Systematic review about etiologic association to the leukoerythroblastic reaction

Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes, myeloblasts, and blasts) as well as, exclusively in myelofibrotic disorders, teardrop cells in the peripheral blood (J Pathol Bacteriol, 42, 1936, 541; Semaine Med, 22, 1902, 373). Research on how to interpret LER and its meaning in clinical practice is scarce, and there is no consensus on the diagnostic criteria. We summarize the current evidence with the aim of clarifying the knowledge on this subject.

We conducted a comprehensive search of the PubMed-MEDLINE, EMBASE and ELSEVIER databases, the Cochrane Library, Google Scholar, and medical journals to identify relevant papers.

Our search identified 425 papers, of which, 35 (11 trials and 24 case reports) ultimately met the inclusion criteria. These showed two principal groups of diseases associated with leukoerythroblastosis (LEB), corresponding to solid and hematological malignancies. The other etiologies, in order of frequency, were hemolytic diseases, infection, and others, while hemorrhage was only reported in the trials group.

The literature on LER is scarce and heterogeneous. The etiological factors of LER are diverse, and its presence in malignant disease is an indicator of disease progression and an adverse prognosis suggesting poor survival. In those cases where LER had neither hematological nor solid neoplasms, its manifestation, prognosis and its impact on our daily clinical practice are unknown.