Daniel Landi

Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning.

We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P = .031) and HLA-mismatched UD (41%; P = .007). Full-donor chimerism (P = .039) and normal enzyme levels (P = .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS.

Complications of implantable venous access devices in patients with sickle cell disease

Implantable venous access devices (VADs) are used in sickle cell disease (SCD) for patients with poor venous access to facilitate chronic blood transfusions and manage acute complications. We attempted to define the frequency of bloodstream infections (BSI) and thrombosis in adults and children with SCD and VADs. We performed a single-institution, retrospective review of VAD-associated infection and thrombosis in patients with SCD. Thirty-two patients (median age 20 years, range, 1-59) had 86 VADs placed (median, 2.7 VADs per patient, range, 1-7) with a total of 41,292 catheter days (median, 1,376 days; range, 323-3,999). Mean catheter lifespan in adults (691 days ± 123) was not significantly higher than children (614 days ± 154). A total of 66 VAD-associated BSI (1.59 infections per 1,000 catheter days) occurred in 17 of 32 (53%) patients. Children with VADs had fewer BSI (3 of 10; 30%) than adults (14 of 22; 64%, P = 0.08). 24 catheter-associated thromboses (0.49 thromboses per 1,000 catheter days) occurred in 10 of 32 (41%) of patients. Children also had fewer VAD-associated-thrombosis (1 of 10; 10%) than adults (9 of 22; 40%, P = 0.08). In conclusion, the use of VADs in SCD was linked to a significant rate of infection and thrombosis.

Presentation and outcomes for children with bone marrow necrosis and acute lymphoblastic leukemia: a literature review.

Bone marrow necrosis is a rare histopathology finding with the majority of cases occurring in the setting of a hematologic malignancy. This article reports a case of diffuse marrow necrosis in a child secondary to acute lymphoblastic leukemia and summarizes the clinical features and outcomes for children with bone marrow necrosis secondary to leukemia from 20 published reports. This review demonstrated that the most common presenting features were bone pain, fever, pancytopenia, and that outcomes were less favorable when compared with those without necrosis. However, contemporary literature suggests that outcomes are similar for children who have bone marrow necrosis secondary to leukemia when compared with overall survival rates for pediatric leukemia.

Characteristics of abdominal vein thrombosis in children and adults

The demographic and clinical characteristics of adults and children with lower extremity deep-vein thrombosis and/or pulmonary embolism (LE DVT/PE) may differ from those with abdominal vein thrombosis (abdominal VT). Abdominal VT can be a presenting sign of an underlying prothrombotic state, and its presence in the setting of known disease might have prognostic implications different from LE DVT/PE. This study describes clinical presentations of abdominal VT compared to LE DVT/PE in adults and children. We analysed prospectively-collected data from consecutive consenting patients enrolled in one of seven Centers for Disease Control and Prevention (CDC) funded Thrombosis and Hemostasis Network Centers from August 2003 to April 2011 to compare the demographic and clinical characteristics of adults and children with abdominal VT. Both adults and children with abdominal VT tended to be younger and have a lower body mass index (BMI) than those with LE DVT/PE. Of patients with abdominal VT, children were more likely to have inferior vena cava (IVC) thrombosis than adults. For adults with venous thromboembolism (VTE), relatively more women had abdominal VT than LE DVT/PE, while the proportions with LE DVT/PE and abdominal VT by sex were similar in children. Children with abdominal VT were more likely to have diagnosed inherited thrombophilia, while trauma was more common in children with LE DVT/PE. In conclusion, both children and adults with abdominal VT were younger with a lower BMI than those with LE DVT/PE. Significant differences exist between children and adults in respect to abdominal VT compared to LE DVT/PE.

Differences in pain management between hematologists and hospitalists caring for patients with sickle cell disease hospitalized for vasoocclusive crisis.

Objectives:Sickle cell disease (SCD) is a chronic disease characterized by multiple vaso-occlusive complications and is increasingly cared for by hospitalists. The purpose of this study is to examine differences in pain management between hematologists and hospitalists. Methods:We performed a single-institution, retrospective review of pain management patterns and outcomes in adult SCD patients hospitalized for vaso-occlusive crisis. Results:Over 26 months, we found a total of 298 patients (120 cared for by the hematologists and 178 by hospitalists), with a mean age of 32 (range 19–58). Patients cared for by hospitalists had a lower total number of hours on a patient controlled analgesia (PCA) device (171 vs. 212 hours, P=0.11). Hospitalists also were significantly more likely to utilize demand only PCA (42% vs. 23%, P=0.002) and had a significantly lower rate of using both continuous and demand PCA (54% vs. 67%, P=0.04). In addition, patients cared for by hospitalists had a significantly shorter hospitalization (8.4 days) compared to hematologists (10 days, P=0.04) with a non-significant difference in 7 and 30 day readmission rates (7.2% vs. 6.7% and 40% vs. 35% respectively). Conclusion:We found patients cared for by hospitalists more frequently utilized home oral pain medication during admission, had shorter lengths of hospitalization, and did not have a significant increase in readmission rates.

Report of a young girl with MYH9 mutation and review of the literature.

MYH9 mutations cause the inherited macrothrombocytopenic syndromes of May-Hegglin anomaly, Fechtner syndrome, Sebastian syndrome, and Epstein syndrome, collectively referred to as MYH9-related disease. We present the case of a girl with MYH9-related disease whose diagnosis was facilitated by platelet electron microscopy and MYH9 sequencing. We discuss our patient’s clinical presentation, now with 12 years of follow-up. We also discuss management and her possible prognosis given her specific MYH9 mutation.

Novel case of recurrent intraventricular atypical central neurocytoma with prominent gangliogliomatous differentiation in a 10-year-old boy with 10 years of follow up: Intraventricular ganglioneurocytoma

Central neurocytoma is a rare neuronal tumor that typically occurs in young adults. Infrequently, these tumors exhibit advanced neuronal maturation and glial differentiation, giving rise to a histologically diverse tumor, in contrast to a typical central neurocytoma. We present a novel case of intraventricular central neurocytoma with prominent gangliogliomatous differentiation that developed atypical features upon recurrence after 10 years of follow up in a 10‐year‐old boy. Our case provides insight into the divergent differentiation capability of a neurocytic tumor and illustrates the diverse histological features of this rare entity.

Immunotherapy for pediatric brain tumors

Immunotherapy, while effective against lymphoid cancers and some solid tumors, has shown less benefit against pediatric brain tumors. Tumor heterogeneity, a suppressive immune microenvironment, and the blood-brain barrier have the potential to diminish any immune-based approach and limit efficacy. More importantly, most pediatric brain tumors are immunologically quiescent, stemming from a low mutational burden. This review focuses on innate vs. adaptive immunotherapeutic approaches and describes how the immunologic context of pediatric brain tumors can help identify well-suited immunotherapies for our patients. In this framework, we will discuss past and current approaches using virotherapy, immunoconjugates, monoclonal antibodies, active immunization, and adoptive cellular therapy, and share our thoughts on how immunotherapy can cure children with brain tumors.