Prognosis: reassuring population averages, but no individual forecast is possible yet¶

KLL is a cancer. It is usually lifelong and cannot be cleared with standard treatment. 1177 puts it plainly: "Om du har KLL går det inte att bli av med sjukdomen" (if you have KLL, you cannot get rid of the disease) (1177 Leukemi).

It also shortens life on average, though by far less than it did. Everything below describes groups. None of it is a prediction for an individual: that would require knowing the person's age, blood counts, stage, biology and other illnesses.

10.1 Swedish registry survival (diagnoses 2007–2024)¶

Relative survival compares survival with that expected for people of the same age and sex in the general population. A figure of 100% would mean no excess mortality.

Group	n	3-year overall survival	5-year overall survival	3-year relative survival	5-year relative survival
All patients, from diagnosis	10,645	82.8%	72.8%	91.4%	86.3%
Age <65 at diagnosis	2,721	95.9%	91.9%	97.4%	94.6%
Age 65–79 at diagnosis	5,446	87.0%	77.4%	93.3%	87.9%
Age ≥80 at diagnosis	2,478	58.8%	41.3%	79.4%	71.2%
Treated, age <65 at treatment start	766	92.2%	84.8%	93.7%	87.4%
Treated, age 65–79	1,538	78.3%	64.3%	84.0%	73.1%
Treated, age ≥80	638	48.1%	28.9%	63.9%	48.6%
Treatment started 2007–2011	727	64.9%	48.3%	71.7%	57.1%
Treatment started 2020–2024	684	82.1%	74.8%	90.0%	83.8% (95% CI 77.8–90.3)

Source: KLL registry report 2025, Tables 1–4 [E].

How the registry explains the improvement. It attributes the better survival after treatment to the treatments themselves, because neither the patient population nor supportive care changed over the period.

Caveats the registry itself flags.

Only 66 patients from the 2020–2024 cohort had been followed for 5 years.
Coverage was 82% for 2024, 91% for 2023 and 94% for 2022, so the latest data must be read "med stor försiktighet" (with great caution).
The southern region, which includes Skåne, historically reported fewer early-stage patients. This was probably under-reporting, because flow cytometry was done in clinical-chemistry labs; the gap has narrowed since.
Relative survival after treatment start shows no significant differences between regions.

Other differences between groups. Women do better than men, for unknown reasons. Median age at diagnosis is 72. A quarter of patients are under 65 at diagnosis and 10% are under 55 (VP8.2 §4).

10.2 Nordic and life-expectancy data¶

Nordic registry data (NORDCAN). Swedish men under 80 who were diagnosed in 2017–2021 reached about 90% five-year relative survival. Older men were about 10 points lower. These values were read from figure descriptions, so they are approximate (Hemminki 2024).
The Netherlands. People diagnosed in 2018 still lost 1.7–8.2 years of life expectancy, depending on age and sex, which is about 20% of their remaining expected lifetime. A 50-year-old man diagnosed in 2018 had 23.5 life-years remaining, compared with 11.3 in 1990. The authors warn that recent estimates "might be underestimated" given newer therapies (van der Straten 2022).
Low-risk biology. A Barcelona-Brno low-risk group (mutated IGHV, no del(17p) or del(11q); about half of patients) had "a life expectancy comparable to the general population" in the chemoimmunotherapy era (Delgado 2017, abstract only).
Mayo Clinic. Among Rai stage 0 patients under 75, survival was shorter than in the matched general population only for those with unmutated IGHV or unfavourable FISH (Shanafelt 2010, abstract only).

10.3 Prognostic indices: useful for groups, never a reason to treat¶

CLL-IPI combines five factors (CLL-IPI 2016, abstract only; VP8.2 §8.4):

Factor	Points
Age >65	1
Binet B–C or Rai I–IV	1
β2-microglobulin >3.5 mg/L	2
Unmutated IGHV	2
del(17p) and/or TP53 mutation	4

Risk group	Points	5-year OS, chemoimmunotherapy era (trial patients, median age 61)	3-year OS, targeted-drug era	3-year OS, chemoimmunotherapy (same analysis)
Low	0–1	93.2%	100%	97.4%
Intermediate	2–3	79.3%	96%	93.1%
High	4–6	63.3%	93.9%	81.8%
Very high	7–10	23.3%	89.4%	57.3%

Targeted-era figures: Langerbeins 2024.

Targeted era. With targeted drugs, the CLL-IPI still predicts progression-free survival but separates overall survival much less well.
Accuracy. A Cochrane review found a pooled C-statistic of 0.72. In the very-high group, the index predicted worse survival than was actually observed (Kreuzberger 2020, abstract only).
Swedish position. Sweden calls the CLL-IPI "av mindre värde vid användande av målriktade behandlingar" (of less value with targeted therapy) and dropped β2-microglobulin from routine tests. That test must be ordered specifically if anyone wants to calculate the score.

IPS-E applies to asymptomatic early-stage disease. It uses three factors (unmutated IGHV; absolute lymphocyte count above 15×10⁹/L; palpable nodes), and it predicts only the chance of needing treatment within 5 years: 8.4% (score 0), 28.4% (score 1), 61.2% (score 2–3) (Condoluci 2020, abstract only). A Czech validation found 11%, 36% and 78% (Smolej 2021).

Guidelines disagree on whether to calculate it:

Sweden: IPS-E "kan inte rekommenderas generellt" (cannot be recommended generally), but may help patients who want detailed information. It changes neither the indication nor the choice of treatment.
EHA: no biological profiling is needed in asymptomatic early stage.
Mayo authors: argue for testing everyone, for counselling and trial eligibility.

[I] IPS-E counts palpable nodes. Whether surgically excised nodes, or nodes seen only on imaging, count the same way is a question for the treating haematologist.

Other models apply only once treatment is under way: the ibrutinib four-factor model, the BALL model at relapse, and the MRD-based CIRI2-CLL after fixed-duration therapy. A CLL-specific comorbidity index predicts outcome independently of the CLL-IPI (Rotbain 2022, abstract only).

10.4 TP53 and IGHV matter less for survival than they did in the chemotherapy era¶

TP53 aberrations.

Then: with chemotherapy-based treatment, del(17p) meant a median survival of 2.5–4 years after treatment (VP8.2 §8.4.4).
Now, with first-line BTKi:
pooled ibrutinib: 4-year OS 88% (Allan 2022);
zanubrutinib: 60-month OS 82.3% (Tam 2026);
CLL-IPI, targeted era: a TP53 aberration alone scores 4 points, which places it in the high-risk group (3-year OS 93.9%); it reaches very high (89.4%) only with further factors, such as unmutated IGHV plus age over 65.
TP53 aberration remains the highest-risk group: shorter PFS, more Richter transformation, and it kept independent prognostic value for OS under targeted therapy.

IGHV status.

Unmutated IGHV mainly means shorter remissions after fixed-duration therapy.
With continuous ibrutinib, 9-year OS was 70% (unmutated) vs 69% (mutated) (RESONATE-2 final).
Under targeted therapy, IGHV lost independent prognostic value for OS while TP53 kept it (Langerbeins 2024).

10.5 Modern trial outcomes and what people with CLL die of¶

Overall survival in recent trials (older or comorbid patients unless noted):

ELEVATE-TN: 72-month OS 83.9%, 75.5% and 74.7% across its arms. Only 2.2–2.8% of patients died of CLL progression; competing causes dominated.
CLL14 (VenO): 6-year OS 78.7%.
GLOW (IV): 66-month OS 79.0%.
SEQUOIA (zanubrutinib): 60-month OS 85.8%; 89.4% after adjusting for COVID-19.
Younger and fitter populations: AMPLIFY 36-month OS 94.1% (AV); CLL17 3-year OS 91.5–96.0%.
German registry: 3-year OS 87.9% with a first-line BTKi (Kutsch 2026, abstract only).

Causes of death in the Netherlands (all patients diagnosed 1996–2020) (van der Straten 2024):

CLL: 34%.
Other causes: 30%, mainly cardiovascular.
Solid cancers: 20%.
Infections: 10% in the text (8% in the paper's own table).
Other blood cancers: 9%.
The 5-year cumulative incidence of death from CLL fell from 16.8% (1996–2002) to 7.6% (2010–2020).

Sweden. Infection was an underlying or contributing cause in 33% of CLL deaths in 2010–2021 (Glimelius 2026, abstract only). The national guideline gives 25–50% (VP8.2 §16.4).

Mayo Clinic, by CLL-IPI risk group (5-year cumulative incidence of death):

CLL-IPI group	From CLL progression	From CLL-related complications (infection, second cancer)	From unrelated causes
Low	0.3%	2.1%	0.6%
Intermediate	2.0%	2.5%	3.1%
High / very high	17.3%	5.7%	8.6%

Source: Wang 2021, CIT era.

[I] For lower-risk biology, the risk of dying from CLL over 5–10 years is small, and comparable to the risks from infection, second cancers and unrelated illness. That is why vaccination, skin checks, cancer screening and cardiovascular health deserve as much attention as blood counts.

10.6 Why historical statistics understate outcomes for someone diagnosed in 2026¶

The registry mostly reflects older treatment. Its cohorts were "främst" (mainly) treated with chemotherapy or chemoimmunotherapy. By 2020–2024, only 25% of first-line treatments were chemoimmunotherapy, and FCR has been removed from first-line recommendations (KLL registry report 2025).
Randomised trials show survival gains for targeted therapy over chemoimmunotherapy: E1912 HR 0.47, ELEVATE-TN 0.62, GLOW 0.46, FLAIR death HR 0.26.
NORDCAN's period method may not yet capture the newest drugs (Hemminki 2023).
COVID-19 depressed survival in the 2020–2022 cohorts.

Effects in the opposite direction:

Earlier diagnosis. The share treated at diagnosis fell from 15% to 10%. Diagnosing earlier lengthens measured "survival from diagnosis" without any change in the disease itself.
[S] Long-term follow-up is missing. True 15–20-year outcomes for people diagnosed in 2026 cannot be measured yet.

10.7 What is needed before any individual prognosis¶

[E/I] Before anyone can give a patient a personal prognosis, they need:

Personal factors: age, sex, other illnesses (comorbidity independently raises CLL-related mortality; Charlson HR 1.35–1.47 per Steingrímsson 2022), performance status, infection history and immunoglobulin levels.
Disease burden and pace: Binet/Rai stage from examination and blood counts, absolute lymphocyte count and its doubling time, node and spleen size, LD and, optionally, β2-microglobulin.
Biology: IGHV (with subset), FISH, and TP53 by NGS with its VAF.
Diagnosis details: whether this is CLL or SLL, and whether the node showed accelerated features.
If treated: MRD depth and duration of response.

In people aged 75 or older, prognostic tests added little beyond stage for overall survival (Shanafelt 2010).

10.8 Three illustrative scenarios, explicitly not describing any individual¶

These are teaching composites built from published group data from different eras and selected populations. They are not a description of, or prediction for, any individual. Each follows the same template: "in published groups resembling this, about N in 100 needed treatment within 5 years, and in trials of current treatments about M in 100 were alive after Y years."

(a) Favourable early-stage biology (Binet A/Rai 0, mutated IGHV, no TP53 aberration)

Need for treatment: with IPS-E 0, about 8 in 100 needed treatment within 5 years (11 in the Czech validation); with one IPS-E point, about 28.
Risk of death (Mayo, low CLL-IPI): 5-year risk of death from CLL progression 0.3%, from CLL-related complications 2.1%, and from unrelated causes 0.6%.
Comparable groups: the Barcelona-Brno low-risk group had life expectancy comparable to the general population. The low-risk watch-and-wait cohort of the CLL12 trial (trial-selected) had 5-year survival of 97.9% and estimated 10-year survival of 95.3% (CLL12).
If treatment is ever needed: after VenO, median PFS was not reached at about 6 years (CLL14).

(b) Intermediate biology (unmutated IGHV, no TP53 aberration)

Need for treatment: about 28 in 100 within 5 years with IPS-E 1, and 61 in 100 with IPS-E 2–3.
CLL-IPI: typically intermediate or high. In the chemoimmunotherapy era, 5-year OS was 79.3% and 63.3%. With targeted drugs, 3-year OS was 96% and 93.9%.
Risk of death (Mayo, intermediate CLL-IPI): 2.0% at 5 years and 10.4% at 10 years from CLL progression (Wang 2021; the 10-year figure comes from the same paper, not from the 5-year table above).
If treated:
continuous ibrutinib: 9-year OS 70%;
VenO (CLL14): median PFS 64.8 months in unmutated IGHV at the 6-year analysis (64.7 months in the 9-year conference data), with retreatment often possible;
CLL17: 3-year PFS about 76–80% across strategies.
Richter risk: higher than in (a), but low in absolute terms (section 13).

(c) High-risk TP53-aberrant disease

Frequency: present in 5–10% of patients at diagnosis.
Chemotherapy era: median survival of 2.5–4 years after treatment.
Targeted era (CLL-IPI): a TP53 aberration alone (4 points) falls in the high-risk group: 3-year OS 93.9%, vs 81.8% with chemoimmunotherapy. Only with further factors (for example unmutated IGHV plus age over 65) does it reach very high: 89.4%, vs 57.3%.
With first-line BTKi:
ibrutinib: 4-year PFS 79%, OS 88%;
zanubrutinib: 60-month PFS 70.7%, OS 82.3%.
Risk of death (Mayo, high/very-high CLL-IPI, chemoimmunotherapy era): 17.3% at 5 years and 30.3% at 10 years from CLL progression (Wang 2021; the 10-year figure comes from the same paper, not from the 5-year table above).
If symptom-free: watch-and-wait is still standard. Early ibrutinib in CLL12 gave no EFS or OS gain in this group.
This is where mixing eras misleads most: the gap between old and new figures is largest here.