Adult T-cell leukaemia/lymphoma
ATLL; ATL; HTLV-1-associated T-cell leukaemia/lymphoma
Adult T-cell leukaemia/lymphoma (ATLL) is a mature CD4+ T-cell malignancy caused by the human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus endemic in southwestern Japan, the Caribbean, sub-Saharan Africa, parts of South America and the Middle East. Approximately 5% of HTLV-1 carriers develop ATLL after a latency of 30–50 years. The Shimoyama classification recognises four clinical variants: acute (most common, leukaemic, hypercalcaemia, very poor prognosis), lymphomatous (no peripheral leukaemic involvement, somewhat better), chronic (smouldering with "favourable" or "unfavourable" subgroups) and smouldering (chronic indolent skin or pulmonary disease without leukaemic involvement). Cutaneous involvement is present at diagnosis in ~50% as plaques, nodules, tumours, erythroderma or non-specific eruptions, and may be the presenting feature. UK practice — particularly in inner-city specialist services — sees disproportionately more ATLL among the Caribbean and Japanese diaspora; HTLV-1 testing of any new "atypical CTCL" in such patients is essential. Mogamulizumab (anti-CCR4) is widely used internationally in relapsed/refractory ATLL (licensed in Japan), but NICE TA754 covers mycosis fungoides and Sézary syndrome only — not ATLL. UK access for ATLL is via individual funding requests, specialist haematology commissioning, or compassionate-use schemes.
Epidemiology
- HTLV-1 endemic in southwestern Japan, Caribbean, sub-Saharan Africa, parts of South America (Peru, Colombia), Middle East and Iran.
- UK — overall HTLV-1 prevalence low (<0.1%) but markedly higher in Caribbean and Japanese diaspora.
- Lifetime ATLL risk in HTLV-1 carriers ~2.5–5% (higher in men and those infected via breastfeeding).
- Latency 30–50 years from infection to ATLL.
- Modes of transmission — vertical (breastfeeding, the dominant mode), sexual, parenteral (blood products, organ transplantation).
Shimoyama clinical subtypes
- Acute (~60%) — leukaemic blood involvement (atypical "flower cells"), high WCC, lymphadenopathy, hepatosplenomegaly, organ infiltration, hypercalcaemia (lytic bone lesions), opportunistic infections; very poor prognosis (median OS ~6–10 months untreated; Cook 2019 international consensus reports median OS ~8.3 months).
- Lymphomatous (~20%) — predominantly nodal/extranodal disease without peripheral blood involvement; cutaneous involvement common; intermediate prognosis (median OS ~10 months).
- Chronic (~15%) — smouldering disease with mild leukaemic involvement (<5% blast cells), mild lymphadenopathy and skin involvement; "favourable" subgroup (normal LDH, normal calcium, no organ involvement) has indolent course; "unfavourable" subgroup behaves more aggressively (median OS ~24 months).
- Smouldering (~5%) — chronic indolent skin and / or pulmonary disease with <1% leukaemic cells; longest survival (median ~3–5 years in modern cohorts; some series report >5 years); some progress to acute / lymphomatous over time.
Cutaneous features
- Cutaneous involvement at diagnosis in ~50% — frequently the presenting feature.
- Patterns include:
- Multiple papules, nodules, tumours.
- Plaques and patches mimicking mycosis fungoides.
- Erythroderma mimicking Sézary syndrome.
- Purpura, "bruise-like" lesions.
- Subtle non-specific maculopapular eruption.
- Pruritus is common.
- Histology and IHC alone cannot distinguish ATLL from MF / Sézary — HTLV-1 serology and PCR for proviral DNA are essential in any "atypical CTCL".
Diagnosis
- HTLV-1 serology (ELISA) plus confirmatory Western blot or PCR for any "atypical" T-cell lymphoma in a patient from an endemic region.
- Peripheral blood — atypical "flower cells" (multilobated nuclei), elevated WCC.
- Bone marrow biopsy.
- CT chest/abdomen/pelvis ± PET-CT.
- Calcium, LDH (prognostic).
- Skin biopsy (if cutaneous lesions) — atypical CD4+ T-cell infiltrate, often dermal-predominant.
- Immunophenotype — CD3+, CD4+, CD8−, CD25+ (high), CCR4+, FOXP3+ (regulatory T-cell-like phenotype).
- Clonal T-cell receptor rearrangement.
- Refer to a haematology / cutaneous lymphoma MDT (UK: Guy's, St George's, Manchester).
Management
- Smouldering and favourable chronic subtypes — observation; topical / phototherapy / low-dose radiotherapy for skin disease; "watch and wait" with treatment if progression.
- Acute and lymphomatous subtypes:
- Zidovudine + interferon-α (the AZT/IFN regimen) — first-line for leukaemic / acute disease; substantial response rates and improved survival.
- Multi-agent chemotherapy (mLSG15: VCAP-AMP-VECP) — standard cytotoxic regimen.
- Mogamulizumab (anti-CCR4 monoclonal antibody) — relapsed / refractory disease; high response rate. Not NICE-approved for ATLL (TA754 covers MF/SS only); UK access via individual funding requests, specialist commissioning or compassionate-use routes.
- Allogeneic haematopoietic stem-cell transplantation in fit younger patients with chemo-sensitive disease — best chance of long-term remission.
- Lenalidomide approved in Japan; emerging in UK practice.
- Brentuximab vedotin in CD30+ disease.
- Strict opportunistic infection prophylaxis (PJP, herpesviruses, strongyloides) — ATLL is profoundly immunosuppressing.
References
- Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia–lymphoma. Br J Haematol; 1991.
- Cook LB et al. Revised adult T-cell leukaemia–lymphoma international consensus meeting report. J Clin Oncol; 2019.
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