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

Background: Pediatric Hodgkin lymphoma (HL) has been treated successfully with risk-adapted and response-adapted therapy. While risk factors like Ann Arbor staging system, B symptoms, bulky disease, and erythrocyte sedimentation rate were measured objectively, B symptoms are subjective tools. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and inflammatory marker levels correlated with B symptoms and disease burden.Materials and Methods: We conducted a retrospective chart review of all children ≤ 14 years old with pathology-confirmed HL treated at our institution. Data included clinical and pathologic features, pretreatment erythrocyte sedimentation rate, ferritin levels; monocyte, neutrophil, and lymphocyte counts; and NLR. Optimum cutoffs of variables significantly associated with B symptoms were determined based on receiver operating characteristic curves.Results: Sixty-four patients were included in the analysis. Sixteen patients (25%) had B symptoms. Patients with B symptoms had higher ferritin levels (P < 0.0001), monocyte counts (P = 0.0060), neutrophil counts (P = 0.0003) and NLR (P < 0.0001), and lower lymphocyte counts (P = 0.0017). Multiple receiver operating characteristic curves were generated to identify the optimum cutoff. Sensitivities and specificities of NLR (cutoff, 3.5) and ferritin (cutoff, 173 ng/mL) were the highest (81.25% and 81.25% [P < 0.0001] and 89.36% and 75% [P < 0.0001], respectively). Patients with NLR > 3.5 and ferritin > 173 (ng/mL) had significantly higher stage, bulky disease, and B symptoms. NLR and ferritin are not predictive of worst outcome in the cohort analyzed.Conclusions: NLR and ferritin levels were associated with high disease burden and B symptoms. Therefore, these variables can be used as measurable tools for B symptoms that can help stratify patients with HL. Larger and prospective studies are needed to validate these findings.

EBV–associated PTLD following allogeneic HSCT is a serious complication associated with significant mortality. In this retrospective study, we evaluated whether lymphocyte subset numbers and CD8:CD20 ratio at time of EBV viremia in children undergoing allogeneic HSCT could predict development of PTLD. Absolute lymphocyte count, lymphocyte subsets, and CD8:CD20 ratio at the time of EBV viremia were analyzed. Patients who were treated preemptively with rituximab for high blood EBV viral load were excluded. Out of 266 patients transplanted during the study period, 26 patients were included in the analysis. Patients were divided into two cohorts; cohort 1 included patients with EBV‐associated PTLD (n = 5; four with proven, one with probable PTLD). Cohort 2 included patients with EBV viremia without PTLD (n = 21). Lymphocyte recovery was slower in the PTLD group. CD8:CD20 ratio was significantly lower in the PTLD group (median 0.15) compared to the non‐PTLD group (median 2.4, P = .012). Using the ROC curve and 1 as the cutoff value, CD8:CD20 ratios were analyzed. In the PTLD group, 4/5 patients (80%) had a ratio <1 whereas in the non‐PTLD group, all 21 patients had a ratio >1. Sensitivity and specificity were 80% and 100%, respectively. Negative and PPVs were 95% and 100%, respectively. Profoundly low T‐cell count and CD8:CD20 ratio may be used to predict development of PTLD in the context of EBV viremia in children post‐allogeneic HSCT. Further studies are needed to validate this finding.

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Background Pediatric Hodgkin lymphoma (HL) has been treated successfully with risk- and response-adapted therapy. While all these risk factors are measured objectively, B symptoms are subjective tools. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and inflammatory marker levels correlated with B symptoms and disease burden. Methods The medical charts of all children ≤14 years old with HL were retrospectively reviewed. Data included, clinical and pathological features, pretreatment ESR, ferritin levels; monocyte, neutrophil, and lymphocyte counts; and NLR. Optimum cutoffs of variables significantly associated with B symptoms were determined based on receiver operating characteristic curves. Results Sixty-four patients were included in the analysis. Sixteen patients (25%) had B symptoms. Patients with B symptoms had higher ferritin levels (p<0.0001), monocyte counts (p=0.0060), neutrophil counts (p=0.0003) and NLR (p <0.0001) and lower lymphocyte counts (p=0.0017). Multiple ROC curves were generated to identify the optimum cut-off. The sensitivities and specificities of NLR (cut-off, 3.5) and ferritin (cut-off, 173 ng/ml) were highest [81.25% and 81.25% (p<0.0001) and 89.36% and 75% (p<0.0001), respectively]. Patients with NLR >3.5 and ferritin>173 (ng/ml) had significantly higher stage, bulky disease, and B symptoms. There was no association between NLR and ferritin with disease outcome. Conclusions NLR and ferritin levels were associated with high disease burden and B symptoms. Therefore, these variables can be used as measurable tools for B symptoms that can help stratify patients with HL. Larger and prospective studies are needed to validate these findings.

PurposeDADA2 is a rare and potentially fatal systemic autoinflammatory disease characterized by reduced or absence of ADA2 enzyme activity resulting from mutations in the ADA2 gene. Symptoms of DADA2 are variable and include vasculitis, immune dysregulation, and cytopenia. Scattered Saudi cases of DADA2 have been reported. We describe clinical, molecular, and outcome characterization of Saudi cases focused on phenotypic variability of DADA2.Methods To summarize the clinical features of Saudi patients with DADA2, we conducted a retrospective observational study in the seven major tertiary medical centers. Analysis of clinical characteristics, diagnostic findings, and treatment outcomes was obtained.ResultsWe identified 21 individuals with DADA2 from 14 families. At the time of the study, the patient's age was between 4 and 26 years (median age of 11.3 years). 20 patients presented during childhood. Homozygous c1447-1451del of ADA2 was the most frequently observed mutation in 38%, followed by c882-2A: G in 29%. Absent ADA2 activity was identified in all tested patients with homozygous mutations. Phenotypic manifestations included vasculopathy (stroke or cutaneous lesion) in 48%, cytopenia in 95%, autoinflammatory features such as intermittent fever, transaminases, and hepatosplenomegaly, and or immunodeficiency in 71% of the patients. 4 patients presented with Hodgkin lymphoma and one patient presented with clinical features mimic transverse myelitis, adding to the clinical spectrum of DADA2. Anti-tumor necrosis factor (anti-TNF) is the main treatment. However, regular blood transfusion, splenectomy, cyclosporine, and hematopoietic stem cell transplant (HSCT) were initiated in other patients because of anti-TNF failure. Morality was reported in 3 patients due to fulminant hepatitis and septic multi-organ failure.ConclusionOur cohort expands the variability of molecular and clinical characteristics of DADA2. Hematological phenotype predominates in the patients. Consensus diagnostic criteria are required to facilitate early diagnosis and initiation of prompt therapy. Evaluation of the rare disease complications such as cancer needs large prospective studies or disease registries

Case Report: 60 years old man, underwent a fully HLA matched Sibling PBSCT for AML (normal karyotype) with a reduced intensity conditioning regimen. He had a very complicated course with multiple bacterial, viral and fungal infections pre-transplant. Post BMT complications were a low positive titer of CMV that required treatment in addition to gut GVHD which developed 4 months after BMT treated with steroids. Six months post-BMT, his immunosuppressant agents was changed mutliple times due to thrombocytopenia and microangiopathy. 14 months after BMT, he presented with diarrhea again, a drop in platelet count, elevation in liver enzymes, high ferritin, normal donor chimersim, negative workup for secondary causes, and a positive BM for macrophages 68%, Despite escalation of the steroid dose and addition of tacrolimus and etoposide, He died 17 months after BMT due to graft and liver failure with sepsis. Case Discussion: Post BMT HLH is an aggressive disease with unknown etiology, poorly understood pathophysiology and dismal outcome if untreated. It's an allo-immune response, full donor chimerism has been reported. There are many proposed diagnostic criteria for Post BMT HLH, one of them defined by Takagi et al, which mandate the presence of graft failure and hemphagocytosis as two major criteria, and a minor criterion's (high fever, hepatosplenomegly, elevated ferritin, and elevated LDH).