Infection and vaccination: the immune defect starts before any treatment¶
12.1 How weakened is immunity in untreated CLL?¶
CLL weakens antibody defences even before any treatment, and infections are the commonest serious complication [E].
- Swedish guideline. About 25% of patients have low antibody levels (hypogammaglobulinaemia) at diagnosis, and the proportion rises with progression and treatment. Infection is a direct or contributing cause in 25–50% of CLL deaths (VP8.2 §16.4).
- Mayo Clinic, 1,485 newly diagnosed patients. 26% had low IgG at diagnosis. Among untreated patients with normal IgG, low IgG developed in 11% by 5 years and 23% by 10 years. Low IgG predicted earlier treatment (3.8 vs 7.4 years) but not worse overall survival in multivariable analysis (Parikh 2015, abstract only).
- Danish nationwide data, 2,905 patients. Before any treatment, 12% had had an infection at 1 year and 31% at 5 years. 54% had some immunoglobulin deficiency. Predictors included male sex, Binet B/C, low IgA and β2-microglobulin above 4 mg/L. These numbers should be checked against the paper (Andersen 2018).
- Swedish Cancer Registry, 2010–2021, treated and untreated patients. Half had at least one infection over a median of 4.8 years. Pneumonia was the commonest bacterial infection (21%) and shingles the commonest named viral one (3.5%) (Glimelius 2026, abstract only).
- Even MBL, the precursor state, is "characterized by immune impairment with sub-optimal response to vaccinations" (WHO-HAEM5).
12.2 Immunoglobulin replacement: for infections, not for a low number alone¶
The guidelines agree that a low IgG level is not enough on its own; there must also be significant infections [E].
| Source | When immunoglobulin replacement is indicated |
|---|---|
| EU regulator (EMA core SmPC) | "Severe or recurrent infections, ineffective antimicrobial treatment and either proven specific antibody failure … or serum IgG level of <4 g/L". Dose 0.2–0.4 g/kg every 3–4 weeks (EMA) |
| Sweden (VP8.2) | "Kan övervägas" (may be considered) with low IgG in combination with severe bacterial infections, repeated respiratory infections needing antibiotics and poor healing despite adequate antibiotics (the Swedish "och" leaves open whether all three must be present). Serious lung disease strengthens the case. Refers to the SLIPI guidelines (not read) and gives no numeric threshold |
| EHA 2026 | Only with recurrent symptomatic or active infections needing hospitalisation, plus laboratory-confirmed hypogammaglobulinaemia (II, B). Subcutaneous preparations give higher trough levels, fewer side effects and better quality of life |
Evidence. In a 1988 randomised trial, replacement cut bacterial infections (23 vs 42) (NEJM 1988). A meta-analysis found fewer major infections (RR 0.45) but no survival benefit (Raanani 2009).
12.3 Preventive antimicrobials depend on the treatment chosen¶
| Situation | Recommendation | Source |
|---|---|---|
| Watch-and-wait | Routine prophylaxis not recommended (IV, D). After shingles, (val)aciclovir "could be considered", alongside zoster vaccination | EHA 2026 |
| Venetoclax + anti-CD20, or bendamustine-rituximab (BR) | Aciclovir 400 mg ×2 or valaciclovir 250–500 mg ×2, continued 6 months after treatment ends | VP8.2 §16.2 |
| Any CLL treatment after a previous herpes infection such as shingles | Antiviral prophylaxis recommended | VP8.2 §16.2 |
| BR or idelalisib | Pneumocystis (PJP) prophylaxis with trimethoprim-sulfamethoxazole. Not listed for BTKi or VenO | VP8.2 §16.2 |
| Past hepatitis B (HBsAg-positive, or HBsAg-negative and anti-HBc-positive) when starting a BTKi or anti-CD20 drug | Consider entecavir or tenofovir, started 1 week before treatment; HBV-DNA every 3 months; continue 18 months after treatment ends | VP8.2 §16.2 |
| Hepatitis B screening | Mandatory before obinutuzumab or rituximab: at least HBsAg and anti-HBc. Active hepatitis B rules these drugs out. HBV status must also be established before acalabrutinib, zanubrutinib or ibrutinib. ASCO recommends three tests (HBsAg, anti-HBc, anti-HBs) before any systemic cancer therapy | Gazyvaro SmPC; Calquence SmPC; ASCO 2020 |
| Mould-active antifungals on BTKi | Not routine. Sweden's guideline has no antifungal section. The pirtobrutinib label says prophylaxis "should be considered" if risk is raised | ECIL 2019; Jaypirca SmPC |
12.4 Vaccinations for an adult with CLL in Skåne, autumn 2026¶
| Vaccine | Recommendation | Cost in Skåne | Notes |
|---|---|---|---|
| Influenza (inactivated) | Every year; people with blood cancer are a named risk group. National start 2 November 2026; Skåne's campaign "startar i november" (starts in November) | Free for risk groups | Relatives should also be vaccinated (VP8.2). The nasal live vaccine is used only for children aged 2–17 |
| COVID-19 (mainly Comirnaty) | One dose a year, preferably in autumn. Covers ages 18–49 with immunosuppression including blood cancers, ages 50–74 with blood cancers, and everyone aged 75 or over | Free for risk groups | Severely immunodeficient people may need extra doses timed around treatment. People with reduced immunity may not skip this season's dose after a recent infection |
| Pneumococcal | National risk-group programme; blood cancer is classed "mycket hög risk" (very high risk). FoHM: one dose of a conjugate vaccine covering at least 20 serotypes; Region Skåne gives one dose of PCV20 (Prevenar 20), not repeated | Free, at the vårdcentral | Conflicts with the national guideline; see 12.5 |
| Shingles (Shingrix, recombinant, not live) | FoHM recommends it for all adults with immunodeficiency from disease or drugs. Two doses, 2–6 months apart. Protection may be lower (60–90%) in severe immunodeficiency | Usually self-paid; see 12.6 | Best completed before any BTKi or anti-CD20 drug |
| RSV | FoHM: everyone aged 75 or over, and people aged 60 or over with severely reduced immunity. Need for a booster unknown | Region Skåne does not offer it; self-paid at private clinics (list price about 2,000 SEK per dose, per March 2026 slides) | [I] Relevant only for people aged 60 or older. EHA notes there is "less evidence" for RSV |
| TBE | Since May 2026, FoHM recommends it for immunocompromised people who live in or regularly visit TBE risk area 1 or 2, or a municipality bordering one. Area 1 in Skåne: Östra Göinge, Sjöbo, Höör, Klippan, Ystad, Kristianstad, Hässleholm. Area 2: Vellinge, Kävlinge, Hörby, Bromölla, Simrishamn. Malmö, Lund, Helsingborg, Landskrona, Trelleborg and Ängelholm are area 3 | Self-paid | VP8.2 (January 2026) still says the same indications as the general population apply; it predates this change |
| Hepatitis B | EHA recommends it during watch-and-wait (III, B). The Swedish CLL guideline is silent. FoHM recommends it for longer or repeated travel to Asia, Africa or South America | Not verified | Response falls from 28.1% before treatment to 3.8% on a BTKi, so vaccinate early |
| Diphtheria/tetanus | Adults: a booster every 20 years | — | — |
| Live vaccines (chickenpox, MMR, BCG, yellow fever, oral typhoid; Zostavax, now deregistered) | Contraindicated. After venetoclax or obinutuzumab, no live vaccines until B cells recover | — | Weigh any exception with an infectious-disease specialist |
Sources: FoHM autumn vaccinations; FoHM influenza; FoHM COVID-19; 1177 Skåne 2026/27; FoHM pneumococcal recommendations, 1 Sep 2026; 1177 Skåne pneumococcal; FoHM shingles; FoHM RSV; 1177 Skåne RSV; FoHM TBE and risk areas; FoHM diphtheria; VP8.2 §16.3; Smittskydd Skåne slides, 19 Mar 2026; Pleyer 2021.
Fees in Skåne (Region Skåne patient fees, archived copy) [E]:
- Vaccination that "ingår i vård och behandling" (is part of care and treatment) is free.
- Other vaccines cost a 200 SEK base fee plus the vaccine.
- Vaccination visits count toward neither the high-cost ceiling (högkostnadsskydd) nor the free-care card (frikort).
12.5 The pneumococcal schedule: two current Swedish positions¶
| Source | What it says |
|---|---|
| FoHM (changed January 2026; unchanged in the 1 September 2026 edition) | Adults in risk groups: one dose of a conjugate vaccine with at least 20 serotypes. Anyone previously given PPV23 or an older conjugate vaccine gets one PCV≥20 dose at least a year later. PPV23 is now added only for asplenia and CSF leak. Effectiveness against disease is not yet proven for PCV20/PCV21, which were licensed on antibody responses |
| Region Skåne (guideline updated 1 April 2026) | Give Prevenar 20, the vaccine Skåne has procured, to people with severe immunosuppression: one dose, "Vaccinationen upprepas ej" (not repeated). PCV21 for adults without a spleen |
| National KLL guideline VP8.2 (27 January 2026) | PCV20. For severely immunosuppressed patients not previously vaccinated, add PPV23 at least 8 weeks later, and give a PPV23 booster after at least 5 years |
| EHA 2026 | PCV20 at diagnosis, PPV23 at least 2 months later, repeated every 5 years |
| Swedish trial data | Conjugate vaccine beat polysaccharide vaccine in untreated CLL (Svensson 2018). After 5 years, serological protection was 10% in CLL vs 32% in controls; repeat conjugate doses improved protection, PPSV23 added nothing (Kättström 2025) |
Further sources: FoHM recommendations; Region Skåne guideline (as shown in an archived copy from 28 April 2026); VP8.2 §16.3.2; EHA 2026.
[I] This is a timing difference, not an error: the KLL guideline text almost certainly predates FoHM's change. One PCV20 dose now is common to every position. Whether PPV23 or a later booster follows is a question for the haematologist.
12.6 Shingrix: free only through a narrow hospital route; otherwise the patient pays, and the price varies¶
The national position [E]. On 12 June 2026, NT-rådet advised regions:
- not to fund general Shingrix vaccination;
- that hospital-based units may offer it, after individual assessment, to "gravt immunsupprimerade" (severely immunosuppressed) patients;
- that each region may write guidelines for this limited use.
NT-rådet will revisit its position after FoHM completes a government-commissioned review (NT-rådet statement).
Region Skåne's own drug guideline [E]. Skånelistan (published 2 January 2026) says the patient pays. It gives the price as "ca 1600 kr/dos" (about 1,600 SEK per dose), two doses 2–6 months apart, outside the high-cost ceiling (Skånelistan, archived copy).
Other 2026 sources quote higher prices, so the price varies by clinic and over time; check locally:
- Smittskydd Skåne slides (March 2026): about 2,300 SEK per dose (slides).
- A January 2026 parliamentary question: "5 000 kronor eller mer" (5,000 SEK or more) for the two doses (Riksdagen).
Total cost at the Skånelistan price. [I] Two doses cost about 3,200 SEK plus the 200 SEK base fee at each visit.
No Skåne guideline was found that applies the NT-rådet exception to haematology or CLL. The only free Skåne programme found covers organ-transplant candidates and recipients (not verified).
Supply. There was a nationwide shortage from mid-December 2025, expected to last until about April 2026. Availability in October 2026 was not verified.
Why it matters. In haematological cancers, the Zoster-039 trial saw 2 shingles cases with Shingrix vs 14 with placebo. Antibody response was 76.8% in untreated CLL vs 40.0% on a BTKi (Pleyer 2022), so timing before treatment matters.
[S] Untreated early-stage CLL seems less likely to qualify as "gravt immunsupprimerad" than CLL on anti-CD20, venetoclax or BTKi treatment, or CLL with hypogammaglobulinaemia and repeated infections. Patients should ask their haematology clinic directly whether it will give Shingrix as part of care.
12.7 Timing around treatment and expected responses¶
Vaccinate early. Sweden: "vaccination bör initieras så fort som möjligt efter diagnos" (vaccination should start as soon as possible after diagnosis), because responses are reduced for at least 6–12 months after anti-CD20 drugs and on BTKi (VP8.2 §16.3). Annual influenza and COVID-19 vaccination should continue during treatment, because a T-cell response may still help.
US guidance (IDSA) (IDSA 2013):
- give inactivated vaccines at least 2 weeks before immunosuppression;
- after regimens with anti-B-cell antibodies, delay vaccination at least 6 months.
How response falls with treatment:
| Vaccine | Untreated CLL | On treatment | Source |
|---|---|---|---|
| COVID-19 mRNA (Israel) | 55.2% responded | 16.0% on BTKi; 13.6% on venetoclax ± anti-CD20; none within 12 months of anti-CD20 | Herishanu 2021 |
| COVID-19 mRNA (Sweden, COVAXID) | 63.3% seroconverted vs 100% of controls | — | Bergman 2021 |
| Shingrix (antibody response) | 76.8% | 40.0% on BTKi | Pleyer 2022 |
| Hepatitis B | 28.1% | 3.8% on BTKi | Pleyer 2021 |
All four were read as abstracts only.
- Who responds worst. In the Swedish pneumococcal trial, low antibody levels and long disease duration predicted poor responses.
- How long the effect lasts. After VenO, normal B cells took about 24 months to recover in CRISTALLO (conference/secondary).
12.8 Household contacts¶
- FoHM recommends yearly influenza vaccination for household contacts of people with "kraftigt nedsatt immunförsvar" (severely reduced immunity).
- Skåne makes this free for those contacts, covering both vaccine and administration.
- The KLL guideline advises relatives to get influenza and COVID-19 vaccines.
- US guidance (IDSA) says household contacts can safely receive MMR, varicella, rotavirus and zoster vaccines; the patient should avoid contact with any vaccine-related skin lesions until they heal.
Sources: FoHM influenza; VP8.2 §19.2; IDSA 2013.
[I] Untreated CLL may not count as "kraftigt nedsatt", so contacts should ask their own vårdcentral whether they qualify for the free dose.