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.