Risk-adapted Treatment for Severe B-Lineage Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation in Children.
BACKGROUND
Optimal management of posttransplant lymphoproliferative disease (PTLD) remains to be defined due to heterogeneity of this condition and lack of predictors of the outcome. Here we report our experience with pediatric PTLD nonresponsive to immunosuppression (IS) withdrawal, managed after stratification into high and low risk according to the presenting features.


METHODS
This is a single-center retrospective review of prospectively enrolled patients. From 2001 to 2011, 17 children were diagnosed with severe B-lineage, CD20+, PTLD after a median of 37 months (range, 5-93) from liver (12), heart (4), or multiorgan (1) transplantation. Treatment was tailored on 2 risk groups: (1) standard-risk (SR) patients received IS reduction and rituximab; (2) high-risk (HR) patients received IS discontinuation, rituximab and polychemotherapy.


RESULTS
The cumulative incidence of rejection at 1 and 5 years after the diagnosis of PTLD was 35% (95% confidence interval [95% CI], 18-69%) and 53% (33-85%), respectively, whereas the disease-free survival at 1 and 5 years was 94% (95% CI, 65-99%) and 75% (45-90%), respectively. Three children died, PTLD-free, from different transplant-related complications: primary nonfunction after retransplantation (liver), cytomegalovirus disease 21 months after PTLD treatment (liver), graft dysfunction 25 months after PTLD (heart).


CONCLUSIONS
Severe B-lineage PTLD after solid organ transplantation may be classified as SR or HR and treated accordingly with a tailored protocol obtaining a satisfactory long-term outcome. This approach accomplishes the control of lymphoproliferation in severe forms as well as the minimization of toxicity in milder PTLDs.
1 Department of Pediatrics, Hospital Papa Giovanni XXIII, Bergamo, Italy. 2 Department of Transplant Surgery, Hospital Papa Giovanni XXIII, Bergamo, Italy. 3 Department of Cardiac Surgery, Hospital Papa Giovanni XXIII, Bergamo, Italy. 4 Department of Pathology, Hospital Papa Giovanni XXIII, Bergamo, Italy. 5 Department of Hematology, Hospital Papa Giovanni XXIII, Bergamo, Italy.
Eugenia
E
Giraldi
Massimo
M
Provenzi
Valentino
V
Conter
Michele
M
Colledan
Stefania
S
Bolognini
Carlo
C
Foglia
Roberta
R
Sebastiani
Roberto
R
Fiocchi
Andrea
A
Gianatti
Lorenzo
L
DʼAntiga
Alessandro
A
Rambaldi
D000293:Adolescent; D000367:Age Factors; D001402:B-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007223:Infant; D007558:Italy; D053208:Kaplan-Meier Estimate; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects* / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents