, Residential living for college students | Two-dose series MenACWY-D Frequency: 8 weeks apart Revaccinate every 5 years if risk remains |
| Men B (nonlive) | Anatomic or functional asplenia (including sickle cell disease), persistent complement component deficiency, complement inhibitor (eg, eculizumab, ravulizumab) use, occupational (microbiologists), pregnancy, MSM outbreak setting | Two-dose primary series MenB-4C at least 1 month apart Or three-dose primary series MenB-FHbp at 0, 1-2, 6 months Revaccinate every 2-3 years if risk remains | |
| IPV | Nonlive | Travel Community risk (eg, wastewater detection of vDPV) | Single booster |
| MMR | Live | No evidence of immunity: HIV (CD4 >200 for 6 months), HCP, outbreak setting, travel | Contraindicated with cancer treatment and other immunocompromising conditions |
| Varicella | Live | Postexposure | Contraindicated with cancer treatment and other immunocompromising conditions |
| MVA (Monkeypox) | Live (replication-deficient) | Postexposure, Occupational exposure (laboratory worker), high risk | Safe to administer in persons with HIV or those on immunosuppressive therapies |
| Monkeypox and smallpox (ACAM2000) | Live | Contraindicated with cancer treatment and other immunocompromising conditions |
Vaccines in Asplenia
The spleen produces antibodies, so removing it or disabling it (as in sickel cell disease, chronic graft-vs host, celiac, autoimmune disease, etc) weakens the immune system. Functionally or anatomically asplenic patients should be vaccinated to decrease the risk of sepsis due to organisms such as Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis. Guidelines are based on CDC recommendations. For additional information, see https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html.
Asplenic patients should receive 4 vaccines initially, followed by repeat doses as specified. Vaccines should be given at least 14 days before splenectomy, if possible. Doses given during the 2 weeks (14 days) before surgery can be counted as valid. If the doses cannot be given before the splenectomy, they should be given at least 14 days after surgery or before discharge, whichever is earliest.
- Haemophilus b conjugate (Hib) vaccine (ACTHIB®) IM once if they have not previously received Hib vaccine
- Pneumococcal conjugate 13-valent (PCV13) vaccine (PREVNAR 13®) IM once
- 2nd dose: Pneumococcal polysaccharide 23-valent (PPSV23) vaccine (PNEUMOVAX 23®) SQ/IM once given ≥ 8 weeks later, then 3rd dose as PPSV23 > 5 years later.
- Note: The above is valid for those who have not received any pneumococcal vaccines previously, or those with unknown vaccination history. If already received prior doses of PPSV23: give PCV13 at least 1 year after last PPSV23 dose.
- Meningococcal conjugate vaccine (MenACWY-CRM, MENVEO®) IM (repeat in ≥ 8 weeks, then every 5 years thereafter)
- Meningococcal serogroup B vaccine (MenB, BEXSERO®) IM (repeat in ≥ 4 weeks).