Premium
Prolonged but reversible neutrophil dysfunctions differentially sensitive to granulocyte colony‐stimulating factor in children with acute lymphoblastic leukaemia
Author(s) -
Lejeune Marylene,
Ferster Alina,
Cantinieaux Brigitte,
Sariban Eric
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00916.x
Subject(s) - chemotherapy , granulocyte , toxicity , phosphatidylserine , granulocyte colony stimulating factor , medicine , immunology , neutrophile , flow cytometry , chemiluminescence , gastroenterology , biology , chemistry , inflammation , biochemistry , phospholipid , membrane , organic chemistry
Treatment of average‐risk acute lymphoblastic leukaemia (ALL) in children consists of 6 months of intensive chemotherapy followed by 18 months of maintenance therapy. Polymorphonuclear leucocyte (PMN) functions from children with ALL were studied in order to evaluate and compare the toxicity of the initial intensive treatment with the toxicity of the subsequent less intensive maintenance treatment. H 2 O 2 and O − 2 production, evaluated by chemiluminescence, were significantly decreased during the intensive period but returned to normal values when maintenance therapy began. In contrast, bactericidal activity against Gram‐positive and Gram‐negative micro‐organisms remained at low levels throughout the treatment but returned to normal values in patients off chemotherapy. PMN from patients on maintenance therapy exhibited an excess of morphological changes associated with apoptosis. This was confirmed by standard two‐colour flow cytometry which revealed an increase in the number of hypodiploid cells, and increased expression of membrane phosphatidylserine together with a drastic reduction in the expression of the Fcγ receptor IIIB (CD16). These defective PMN were differentially sensitive to the effects of granulocyte colony stimulating factor (G‐CSF): G‐CSF induced similar increase in chemiluminescence in control and patient PMN; GSF partially corrected the defective bactericidal activity; G‐CSF did not affect the accelerated PMN apoptosis. These observations indicate that ALL children undergoing chemotherapy present PMN defective functions which are partially sensitive or even resistant to G‐CSF.