Does he need treatment now? Only if one of seven iwCLL criteria is documented¶
Sweden, EHA and every other guideline cited here use the same rule. Treatment starts only when "active disease" under the iwCLL 2018 criteria is documented. EHA grades this rule level I, grade A (VP8.2 ch. 10; EHA 2026) [E].
iwCLL 2018 is still the current iwCLL guideline. No update had been published by 7 October 2026, and the next iwCLL workshop is in September 2027 (iwcll.org).
Stage alone does not decide treatment. iwCLL says patients in Binet stage B or Rai intermediate risk "can be monitored without therapy until they have evidence for progressive or symptomatic disease".
5.1 The seven criteria¶
| # | iwCLL 2018 (verbatim essentials) | Swedish VP8.2 | Comment |
|---|---|---|---|
| 1 | "Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. Cutoff levels of Hb <10 g/dL or platelet counts <100 × 10⁹/L are generally regarded as indication for treatment. However, in some patients, platelet counts <100 × 10⁹/L may remain stable over a long period; this situation does not automatically require therapeutic intervention." | B: new or worsening anaemia or thrombocytopenia caused by marrow failure | Autoimmune causes must be excluded |
| 2 | "Massive (ie, ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly." | D: spleen >6 cm below the rib margin, or progressive or symptomatic enlargement | — |
| 3 | "Massive nodes (ie, ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy." | E: node conglomerate >10 cm, or progressive or symptomatic enlargement | — |
| 4 | "Progressive lymphocytosis with an increase of ≥50% over a 2-month period, or lymphocyte doubling time (LDT) <6 months." | F: not sufficient on its own at low counts | See 5.5 |
| 5 | "Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids." | C | Steroids come first |
| 6 | "Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine)." | G: "innocent by-stander" infiltration is not an indication | — |
| 7 | Disease-related symptoms, any of: "Unintentional weight loss ≥10% within the previous 6 months"; "Significant fatigue (ie, ECOG performance scale 2 or worse; cannot work or unable to perform usual activities)"; "Fevers ≥100.5°F or 38.0°C for 2 or more weeks without evidence of infection"; "Night sweats for ≥1 month without evidence of infection." | A: weight loss >10% in 6 months; marked fatigue (stated as "WHO funktionsstatus > 2"); fever >38.0 °C for >2 weeks; night sweats for >1 month | See note below |
Sources: iwCLL 2018; VP8.2 ch. 10.
Note on the fatigue criterion. The Swedish text says "> 2" where iwCLL says "2 or worse". [I] This is probably a wording difference rather than a deliberately stricter threshold, but it is worth asking how it is applied.
Symptoms with other causes. Germany asks clinicians to rule out other causes of B symptoms first, such as infection and gastrointestinal, endocrine or metabolic disease. It defines qualifying night sweats as soaking hair and clothing or bedding for more than a month (S3 v2.0).
5.2 What is explicitly not an indication¶
None of the following starts treatment on its own (iwCLL 2018; EHA 2026; VP8.2 ch. 10, §17.1) [E]:
- Low antibody levels (hypogammaglobulinaemia), or a monoclonal or oligoclonal paraprotein.
- A high lymphocyte count. Leukostasis is rare in CLL, so iwCLL says "the absolute lymphocyte count should not be used as the sole indicator for treatment".
- A "high-risk" score or genetic result. EHA says high risk on CLL-IPI or IPS-E "is not an indication to start treatment" without active disease. The same applies to TP53 or IGHV results in an asymptomatic patient.
- Asymptomatic relapse in later lines of treatment.
- "Innocent bystander" CLL cells found in another organ.
- Autoimmune anaemia or low platelets that still respond to steroids. Sweden treats these with prednisolone 1 mg/kg first, then rituximab-based regimens, and only then with CLL-directed therapy.
5.3 Why asymptomatic CLL is observed: decades of early-treatment trials¶
| Trial | Agent | Population | Progression / event-free survival | Overall survival |
|---|---|---|---|---|
| CLL Trialists' meta-analysis (6 trials, 2,048 patients) | Chlorambucil ± prednisone | Early disease | — | 10-year survival 44% vs 47%, not significant |
| French trials (1,535 patients) | Chlorambucil | Binet A | Progression slowed. In the first trial, 49% of untreated patients had neither progressed nor needed therapy after more than 11 years | Relative risk of death 1.14 and 0.96 (NS) |
| GCLLSG CLL1 (877 enrolled) | Fludarabine | High-risk Binet A | PFS prolonged | Not prolonged (summary level only) |
| CLL7 (201 randomised) | FCR | High-risk Binet A | Median EFS not reached vs 18.5 months | 5-year OS 82.9% vs 79.9% (p=0.864). Infections in 41.5% of FCR-treated patients |
| CLL12 (363 randomised, plus 152 low-risk watch-and-wait) | Ibrutinib vs placebo | Increased-risk asymptomatic Binet A | Progression HR 0.276 | No benefit: 5-year survival 93.3% vs 93.6% (watch-and-wait cohort 97.9%). More bleeding (36.5% vs 14.9%), arrhythmias (22.4% vs 9.5%) and hypertension (19.4% vs 8.3%) |
| CLL12 genetic subgroups (2026) | Ibrutinib | As above | No EFS gain with del(17p)/TP53 | "No OS benefits in any genetic subgroup" |
Sources: CLLTCG 1999; Dighiero 1998; CLL1 registry record; CLL7, Leukemia 2020; CLL12 final, JCO 2025; CLL12 EHA 2023 abstract (conference); CLL12 genetics, Blood 2026. All except CLL7 were read as abstracts only.
[E] No randomised trial, meta-analysis or subgroup analysis has shown an overall-survival benefit from treating asymptomatic CLL early. This holds in every recognised high-risk subgroup, whether defined by IGHV, FISH, TP53, lymphocyte doubling time or composite scores.
EHA 2026 says several trials "were not able to show any benefit in terms of OS following treatment, even with targeted drugs, in asymptomatic early‐stage patients in the presence of high‐risk disease characteristics". The CLL12 investigators concluded that "watch and wait remains the standard of care irrespective of risk factors".
[I] Treating early buys time, but it costs toxicity. Survival comes out the same because effective treatment given when the disease becomes active works just as well.
5.4 The open questions: EVOLVE and PreVent-ACaLL¶
EVOLVE (SWOG S1925, NCT04269902) [E]
- Compares venetoclax-obinutuzumab given early with the same treatment given later.
- Population: asymptomatic patients with CLL-IPI ≥4 and/or a complex karyotype, diagnosed within the previous 18 months.
- Primary endpoints: overall survival, and quality of life at 2 years.
- Status: still recruiting (registry updated 6 October 2026). Estimated primary completion is 1 October 2028. No Swedish site is listed.
PreVent-ACaLL (EU CT 2024-511072-33-00) [E]
- Tested a short course of acalabrutinib-venetoclax against observation in patients at high risk of infection or early treatment, as predicted by the CLL-TIM model.
- Recruitment ended in Sweden on 8 November 2024 and in Denmark on 19 June 2025 (CTIS record).
- No efficacy results have been found.
- ClinicalTrials.gov still says "recruiting", but that record was last updated in December 2023.
[I] Clinical trials are the only route to early treatment that guidelines endorse, and no such trial is recruiting in Sweden or nearby Denmark today (section 17).
5.5 Lymphocyte doubling time: four different wordings¶
| Source | Wording |
|---|---|
| iwCLL 2018 | LDT under 6 months, or a rise of ≥50% within 2 months. LDT is estimated by linear regression of counts taken every 2 weeks over 2–3 months. "Patients with initial blood lymphocyte counts <30 × 10⁹/L may require a longer observation period." Other causes, such as infection or steroids, must be excluded |
| EHA 2026 | Prints ">30 G/L", the opposite direction. The July 2026 correction did not change this sentence. [I] Probably a transcription error |
| German S3 v2.0 and Onkopedia | LDT counts only from a baseline of at least 30,000/µL (30×10⁹/L) |
| Swedish VP8.2 | This criterion alone is not enough at low counts. Patients under 30×10⁹/L should be followed for longer |
Sources: iwCLL 2018; EHA 2026 and correction; S3 v2.0; Onkopedia; VP8.2 ch. 10.
A short doubling time does carry prognostic information. An LDT of 12 months or less predicted an earlier need for therapy, with a median of 23 months vs not reached (Baumann 2021, abstract only). That is a prognosis, not a reason to treat.
[I] If treatment is ever proposed mainly because counts are "doubling fast" from a low baseline, J should ask three things: how the LDT was calculated, over what period, and whether infection or steroids were ruled out.
5.6 How many people in Sweden need treatment, and when¶
| Source | Needing treatment at diagnosis | Over the whole course |
|---|---|---|
| VP8.2 ch. 1, §4.2, §7.5 | About 15% (about 85% do not) | About two-thirds eventually need treatment; median age at treatment start 75 |
| VP8.2 ch. 10 | — | "Cirka en tredjedel av patienterna behöver aldrig behandling" (about a third never need treatment). This is an estimate; no registry figure exists |
| VP8.2 patient leaflet | 10–15% (85–90% need none) | 60–65% eventually treated. "Det gör heller ingen nytta att sätta in behandling för tidigt" (starting treatment too early does no good) |
| KLL registry 2007–2024 | 12% overall; 15% in 2007–2011; 10% in 2020–2024 | Not reported |
Sources: VP8.2 ch. 1; VP8.2 patient leaflet; KLL registry report 2025, pp. 7, 10.
The sources agree on the direction and differ only slightly on the numbers. The registry links the falling share treated at diagnosis to earlier diagnosis.
5.7 Watch-and-wait (aktiv exspektans) is active care, not neglect¶
What the visits involve. Follow-up in Sweden is lifelong, usually at an internal-medicine or haematology unit (VP8.2 ch. 14) [E]. Each visit covers:
- Blood tests: Hb, white cells with differential, platelets, LD and creatinine.
- Palpation of the lymph nodes, liver and spleen.
- Questions about general symptoms.
- Checks for autoimmune cytopenias.
How often.
- Every 3–12 months, depending on disease activity.
- Once a year for "stillsam" (quiet) CLL: stable lymphocytes below 20–30×10⁹/L, otherwise normal counts, and no lymphadenopathy. [I] Whether J fits this depends on whether he still has enlarged nodes.
- Germany suggests every 3 months in the first year, then every 3–12 months.
Primary care. Selected stable patients may be followed in primary care, provided there are clear rules for referring them back.
More than blood tests. EHA describes "comprehensive management during active surveillance": vaccination, infection prevention, skin-cancer awareness and lifestyle support. It openly acknowledges the "watch, wait, worry" experience. The Swedish guideline recommends offering psychosocial support, noting that a cancer diagnosis can be harder to cope with when treatment does not start straight away (VP8.2 §18.2).
When to contact the clinic between visits, per the national patient leaflet:
- Increasing, unexplained fatigue.
- Heavy night sweats for weeks.
- A full feeling in the abdomen, or enlarged nodes.
- Unintended weight loss.
- Recurrent fever without a known infection.