Julie Talano

Association of Crohn’s Disease, Thiopurines, and Primary Epstein-Barr Virus Infection with Hemophagocytic Lymphohistiocytosis

OBJECTIVE To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well-defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH. STUDY DESIGN We conducted a retrospective study of all children who developed HLH over an 8-year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD. RESULTS Among children in Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in children with IBD. Common characteristics include: Crohns disease (CD), thiopurine administration, fever lasting more than 5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin. Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was more than 100-fold greater for children with CD (P < .00001). CONCLUSIONS Pediatric patients with CD are at increased risk for developing HLH; primary Epstein-Barr virus infection and thiopurine administration may be risk factors.

Severe hypercholesterolemia mediated by lipoprotein X in a pediatric patient with chronic graft-versus-host disease of the liver

We describe a case of extreme hypercholesterolemia, mediated by lipoprotein X, in a 12‐year‐old Caucasian female who underwent an unrelated allogenic bone marrow transplant for relapsed acute myelocytic leukemia (AML). Her post‐transplant course was complicated by severe chronic graft‐versus‐host disease (GVHD) of the liver. Previously normal serum cholesterol and triglycerides rose to 1,122 mg/dl (29.0 mmol/L) and 1,100 mg/dl (12.4 mmol/L), respectively. Serum cholesterol appeared to be dominantly carried by lipoprotein X. Intra‐hepatic cholestasis leading to reflux of bile lipoproteins into the blood stream and subsequent formation of lipoprotein X appears to be the mechanism underlying this phenomenon. Pediatr Blood Cancer 2008;50:1280–1281.

Voriconazole-induced blistering in the setting of graft versus host disease: A report of 2 patients

Voriconazole is a newer triazole antifungal agent with a wide spectrum of activity against yeast, fungi and molds including many Candida, Aspergillus, and Fusarium species. Its use continues to increase, particularly in immunocompromised patients, owing to its broad coverage, availability in both intravenous and oral preparations, and safety profile. The detection of adverse events in these patients may be complicated by their preexisting comorbidities and polypharmacy. We describe 2 patients with hematologic malignancies status post allogeneic bone marrow transplantation who developed blistering eruptions on the extremities related to voriconazole use. A history of graft versus host disease in each patient confounded and delayed the diagnosis. It is imperative to recognize voriconazole-induced blistering as a separate and distinct entity in such patients with a history of graft versus host disease, since delayed withdrawal of voriconazole use could result in unnecessary and potentially dangerous increases in immunosuppressive therapy.

Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis

Optimal salvage therapy for refractory HLH is unknown.In our patient, ruxolitinib treatment led to clinical remission of refractory HLH.

The safety and efficacy of clofarabine in combination with high-dose cytarabine and total body irradiation myeloablative conditioning and allogeneic stem cell transplantation in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia

Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 – 52 mg/m2), cytarabine 1000 mg/m2, and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1–22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors. Probabilities of neutrophil, platelet engraftment, acute GvHD, and chronic GvHD were 94%, 84%, 49%, and 30%, respectively. Probability of day 100 TRM was 8.1%. 2-year EFS (event free survival) and OS (overall survival) were 38.6% (CI95: 23–54%), and 41.3% (CI95: 25–57%). Multivariate analysis demonstrated overt disease at time of transplant (relative risk (RR) 3.65, CI95: 1.35–9.89, P = 0.011) and umbilical cord blood source (RR 2.17, CI95: 1.33–4.15, P = 0.019) to be predictors of worse EFS/OS. This novel myeloablative conditioning regimen followed by alloSCT is safe and well tolerated in CAYA with very poor-risk ALL or AML. Further investigation in CAYA with better risk ALL and AML undergoing alloSCT is warranted.