Acute promyelocytic leukemia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]

Differentiating Acute promyelocytic meukemia from other Diseases

Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a bone marrow biopsy or aspirate. Definitive diagnosis requires testing for the RARα fusion gene. This may be done by polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH), or conventional cytogenetics of peripheral blood or bone marrow.

Characteristic	Causes	Laboratory abnormalities	Physical examination	Therapy	Other associations
Acute promyelocytic leukemia	Prior exposure to alkylating agents Prior exposure to topoisomerase II inhibitors Translocation between chromosomes 15 and 17 Creation of PML-RARalpha gene product Differentiation block in myeloid cells	Low white blood cell count (typically) Anemia Neutropenia Thrombocytopenia Low fibrinogen Elevated prothrombin time (PT) Elevated partial thromboplastin time (PTT)	Mucosal bleeding Petechiae Ecchymoses Evidence of infection Pallor Thrombosis	All-trans retinoic acid (ATRA) Arsenic trioxide Cytarabine Anthracycline	Presence of Auer rods in promyelocytes High risk for early death from hemorrhagic complications
Acute myeloid leukemia	Chromosomal instability Sporadic mutations Prior exposure to benzene Prior exposure to alkylating agents Prior exposure to topoisomerase II inhibitors Germline RUNX1 mutation	Anemia Thrombocytopenia Neutropenia Elevated LDH Elevated uric acid Elevated phosphorus Elevated potassium Low calcium Greater than 20% myeloblasts on bone marrow aspirate	Pyrexia Evidence of infection Pallor Mucosal bleeding (less common than in acute promyelocytic leukemia) Bruising (less common than in acute promyelocytic leukemia)	Cytarabine Anthracycline Enasidenib Liposomal daunorubicin plus cytarabine Gemtuzumab ozogamycin Midostaurin Stem cell transplant	Variable prognosis based on cytogenetic and molecular profile Four new FDA-approved therapies became available in 2017
Acute lymphoblastic leukemia	Chromosomal instability Sporadic mutations	Anemia Thrombocytopenia Neutropenia Elevated LDH Elevated uric acid Elevated phosphorus Elevated potassium Low calcium Greater than 20% lymphoblasts on bone marrow aspirate	Neurologic deficits Pallor Lymphadenopathy	HyperCVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) R-HyperCVAD (inclusion of rituximab) Peg-asparaginase Intrathecal methotrexate Intrathecal cytarabine Blinatumomab (bispecific T cell engager) Inotuzumab ozogamycin (anti-CD22 antibody) Tisagenlecleucel (chimeric antigen receptor T (CAR-T) cell therapy) Stem cell transplant	Sanctuary sites include the central nervous system (CNS) and testes
Chronic myeloid leukemia	Translocation between chromosomes 9 and 22 Creation of BCR-Abl gene product	Elevated white blood cell count Presence of white blood cell precursors at various stages of maturation Presence of excess metamyelocytes, basophils, eosinophils, and band cells	Splenomegaly Abdominal tenderness Pallor Evidence of infection	Imatinib Nilotinib Dasatinib Bosutinib Ponatinib Omacetaxine* Immunosuppressive therapy	High response rate to tyrosine kinase inhibitors Risk for development of T315I kinase domain mutation Typically does not require stem cell transplant
Chronic lymphocytic leukemia	Chromosomal instability Sporadic mutations Infections	Elevated absolute lymphocyte count (in all stages) Presence of >5000 clonal B cells per microliter in peripheral blood Anemia (in Rai stage III) Thrombocytopenia (in Rai stage IV)	Lymph node enlargement in Rai stage I Splenomegaly in Rai stage II Hepatomegaly in Rai stage II Pallor Bleeding	Fludarabine Cyclophosphamide Rituximab Obinutuzumab Ofatumumab Ibrutinib Venetoclax	Associated with autoimmune hemolytic anemia, which occurs in 10-25% of patients with CLL Associated with immune thrombocytopenia purpura Associated with pure red cell aplasia Treatment with corticosteroids or anti-leukemic therapy will correct the autoimmune complications of CLL