Related Experiment Videos
Immunodeficiency-related lymphoproliferative disorders: prospective data from the United Kingdom Children's Cancer
C R Pinkerton1, I Hann, C L Weston
1Department of Paediatric Oncology, Royal Marsden NHS Trust, Downs Road, Sutton, Surrey SM2 5PT, UK. rossp@icr.ac.uk
Insights
Pediatric lymphoproliferative disease (LPD) in immunosuppressed children shows varied outcomes. Reducing immunosuppression or using chemotherapy can lead to remission, but outcomes remain challenging for transplant recipients.
Area of Science:
- Pediatric Hematology/Oncology
- Immunology
- Transplant Medicine
Background:
- Lymphoproliferative disease (LPD) can occur secondary to iatrogenic or congenital immunosuppression in children.
- Understanding LPD in this vulnerable population is crucial for effective management and improved outcomes.
Purpose of the Study:
- To characterize pediatric LPD in immunosuppressed patients.
- To evaluate treatment strategies including immunosuppression reduction and chemotherapy.
- To identify factors influencing disease outcomes.
Main Methods:
- Prospective collection of clinical data and biological samples from 42 children with LPD.
- Central pathology review and classification using established systems (Revised European-American Classification, Pittsburgh, Murphy grouping).
- Assessment of Epstein-Barr virus status, clonality, treatment responses, and patient survival.
Main Results:
- LPD occurred in children with transplant-related immunosuppression, congenital immunodeficiency, or HIV.
- Pathology showed diverse features, with high-grade B-cell lymphomas being common.
- Reduced immunosuppression led to resolution in 14/24 transplant patients; chemotherapy showed a 14/18 response rate.
Conclusions:
- No clear predictors of outcome were identified in solid organ transplant recipients.
- Close monitoring during immunosuppression reduction is essential for transplant patients.
- Early chemotherapy for B-cell non-Hodgkin's lymphoma (NHL) may be effective in this population.
Abstract:
Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease (LPD) secondary to organ/bone marrow transplant-related immunosuppression (30: 11 liver, 10 heart/lung, 8 kidney and 1 bone marrow), other drug-induced immunosuppression (2), congenital immunodeficiency (8) or human immunodeficiency virus (HIV)-related immune dysfunction (2). Ages ranged from 10 months to 17 years and there were 15 girls. Pathology was centrally reviewed and showed polymorphic features in 5 cases, monomorphic in 23, mixed pattern in 5 patients and 9 other types. Using the Revised European-American Classification of Lymphoid Neoplasms, 5 were B lymphoblastoid, 24 were high-grade B and 14 were other subtypes. Using the Pittsburgh classification, 9 were lymphadenopathic, 10 were systemic, 25 were lymphomatous and, with the Murphy grouping for non-Hodgkin's lymphoma (NHL), 10 were localized and 32 non-localized. Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive. Thirty-five patients were evaluable for clonality; 24 were monoclonal and 11 were polyclonal. Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24, which was sustained in 11. Nineteen patients received chemotherapy, 14/18 evaluable responded, which was sustained in 8 cases. Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died. In the largest group of patients, solid organ transplants, no significant clinical or biological characteristics that predicted outcome were identified. In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective.