======Acute Myeloblastic Leukemia======

=====Epidemiology=====
  * Most common acute leukemia in adults
  * Median age at diagnosis 65
  * M > F

=====Etiology=====
  * Can arise from an underlying hematologic disorder (MDS, ET/PV)
  * Consequency of prior therapy
    * Topoisomerase agents
    * Radiation
  * Chemical: smoking, dry cleaning, paint
  * Family/hereditary: Trisomy 21, Fanconi, ataxia telangectasia

=====Manifestations=====
  * Marrow failure: fatigue, dyspnea, easy bleeding/bruising, infection
  * Extramedullary spread
    * Lekemia cutis
    * Gingival involvement (M5 or ?myeloblastic)
    * Myeloid sarcoma
  * WBC variable
  * DIC in APL

=====Diagnosis=====
  * Blasts 20% in bone marrow or peripheral blood
  * Cytogenic t(8, 21), inv 10, t(15,17) often with less than 20%
  * Also sometimes less than 20% with myeloid sarcoma
  * Auer rods not always present, but nearly pathognomonic

=====Classification=====
  * FAB: M1 through M5
  * AML with MDS
  * AML NOS

=====Genomics=====
  * FLIP3
  * TP53
  * IDH1/IDH2

=====Risk Stratification===== 
^  Risk category  ^ Management  ^  ^
| Poor | Treatment -> transplant | complex karyotype, TP53 |
| Intermediate | Treatment -> transplant |  |
| Favorable | Treatment, no transplant | t(15,17) or APL |

* Usually allogeneic transplant

=====Evaluation=====
  * H&P
  * ECOG
  * CBC with diff, CMP, uric acid, LDH
  * Coags
  * BM with cytogenetics and molecular studies
  * +/- CNS imaging if neuro symptoms
  * +/- LP (FLIP3, TP53, M5, etc.)
  * TTE/MUGA (anthrocyclines)
  * MUGA
  * Antimicrobials

=====Treatment=====
  * Induction: age, ECOG, cytogenics
    * Usually 7+3
    * Hypomethylating agent + venetoclax
      * older
      * unable to tolerate
      * complex cytogentics (TP53)
    * recheck BM in 28 days
      * Remission: less than 5% blasts
      * Consider reinduction if more than 5% blasts
        * 5+3
        * higher intensity (cytarabine, FLAG-IDA, CLAG-M)
  * Consolidation
    * HIDAC 3-4 cycles
    * Liposomal cytarabine/daunorubicin 1-2 cycles
    * Hypomethylating agent + venetoclax
  * Other FDA approved drugs
    * Glasdegib
    * Ivosidenib
    * Enasidenib
    * ?

=====Supportive care=====
  * Transfusions
    * Leukodepleted
    * irradiated
  * PPx
  * Prompt treatment of neutropenic fever
  * G-CSF/GM-CSF for septic shock: usually not given due to theoretical risk of inducing more blasts

=====Acute Promyeoblastic Leukemia=====
  * Highly curable
  * Frequently associated with DIC with previous regimen of cytarabine and daunorubicine
  * Tretinoin/Antimicrobials
    * side effect: differentiation syndrdome, treat with steroids
  * Arsenic Trioxide: monitor QT
  * Idarubicin? Mylotarg? For high-risk (WBC > 10)