COVID-19 and acute promyelocytic leukemia: similar clinical spectrum and diagnostic challenges

COVID-19 is an infectious disease caused by the severe acute respiratory syndrome virus (SARS-CoV-2) (Lu et al. 2020). It presents, among other clinical signs, with cytopenias or leukocytosis and coagulopathy, laboratory fi ndings that are also observed in about 80% of patients with acute promyelocytic leukemia (APL). APL is a rare hematological neoplasm characterized by the translocation t(15;17)(q22;q11-21) and fusion of the PML-RARα gene (Rowley et al. 1977). The initial clinical picture is severe; however, if diagnosed early and treatment is immediately established, and high cure rates can be achieved (Kamath et al. 2019). Here we present a report of a patient for whom the initial diagnostic impression was COVID-19 on account of clinical signs of severe acute respiratory syndrome presented in the midst of the pandemic caused by SARS-CoV-2. We describe the laboratory investigations that were essential to identify the concomitant diagnosis of APL masked by COVID-19 symptoms.

Case report: A 27-year-old man presented with fever, unexplained asthenia, ecchymosis, epistaxis, mild gingival hemorrhage, anosmia, skin pallor, cough, dyspnea, and 90% oxygen saturation. He underwent testing for SARS-CoV-2 using RT-PCR from a nasopharyngeal swab in June 2020, the result of which demonstrated the presence of SARS-CoV-2 RNA. Laboratory investigation of coagulation times revealed severe coagulopathy. Analysis of inflammation markers (C-reactive protein, procalcitonin, and ferritin) showed marked increases in all markers, confirming a systemic inflammatory syndrome. His complete blood count revealed significant anemia, leukopenia, thrombocytopenia, and left shift toward promyelocytes. The results of laboratory tests are shown inTable I.

Table
Laboratory parameters with reference values adjusted for sex.

Parameter	Patient	Normal range
Hb (g/dL)	5.3	12.0–16.0
WBC (mm³)	2,300	4,000–11,000
Platelet (mm³)	14,000	150,000–450,000
PT (seconds)	21.4	9.3 – 13.3
aPTT (seconds)	53.2	25.4 – 36.9
Fibrinogen (mg/dL)	72.0	180.0–350.0
D-dimer (ng/mL)	28.000	< 500.0
LDH (U/L)	629.00	120.0–246.0
Creatinine (mg/dL)	0.59	0.60–1.10
Urea (mg/dL)	32.0	15.0–45.0
ALP (U/L)	80.0	35.0–104.0
GGT (U/L)	96.0	< 38.0
AST (U/L)	95.0	< 40.0
ALT (U/L)	73.0	10.0–49.0
CRP (mg/dL)	28.30	< 1.0
PCT (ng/dL)	13.7	< 0.1
Ferritin (ng/dL)	739.0	22.0–322.0

• Hb: hemoglobin; WBC: white blood cell; PT: prothrombin time; aPTT: activated partial thromboplastin time; ALP: alkaline phosphatase; GGT: gamma glutamyl transferase; AST: aspartate aminotransferase; ALT: alanine transferase; CRP: c-reactive protein; PCT: procalcitonin.

Based on the analysis of the initial laboratory results, venous thromboembolism prophylaxis was started using low molecular weight heparin, corticosteroid, and empirical antimicrobial treatment with cefepime, vancomycin, and liposomal amphotericin B. Then, due to the increase in promyelocytes observed in the blood counts performed after the diagnosis of COVID-19, the patient was evaluated by the infectious disease and hematology teams, who decided to perform a bone marrow biopsy to investigate the possibility of acute leukemia associated with COVID-19. The bone marrow was sent for immunophenotyping by flow cytometry and to assay for molecular rearrangementPML- RARα, due to the suspicion of acute promyelocytic leukemia.

Immunophenotyping by multiparametric flow cytometry revealed a profile compatible with APL, with the presence of 73.8% blasts with elevated SSC (side scatter) and FSC (forward scatter), heterogeneous expression of the CD13 antigen, and homogeneous expression of the CD33 antigen, in association with intracytoplasmic myeloperoxidase (MPO), CD117 and CD45 antigens. Antigens CD34 and HLA-DR, as well as antigens of T lymphoid lineage (CD3 and CD7), lineage B (CD19 and CD79a) and NK cells (CD56) were negative (Fig. 1). The presence of thePML-RARαfusion gene was confirmed by RT-PCR, thereby confirming the diagnosis of APL, as recommended by the WHO (Swerdlow et al. 2017).

Figure 1
Result of the analysis by fl ow cytometry. The cells stained in red indicate the “blasts” of acute promyelocytic leukemia and the cells stained in blue indicate the residual lymphocytes. Immunophenotyping was performed using a panel of monoclonal antibodies standardized by the EuroFlow group. The acquisition of the events was performed in the fl ow cytometer FACS Canto II (Becton Dickinson-BD) and the data were analyzed using the Infi nicyt^TM software.

Immediately after confirming the diagnosis of APL, the patient was requested to be transferred to the oncology hospital to begin therapy with all-trans-retinoic acid. However, after three days of hospitalization in the emergency care unit, the patient developed severe respiratory failure and successive cardiac arrests, after which he died.

The importance of reporting this case is that it is difficult to rule out the hematological neoplasms underlying COVID-19. Even mild cases of COVID-19 can exacerbate the severity of hematological neoplasms, increasing the mortality rate among patients with coincident hematological neoplasms and COVID-19 (Passamonti et al. 2020). In the specific case of APL, which usually presents with coagulopathy, thrombocytopenia, and hyperfibrinolysis, the diagnosis and management of this neoplasia was extremely challenging in this patient diagnosed with COVID-19, which is also related to thrombotic events (Bikdeli et al. 2020).

In conclusion, hematological neoplasms can present complex and diverse clinical manifestations, representing a great challenge for clinical diagnosis. Multidisciplinary assessment and meticulous differential diagnosis, especially including neoplasms whose clinical spectrum is similar to those of COVID-19, is crucial during the pandemic period.

REFERENCES

• BIKDELI B ET AL. 2020. Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of- the-Art Review. J Am Coll Cardiol 75: 2950-2973.
• KAMATH GR, TREMBLAY D, COLTOFF A, CARO J, LANCMAN G, BHALLA S, NAJFELD V, MASCARENHAS J & TAIOLI E. 2019. Comparing the epidemiology, clinical characteristics and prognostic factors of acute myeloid leukemia with and without acute promyelocytic leukemia. Carcinogenesis 40: 651-660.
• LU H, STRATTON CW & TANG YW. 2020. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol 92: 401-402.
• PASSAMONTI F ET AL. 2020 ITA-HEMA-COV Investigators. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol 7: e737-e745.
• ROWLEY JD, GOLOMB HM & DOUGHERTY C. 1977. 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1: 549-550.
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Publication Dates

• Publication in this collection
  05 Aug 2022
• Date of issue
  2022

History

• Received
  8 Feb 2021
• Accepted
  1 Apr 2021