Smartly linked APL diagnostics
A clinical challenge: acute promyelocytic leukaemia (APL) is a medical emergency, but it is rare, and symptoms are non-specific.
APL is a distinct form of acute myeloid leukaemia (AML), characterised by the presence of abnormal promyelocytes that trigger dysregulated coagulation very frequently resulting in disseminated intravascular coagulopathy (DIC). DIC can cause life-threatening bleeding and thrombotic complications, especially in the early stages of the disease. Consequently, haemostasis plays a critical role in the clinical presentation of this rare disease. Effective management of these coagulation abnormalities is vital for the successful treatment and improving the prognosis of patients with APL.
APL is highly curable if recognised early and promptly treated with agents such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) that induce differentiation of the malignant clone, thereby reducing the DIC trigger, but delay results in the rapid evolution of bleeding abnormalities with a high mortality rate. Improved linkage of diagnostic information from haemostasis, haematology, and clinical flow cytometry allows for earlier recognition of suspected APL, followed by genetic confirmation, which is essential for the timely design of a targeted treatment plan. This contributes to a higher quality of care, especially for patients with such rare conditions, where rapid and accurate diagnosis is vital for improved outcomes.
Sysmex’s products can reduce uncertainty and assist clinicians in making timely decisions that prompt early interventions, ultimately improving patient outcomes and enhancing the quality of care.
Doctors must be empowered to make swift decisions based on comprehensive, reliable information continuously available during the treatment process. This is particularly critical for the care of APL patients as their clinical condition can change rapidly. Serial testing is also essential to confirm treatment success. The availability of multiple diagnostic test results facilitates rapid clinical decision-making, giving each patient the best chance of a cure.
Reference: Yilmaz M, Kantarjian H, Ravandi F. Acute promyelocytic leukemia current treatment algorithms. Blood Cancer J. 2021 Jun
30;11(6):123. doi: 10.1038/s41408-021-00514-3. PMID: 34193815; PMCID: PMC8245494.
Comprehensive diagnostics and timely action are key
A 32-year-old female, previously well, attended her general practitioner (GP) because of fever and fatigue. Physical examination revealed some bruising but was otherwise normal. The GP suspected a seasonal acute viral illness and advised the patient to return if she did not feel better in a couple of days.
That evening, the patient was seen at the emergency department because of a severe nosebleed. A complete blood count and differential (CBC DIFF) and coagulation screen were requested.
- The blood count results were as follows: haemoglobin 8.7 g/dL, white blood cell count (WBC) 2.1 x 109/L (neutrophils 0.6 x 109/L), platelet count (PLT) 49 x 109/L.
- The peripheral blood smear examination revealed abnormal promyelocytes, many of which exhibited bilobed nuclei and an abundance of cytoplasmic granules, including Auer rods, in keeping with APL.
- The coagulation screen results were in keeping with a disseminated intravascular coagulopathy (DIC): prothrombin time 14 seconds, activated partial thromboplastin time 29 seconds, fibrinogen 0.9 g/L, and D-dimer 15.7 mg/L (FEU).
The patient was admitted to hospital and all-trans retinoic acid (ATRA) therapy commenced immediately.
- Flow cytometry, performed on the peripheral blood, confirmed the presence of large numbers of primitive cells, with high FSC and SSC (due to size and granularity, respectively) and were CD117+, CD64+, CD33+ and CD13+ but HLA-DR and CD34 negative, highly suggestive of APL.
- FISH analysis confirmed a t(15;17)(q22;q12) translocation. Arsenic trioxide (ATO) was added to the ATRA therapy.
- The CBC revealed that the patient was low risk (WBC <10x109/L, PLT>40x109/L), hence no need for additional chemotherapy. She did, however, require a temporary dose reduction of ATO because of worsening neutropenia.
Subsequent CBC DIFF and coagulation test monitoring revealed an excellent treatment response, with full resolution of the neutropenia and coagulopathy.
Bone marrow immunophenotyping four weeks later confirmed that she had gone into complete remission. She continued with four cycles of consolidation therapy as an outpatient, during which no further side effects were observed.
Molecular testing was negative on therapy completion and the patient was asked to return for a CBC DIFF test every three months.
