AITL primary-refractory or early-relapse: failure to achieve CR after induction (interim...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-AITL-TRANSFORMATION-PROGRESSION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-AITL`
Sources	`SRC-ESMO-PTCL-2024` `SRC-NCCN-BCELL-2025`

Red Flag Origin

Definition	AITL primary-refractory or early-relapse: failure to achieve CR after induction (interim PET Deauville 4-5 with stable/progressive disease), progression on therapy, or relapse <12 months from end of 1L. Routes to salvage (romidepsin / belinostat / pralatrexate / GEM-P) ± auto- or allo-HCT consolidation per ECOG/PS.
Clinical direction	intensify
Category	transformation-progression

Trigger Logic

{
  "any_of": [
    {
      "finding": "aitl_refractory",
      "value": true
    },
    {
      "finding": "aitl_relapse_lt_12mo",
      "value": true
    },
    {
      "finding": "progression_on_therapy",
      "value": true
    },
    {
      "comparator": ">=",
      "finding": "interim_pet_deauville",
      "threshold": 4
    },
    {
      "all_of": [
        {
          "finding": "post_treatment_response",
          "value": "stable_or_progressive"
        },
        {
          "comparator": "<",
          "finding": "months_since_eot",
          "threshold": 12
        }
      ]
    }
  ],
  "type": "composite"
}

Notes

AITL has the worst PFS among PTCL subtypes — 5-yr PFS 18-25% with CHOP-class regimens; primary-refractory disease occurs in ~30%. Salvage options: romidepsin (HDAC-inhibitor; AITL/TFH-phenotype particularly sensitive due to TET2/IDH2/DNMT3A epigenetic background), belinostat (BELIEF trial ORR 26% in AITL specifically), pralatrexate (PROPEL ORR 32%), GEM-P / GDP. Allo-HCT after CR2 is the only consistent curative path; auto-HCT in CR1 controversial (no AITL- specific RCT — ECHELON-2 explicitly excluded auto-HCT effect on AITL subgroup). Brentuximab-vedotin re-treatment if CD30+ and not used in 1L. Direction "intensify" — operationally re-routes to salvage workup rather than 1L choice.

Used By

No reverse references found in the YAML corpus.