Hemophagocytic lymphohistiocytosis is a sign of poor outcome in pediatric Epstein‐Barr virus‐associated post‐transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation

Abstract

EBV-related PTLD developing after HSCT is a potentially life-threatening disease.HLH is uncommon after allogeneic HSCT. Data on outcome of patients with PTLD and concomitant HLH after allogeneic HSCT are limited. In this retrospective study, we collected demographic, clinical, laboratory, and outcome data for 408 patients who underwent allogeneic HSCT from 2006 to 2015. Graft source included CB (n = 135; 33.1%), PBSCs (n = 34; 8.3%), and BM (n = 239; 58.6%). Eight out of 408 patients (2%) developed EBV-PTLD with a median age at HSCT of 5.9 years (range: 2.3-17.3). All eight patients received ATG as part of the conditioning regimen. Graft source was PBSC in three patients (37.5%), BM in four patients (50%), and CB in one patient (12.5%). Donors were matched unrelated in five patients (62.5%) and matched sibling in three patients (37.5%). Seven out of eight patients developed EBV-PTLD within the first 100-day post-HSCT. Lymph node biopsy revealed early lesions in three patients, polymorphic in three patients, and monomorphic PTLD in two patients. Three patients (37.5%) died within 1 month of EBV-PTLD diagnosis. All deceased patients developed HLH manifestations with two of them meeting HLH diagnostic criteria and one having an incomplete workup. PTLD after allogeneic HSCT with manifestations of HLH is associated with high mortality. Early identification and treatment of EBV-PTLD seems imperative to control the disease, especially if signs of HLH are evolving. K E Y W O R D S

EBV Associated Post-Transplant Lymphoproliferative Disorder Complicated with Haemophagocytic Lymphohistiocytosis After Allogeneic Stem Cell Transplant: A Rare Complication with Fatal Outcome

“…One retrospective study showed high mortality (37.5%) in EBV PTLD within 100days post-transplant and all deceased patients developed HLH manifestations. 8 The presented case also responded initially with tapering of immunosuppression, high dose steroid and weekly rituximab with chemotherapy directed against HLH but ultimately died on day +137 post-transplant.…”

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

“…For the same risk factors explored in both studies, those from Kalra et al [67] were retained as the analyses were done on a larger sample. In addition, the Ali et al [31] and Althubaiti et al [32] studies were carried out with non-disjoint samples, but both were retained because different variables were explored. The reasons for exclusion of these articles were as follows: Two articles were excluded because their sample is a subset of the sample from two other articles.…”

“…The method used to diagnose PTLD was not detailed in one study. The length of follow-up was an important source of variation between studies; in some cases the follow-up period was not reported [31,32,34,40,46,48,52,55,59,61,63,73,81,83,86,90,94,98,100].…”

Hematopoietic stem cell transplantation complicated with EBV associated hemophagocytic lymphohistiocytosis in a patient with DOCK2 deficiency

“…8,9 Asano et al 10 reported that secondary HLH developed in 37 out of 5427 HSCT cases, and four out of 37 were PID. Ali et al 11 reported EBV-associated HLH in three out of 408 patients who underwent allogeneic HSCT, and all three patients died. Epstein-Barr virus is the most frequently associated infectious agent with HLH.…”