CD22 expression on lymphoblasts in relapsed/refractory B-cell acute lymphoblastic leukemi...

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

ID	`RF-BALL-CD22-POS-INO-CANDIDATE`
Type	Red flag
Status	reviewed 2026-04-29
Diseases	`DIS-B-ALL`
Sources	`SRC-INOVATE-KANTARJIAN-2016` `SRC-NCCN-ALL-2025`

Red Flag Origin

Definition	CD22 expression on lymphoblasts in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) — CD22 expressed on >90% B-ALL blasts; flow cytometric / IHC confirmation typically available at diagnosis. Gates inotuzumab ozogamicin (INO; anti-CD22 calicheamicin ADC) for R/R adult B-ALL. INO-VATE ALL (Kantarjian 2016 NEJM): inotuzumab vs standard chemotherapy in R/R B-ALL — CR/CRi 80.7% vs 29.4%, MRD-negative 78.4% of responders, mPFS 5.0 vs 1.8 mo, mOS 7.7 vs 6.7 mo. Bridge to alloHCT is the curative-intent goal — INO-induced remission + prompt transplant in MRD-negative responders associated with durable disease control. Distinct from blinatumomab (anti-CD19 BiTE) — alternative or sequential R/R B-ALL option. CD22-loss escape uncommon; Ph-positive B-ALL also eligible (combined with TKI).
Clinical direction	intensify
Category	high-risk-biology

Trigger Logic

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "cd22_expression",
          "value": "positive"
        },
        {
          "finding": "cd22_status",
          "value": "expressed"
        },
        {
          "finding": "cd22_flow",
          "value": "positive"
        },
        {
          "comparator": ">=",
          "finding": "cd22_blast_percent",
          "threshold": 20
        }
      ]
    },
    {
      "any_of": [
        {
          "comparator": ">=",
          "finding": "prior_lines_count",
          "threshold": 1
        },
        {
          "finding": "relapsed_refractory_ball",
          "value": true
        },
        {
          "finding": "primary_refractory",
          "value": true
        },
        {
          "finding": "post_blinatumomab_failure",
          "value": true
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

Dosing: cycle 1 0.8 mg/m² day 1, 0.5 mg/m² days 8 + 15; cycles 2-6 (responders) 0.5 mg/m² days 1/8/15. Hepatic veno-occlusive disease / sinusoidal obstruction syndrome (VOD/SOS): ~11% any time, ~22% in post-alloHCT recipients bridged from INO — rate strongly tied to dual-alkylator conditioning (especially busulfan-based). Mitigation: shorter INO duration (2 cycles maximum pre-HCT in MRD- negative responders), avoid dual-alkylator conditioning, defibrotide standby. QTc prolongation, hyperbilirubinemia, thrombocytopenia G3+ ~37%. Pre-medication: corticosteroid + antihistamine + acetaminophen. Sequencing: INO → alloHCT bridge superior; INO post-blinatumomab feasible (different antigen). NCCN-ALL-2025 supports both INO and blinatumomab in R/R adult B-ALL; choice driven by CD22/CD19 expression, prior exposure, donor availability, comorbidity profile. STUB — requires clinical co-lead signoff.

Used By

No reverse references found in the YAML corpus.