OpenOnco · Treatment Plan

Treatment plan — Acute Myeloid Leukemia

PLAN-BMA-FLT3_ITD_AML-V1 · v1 · 2026-08-17

Patient

BMA-FLT3_ITD_AML · Algorithm: ALGO-AML-1L

DiagnosisAcute Myeloid Leukemia

MOH / ICD-10C92.0

ICD-O-39861/3; C42.1

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
ESCAT: clinical review pendingBIO-FLT3-D835	TKD point mutation (D835Y/V/H/F; ~7% AML, often co-occurs with ITD)	IB	Standard care SRC-CIVIC: Level D (Supports, Sensitivity/Response) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Poor Outcome)	FLT3-D835 (TKD) in newly-diagnosed AML: midostaurin + 7+3 was studied in FLT3-mutant (ITD or TKD) AML in RATIFY (Stone 2017) — benefit driven primarily by ITD subset, with smaller magnitude in TKD. Quizartinib (type II FLT3i) is INACTIVE against TKD D835 (target alternate conformation). Gilteritinib (type I) and midostaurin retain activity. ELN 2022 prognostic impact of D835 alone is intermediate.	midostaurin + 7+3 + HiDAC consolidation + midostaurin maintenance consider gilteritinib (off-label intensification or post-induction maintenance, trial)	SRC-RATIFY-STONE-2017 SRC-NCCN-AML-2025 SRC-ELN-AML-2022
ESCAT: clinical review pendingBIO-FLT3-D835	TKD point mutation (D835Y/V; relapsed/refractory)	IA	Standard care SRC-CIVIC: Level D (Supports, Sensitivity/Response) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Poor Outcome)	FLT3-D835 in R/R AML: gilteritinib superior to salvage chemo (ADMIRAL, Perl 2019 — pre-specified subset analysis showed activity across both ITD and D835/TKD; D835 subset response rates similar to ITD overall). Gilteritinib is preferred type-I FLT3i for D835-mutant R/R disease. Quizartinib remains contraindicated (no D835 activity).	gilteritinib monotherapy (2L bridge to allo-SCT) gilteritinib + venetoclax + azacitidine (off-label, trial)	SRC-ADMIRAL-PERL-2019 SRC-NCCN-AML-2025 SRC-ELN-AML-2022
ESCAT: clinical review pendingBIO-FLT3-D835	F691L gatekeeper resistance mutation (post-FLT3i)	IIA	Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Poor Outcome) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	FLT3-F691L is a gatekeeper mutation arising under FLT3-TKI selective pressure (gilteritinib, quizartinib). Confers cross-resistance to most current FLT3i. Crenolanib (investigational type-I) and next-gen FLT3i retain partial activity. No approved targeted option — clinical trial enrollment or salvage chemo + allo-SCT.	salvage chemo + allo-SCT (preferred when fit) clinical trial (next-gen FLT3i, crenolanib, FF-10101) venetoclax + azacitidine (off-label salvage)	SRC-ADMIRAL-PERL-2019 SRC-ELN-AML-2022
ESCAT: clinical review pendingBIO-FLT3-ITD	internal tandem duplication (juxtamembrane domain — ~25% of AML)	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Poor Outcome) SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	FLT3-ITD in newly-diagnosed AML: midostaurin + 7+3 induction + high-dose cytarabine consolidation + maintenance improved OS vs chemo alone in fit adults (RATIFY, Stone NEJM 2017 — 4-yr OS HR 0.78). Quizartinib + 7+3 + maintenance also superior in QuANTUM-First (Erba Lancet 2023 — 4-yr OS HR 0.78). FLT3-ITD remains a poor-risk marker (ELN 2022) when allelic ratio high; allo-SCT in CR1 indicated.	midostaurin + 7+3 induction + HiDAC consolidation + midostaurin maintenance quizartinib + 7+3 induction + HiDAC consolidation + quizartinib maintenance (FLT3-ITD specifically) allo-SCT in CR1 (high-allelic-ratio FLT3-ITD or other adverse-risk features)	SRC-RATIFY-STONE-2017 SRC-QUANTUM-FIRST-ERBA-2023 SRC-NCCN-AML-2025 SRC-ELN-AML-2022 SRC-ESMO-AML-2020
ESCAT: clinical review pendingBIO-FLT3-ITD	internal tandem duplication (relapsed/refractory AML)	IA	Molecular evidence option SRC-CIVIC: Level A (Supports, Poor Outcome) SRC-CIVIC: Level B (Supports, Poor Outcome) Resistance or avoidance signal SRC-CIVIC: Level B ⚠ Resistance SRC-CIVIC: Level D ⚠ Resistance Trial or research option SRC-CIVIC: Level C (Supports, Sensitivity/Response) SRC-CIVIC: Level D (Supports, Sensitivity/Response)	FLT3-ITD in relapsed/refractory AML: gilteritinib monotherapy superior to salvage chemo (ADMIRAL, Perl NEJM 2019 — OS 9.3 vs 5.6 mo, HR 0.64). Gilteritinib is preferred 2L for FLT3-mutant R/R AML and is a bridge to allo-SCT. Quizartinib also active R/R (QuANTUM-R) but FDA label is 1L only (R/R label withdrawn).	gilteritinib monotherapy (2L bridge to allo-SCT) gilteritinib + venetoclax + azacitidine (off-label intensification, trial)	SRC-ADMIRAL-PERL-2019 SRC-NCCN-AML-2025 SRC-ELN-AML-2022

Primary current-line option

Aggressive plan

★ DEFAULT

Indication

IND-AML-1L-7-3

Regimen

7+3 Induction (cytarabine + daunorubicin/idarubicin) ± midostaurin

Drugs + NSZU

Cytarabine (DRUG-CYTARABINE) 100-200 mg/m²/day · continuous IV infusion days 1-7 · IV ✓ NSZU covered
Daunorubicin (DRUG-DAUNORUBICIN) 60-90 mg/m² (or idarubicin 12 mg/m² as alternative) · IV bolus days 1-3 · IV ✓ NSZU covered
Midostaurin (DRUG-MIDOSTAURIN) 50 mg PO BID — ONLY if FLT3-ITD/TKD positive · days 8-21 of induction (and continuation through consolidation + maintenance) · PO ⚠ NSZU — not for this indication

Supportive care

SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

Reason

Primary current-line option selected by ALGO-AML-1L at step 7.

Other current-line alternatives (4 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

Indication

IND-AML-1L-VEN-AZA

Regimen

Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule

Drugs + NSZU

Venetoclax (DRUG-VENETOCLAX) Cycle 1 ramp: day 1 = 100 mg, day 2 = 200 mg, day 3 = 400 mg → days 4-28 = 400 mg PO daily; subsequent cycles = 400 mg daily continuously · PO daily; reduce to ~70-100 mg if combined with strong CYP3A4 inhibitor (posaconazole) · PO ⚠ NSZU — not for this indication
Azacitidine (DRUG-AZACITIDINE) 75 mg/m²/day · SC or IV days 1-7 of each 28-day cycle · SC ⚠ NSZU — not for this indication

Supportive care

SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-AML-1L-7-3-GO-CBF

Regimen

7+3 + fractionated gemtuzumab ozogamicin (CD33+ AML, 1L; ALFA-0701)

Drugs + NSZU

Cytarabine (DRUG-CYTARABINE) 100-200 mg/m²/day · Continuous IV infusion days 1-7 · IV ✓ NSZU covered
Daunorubicin (DRUG-DAUNORUBICIN) 60 mg/m² (per ALFA-0701; 90 mg/m² acceptable when GO not added per ECOG-ACRIN — but 60 mg/m² standard with concurrent GO due to additive cardiotoxicity / mortality concern) · IV bolus days 1-3 · IV ✓ NSZU covered
Gemtuzumab ozogamicin (DRUG-GEMTUZUMAB-OZOGAMICIN) 3 mg/m² (max 4.5 mg total per dose) IV — fractionated · Days 1, 4, 7 of induction · IV ✗ Not registered in UA

Supportive care

SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

Hard contraindications

CI-LVEF-LOW-FOR-ANTHRACYCLINE

Reason

Current-line alternative presented for HCP consideration

Aggressive plan

Indication

IND-AML-1L-CPX351-SECONDARY

Regimen

CPX-351 (Vyxeos) for tAML / AML-MRC 1L

Drugs + NSZU

Liposomal cytarabine-daunorubicin (DRUG-CPX-351) Induction 100 units/m² IV (= cytarabine 100 mg/m² + daunorubicin 44 mg/m²) days 1, 3, 5 · Cycle 1; re-induction days 1, 3 if needed · IV ✗ Not registered in UA
Liposomal cytarabine-daunorubicin (DRUG-CPX-351) Consolidation 65 units/m² IV days 1, 3 · Up to 2 consolidation cycles, every 5-8 weeks after count recovery · IV ✗ Not registered in UA

Supportive care

SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

Hard contraindications

CI-LVEF-LOW-FOR-ANTHRACYCLINE

Reason

Current-line alternative presented for HCP consideration

supportive_care

Indication: IND-EMERG-TLS-PROPHYLAXIS-RASBURICASE
Regimen: —
Reason: Current-line alternative presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Where to order	Needed for
TEST-BM-ASPIRATE	Bone Marrow Aspirate	Critical	histology	—	aggressive, standard
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	aggressive, standard
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-COAG-PANEL	Coagulation Panel	Critical	lab	—	all tracks
TEST-FISH-PANEL	FISH (Fluorescence In Situ Hybridization)	Critical	genomic	CSD Lab ✓ (code TBC)	aggressive, standard
TEST-FLOW-CYTOMETRY	Flow Cytometry	Critical	histology	CSD Lab ✓ (code TBC)	aggressive, standard
TEST-HBV-SEROLOGY	Hepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs)	Critical	lab	—	aggressive, standard
TEST-HCV-ANTIBODY	HCV Antibody	Critical	lab	—	aggressive, standard
TEST-HIV-SEROLOGY	HIV Antibody/Antigen	Critical	lab	—	aggressive, standard
TEST-KARYOTYPE	Karyotype	Critical	genomic	CSD Lab ✓ (code TBC)	aggressive, standard
TEST-LDH	Lactate Dehydrogenase	Critical	lab	—	all tracks
TEST-LFT	Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)	Critical	lab	—	all tracks
TEST-NGS-MYELOID-PANEL	Myeloid NGS Panel	Critical	genomic	CSD Lab ✓ (code TBC)	aggressive, standard
TEST-PERIPHERAL-SMEAR	Peripheral Blood Smear	Critical	lab	CSD Lab ✓ (code TBC)	aggressive, standard
TEST-PREGNANCY	Beta-HCG	Critical	lab	—	aggressive
TEST-CMV-SEROLOGY	CMV IgG/IgM	Standard	lab	—	aggressive
TEST-ECHO	Echocardiography	Standard	imaging	—	aggressive
TEST-URIC-ACID	Serum Uric Acid	Standard	lab	—	aggressive, standard
TEST-D-DIMER	D-Dimer	Desired	lab	—	aggressive

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

AML with core-binding-factor (CBF) cytogenetics: t(8;21)(q22;q22.1) with RUNX1::RUNX1T1 fusion OR inv(16)(p13.1q22) / t(16;16)(p13.1;q22) with CBFB::MYH11 fusion. ~10-15% of de novo adult AML, ~25% of pediatric AML. ELN 2022 favorable risk; standard 7+3 induction + 3-4 cycles HiDAC consolidation is curative-intent in CR1 (5-year OS 60-75%); upfront alloHCT is NOT recommended in CR1 default. Adding gemtuzumab ozogamicin to induction (ALFA-0701, AML-19) further improves OS specifically in CBF AML (HR 0.69). c-KIT mutations (D816, exon-8) co-occur in ~25% of CBF AML and may downgrade favorability — warrant MRD-directed approach.
De-escalate direction reflects "do NOT add upfront alloHCT" — CBF AML receives curative chemo (7+3 ± GO + HiDAC × 3-4) without transplant in CR1; alloHCT reserved for MRD-positive after consolidation OR relapse. KIT D816 mutation (~15-25%…
RF-AML-CORE-BINDING-FACTOR-FAVORABLESRC-NCCN-AML-2025SRC-ELN-AML-2022SRC-ESMO-AML-2020
AML emergency triad: hyperleukocytosis (WBC ≥100 K/μL), tumor lysis syndrome (LDH >2× ULN, uric acid >7.5 mg/dL, K+ rising, phosphate rising, Ca2+ falling), or symptomatic leukostasis (dyspnea, altered mental status, retinal hemorrhage)
Triggers HOLD on regimen selection until emergency stabilization: cytoreduction with hydroxyurea ± leukapheresis, IV hydration + rasburicase / allopurinol for TLS, electrolyte correction, urgent ICU/heme consult. Plan generation does not…
RF-AML-EMERGENCY-TLS-LEUKOSTASISSRC-NCCN-AML-2025SRC-ELN-AML-2022SRC-ESMO-AML-2020
AML with FLT3-ITD or FLT3-TKD mutation — addition of midostaurin (or gilteritinib in r/r) to induction is required (RATIFY trial)
Triggers addition of midostaurin 50 mg PO BID days 8-21 to 7+3 induction + HiDAC consolidation in fit patients. Gilteritinib is the r/r-AML standard. NOT applicable for unfit patients on ven+aza (FLT3-targeting in that setting under…
RF-AML-FLT3-ACTIONABLESRC-NCCN-AML-2025SRC-RATIFY-STONE-2017SRC-ELN-AML-2022
AML with adverse-risk biology per ELN 2022: TP53 mutation, complex / monosomal karyotype, RUNX1 / ASXL1 mutation, KMT2A rearrangement (other than t(9;11)), inv(3) / t(3;3), -5/del(5q), -7, FLT3-ITD without NPM1, or therapy-related
ELN-2022 adverse-risk patients are alloHCT candidates upfront if fit. Adds urgency to donor search and shifts the post-induction pathway (skip consolidation HiDAC if rapidly bridging to allo). FLT3-ITD with high allelic ratio + NPM1-wt is…
RF-AML-HIGH-RISK-BIOLOGYSRC-NCCN-AML-2025SRC-ELN-AML-2022
AML patient with positive HBV / HCV / HIV serology, latent TB, or active uncontrolled infection — needs antiviral prophylaxis (HBV-active prophylaxis with entecavir/tenofovir; HCV expert consult; ART optimization for HIV; TB treatment) before induction
Direction "hold" surfaces a workup-prerequisite annotation. AML induction (anthracycline + cytarabine) and ven+aza both cause profound immunosuppression with high HBV-reactivation risk if HBsAg+ or anti-HBc+ without prophylaxis. HBV…
RF-AML-INFECTION-SCREENINGSRC-NCCN-AML-2025SRC-ELN-AML-2022
NPM1 mutation (most commonly type-A: c.860_863dupTCTG / p.W288fs) in AML — ~30% of adult AML; ~50% of cytogenetically normal AML. ELN-2022 favorable risk when NPM1-mutated WITHOUT FLT3-ITD; standard 7+3 induction first-line (no upfront alloHCT in CR1; consolidation HiDAC × 3-4 cycles is curative-intent). MRD qPCR (NPM1-mut transcript) for monitoring.
De-escalate direction reflects "do NOT intensify to upfront alloHCT" — favorable-risk patients receive standard chemo with curative intent; alloHCT reserved for MRD-positive after consolidation OR early relapse. NPM1-mut + FLT3-ITD…
RF-AML-NPM1-MUT-FAVORABLESRC-NCCN-AML-2025SRC-ELN-AML-2022SRC-ESMO-AML-2020
AML eligible for CPX-351 (Vyxeos) liposomal cytarabine+daunorubicin per the FDA-approved subset: therapy-related AML (t-AML, post-cytotoxic / post-radiation), AML with myelodysplasia-related changes (AML-MRC) per WHO criteria (multilineage dysplasia OR MDS-related cytogenetics OR antecedent MDS/CMML). Phase-3 Lancet 2018 (Lancet 2018;392:2088; Lancet Haematology 2020;7:e552 5-yr follow-up): mOS 9.56 vs 5.95 mo for 7+3, HR 0.69; 5-yr OS 18% vs 8%. Eligibility window age 60-75 + fit-for-intensive-chemo. Routes 1L AML to CPX-351-SECONDARY indication over standard 7+3 when this RF fires.
Distinguish from RF-AML-HIGH-RISK-BIOLOGY (broader ELN-adverse category — includes TP53, complex karyotype, FLT3-ITD-no-NPM1, etc.): this flag is the CPX-351-eligibility-specific subset. Both can fire for the same patient; algorithm gates…
RF-AML-SECONDARY-AML-MRC-CPX351-ELIGIBLESRC-NCCN-AML-2025SRC-ELN-AML-2022
AML refractory or relapsed: <5% blast clearance after induction, or relapse after CR (early relapse <6 mo, late relapse ≥6 mo). Switch to salvage chemotherapy (FLAG-IDA, MEC) ± targeted (FLT3+: gilteritinib; IDH+: ivosidenib/enasidenib) + alloHCT bridge
Direction "intensify" — but operationally this is a 2L+ flag that re-routes plan generation to salvage workup rather than 1L choice. At 1L this flag implies "the patient is not fitting the 1L pathway — switch to refractory-AML algorithm"…
RF-AML-TRANSFORMATION-PROGRESSIONSRC-NCCN-AML-2025SRC-ELN-AML-2022
Burkitt lymphoma high-risk features: HIV+ AND CD4 <100 OR ECOG ≥3 OR LDH >3× ULN OR CNS involvement OR bulky abdominal disease — selects more intensive CODOX-M/IVAC over DA-EPOCH-R
CALGB 10002 / CALGB 50202 evidence that DA-EPOCH-R is sufficient for most adult Burkitt INCLUDING HIV-associated, but high-risk features push to CODOX-M/IVAC (Magrath) or hyper-CVAD/MA. CNS involvement is mandatory CODOX-M/IVAC (HD-MTX…
RF-BURKITT-HIGH-RISKSRC-NCCN-BCELL-2025SRC-ESMO-BURKITT-2024

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.CI-LVEF-LOW-FOR-ANTHRACYCLINE
Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.CI-LVEF-LOW-FOR-ANTHRACYCLINE

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Aggressive plan (IND-AML-1L-7-3)

Do not start induction without baseline echo / LVEF if there is any cardiac suspicion — cumulative anthracycline cardiotoxicity can be fatal.
Do not wait for FLT3 results to start d1-d7 cytarabine + anthracycline — midostaurin starts on day 8, so induction is not delayed.
Do not skip TLS prophylaxis (allopurinol ± rasburicase) in patients with high WBC or high tumor activity.
Do not skip HBV/HCV/HIV screening before induction — HBV reactivation on chemotherapy can be fatal.
Do not prescribe without discussing fertility in young patients — anabolic-induced gonadotoxicity is often irreversible.
Do not start without a validated donor search for ELN-adverse-risk patients — the alloHCT window closes quickly.

Standard plan (IND-AML-1L-VEN-AZA)

Do not skip the 3-day venetoclax ramp + TLS prophylaxis — fatal TLS cases described when skipping the ramp.
Do not use full-dose venetoclax (400 mg) with a strong CYP3A4 inhibitor (azole) — reduction to ~70-100 mg required.
Do not skip HBV screening + prophylaxis — reactivation on HMA + venetoclax described.
Do not expect a rapid response — azacitidine requires 4-6 cycles; do not stop earlier without progression.
Do not skip G-CSF in febrile neutropenia — cumulative cytopenias expected; antimicrobial prophylaxis is mandatory.

Aggressive plan (IND-AML-1L-7-3-GO-CBF)

Do not add GO in adverse-risk AML (TP53-mutant, complex karyotype, monosomy 7) — no benefit + toxicity persists.
Do not use daunorubicin 90 mg/m² with GO — cardiotoxicity + early mortality signal in SWOG-S0106 was specifically due to this combination.
Do not add GO without CD33 validation — CD33-flow ≥20% blasts required; CD33-low/negative AML — no benefit signal.
Do not give GO within 90 days before planned alloHCT — VOD/SOS risk in the post-transplant window is dramatically increased.
Do not skip baseline LFT + daily monitoring of bilirubin / weight gain during GO — VOD/SOS is the dominant safety concern.
Do not skip ECHO — anthracycline cardiotoxicity + GO-specific cardiac signal require LVEF tracking.
Do not skip TLS prophylaxis + HBV/HCV/HIV screening — standard 7+3 vigilance.

Aggressive plan (IND-AML-1L-CPX351-SECONDARY)

Do NOT use CPX-351 in patients with de novo AML without MRC-features — FDA approval is narrow: only tAML / AML-MRC / antecedent MDS-CMML.
Do NOT mix or substitute with free cytarabine + daunorubicin — fatal dosing errors documented (units/m² vs mg/m²).
Do NOT prescribe with LVEF <50% — liposomal anthracycline is still cardiotoxic.
Do NOT skip pre-cycle ECHO + cumulative-anthracycline tracking.
Do NOT start without alloHCT-pathway planning — survival benefit predominantly via bridge to HCT.
Do NOT stop on delayed recovery (>day 35) — this is expected for the liposomal formulation; G-CSF + transfusion support.
Do NOT skip TLS prophylaxis in high WBC or high tumor activity.

supportive_care (IND-EMERG-TLS-PROPHYLAXIS-RASBURICASE)

Do not use rasburicase in G6PD-deficient patients — fatal oxidative haemolysis + methemoglobinemia.
Do not forget to screen G6PD in patients of Asian / African / Mediterranean ancestry before starting rasburicase.
Do not use alkalinization (NaHCO3) — risk of calcium phosphate + uric acid precipitation; abandoned per modern protocols.
Do not ignore hyperkalemia — fatal arrhythmia risk; Kayexalate / insulin-glucose / calcium gluconate + hemodialysis on standby.
Do not delay chemotherapy with adequate prophylaxis — disease control critical for AML hyperleuk / Burkitt; balance risk.
Do not forget IV hydration target — UO ≥100-150 mL/h; loop diuretics for maintenance.
Do not forget to process the blood sample on ice + rapid transport — uric acid measurement falsely low post-rasburicase (in vitro continued urate degradation).

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · 7+3 Induction (cytarabine + daunorubicin/idarubicin) ± midostaurin

28-day cycles × 1 induction (re-induction if not in CR after day 14 BM); then 3-4 consolidation HiDAC cycles for younger fit; alloHCT for adverse-risk or post-CR1 in adverse / intermediate

Standard plan

Induction · Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule

28-day cycles × Continue until progression / unacceptable toxicity (median ~12 cycles in VIALE-A; ~25-30% achieve durable remission)

Aggressive plan

Induction · 7+3 + fractionated gemtuzumab ozogamicin (CD33+ AML, 1L; ALFA-0701)

28-day cycles × 1 induction; consolidation HiDAC × 3-4 cycles ± additional fractionated GO 3 mg/m² day 1 of consolidation cycles 1-2 (per ALFA-0701 protocol). No upfront alloHCT in CR1 for favorable-risk per ELN 2022.

Aggressive plan

Induction · CPX-351 (Vyxeos) for tAML / AML-MRC 1L

35-day cycles × 1-2 induction + up to 2 consolidation; alloHCT in CR1 if eligible

MDT brief

Discussion questions (1, 0 blocking)

OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist

MDT talk tree (2 steps)

#	Owner	Topic	Action
1	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
2	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.

Biomarker coverage: 0/0 known (100%), 0 missing, 0 default-track gaps
Unevaluated RedFlags: RF-AML-CD33-POS-GO-CANDIDATE, RF-AML-CORE-BINDING-FACTOR-FAVORABLE, RF-AML-EMERGENCY-TLS-LEUKOSTASIS, RF-AML-FLT3-ACTIONABLE, RF-AML-FRAILTY-AGE, RF-AML-HIGH-RISK-BIOLOGY, RF-AML-IDH1-MUT-ACTIONABLE, RF-AML-IDH2-MUT-ACTIONABLE, RF-AML-INFECTION-SCREENING, RF-AML-KMT2A-ACTIONABLE, RF-AML-MEASURABLE-RESIDUAL-DISEASE, RF-AML-NPM1-MUT-FAVORABLE, RF-AML-ORGAN-DYSFUNCTION, RF-AML-SECONDARY-AML-MRC-CPX351-ELIGIBLE, RF-AML-TP53-ADVERSE, RF-AML-TRANSFORMATION-PROGRESSION, RF-ANKRD26-CONFIRMED-CARRIER, RF-CASCADE-LFS-FDR-POSITIVE, RF-CEBPA-CONFIRMED-CARRIER, RF-DDX41-CONFIRMED-CARRIER, RF-ETV6-CONFIRMED-CARRIER, RF-IATROGENIC-ALKYLATOR-TAML-PREVENTION, RF-IATROGENIC-ANTHRACYCLINE-CARDIO-PREVENTION, RF-IATROGENIC-ANTHRACYCLINE-LATE-CARDIO-PREVENTION, RF-IATROGENIC-ASCT-SECONDARY-MDS-AML-PREVENTION, RF-IATROGENIC-PLATINUM-LATE-PREVENTION, RF-IATROGENIC-PRIOR-RADIATION-PREVENTION, RF-IATROGENIC-TOPO2-TAML-PREVENTION, RF-LI-FRAUMENI-CONFIRMED-CARRIER, RF-LI-FRAUMENI-FAMILY-HISTORY-SUSPICION, RF-LIFESTYLE-TOBACCO-CANCER-PREVENTION, RF-MPN-SECONDARY-LEUKEMIA-PREVENTION, RF-OCC-BENZENE-MALIGNANCY-PREVENTION, RF-OCC-FORMALDEHYDE-PREVENTION, RF-OCC-IONIZING-RADIATION-PREVENTION, RF-OCC-PAINTERS-PREVENTION, RF-RUNX1-CONFIRMED-CARRIER

Technical MDT skill metadata (1/16 activated in this plan)

All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).

Specialist	skill_id	Version	Last reviewed	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-ALFA-0701-CASTAIGNE-2012: Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study (2012)
SRC-ELN-AML-2022: Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel (2022)
SRC-LANCET-CPX351-2018: CPX-351 (cytarabine and daunorubicin) Liposome for Injection vs Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary AML (2018)
SRC-NCCN-AML-2025: NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia (v.X.2025)
SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
SRC-RATIFY-STONE-2017: Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation (2017)
SRC-VIALE-A-DINARDO-2020: Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia (2020)

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-08-17.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT06221683	Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML	PHASE2	RECRUITING	Children's Hospital of Soochow University	—	Single country
NCT06972641	Molecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation	PHASE2 / PHASE3	RECRUITING	Ruijin Hospital	—	Biomarker: enriched Single country
NCT05586074	HEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML	PHASE3	RECRUITING	Sunshine Lake Pharma Co., Ltd.	—	Biomarker: unclear Single country
NCT06824168	Evaluation of Two Dose Levels of Quizartinib as Maintenance in FLT3-ITD (+) Acute Myeloid Leukemia Patients in Complete Remission	PHASE2	RECRUITING	Daiichi Sankyo	—	Biomarker: enriched
NCT07712848	DEC3-VEN vs. Venetoclax-Based vs. DA Regimens in Newly Diagnosed AML	PHASE3	RECRUITING	The Second Affiliated Hospital of Kunming Medical University	—	Single country
NCT03013998	Study of Biomarker-Based Treatment of Acute Myeloid Leukemia	PHASE1 / PHASE2	RECRUITING	Beat AML, LLC	—	Surrogate endpoint only Single country
NCT02115295	Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—	Single country
NCT07478991	Azacytidine, Venetoclax Plus Minus Quizartinib for First Line Older/Unfit AML Patients (VENP-A-QUI)	PHASE3	RECRUITING	PETHEMA Foundation	—	Single country
NCT07259707	Gilteritinib Plus VA Followed By Consolidation Chemotherapy in Newly Diagnosed FLT3-ITD+ AML	PHASE2	RECRUITING	First Affiliated Hospital of Zhejiang University	—	Biomarker: enriched Small N (<50) Single country
NCT05024552	Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML	PHASE1	RECRUITING	H. Lee Moffitt Cancer Center and Research Institute	—	Biomarker: enriched Phase 1 only Small N (<50) Single country

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

Option availability in Ukraine

Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).

Option	UA registration	NSZU	Cost orientation	Access pathway
Aggressive plan 7+3 Induction (cytarabine + daunorubicin/idarubicin) ± midostaurin (REG-AML-7-3)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule (REG-VEN-AZA-AML)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan 7+3 + fractionated gemtuzumab ozogamicin (CD33+ AML, 1L; ALFA-0701) (REG-AML-7-3-GO) 1/3 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Aggressive plan CPX-351 (Vyxeos) for tAML / AML-MRC 1L (REG-CPX351-AML) 2/2 component drug(s) not registered in Ukraine +1	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
supportive_care — No regimen components on this track — availability unknown	— unknown	— unknown	₴-? — verify pathway	not recorded
Trial · NCT06221683 Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06972641 Molecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05586074 HEC73543 Versus Salvage Chemotherapy in R/R FLT3-ITD AML No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06824168 Evaluation of Two Dose Levels of Quizartinib as Maintenance in FLT3-ITD (+) Acute Myeloid Leukemia Patients in Complete Remission No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07712848 DEC3-VEN vs. Venetoclax-Based vs. DA Regimens in Newly Diagnosed AML No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT03013998 Study of Biomarker-Based Treatment of Acute Myeloid Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT02115295 Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07478991 Azacytidine, Venetoclax Plus Minus Quizartinib for First Line Older/Unfit AML Patients (VENP-A-QUI) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07259707 Gilteritinib Plus VA Followed By Consolidation Chemotherapy in Newly Diagnosed FLT3-ITD+ AML No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05024552 Vyxeos Plus Gilteritinib in Relapsed or Refractory, FLT3-Mutated AML No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-17.

plan_id: PLAN-BMA-FLT3_ITD_AML-V1 | version: 1 | generated: 2026-08-17T08:06:31.772064+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.