AML-M3; acute promyelocytic leukemia
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Epidemiology
2-3% of AML
Pathology
- hypergranular promyelocytes
- often many Auer rods/cell
- may have reniform or bilobed nuclei
- associated coagulopathy
Genetics
- t(15,17) associated with better prognosis
- abnormalities in chromosomes associated with poorer prognosis
- SP140 may play a role
- t(15;17)(q24;q21) involving PML with RARA
- transcript arrests leukemic cells in promyelocyte stage[2]
- t(11;17)(q32;q21) involving ZBTB16 with RARA
- t(5;17)(q32;q11) involving NPM1 with RARA
Clinical manifestations
- bleeding from thrombocytopenia & DIC
- fever, diaphoresis, malaise may be noted
- disseminated intravascular coagulation (DIC) unique among acute leukemias
Laboratory
- PCR/ISH for acute promyelocytic leukemia (see Genetics)
- t(15;17)(q24;q21) involving PML with RARA
- evidence of disseminated intravascular coagulation
- complete blood count (CBC): thrombocytopenia
- peripheral blood smear: schistocytes (DIC)
- elevated plasma D-dimer[2] (DIC)
- prothrombin time & aPTT may be elevated (DIC)
- fibrinogen in plasma may be low (DIC)
- complete blood count (CBC):
- peripheral blood smear:
- immature granulocytes, promyelocytes
- schistocytes
Management
- all-trans retinoic acid (ATRA)
- soon as possible if acute promyelocytic leukemia is suspected without waiting for conformation[2][5]
- releases block in promyelocyte maturation
- alone produces remissions of short duration
- resolves disseminated intravascular coagulation[2]
- anthracyclines in combination with ATRA produce remission of longer duration & possibly cures in 50-60% of patients
- ATRA + arsenic trioxide
- may be treatment of choice for initial therapy[4]
- equivalent to ATRA + anthracycline
- may induce a differentiation syndrome characterized by hypoxia, pulmonary infiltrates & fever
- glucocorticoids (dexmethasone) with brief interruption of therapy is effective for differentiation syndrome
- refractory cases
- arsenic trioxide is used for refractory cases[3]
- butyrate is also used for refractory cases
- allogeneic stem cell transplantation
- generally NOT recommended during 1st remission
More general terms
Additional terms
- Auer rod
- chromosomal translocation t15q22:17q11 (fps, AML-M3)
- PCR/in-situ hybridization for acute promyelocytic leukemia
- promyelocyte
- retinoic acid receptor alpha; RAR-alpha; nuclear receptor subfamily 1 group B member 1 (RARA, NR1B1)
- transcription factor PML; tripartite motif-containing protein 19; RING finger protein 71 (PML, MYL, RNF71, TRIM19)
References
- ↑ Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 726
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022
- ↑ 3.0 3.1 Powell BL, Moser B, Stock W, Gallagher RE et al Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20705755
- ↑ 4.0 4.1 Lo-Coco F, Avvisati G, Vignetti M et al Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23841729
- ↑ 5.0 5.1 Altman JK, Rademaker A, Cull E et al Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res. 2013 Sep;37(9):1004-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23768930