What are the typical presentations of Acute Promyelocytic Leukemia (APL)?

From the Guidelines

Acute promyelocytic leukemia (APL) is a medical emergency that typically presents with symptoms of pancytopenia, including fatigue, weakness, infections, and bleeding, and requires immediate treatment with all-trans retinoic acid (ATRA) to reverse the coagulopathy, even before genetic confirmation. The hallmark feature of APL is a severe coagulopathy with disseminated intravascular coagulation (DIC), which can cause life-threatening hemorrhage. Patients often exhibit petechiae, ecchymoses, gingival bleeding, epistaxis, or intracranial hemorrhage. Laboratory findings include thrombocytopenia, anemia, and abnormal coagulation studies with elevated PT, PTT, decreased fibrinogen, and elevated D-dimer levels. Some key points to consider in the management of APL include:

• The use of supportive measures to counteract the coagulopathy, such as transfusions of fibrinogen and/or cryoprecipitate, platelets, and fresh-frozen plasma, to maintain the fibrinogen concentration above 100-150 mg/dL, the platelet count above 30-50 × 10^9/L, and the INR below 1.5 1.
• The importance of monitoring platelet counts and routine coagulation parameters, including prothrombin time, activated partial thromboplastin time, and thrombin time, as well as levels of fibrinogen and fibrinogen-fibrin degradation products, at least daily and more frequently if required, until disappearance of all clinical and laboratory signs of the coagulopathy 1.
• The need to avoid central venous catheterization, lumbar puncture, and other invasive procedures before and during remission induction therapy due to the high risk of hemorrhagic complications 1.
• The use of ATRA and arsenic trioxide (ATO) as the cornerstone of treatment for APL, with the addition of chemotherapy in certain cases 1.
• The importance of prophylactic corticosteroids to reduce the risk of APL differentiation syndrome 1. Overall, the management of APL requires a multidisciplinary approach, with careful attention to supportive care, monitoring, and treatment with ATRA and ATO, as well as chemotherapy in certain cases.

From the Research

Acute Promyelocytic Leukemia Presentation

• Acute promyelocytic leukemia (APL) is characterized by the proliferation of blasts with distinct morphology and a specific balanced reciprocal translocation t(15;17) 2.
• APL is associated with life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC) 2, 3.
• The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL 2.
• However, hemorrhage-related death during the early phase of therapy remains a serious problem, with population-based studies showing that the incidence of early death during induction chemotherapy is nearly 30% 2.

Clinical Features

• Bleeding is the leading cause of death for patients with APL, with overt DIC occurring in 77.6% of patients 3.
• Severity of DIC is associated with bone marrow leukemic cell percentages, but unrelated to bleeding 3.
• Patients with bleeding have significantly higher WBC counts, more prolonged prothrombin time (PT), and activated partial thromboplastin time (APTT) 3.
• PT is valuable in prediction of bleeding, with patients having PT ≧ 5 s having a relative risk of 6.14 for bleeding 3.

Treatment Outcomes

• Recombinant human soluble thrombomodulin (rTM) has been used for treatment of DIC since 2008 in Japan, and has been shown to produce potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL 2, 4.
• rTM administration may be an effective, safe, and feasible therapeutic modality, producing a rapid resolution without progression of hemorrhage 4.
• Advances in the management of coagulopathy in APL have improved patient outcomes, but hemorrhagic death still remains a major problem during the early phase of treatment 5.
• Thrombosis is also a non-negligible cause of morbidity and mortality in patients with APL, and can occur concomitantly with hemorrhagic events 5, 6.