Grand Rounds

Leukoerythroblastosis in a child with sickle cell disease - what’s the diagnosis?

Tânia Cristina Parreira Lança Pessoa¹, Joana Pais de Faria², Ana Cristina Silva Paulo da Costa e Castro², Marisa Raquel Inácio de Oliveira², Raquel Dias Batista Maia^2
1Pediatric Department, Hospital Nossa Senhora do Rosário, Unidade Local de Saúde do Arco Ribeirinho, Barreiro, Portugal, ²Pediatric Hematology Unit, Hospital Dona Estefânia, Unidade Local de Saúde de São José, Lisboa, Portugal

Address for Correspondence: Tânia C. Pessoa, Hospital Nossa Senhora do Rosário, Av. Movimento das Forças Armadas - Serviço de Pediatria, 2830-003 Barreiro, Portugal. Email: tania.cpessoa@gmail.com

Keywords: Aplastic anemia, Leukoerythroblastosis, Parvovirus B19, Sickle cell disease

Clinical Problem:
A 7-year-old girl with SCD, attending a routine consultation at her referral center, performed a laboratory evaluation that revealed hemoglobin (Hgb) 4,3 g/dL (baseline Hgb 8-9 g/dL), hematocrit 12.1%, reticulocyte count 11.90 x 10^9/L (0,64%), white blood cell (WBC) count of 68.74 x 10^9/L, neutrophils 46.19 x 10^9/L (67.2%), lymphocytes 16.02 x 10^9/L (23.3%), monocytes 5.50 x 10^9/L (8%), eosinophils 0.76 x 10^9/L (1.1%), basophils 0.27 x 10^9/L (0.4%), platelets 737 x 10^9/L. Peripheral blood smear showed marked anisopoikilocytosis, some drepanocytes, blister cells, many erythroblasts, and myeloid left shift, without abnormal hematolymphoid cell populations. The remaining blood test results were unremarkable (normal renal function and electrolytes, total bilirubin 1.08 mg/dL, aspartate aminotransferase 84 U/L, alanine aminotransferase 19 U/L, lactate dehydrogenase 1604 U/L, C-reactive protein 7.5mg/L, ferritin 703 ng/mL, normal folic acid and vitamin B12 levels).
The only notable symptoms were mild intermittent low back pain with a 3-day duration and acute fatigue during major physical activities. She presented a good general condition, pale but hydrated mucous membranes, fever 38ºC (first febrile peak), tachycardia (150 bpm), systolic murmur and no organomegalies. Given these findings, the child was admitted to the hospital.
Etiologic evaluation revealed positive parvovirus B19 IgG and IgM antibodies and, subsequently, detection of parvovirus B19 in her blood by polymerase chain reaction (PCR). The remaining serologies showed cytomegalovirus (CMV) IgG positive and IgM negative antibodies; Epstein-Barr virus (EBV) IgG positive and IgM negative antibodies; Epstein-Barr virus nuclear antigen (EBNA) positive and Mycoplasma pneumoniae IgG and IgM negative. CMV and EBV PCR were also negative, as well as PCR for influenza A and B and SARS-CoV-2.
The child received a red blood cell (RBC) transfusion and intravenous fluid therapy. Within 12 hours, laboratory results showed improvement with Hgb 7.4 g/dL, WBC 38.65 x 10^9/L, platelets 677 x 10^9/L. After an additional 48 hours, Hgb increased to 8.3 g/dL without further transfusions, WBC decreased to 13.55 x 10^9/L, platelets to 574 x 10^9/L, and reticulocytes rose to 20.56%, indicating a return of Hgb to baseline levels, reticulocytosis, and resolution of leukocytosis. The patient was discharged on the third day from admission.

Is the association with leukoerythroblastosis a red flag regarding malignancy?