Acute Leukemia (AML / ALL)
Malignant proliferation of immature myeloid (AML) or lymphoid (ALL) blasts. The intern manages complications: TLS, DIC, leukostasis, infections, and transfusion support.
🔍 Overview
Overview
Acute leukemia = rapid clonal expansion of immature hematopoietic cells (blasts) in the bone marrow, spilling into blood. AML (acute myeloid): median age 68, most common adult acute leukemia. ALL (acute lymphoblastic): bimodal -peak in children 2-5y + second peak > 60y. Diagnosis: ≥ 20% blasts in marrow or blood (WHO). Exception: AML with recurrent genetic abnormalities (e.g. t(8;21), inv(16)) can be diagnosed at any blast %. APL (acute promyelocytic leukemia, M3): medical emergency -presents with severe DIC. Treat with ATRA immediately on suspicion, before confirmation. The intern's role: you will not choose chemo regimens -you WILL manage TLS prevention, febrile neutropenia, DIC, transfusion, electrolytes, and pain.
🧪 Workup
Workup
- CBC with differential + peripheral smear -blasts (≥ 20%), may see Auer rods (AML, especially APL). WBC can be markedly elevated (leukostasis risk if > 100K) or low (aleukemic leukemia).
- Bone marrow biopsy + aspirate -definitive. Send: morphology, flow cytometry (lineage: myeloid vs lymphoid), cytogenetics (karyotype), FISH (specific translocations), molecular testing (FLT3, NPM1, IDH1/2, TP53 for AML; BCR-ABL for ALL).
- Coags + fibrinogen -DIC screen (especially APL). If DIC + blasts → start ATRA immediately.
- BMP + uric acid + LDH + phosphate -TLS risk assessment
- G6PD -before rasburicase
- Type & screen -will need multiple transfusions
- HLA typing -early if transplant candidate (start sibling/unrelated donor search)
- Lumbar puncture -ALL requires CNS staging (LP with intrathecal chemotherapy). AML: LP only if CNS symptoms.
- Echo -baseline EF before anthracycline-containing induction
- Infectious workup -blood/urine cultures, CXR, consider fungal markers if prolonged neutropenia expected
🚨 Management
Management
- APL (M3 AML) -EMERGENCY: Start ATRA (all-trans retinoic acid) immediately if APL suspected (Auer rods, DIC, promyelocytic morphology). Do NOT wait for FISH confirmation. ATRA + arsenic trioxide (ATO) cures > 90% of APL. Lo-Coco, 2013
- AML induction: "7+3" -cytarabine 7 days + daunorubicin 3 days. Targeted: add midostaurin if FLT3+ RATIFY, 2017, gemtuzumab ozogamicin if CD33+ favorable risk. Unfit elderly: azacitidine + venetoclax VIALE-A, 2020.
- ALL induction: Multi-agent (vincristine, prednisone, daunorubicin, asparaginase ± cyclophosphamide). Ph+ ALL: add dasatinib or ponatinib (TKI) [GRAAPH-2005]. CNS prophylaxis with intrathecal methotrexate.
- Consolidation → Transplant: Intermediate/high-risk AML and high-risk ALL → allogeneic stem cell transplant in CR1.
- Intern-managed complications:
- TLS prevention: Aggressive IVF + allopurinol (prophylaxis) or rasburicase (treatment/high-risk). Check TLS labs q6-8h.
- Leukostasis (WBC > 100K): Emergent leukapheresis + hydroxyurea 50-100 mg/kg. Symptoms: dyspnea, confusion, visual changes (WBC plugging microvasculature).
- DIC: Aggressive blood product support (cryoprecipitate for fibrinogen < 100-150, platelets for < 50K with bleeding). Treat the leukemia (definitive DIC treatment).
- Febrile neutropenia: Cefepime or meropenem within 1 hour. See neutropenic fever protocol.
- Transfusion: pRBC for Hgb < 7-8. Platelets for < 10K (prophylactic) or < 50K with bleeding. Irradiated + leukoreduced products.
💊 Medications
| Drug | Dose | Route | Notes |
|---|---|---|---|
| ATRA (tretinoin) | 45 mg/m²/day divided BID | PO | APL -start immediately on suspicion. Differentiates promyelocytes. Risk: differentiation syndrome (fever, dyspnea, edema, pleural effusion) → dexamethasone 10 mg BID. Lo-Coco, 2013 |
| Arsenic trioxide | 0.15 mg/kg IV daily | IV | APL (with ATRA). Cure rate > 90%. QTc monitoring (arrhythmia risk). Hepatotoxicity. |
| Cytarabine (Ara-C) | 100-200 mg/m²/day × 7d (induction) | IV | Backbone of AML "7+3." High-dose for consolidation. Cerebellar toxicity at high dose (check cerebellar function daily). |
| Venetoclax | 400 mg daily (after ramp-up) | PO | BCL-2 inhibitor. With azacitidine for unfit AML. High TLS risk -ramp-up dosing + rasburicase. VIALE-A, 2020 |
| Midostaurin | 50 mg BID days 8-21 | PO | FLT3 inhibitor added to 7+3 for FLT3-mutated AML. RATIFY, 2017 |
| Hydroxyurea | 50-100 mg/kg/day | PO | Cytoreduction for leukostasis (WBC > 100K). Bridge until definitive chemo. Also for SCD maintenance. |
🏥 Rounds
Pimp Questions
❓ Why must you start ATRA immediately when APL is suspected?
APL (M3 AML) presents with severe DIC that is rapidly fatal without treatment. ATRA differentiates the malignant promyelocytes, which resolves the DIC within days. Mortality from APL-related hemorrhage is highest in the first 48-72 hours. Waiting for FISH confirmation of t(15;17) PML-RARA can take 2-5 days -too long. Start ATRA on clinical/morphologic suspicion (Auer rods + DIC + promyelocytic morphology). If wrong, ATRA has minimal toxicity.
❓ What is differentiation syndrome and how do you manage it?
Differentiation syndrome (formerly "ATRA syndrome") occurs when ATRA/ATO causes rapid maturation of leukemic promyelocytes → release of cytokines → capillary leak. Features: fever, dyspnea, weight gain, pulmonary infiltrates, pleural/pericardial effusions, hypotension. Can be fatal. Treatment: dexamethasone 10 mg IV BID + continue ATRA (unless life-threatening). Hold ATRA only if severe. Occurs in ~25% of APL patients, typically within first 1-2 weeks.
❓ What is leukostasis and at what WBC does it occur?
Leukostasis = symptomatic hyperviscosity from WBC plugging microvasculature. Typically when WBC > 100K (lower threshold for AML blasts -larger and stickier than ALL blasts). Symptoms: dyspnea, hypoxia, confusion, visual changes, headache. Treatment: emergent leukapheresis + hydroxyurea. Do NOT transfuse pRBCs before reducing WBC (increases viscosity). AML leukostasis is more dangerous than ALL at the same WBC.
❓ What molecular markers are most important in AML and why?
FLT3-ITD: present in ~30% AML. Worse prognosis. Add midostaurin to 7+3 RATIFY, 2017. NPM1: favorable if FLT3-negative -may not need transplant in CR1. IDH1/IDH2: targetable with ivosidenib/enasidenib. TP53: very poor prognosis -poor response to standard chemo. t(8;21), inv(16): core-binding factor AML -favorable, respond well to high-dose cytarabine consolidation.
❓ Why are blood products in leukemia patients irradiated and leukoreduced?
Irradiated: prevents transfusion-associated graft-versus-host disease (TA-GVHD) -donor lymphocytes in the blood product attack the immunocompromised recipient's tissues. TA-GVHD is > 90% fatal. Irradiation inactivates donor lymphocytes. Leukoreduced: removes WBCs → prevents febrile non-hemolytic transfusion reactions, CMV transmission, and HLA alloimmunization (important for future transplant candidates).
Clinical Examples
📋 Case 1, APL (Acute Promyelocytic Leukemia) with DIC
Patient: 32F with 10 days of fatigue, bruising, and epistaxis. WBC 3.2K with 45% blasts, Hgb 7.1, platelets 18K. PT 19, fibrinogen 82. Smear: bilobed blasts with heavy granulation and Auer rods.
Key findings: APL [t(15;17) PML-RARA] with DIC, the hematologic emergency. APL is the most curable leukemia but the most dangerous at presentation due to DIC-related hemorrhage.
Management:
- Start ATRA (all-trans retinoic acid) 45 mg/m²/day IMMEDIATELY, do not wait for FISH confirmation
- Aggressive product support: cryoprecipitate to keep fibrinogen > 150 mg/dL, platelets > 30-50K (higher thresholds for APL)
- Arsenic trioxide (ATO) + ATRA for low-risk APL (WBC < 10K) Lo-Coco, 2013
- Watch for differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates), treat with dexamethasone 10 mg IV BID
- FISH for PML-RARA t(15;17) to confirm
Teaching point: APL is a clinical diagnosis, start ATRA on morphologic suspicion alone (Auer rods + DIC). Waiting for FISH costs lives. ATO+ATRA cures > 95% of low-risk APL without traditional chemotherapy.
📋 Case 2, AML with Leukostasis
Patient: 65M with 1 week of confusion and dyspnea. WBC 142K with 88% blasts, Hgb 8.2, platelets 34K. SpO₂ 88% on room air. CXR: bilateral interstitial infiltrates. CT head: no bleed.
Key findings: Leukostasis, WBC > 100K with symptomatic microvascular plugging (pulmonary: hypoxia; CNS: confusion). AML blasts are large and sticky, leukostasis occurs at lower WBC than ALL.
Management:
- Emergent leukapheresis to rapidly reduce WBC (temporizing, effect lasts hours)
- Hydroxyurea 50-100 mg/kg/day to cytoreduction (start immediately, even before pheresis)
- DO NOT transfuse pRBCs until WBC is reduced (increases viscosity → worsens leukostasis)
- TLS prophylaxis: aggressive IVF + rasburicase (tumor lysis is imminent with cytoreduction)
- Expedite bone marrow biopsy, cytogenetics, and molecular markers for definitive therapy
Teaching point: Leukostasis is a clinical diagnosis, there is no specific WBC threshold. Do not wait for confirmatory tests. The immediate goal is cytoreduction, not diagnosis. Avoid pRBC transfusion until WBC is lowered.
📋 Case 3, Newly Diagnosed ALL in Young Adult
Patient: 22M with 3 weeks of fatigue, bone pain, and fever. WBC 48K with 72% lymphoblasts, Hgb 9.4, platelets 28K. Mediastinal mass on CXR. Flow cytometry: TdT+, CD10+, CD19+, CD22+.
Key findings: B-cell ALL. Young adult with mediastinal mass (T-cell features possible). Must check for Philadelphia chromosome [t(9;22) BCR-ABL], present in 25% of adult ALL and changes therapy entirely.
Management:
- FISH for BCR-ABL (Philadelphia chromosome), if positive, add dasatinib or ponatinib to chemotherapy
- Pediatric-inspired regimen (hyper-CVAD or DFCI protocol), AYA patients (< 40) have better outcomes with pediatric protocols CALGB 10403, 2019
- LP with intrathecal methotrexate (CNS prophylaxis, ALL has high CNS tropism)
- TLS prophylaxis: IVF + allopurinol (or rasburicase if high risk)
- HLA typing for siblings early, allogeneic transplant may be indicated in CR1 for high-risk features
Teaching point: Always check for Philadelphia chromosome in adult ALL, it's present in 25% of cases and is the single most important prognostic and therapeutic marker. Ph+ ALL gets TKI + chemo, not chemo alone.
Sample Presentation
Ms. Chen is a 58-year-old woman presenting with 2 weeks of fatigue, easy bruising, and gum bleeding. Exam: pallor, petechiae, gingival hyperplasia. Labs: WBC 68K with 78% blasts, Hgb 6.8, platelets 12K, LDH 1200, uric acid 9.2. Smear: large blasts with Auer rods. PT 18, fibrinogen 95.
Key Points: AML with Auer rods + DIC (fibrinogen 95, prolonged PT) → high suspicion for APL. Start ATRA immediately. Aggressive product support: cryoprecipitate for fibrinogen > 150 (higher target in APL), platelets for > 30-50K (APL bleeding threshold). TLS prevention: IVF + rasburicase (uric acid 9.2 + high WBC). Confirm with FISH for PML-RARA t(15;17).
- CBC daily during induction -track nadir (typically days 10-21 for AML). Expect 2-4 weeks of pancytopenia.
- TLS labs q6-8h -K⁺, PO₄, Ca²⁺, uric acid, Cr, LDH during first 72h of treatment
- Coags + fibrinogen daily -especially APL. Keep fibrinogen > 100-150 with cryoprecipitate.
- Daily assessment: fever curve, exam (skin for leukemia cutis, gums for infiltration, fundoscopy for leukostasis, neuro for CNS leukemia)
- Day 14 bone marrow (AML) -assess for residual disease. If persistent blasts → may need re-induction.
- QTc -on arsenic trioxide. Hold if QTc > 500 ms. Correct K⁺ and Mg²⁺ aggressively.
- Cerebellar function -on high-dose cytarabine. Dysarthria, ataxia, nystagmus → stop immediately (irreversible).
- MRD (measurable residual disease) -flow cytometry or molecular testing post-induction. Guides consolidation/transplant decision.
📋 Summary
Summary
What You Are Actually Managing
Rapid clonal expansion of immature myeloid (AML) or lymphoid (ALL) blasts. The oncologist chooses the chemotherapy; the ward team manages the complications that kill first: tumor lysis, DIC, leukostasis, neutropenic infection and transfusion support.
Confirm and Type It Fast
Peripheral smear, then bone marrow aspirate and biopsy with flow cytometry, cytogenetics and molecular testing. Blasts above 20% makes the diagnosis. Auer rods mean myeloid. Cytogenetics decide both prognosis and treatment, so do not start therapy that would make the marrow uninterpretable before it is sampled.
APL Is the One You Diagnose Clinically
Suspect acute promyelocytic leukemia and start ATRA 45 mg/m²/day immediately, before the cytogenetics confirm it. APL kills through catastrophic DIC and intracranial hemorrhage in the first days, and ATRA reverses the coagulopathy. Support aggressively: keep fibrinogen above 150 and platelets above 50,000. With ATRA plus arsenic trioxide the cure rate exceeds 90%, so the early death is the only thing standing between the patient and a cure.
Watch for Differentiation Syndrome
ATRA and arsenic cause fever, dyspnea, hypoxemia, pulmonary infiltrates, weight gain, hypotension and renal dysfunction, usually in the first 2 weeks. Treat with dexamethasone 10 mg IV BID at the first suspicion and do not wait for confirmation, because it progresses to respiratory failure. Hold the differentiating agent in severe cases.
Tumor Lysis Prophylaxis From the Start
Aggressive IV fluids plus allopurinol; rasburicase for high risk or an already high uric acid (contraindicated in G6PD deficiency, where it causes hemolysis). Monitor potassium, phosphate, calcium, uric acid and creatinine every 6 to 8 h. Do not give calcium for asymptomatic hypocalcemia, since calcium-phosphate precipitation worsens the kidney injury. Venetoclax carries a particularly high risk, which is why it is ramped up rather than started at full dose.
Leukostasis Is a Different Emergency
WBC above 100,000 in AML with dyspnea, hypoxemia, confusion or visual change. Cytoreduce with hydroxyurea 50 to 100 mg/kg/day and consider leukapheresis, and start definitive therapy urgently. Do not transfuse red cells before cytoreduction: raising the hematocrit raises viscosity and can precipitate stroke or infarction. Platelets are safe and should be given.
Neutropenic Fever Is a One-Hour Problem
Cultures then broad-spectrum antipseudomonal antibiotics within 1 hour, before imaging and before the source is known. A single temperature of 38.3°C, or 38.0°C sustained for an hour, with an ANC below 500 counts. Add antifungal cover for persistent fever beyond 4 to 7 days, and remember these patients may have no localizing signs because they cannot mount inflammation.
Transfusion and Supportive Details That Matter
Use irradiated and leukoreduced products to prevent transfusion-associated GVHD and CMV transmission in a potential transplant candidate. Platelets below 10,000, or below 50,000 with bleeding or a procedure. All ALL patients need CNS prophylaxis with intrathecal chemotherapy, because the CNS is a sanctuary site systemic therapy does not reach. Add PJP prophylaxis and antiviral prophylaxis, and discuss fertility preservation before induction, not after.
📄 One Pager
Text version
One-Pager
Acute Leukemia
AML / ALL / APL
APL Emergency
Auer rods + DIC → start ATRA now. Don't wait for FISH. Cryoprecipitate for fibrinogen > 150. ATRA + arsenic trioxide cures > 90%.
Trials
Lo-Coco 2013 (ATRA+ATO for APL) · RATIFY 2017 (midostaurin for FLT3+ AML) · VIALE-A 2020 (aza+venetoclax)
Related Topics
AmyloidosisAnemia WorkupAnemia WorkupAnticoagulation ManagementChemotherapy ToxicitiesDIC