Fludarabine-based reduced intensity regimen for matched related donor hematopoietic stem cell transplantation in acquired severe aplastic anemia.

Different conditioning regimens have been evaluated in matched-related donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acquired severe aplastic anemia (SAA) with varying results. In this manuscript, we report our experience with fludarabine (120mg/m2), very low dose cyclophosphamide (1200mg/m2) and antithymocyte globulin (7.5mg/kg). Low dose total body irradiation (2Gy) was added to the conditioning regimen for patients older than 15 years. Nineteen patients (median age 23years) underwent transplant between 2008 and 2015. The majority (89%) were younger than 40 years. Stem cell source was BM (n=11) or PBSC (n=8). GvHD prophylaxis consisted of cyclosporine and either a short course of methotrexate (n=9) or mycophenolate mofetil (n=10). Eighteen (94.7%) patients achieved sustained engraftment. The median times to neutrophil and platelet engraftments were 19 (range: 14-34) and 17.1 (range: 12-25) days, respectively. The day-30 cumulative incidence of neutrophil and platelet engraftment was 89.4% and 94.7%, respectively. No secondary graft rejection was observed. The 1-year cumulative incidence of aGvHD (grade II-IV) and cGvHD was 11.7% and 0%, respectively. The 2-year GvHD-free survival rate was 78.6% (95% CI: 52.5-91.4%). Fludarabine-based reduced intensity regimen for MRD allo-HSCT in SAA compares favorably to other available regimens. This regimen deserves further investigations with larger cohort of patients.

Complete heart block in a patient with acute lymphoblastic leukaemia: teicoplanin as a possible cause and review of literature.

WHAT IS KNOWN AND OBJECTIVE: Teicoplanin is a glycopeptide antibiotic used against documented or presumed methicillin-resistant infections. We report a 31-month-old boy with acute lymphocytic leukaemia who developed permanent complete atrioventricular block (CAVB) necessitating pacemaker insertion after receiving teicoplanin for Staphylococcus epidermidis bacteremia. CASE SUMMARY: Clinical assessment of the child revealed febrile neutropenia. After thorough assessment and work-up, the patient was started on teicoplanin intravenously after which he had sudden onset of bradycardia. Electrocardiography showed CAVB that eventually required permanent pacemaker insertion. Twenty-nine months from the incident, the patient is doing well. WHAT IS NEW AND CONCLUSION: We report on a case of teicoplanin-associated CAVB in a child with acute lymphoblastic leukaemia (ALL). This is one of only two similar cases reported in the literature. Teicoplanin remains the most probable cause. The use of teicoplanin should be approached cautiously in the setting of immunosuppression. Whether VZV contributed and teicoplanin triggered remains speculative. Physicians should be aware of this possible complication.

Predictors of bone loss in childhood hematologic malignancies: a prospective study.

SUMMARY: Twenty-nine children with malignancies and age, gender-matched controls were prospectively studied over 14 months. Patients had higher parathyroid hormone (PTH) levels and fat mass, lower bone mass, and bone mass increments at follow-up than controls. Lean mass, age at diagnosis, systemic and intrathecal therapy were predictors of bone mass changes on adjusted analyses. INTRODUCTION: Children with hematologic malignances have low bone mass. We prospectively investigated anthropometric, clinical, and hormonal predictors of changes in bone mass in children receiving cancer therapy. METHODS: Twenty-nine children, mean age of 9 ± 2.9 years and 32 age and gender-matched controls, were studied. Seven had completed their course 40 ± 22 weeks prior, while 22 were still receiving therapy for 80 ± 28 weeks. Age at diagnosis, calcium intake, exercise activity, systemic corticosteroids in dexamethasone (Dex) dose, and methotrexate (MTX), and intrathecal MTX therapy received within follow-up period were assessed. Routine chemistries, PTH, 25-hydroxy vitamin D (25-OHD), bone remodeling markers, bone mass, and body composition were measured at baseline and 14 months. RESULTS: Patients had lower exercise activity, sun exposure, and bone markers levels than controls. They had higher PTH levels and fat mass, lower bone mass at the spine, hip, and total body, and lower increments at these sites on follow-up. Predictors of bone mass changes on univariate analyses were: age at diagnosis (R = -0.50 to -0.44, p < 0.05), Dex-MTX doses (R = -0.58 to -0.41, p < 0.05), intrathecal therapy (p < 0.03),% changes in lean mass (R = 0.37 to 0.54, p < 0.04), 25-OHD levels (R = 0.39, p < 0.03), and PTH levels (R = -0.47 to -0.41, p < 0.05). Lean mass, age at diagnosis, systemic and intrathecal therapy were predictors of bone mass changes on adjusted analyses. CONCLUSION: This study provides insight into the pathophysiology of bone loss in children receiving cancer therapy and possible interventions to optimize their skeletal health.

Zinc and biotin deficiencies after pancreaticoduodenectomy.

We report zinc and biotin deficiencies after pancreaticoduodenectomy in a 16 year old female presenting clinically with marked alopecia, total body hair loss, dry skin with scales, and maculopathy with significant vision loss. These micronutrient deficiencies likely occurred due to resection of the duodenum and proximal jejunum, sites of primary absorption of several micronutrients and their protein carriers, including zinc and biotin. Early diagnosis is essential to prevent irreversible sequelae. Adequate supplementation of zinc and biotin as well as dietary advice is needed for clinical improvement.

Wernicke's encephalopathy during total parenteral nutrition in a child with acute lymphoblastic leukemia and acute pancreatitis.

We herein describe a 16-year-old child with acute lymphoblastic leukemia and acute pancreatitis who developed Wernicke's encephalopathy secondary to prolonged total parenteral nutrition (TPN) that lacked vitamin B1 supplementation. The patient showed a direct and complete response to thiamine therapy. Diagnostic challenges are discussed and recommendations for prophylactic vitamin B1 supplementation in children with leukemia who are placed on TPN are made.

Hematopoietic stem cell transplantation in Lebanon: first comprehensive report.

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.

Cerebral sinus thrombosis in a patient with humoral immunodeficiency on intravenous immunoglobulin therapy: a case report.

We present the case of an 11-year-old boy with humoral immunodeficiency on monthly intravenous immunoglobulins (IVIG) infusions, evaluated for recurrent, brief, neurological deficits secondary to cerebral sinus thrombosis without any identifiable hypercoagulability state. Etiologic possibilities for the thrombotic event are presented with special discussion of IVIG-related cerebral thrombosis. To the best of our knowledge, our patient represents the first reported case of Bruton's disease on IVIG therapy developing a cerebral ischemic event and the second reported case of cerebral sinus thrombosis associated with IVIG use for any disease. Potential concerns regarding the risk of cerebral thrombosis during IVIG therapy in this and other disorders are reviewed.

L-asparaginase-induced posterior reversible encephalopathy syndrome during acute lymphoblastic leukemia treatment in children.

L-asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. The purpose of this article is to present the first case-series of posterior reversible encephalopathy syndrome (PRES) associated with L-asparaginase treatment. We report 3 cases of children with acute lymphoblastic leukemia who developed seizures and altered sensorium after L-asparaginase therapy. MRI showed increased T(2) signal intensity predominant in the posterior regions of the brain suggestive of PRES. Two of our patients developed septic shock and deteriorated whereas one patient improved and recovered completely.

Addition of ketamine to propofol for initiation of procedural anesthesia in children reduces propofol consumption and preserves hemodynamic stability.

BACKGROUND: There is no ideal anesthesia protocol to perform short invasive procedures in pediatric oncology. The combination of propofol and ketamine may offer advantages over propofol alone. METHODS: In a prospective, randomized, double-blind study, we analyzed 63 consecutive procedures performed in 47 oncology children. All patients received 1 mug/kg fentanyl, followed by propofol 1 mg/kg in group P (n=33) or propofol 0.5 mg/kg and ketamine 0.5 mg/kg in group PK (n=30) for the initiation of anesthesia. The need for supplementation with propofol and/or fentanyl to maintain an adequate level of anesthesia was recorded. The hemodynamic and respiratory profile, recovery time and the occurrence of side effects were compared. RESULTS: Significantly more children required propofol (100% vs. 83.3%) and fentanyl (75.5% vs. 43.3%) rescue doses, and developed hypotension (63.6% vs. 23.4%) and bradycardia (48.5 vs. 23.4%) in group P compared with group PK, with a comparable incidence of respiratory adverse events and recovery times. However, 40% of children in group PK were agitated following recovery compared with 6% in group P. CONCLUSIONS: The combination of propofol and ketamine for invasive procedures in pediatric oncology resulted in reduced propofol and fentanyl consumption and preserved hemodynamic stability, but more children in the combination group recovered with agitation.

Treatment of pediatric Hodgkin's disease with chemotherapy alone or combined modality therapy.

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease <13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.

The sonographic appearance of lesions of the spleen and pancreas in an infant with Langerhans' cell histiocytosis.

Langerhans' cell histiocytosis (LCH), the term now used to describe the group of diseases known as histiocytosis X, is a rare disorder of the bone marrow-derived histiocytes that may involve the skin, bone, bone marrow, liver, spleen, lungs, lymph nodes, and rarely the pancreas. Sonographically demonstrable lesions of the spleen and pancreas have not been reported. We present a case of disseminated LCH in a 4-week-old infant to demonstrate the sonographic appearance of splenic and pancreatic lesions that occur with this disease.