Acute myelogenous leukemia (AML) Flashcards
Hematology Review - AML
- AML is a heterogeneous hematologic malignancy characterized by the clonal
expansion of myeloid blasts in the peripheral blood, bone marrow, & other tissues. - Leukemia cells have limited ability to differentiate and are therefore not capable
of performing the functions of normal white blood cell - AML is the most common form of acute leukemia
AML – Signs and Symptoms
AML is rapidly fatal if not treated!!!!!!!
Cytopenias:
Anemia
Fatigue, malaise, weakness
Thrombocytopenia
Easy bruising, petechiae, ecchymosis
Heavy and / or prolonged menses
Bleeding such as epistaxis, gingival bleeding, conjunctival hemorrhage
Neutropenia
Infection
Signs and symptoms may be absent due to non-functioning nature of the malignant WBC clone
High “Blast” Count
AML: Workup and Diagnosis
Workup:
Laboratory tests
CBC with differential, chemistries, coagulation studies
Examination of peripheral blood smear
Bone marrow biopsy
Cytogenetics, immunophenotyping and cytochemistry
Cardiac echocardiogram or MUGA
Treatment often includes anthracyclines
Diagnosis
BLASTS = BAD!
Peripheral blasts
Blasts in bone marrow biopsy sample
Greater than 20% = a diagnosis of AML
Risk Assessment and Prognosis
AML
Important predictors of outcomes in adult AML
patients:
Age – outcomes are better in patients less
than 60 years old.
Performance status – “fitter” patients do
better
Duration of first remission
Cytogenetics and molecular abnormalities
– MOST IMPORTANT
Favourable risk means overall survival 66% or
Adverse risk OS 12%
Need to make decision for allogenic transplant
AML - Treatment
Initiate immediately after definitive diagnosis is made.
Chemotherapy:
Intensive chemotherapy
When goal is cure
Most patients, unless considered unfit
Low-intensity chemotherapy
When goal is altering the natural course of the disease
Less fit or elderly patients
Appropriate supportive care
Blood/Platelet transfusions, pain control, antinauseants with chemotherapy,
infection prevention
AML – Treatment Plan
Fit patients with High Risk AML in Alberta:
LB is high risk so consult transplant program to initiate
search for a suitable stem cell transplant donor
Human leukocyte antigen (HLA) typing is ordered for LB and
her siblings
Induction Chemotherapy -> Consolidation Chemotherapy -> Allogeneic Stem Cell Transplant
AML Induction - Goals
- “Induction” Chemotherapy
– Goal is to “Induce” a complete remission (CR) - disappearance of clinical and bone marrow evidence of leukemia
– Bone marrow to have normal cellularity with < 5% blasts and no leukemic clone
– No “Blasts” in the peripheral blood - AND restoration of normal hematopoiesis
– Neuts ≥1.0 and Plt >100
what is “7+3” or “three and seven”
3 days of daily IV push anthracycline
Calgary uses Idarubicin 12 mg/m2 IV push over 5 minutes once daily X
3 days
Some centres use Daunorubicin
Toxicities similar to those discussed for doxorubicin
7 days of daily continuous infusion cytarabine
Cytarabine 100-200 mg/m2/day IV continuous infusion for 7 days
Patients commonly get a rash
**Midostaurin – oral agent for FLT3 positive AML
AML Supportive Care – Lots of DRPs!!!!
INFECTIONS!!!
After giving “induction” chemotherapy, patients experience a very deep and extended
period of deep neutropenia
Prophylaxis of opportunistic infections:
Febrile Neutropenia – High risk Category - Refer to FN lecture
TLS prophylaxis
Typically lower risk than ALL patients but usually still need allopurinol
Mucositis
Rash – cytarabine or allopurinol or something else????
AML – Consolidation
Given after a CR is achieved with induction therapy
HIDAC = HIgh Dose Ara-C (cytarabine)
3000 mg/m2 IV over 2-3 hours q12h on days 1,3,5 (6 doses)
Cycle is repeated approximately every 28 days for 3-4 cycles
Adverse Effects:
Ocular Toxicity!
Doses of cytarabine that are greater than 1g/m2 for 2 doses will lead to corneal toxicity
in most patients
Symptoms include excessive tearing, pain, photophobia and sensation of foreign body
Steroid eye drops are absolutely necessary for duration of HIDAC therapy and continuing
until 48 hours after the last dose. (Dexamethasone eye drops or Prednisolone eye drops)
Cerebellar Toxicity
Neurologic assessment (including handwriting assessment) `
What is an Allogeneic HSCT?
Sometimes cells are
“fresh” and not
cryopreserved
AHS regimen example
is “FlubupATG”
An intense regimen
using Fludarabine,
Busulfan and Rabbit
Anti-Thymocyte
Globulin
Purpose of an Allogeneic HSCT
To rescue the recipient from myeloablative therapy given for treatment of malignant disease
Same rationale as Autologous HSCT
To replace the abnormal hematopoietic component
AKA to replace malignant progenitor cells with health progenitor cells from a donor
To establish a graft-versus-leukemia (tumor) effect
Donor cells recognize and destroy the residual malignant cells in the host
Advantage over Autologous HSCT
In Alberta, Allo-HSCT is part of the clinical guidelines for treatment of appropriate patients with
AML or ALL, select patients with CML, and select patients with other hematologic malignancies
Stem Cell Source – Anatomic Site
Bone Marrow
Cells are obtained through a bone marrow harvest
Procured through multiple needle aspirations into
the posterior iliac crest
Obtained under general or regional anesthesia
Peripheral Blood
Cells are obtained using apheresis
Umbilical Cord Blood
Pharmacist Role in the Transplant Team
Lots of DTP’s in HSCT
Chemotherapy toxicity management:
Seizure prophylaxis
Some chemo agents in high dose can reduce seizure threshold
Mucositis
Mouth care, pain control
Nausea/vomiting
Antinauseants
Organ toxicities (hepatic, renal, etc)
Dose adjustments
Pharmacokinetic monitoring of chemotherapy agents (busulfan)
GVHD prophylaxis/treatment (allo):
Immunosuppression
Cyclosporine therapeutic drug monitoring
Prednisone Tapers
GVHD Symptom Management
Infection prophylaxis/treatment:
Management of febrile neutropenia
Prophylaxis for Pneumocystis, Herpes viruses, fungal infection
Treatment of infections
