Skip to content

Decision tree

The two diagrams follow the Swedish guideline (VP8.2) and EHA 2026. They show the order of questions a specialist works through — they do not choose a treatment for J. The details behind every box are listed under the diagrams.

Colours: blue = a question · green = no treatment now · purple = the treatment path · orange = a warning sign.

From diagnosis to treatment decision

%%{init: {"flowchart": {"nodeSpacing": 24, "rankSpacing": 36}}}%%
flowchart TD
    S(["Reported diagnosis: KLL"]) --> D1{"Step 1<br/>Diagnosis<br/>confirmed?"}
    D1 -->|"≥ 5 × 10⁹/L in blood"| CLL["CLL"]
    D1 -->|"< 5 × 10⁹/L,<br/>enlarged nodes"| SLL["SLL<br/>(same disease)"]
    D1 -->|"small nodes,<br/>no prolif. centres"| MBL["Possible<br/>tissue MBL"]
    D1 -->|"red flags<br/>in the PAD"| RF["Expert review:<br/>Richter or other<br/>lymphoma?"]
    CLL --> B["Step 2 · Baseline tests<br/>+ vaccines, contact nurse,<br/>records, second opinion"]
    SLL --> B
    B --> T{"Step 3<br/>iwCLL treatment<br/>criterion met?"}
    T -->|No| W["Active surveillance<br/>= standard care"]
    T -->|Yes| P["Pre-treatment<br/>work-up"]
    W -->|"new symptoms<br/>or changes"| T
    W -->|"rapid growth,<br/>rising LD"| R["Suspect Richter:<br/>PET-CT → biopsy"]
    P --> N2(["Treatment choice:<br/>next diagram"])
    classDef q fill:#e3f0fb,stroke:#1565c0,color:#0d1b2a
    classDef watch fill:#e6f4ea,stroke:#2e7d32,color:#0b2e13
    classDef treat fill:#efe9f8,stroke:#5e35b1,color:#1a1033
    classDef warn fill:#fff1e0,stroke:#e65100,color:#3e1f00
    classDef plain fill:#f4f6f8,stroke:#607080,color:#1b1f24
    class D1,T q
    class W watch
    class P,N2 treat
    class RF,R warn
    class S,CLL,SLL,MBL,B plain

If treatment is indicated

flowchart TD
    Q1{"Q1 · TP53 aberrant?<br/>del(17p) and/or TP53 mutation"}
    Q1 -->|Yes| A1["Sweden: continuous second-generation<br/>BTK inhibitor first<br/>(acalabrutinib or zanubrutinib);<br/>alternatives: VO 12 or AV 14 months *"]
    Q1 -->|No| Q2{"Q2 · IGHV status?"}
    Q2 -->|Mutated| A2["Fixed duration first:<br/>VO 12 or AV 14 months<br/>(continuous BTKi not subsidised)"]
    Q2 -->|"Unmutated<br/>or del(11q)"| A3["VO or AV first;<br/>continuous BTKi may be considered<br/>(subsidised)"]
    A1 --> M["Q3 · Comorbidities adjust the choice<br/>Q4 · Fixed duration or continuous?<br/>Q5 · Trial: CLL18/MOIRAI at Lund?"]
    A2 --> M
    A3 --> M
    M --> O(["Options to discuss with the haematologist,<br/>optionally confirmed by a second opinion"])
    classDef q fill:#e3f0fb,stroke:#1565c0,color:#0d1b2a
    classDef treat fill:#efe9f8,stroke:#5e35b1,color:#1a1033
    classDef plain fill:#f4f6f8,stroke:#607080,color:#1b1f24
    class Q1,Q2 q
    class A1,A2,A3,O treat
    class M plain

* AV (acalabrutinib + venetoclax) was never tested in TP53-aberrant disease: the AMPLIFY trial excluded it.

Step 1 · Confirming the diagnosis

  • Combine the node pathology report (PAD) with blood flow cytometry (the clonal B-cell count); ask for haematopathology review if anything is atypical (The diagnosis).
  • Red flags in the PAD: sheets of large cells, Hodgkin/Reed-Sternberg cells, expanded proliferation centres or Ki-67 > 40%, an atypical phenotype, cyclin D1/SOX11 positivity. These call for expert review; Richter transformation or another lymphoma leaves this tree (PET-CT, biopsy, trials — Richter transformation).
  • Small nodes without proliferation centres and fewer than 5 × 10⁹/L clonal B cells can mean tissue-based MBL (ICC definition): discuss it.

Step 2 · Baseline and protection

  • Examination, Binet/Rai stage (palpation and blood counts only), blood counts, chemistry, LD, protein electrophoresis/immunoglobulins, DAT (Tests and work-up).
  • Start now: vaccinations, contact nurse, Min vårdplan, records and the second-opinion referral (Infections and vaccination; Second opinion).

Step 3 · Is treatment indicated?

At least one iwCLL 2018 criterion must be documented: marrow failure; massive, progressive or symptomatic spleen or nodes; a lymphocyte rise of ≥ 50% within 2 months or a doubling time under 6 months (interpret with care at low counts); steroid-refractory autoimmune cytopenia; symptomatic disease outside the nodes; defined B symptoms (Does he need treatment now?).

Active surveillance — no criterion met

  • Visits every 3–12 months (yearly if the CLL is "quiet"): blood counts, LD, creatinine, nodes, liver and spleen, symptoms, autoimmune cytopenias.
  • Vaccinations: PCV20, influenza, COVID-19, Shingrix; RSV, TBE and hepatitis B when they apply; no live vaccines.
  • Fever of 38.0 °C or more → call; skin checks; cancer screening; heart health; keep exercising.
  • Optional: IGHV with or without IPS-E for counselling — never a reason to start treatment.
  • No early treatment outside trials; no early-treatment trial is open nearby.
  • Back to step 3 on new symptoms, growing nodes or spleen, falling haemoglobin or platelets, or a rapid lymphocyte rise.
  • Rapid node growth, a marked LD rise or heavy B symptoms → suspect Richter → PET-CT → biopsy.

Before treatment — a criterion is met

Recent results are needed: FISH and TP53 sequencing, IGHV (once), bone marrow and CT (Swedish practice), HBV/HCV/HIV, kidney function, TLS blood tests, ECG and blood pressure if a BTK inhibitor is considered, a medicine and supplement review, and vaccinations completed where possible.

Choosing treatment: Q1–Q5 in detail

  • Q1 · TP53 aberrant: Sweden recommends a continuous second-generation BTK inhibitor first (acalabrutinib or zanubrutinib; subsidised), with VO for 12 months or AV for 14 months as alternatives. EHA: continuous unless a shared decision favours fixed duration. No chemoimmunotherapy.
  • Q2 · IGHV mutated: VO (12 months) or AV (14 months) first; a continuous BTK inhibitor is not subsidised; EHA advises against continuous therapy.
  • Q2 · IGHV unmutated (or del(11q)): VO or AV first; a continuous BTK inhibitor "may be considered" (subsidised). Remissions after fixed duration are shorter, but retreatment is usually possible.
  • Q3 · Comorbidities: with heart disease or anticoagulation, BCL2-inhibitor regimens are favoured — no warfarin with a BTK inhibitor, no BTK inhibitor after ventricular arrhythmia, and AV is preferred over IV. With reduced kidney function venetoclax is possible with extra TLS precautions; covalent BTK inhibitors need no dose change above CrCl 30. With infections, low IgG or older age, weigh the infection burden of obinutuzumab.
  • Q4 · Preference: fixed duration (about one year, then treatment-free) or continuous (tablets, indefinitely, with cumulative side effects).
  • Q5 · Trial: CLL18/MOIRAI at Lund (all arms time-limited; TP53 aberration and SLL allowed); other first-line trials run in Stockholm or Denmark (Clinical trials).
  • Result: evidence-based options to discuss — VO, AV, (IV), continuous acalabrutinib or zanubrutinib, or CLL18 — optionally confirmed by a ny medicinsk bedömning. Not routine in Sweden: triplets, BTK inhibitor plus anti-CD20, first-line pirtobrutinib, chemoimmunotherapy (BR only exceptionally). See the treatment decision matrix, the treatment landscape and, for options outside Sweden, World-class options abroad.