Leukemoid reactions and chronic chronic myeloproliferative diseases in children: similarity and differences

Abstract

The publication presents three clinical cases with a similar debut of disease and changes in the hemogram in children under the age of 1. Patients were noted with: pale skin and pale visible mucous membranes, hepatolyenial syndrome, bilateral pneumonia, poor weight gain, anemia, changes in platelet count, increased value of lactate dehydrogenase (LDH) in serum, hyperleucocytosis and hyperplasia of granulocyte cells. Two patients had blasts, but no acute leukemia criteria in myelogram. These patients were diagnosed with leukemoid reaction (LR) for bilateral pneumonia, chronic myeloproliferative disease (СMPD)/chronic myelomonocytic leukemia (CMМL) with eosinophilia and with t(1; 5)(q21; q32) and rearrangement of the TPM3-PDGFRβ gene and juvenile myelomonocytic leukemia (JMML) with the mutation of the PTPNll gene (c.181G>A). Much attention is paid to pathological changes in the general blood test, histological and genetic aspects, clinical course of disease, differential diagnosis between the LR and the corresponding variant of hemoblastosis as well as to review of the literature.
In the first clinical case hemogram showed hyperleukocytosis of more than 170×109/l with rejuvenation in the leukocyte count before blasts, anemia, hypertrombocytosis of more than 1300×109/l, hepatolienal syndrome, which gave reasons to suspect СMPD, in particular JMML or CMML. With LR anemic syndrome is extremely rare. A child with LR anemia had hypochromic iron deficiency. In patients with CMPD/CMML and JMML iron deficiency was not detected, but there was a significant increase in serum vitamin B12 levels. Hyperosinophilia was determined in the second and third clinical cases. In addition to that lymphadenopathy was diagnosed. The patient with JMML was also diagnosed with hyperplasia of the lymph nodes in the mediastinum. A girl with CMPD/CMML had a specific skin lesion, which can be found in a third of patients with JMML. During histological examination of the lymph node and skin tissue similar changes were revealed in these individuals. Biopsy material was presented by monocytes cells with a large number of immature and mature eosinophils. CMPD/CMML associated with eosinophilia and JMML are extremely rare diseases in children. They are clinically similar and show similar lab test results. In these children the diagnosis was based on a combination of clinical, histological, immunohistochemical, molecular genetic methods. Therefore each doctor must be especially attentive to patients with hepatosplenomegaly, polylymphadenopathy, underweightness, changes in hemogram, such as eosinophilia, presence of intermediate forms of granulocytes, blastemia, monocytosis, normoblastosis with an altered number of platelets from hypertrombocytosis to moderate thrombocytopenia, increased LDH. The child should be referred for a consultation with a hematologist to verify the diagnosis using appropriate diagnostic criteria, including molecular. Final verification is possible only with the help of molecular genetic tests. Identification of the molecular genetic mutations allows to diagnose correctly and to choose the right treatment plan. Treatment with imatinib in children with t (1; 5) (q21; q32) and the rearrangement of the TPM3-PDGFRβ gene gives a chance of recovery with hematological remission. Imatinib should be recommended as the first treatment for these patients. The research was carried out in accordance with the principles of the Helsinki Declaration.
The study protocol was approved by the Local Ethics Committee (LEC) of all participating institution. The informed consent of the patient was obtained for conducting the studies.