Children Transient Pancytopenia Preceding Hybrid Acute Leukemia
Authors: Yang Donglin , Bai Yusheng , Qin Lan , Du Xiaojun , Ma Xihu , Liu Wei , Feng Sizhou , Han Ming-Zhe 
Published: April 2020

Abstract
Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL) is a rare event usually affecting children and adolescents. The aplastic episode may last for only some days or a few weeks and is generally followed by temporary normalization of peripheral blood counts prior to the subsequent development of overt ALL. ALL, usually of B-cell common type and infrequently of T-cell type, occurs in most of such cases within 6 months from the onset of the marrow aplasia. To the best of our knowledge, pre-ALL with a hybrid acute leukemia (HAL) immunophenotype has not been reported. The mechanism of pre-ALL remains obscure. Parvovirus B19, which exhibits a marked tropism to human BM and replicates only in erythroid progenitor cells causing anemia, thrombocytopenia, neutropenia, or a combination of all three in immunocompromised patients, may be one of possible explanations. We present the first case of B19-associated pre-ALL characterized by a HAL (T lymphocyte and myelocyte) immunophenotype. An 11-year-old boy presented with fever and rhinorrhagia. On physical examination, he had no lymphadenopathy or hepatosplenomegaly. A complete blood cell count revealed severe pancytopenia with haemoglobin 3.5g/L, white blood cells (WBC) 0.65×109/L and platelet count 3×109/L. Iliac bone marrow aspiration (BMA) showed hypoplasia with an absence of lymphoblasts. A diagnosis of acute aplastic anaemia was suspected, and he was treated with supportive treatment (antibiotics, granulocyte colony-stimulating factor, transfusion of blood and platelets). During a follow-up visit, 2 weeks after presentation, peripheral blood parameters and BMA became normal, and traditional Chinese drug was administered. At 8 weeks after presentation, he presented with leukocytosis. Physical examination Revealed extensive superficial lymphadenopathy, with no hepatosplenomegaly. Parvovirus B19 IgG and IgM antibodies were positive by enzymelinked immunosorbent assay, whereas B19- specific DNA was negative. Hepatitis virus A, B and C, HIV, EBV, and CMV serology were negative. The peripheral blood counts revealed WBC of 24×109/L with 5% blast cells and a BMA showed hyperplasia with 95% blast cells. Analysed by flow cytometry, the blast cells were divided into 2 groups: the major one (68% of all cells), being positive for the CD38, CD10, CD7, CD4, m/C CD3 antigens; another minor one (23%), being positive for the MPO, CD33, CD11, CD13, CD15, CD38, CD10, CD4, CD7, m/C CD3 antigens. Positive expression of membrane antigens supported a diagnosis of HAL (T lymphocyte and myelocyte). Conventional cytogenetic analysis revealed normal karyotype and T-cell receptor γ gene rearrangement was noted. The patient achieved complete remission after one cycle of VDCAD regimen (vincristin, daunorubicin, cyclophosphamide, cytarabine and dexamethasone). However, 1 months after complete remission, the patient relapsed. He achieved the second complete remission after reinduction regimen and gived up further chemotherapy. In this report, we document that pre-ALL may precede HAL (T lymphocyte and myelocyte) for the first time. B19 is possibly one of several factors capable of triggering the onset of pre-ALL.