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Impaired B-cell reconstitution in children after chemotherapy for standard or medium risk acute precursor
Verena Wiegering1, Jana Frank, Sandra Freudenberg
1Department of Pediatric Haematology, Hemostaseology, Oncology and Stem Cell Transplantation.
Insights
Childhood acute lymphoblastic leukemia (ALL) chemotherapy effectively treats cancer but severely impacts immunity. This study found that while T-cells recover quickly, B-cells, especially naive B-cells, remain depleted for years after treatment.
Area of Science:
- Pediatric Oncology
- Immunology
- Hematology
Background:
- Chemotherapy for childhood acute lymphoblastic leukemia (ALL) is effective but causes significant immune suppression.
- Understanding immune reconstitution post-therapy is crucial for long-term patient health.
Purpose of the Study:
- To investigate immune reconstitution, specifically T-cell and B-cell recovery, in children treated for ALL.
- To assess the duration and extent of immune disturbances following standard chemotherapy regimens.
Main Methods:
- A cohort of 48 children with standard or medium-risk ALL treated with the ALL-Berlin-Frankfurt-Münster (BFM) protocol was studied.
- Immune cell compartments, focusing on T-cells and B-cells, were analyzed during and after chemotherapy.
Main Results:
- T-cell recovery was rapid after treatment cessation.
- B-cell counts, particularly naive B-cells, were significantly reduced during and post-therapy.
- Disturbed B-cell distribution persisted for up to 5 years, indicating ongoing immune reconstitution.
Conclusions:
- Standard ALL chemotherapy regimens cause profound and long-lasting B-cell depletion.
- Immune recovery, especially for B-cells, is a gradual process that can extend years beyond treatment completion.
Abstract:
Chemotherapy for childhood acute lymphoblastic leukemia (ALL) is a highly effective treatment, but at the same time causes significant suppression of the patient's immunity. Immune reconstitution was studied in a homogeneous cohort of 48 children with standard or medium risk ALL treated according to the ALL-Berlin-Frankfurt-Münster (BFM) protocol. Whereas the T-cell compartment was only moderately affected and recovered to normal levels quickly after treatment cessation, B-cells were significantly reduced during and after therapy. In particular, the naive B-cell compartment declined. Even 5 years after the end of therapy, B-cell distribution was disturbed and patients showed an ongoing reconstitution. Thus, even standard regimens for chemotherapy cause severe B-cell depletion that resolves only gradually.
