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Decrease of CD4+ and B-lymphocyte populations is not associated with severe infectious complications in children with
Stavroula Kostaridou1, Sophia Polychronopoulou, Katherine Psarra
1Department of Pediatric Hematology/Oncology, Aghia Sophia Children's Hospital, Athens, Greece.
Insights
Children with acute lymphoblastic leukemia (ALL) undergoing maintenance therapy show suppressed immune systems, specifically reduced lymphocytes and immunoglobulins. Despite this, they experience minor infections without increased severity during this phase.
Area of Science:
- Pediatric Oncology
- Immunology
- Hematology
Background:
- Maintenance therapy for childhood acute lymphoblastic leukemia (ALL) can impact immune function.
- The specific alterations in lymphocyte subpopulations and immune competence during this phase are not well understood.
- Infectious complications in ALL patients during maintenance, especially without neutropenia, require further investigation.
Purpose of the Study:
- To assess lymphocyte subpopulation disturbances during maintenance therapy for childhood ALL.
- To determine the incidence, type, and severity of infections during maintenance in the absence of neutropenia.
- To evaluate immune competence in children with ALL during maintenance therapy.
Main Methods:
- Studied 28 children with ALL undergoing maintenance therapy (ALL-BFM 90/95 protocol).
- Analyzed complete white blood cell (WBC) counts and peripheral blood lymphocyte (PBL) subsets using flow cytometry.
- Measured serum immunoglobulin levels (IgG, IgA, IgM) and recorded all infectious episodes.
- Compared findings with 41 age-matched immunocompetent children.
Main Results:
- Significantly lower absolute WBC and PBL counts were observed in ALL patients compared to controls.
- Key lymphocyte subsets, including B-lymphocytes, total CD4+, and memory CD4+ cells, were significantly decreased.
- All patients exhibited lower serum immunoglobulin levels.
- 22 of 28 patients experienced 74 episodes of minor infections (mostly viral respiratory), with no prolonged hospitalizations.
Conclusions:
- Children with ALL on maintenance therapy exhibit profound immunosuppression characterized by reduced lymphocyte counts and immunoglobulin levels.
- Despite significant immune suppression, the incidence and severity of systemic infections were not notably increased during this phase.
- Further research may be needed to understand the clinical implications of these immune alterations in pediatric ALL patients.
Abstract:
The suppression of lymphopoiesis and immune competence during the maintenance phase in children with acute lymphoblastic leukemia (ALL) and the occurrence of infectious complications remain an unexplored area. In this study we assessed lymphocyte subpopulation disturbances during maintenance for childhood ALL along with the incidence, type, and severity of infections that occur during that period in the absence of neutropenia. Twenty-eight children (13 boys, 15 girls) with ALL aged 3-14 years (median 7 years) and treated according to the ALL-BFM 90/95 protocol were studied during maintenance for ALL. Complete white blood cell (WBC) counts and peripheral blood lymphocyte (PBL) analyses were performed. Major lymphocyte subsets (CD19+, CD3+CD4+, CD3-CD8+, CD3-CD16+CD56+, CD45RA-, CD45RO+) and markers of T-cell activation (CD25, CD38, CD69, HLA-DR) were analyzed with flow cytometry. Serum immunoglobulin G (IgG), IgA, and IgM levels were measured by a nephelometric assay. All infectious episodes during the study period were recorded in detail. Additionally, 41 age-matched immunocompetent children were used as controls. Absolute WBC counts (median, 3627/microL) and PBL counts (median, 1206/microL) were significantly below the age-adjusted control values (7400/microL and 2673/microL, respectively; P < .0001). B-lymphocyte, total CD4+, and memory CD4+ (CD4+CD45RO+) subsets were also significantly decreased (33/microL versus 377/microL [P < .0001], 531/microL versus 1045/microL [P < .01], and 80/microL versus 299/microL [P < .001], respectively). Significantly lower immunoglobulin levels were found in all patients. Twenty-two of the 28 patients presented with 74 episodes of a variety o minor infections (mostly respiratory viral [39], skin [7], and gastrointestinal [3]), none demanding prolonged hospital treat ment. Our findings demonstrate a profound immunosuppression throughout maintenance therapy in children with ALL tha has no major clinical impact in terms of increased incidence or severity of systemic infections.
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