Case Presentation:
A 32-year-old female patient was presented to emergency department with hematuria, heavy menorrhagia, and mild epistaxis. Scattered petechiae and ecchymosis were observed during physical examination. Initial work-up showed high WBC count and accordingly patient was admitted for further evaluation.
Complete blood cell count showed WBC 93.60 × 109/L, hemoglobin (Hb) 6.6 g/dL, platelets (PLT) 32 × 109/L and WBC differential revealed 68% blasts. The coagulation profile was abnormal; prothrombin time PT and activated partial thromboplastin time APTT were prolonged [PT 18.9 reference range 11,9-15,9 seconds); APTT 42,49 (reference range 28,7-39,7 seconds)], and D-dimer was elevated to 10.11 μg/ml (reference range is ≤0.5 μg/ml). Renal and liver profiles were unremarkable.
Bone marrow biopsy revealed a hypercellular marrow with 94% blasts and abnormal promyelocytes characterized by a bilobed or butterfly nucleus and abundant cytoplasm with azurophilic granules and rare Auer rods (shown in Fig.1a-1c).
Immunophenotyping of bone marrow aspirate by multi-parameter flow cytometry identified the blast cells that were positive for CD45 with an intermediate to high side scatter. The blasts showed positivity for CD34+ (partial), CD117+, CD33+, CD13+, MPO, CD64, CD38, CD58, CD11c (partial), CD11b+, CD56+ (dim), CD2+, and CD7+. They were negative for CD14, HLA-DR, and all other T/B lineage antigens (shown in Fig. 1d-1e].
Fluorescence in situ hybridization (FISH) was positive for translocation t(15;17) and quantitative real-time polymerase chain reaction (qPCR) confirmed the presence of short isoform bcr-3 of PML/RARα (shown in Fig. 2a-2c). As a routine work-up for mutation testing in AML, FLT3-ITD was detected by PCR followed by gel electrophoresis (shown in Fig. 2d].
The patient was diagnosed with APL and was started on ATRA and ATO plus IDA protocol as an induction regimen. Prednisone 100 mg daily was administered for ATRA syndrome prophylaxis and platelets were infused to maintain the patient’s platelets above 50 ×109/L, as well as fresh frozen plasma to correct coagulopathy.
After eight days of ATO administration, the patient developed fever (39 °C), chest tightness and shortness of breath. Upon examination, right arm was swollen and mildly tender. Chest X-ray showed mild bilateral infiltrate mainly right side. Doppler ultrasound of right upper limb confirmed acute deep vein thrombosis (DVT) involving right median and distal cephalic vein. Computed tomography pulmonary angiogram showed no evidence of pulmonary embolism. Head Computerized Tomography was unremarkable. Electrocardiogram revealed sinus tachycardia. Considering these as promyelocyte differentiation syndrome, chemotherapy was put on hold and patient was placed under continuous oxygen therapy, with 10 mg BID of dexamethasone. Enoxaparin 80 mg was administered daily for upper DVT. Three days after chemotherapy was on hold, symptoms improved, and chemotherapy was continued.
The patient then entered a bone marrow suppression period and developed a second episode of high grade fever. Blood culture was positive for methicillin-susceptible Staphylococcus aureus. Patient was started on cefazolin, and ciprofloxacin. Caspofungin was also given considering the possibility of fungal infection. During that time chemotherapy was put on hold and then resumed after the infection was resolved.
Repeated bone marrow was done on the 51st day of induction chemotherapy, which has been interrupted several times, and it showed complete remission. PML/RARα by qPCR was below detection limit and FLT3-ITD was not detected (shown in Fig. 2b). At the time of writing this report, patient was started on the consolidation chemotherapy.