Leukemia

Acute Leukemia - Robert Corty

Background

  • Unchecked proliferation of WBC precursors causes marrow failure
  • Can be fatal in days to months
  • Pt’s with suspected acute leukemia require hospitalization for urgent diagnosis & treatment
  • APL has both the highest in-hospital mortality & highest cure rate
  • Types:
    • AML = Acute Myeloid Leukemia – most common
    • APL = acute promyelocytic leukemia translocation (15;17)
    • ALL = acute lymphocytic leukemia
  • Risk Factors:
    • ionizing radiation
    • chemical exposures(e.g benzene)
    • HIV
    • immunosuppression
    • myeloproliferative disorders
    • aplastic anemia
    • chemotherapy, specifically, alkylating agents and topoisomerase inhibitors

 

Presentation

  • Leukocytosis, often blastocytosis: leukemia cutis, gingival hypertrophy, leukostasis
  • Functional Leukopenia, often neutropenia: recurrent infections
  • Anemia: fatigue, pallor, dyspnea
  • Thrombocytopenia: gingival bleeding, epistaxis, petechiae, ecchymoses, menorrhagia
  • Extramedullary hematopoiesis: splenomegaly, hepatomegaly, lymphadenopathy

 

Evaluation

  • Diagnosis of acute leukemia requires one of the following:
    • 20% blasts in peripheral blood
    • > 20% blasts in bone marrow biopsy
    • Any pathognomonic cytogenetic abnormality of t(8;21), inv(16), t(15;17)
  • Check for the presence of these time-sensitive conditions.
    • DIC – check fibrinogen, PT, PTT, platelets 
    • TLS – check uric acid, phosphate, LDH, K+
    • Neutropenic fever – check temp, neutrophil count  
    • Leukostasis  (see below)
    • Presumptive APL – promyelocytes on diff, DIC or Auer rods on smear
  • Confirm if peripheral flow cytometry ordered/in process
  • Use hematology admission order set
    • Set RBC and Plt transfusion thresholds
    • Order nurse-driven electrolyte repletion
    • ECG and TTE to establish pre-chemotherapy cardiac function
    • Daily labs: CBC, TLS, DIC
    • TLS prophylaxis

 

Management

  • Page heme fellow
    • Discuss chemo plan and order double lumen PICC for reliable access
    • If findings suggest APL discuss starting ATRA
    • Subspecialized lab tests: bone marrow biopsy, cytogenetics, FISH
  • Monitor for Common Complications/Emergencies: (see individual sections)
    • TLS, DIC, Febrile Neutropenia, Leukostasis

 

Additional Information

  • Obtain blood product consent on admission
  • APL Specific findings: promyelocytes on differential or Auer rods on smear
  • Differentiation syndrome: promyelocytes differentiate
    • Symptoms and signs: fever, SOB, Hypotn, peripheral edema, pleural effusion, AKI
    • Diagnosis: No defined criteria.  If suspicious, discuss with hematology fellow
    • Management: steroids.  If critically ill, hold ATRA and ATO and consider hydroxyurea

 

 

Leukemia Treatment Overview

  • General strategy is to use “induction” chemo to try to induce clinicopathologic (as opposed to molecular) “remission”
  • Defined as absence of symptoms, normal CBC, and < 5% blasts in bone marrow (on day 28)
  • Then waiting in hospital until neutrophil count > 500 (typically ~3 weeks)
  • From there, bone marrow transplant (for high risk disease) or “consolidation” chemo for normal-risk or low-risk disease

 

AML

Induction

  • Typical is “7+3” i.e. idrarubicin on days 1-3 and cytarabine on days 1-7
  • If therapy-related AML, MDS-related AML, or AML with cytogenetics similar to MDS, use “Vyxeos” which is liposomal daunorubicin and cytarabine on days 1, 3, and 5
  • If low-risk dz (t(8;21) or inv(16)), use cytarabine on days 1-7, and 3 days of low-dose daunorubicin + gemtuzumab-ozogamicin
  • There are other induction regimens that can be used depending on specific cytogenetics and patient frailty, which is beyond beyond the scope of the handbook

 

Consolidation

  • Typically  “HiDAC”(high-dose Ara-C – brand name for cytarabine)
    • Generally too toxic for pts with age > 60, so a dose reduction is used
  • In the case of relapse, typical treatment is a different high-dose chemo and BMT if possible

 

ALL

  • Typical induction is “HyperCVAD” (hyper-fractionated cyclophosphamide, vincristine, doxorubicin (“A” due to trade name Adriamycin), and dexamethasone
  • If t(9;22) (known as Philadelphia chromosome), use tyrosine kinase inhibitor (TKI)
  • If CD20+, use rituximab (requires CNS prophylaxis)

 

Common Chemotherapy Regimens for Leukemia Encountered as Inpatient

Regimen

Components

Use

7+3

 

Cytarabine (Ara-C) x 7 d & Anthracycline  (e.g. idarubicin x3 d)

AML induction

Vyxeos

Cytarabine + liposomal daunorubicin

AML-MRC or t-AML

CLAG-M

Cladribine, cytarabine (Ara-C), Filgrastim (G-CSF), mitoxantrone

AML induction (relapsed/refractory)

HIDAC

High-dose cytarabine

AML consolidation

ATRA

All-trans retinoic acid

given with arsenic trioxide (ATO)

APL (APML)

HyperCVAD/MA

CVAD = Cyclophosphamide, vincristine, doxorubicin, dexamethasone

MA = methotrexate/cytarabine 

(Given as alternating cycles)

ALL

R-CHOP

Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone

NHL

R-EPOCH

Etoposide plus the drugs above

(dosing is different)

NHL

ABVD

Doxorubicin, bleomycin, vinblastine, dacarbazine

HL