Irina Zaidman

Detection, control, and management of a respiratory syncytial virus outbreak in a pediatric hematology-oncology department.

Background: Immunocompromised patients are at increased risk for severe respiratory syncytial virus (RSV) infection. Palivizumab is approved for prevention of RSV in specific populations but not for treatment. Few studies demonstrated the safety and successful treatment with intravenous (IV) palivizumab. We describe our experience with IV palivizumab treatment for RSV in a pediatric hematology-oncology department during an outbreak. Methods: During a short period of renovations, oncology patients were placed in a general pediatric ward. After a case of severe fatal RSV pneumonia in a 2-year-old male patient with acute myeloid leukemia, all patients were actively screened twice weekly regardless of symptoms. Respiratory samples were tested for RSV using rapid immunochromatography detection, immunofluorescence, or reverse transcriptase polymerase chain reaction. A single dose of palivizumab (15 mg/kg) was given to children below 3 years of age who tested positive for RSV. Results: Over a 6-week period, 12 patients tested positive for RSV. Seven patients were treated with palivizumab. Five patients had respiratory symptoms, and 2 were asymptomatic. No adverse events were attributed to IV palivizumab treatment. Early-treated patients had no complications attributed to RSV. Conclusions: Containment of RSV outbreak in high-risk children is difficult. Screening with reverse transcriptase polymerase chain reaction and the early use of IV palivizumab is safe and may prevent complications of RSV infection among these patients.

Hematopoietic stem cell transplantation in infants

It is rare for infants, who are less than 365 days old, to receive hematopoietic stem cell transplantation (HSCT). Our objective was to review the indications, survival, and late effects of infants who received HSCT.

The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia.

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD-positive AML compared with what has been reported in those treated with chemotherapy alone.

Mycobacterium phocaicum bacteremia: an emerging infection in pediatric hematology-oncology patients.

Nontuberculous mycobacteria may cause central venous catheter-associated bacteremia. Between March 2011 and October 2013, 6 cases of Mycobacterium phocaicum bacteremia were found in the pediatric hematology-oncology department. All patients recovered. No positive blood culture was documented after removal of the central venous catheter. All 4 patients with pulsed field gel electrophoresis had the same pattern, different from the water sample, suggesting a common water source.

Infections and neutrophils in the pathogenesis of bronchiolitis obliterans syndrome in children after allogeneic stem cell transplantation.

It is plausible that infections post‐hematopoietic SCT play a role in the pathogenesis of BOS. A prospective study for children with history, questionnaire, examination, PFTs, and blood counts at one, three, six, nine, 12, 18, and 24 months post‐SCT was conducted. Between September 2009 and September 2011 (n = 39), six developed BOS at 200 days (range 94–282), three patients had probable clinical respiratory infection, and all six had higher neutrophil count compared to non‐BOS patients (4.7 vs. 2.4 at three months and 6.3 vs. 2.9 at six months ×109/L, p = 0.03). Contribution of clinical and subclinical infection needs to be considered in the pathogenesis of BOS.

Safety and Role of Gastrointestinal Endoscopy in the Management of Gastrointestinal Acute GVHD in Children After Hematopoietic Stem Cell Transplantation.

Gastrointestinal (GI) endoscopy and biopsy is a common procedure to confirm the diagnosis of acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Its safety and benefits in aGVHD management is unclear. We aimed to review the safety and benefits of GI endoscopy and biopsy for GI-aGVHD management. From January 2000 to December 2009, 450 Children received allo-HSCT at SickKids. Seventy-nine (17.5%) patients underwent GI endoscopy and biopsy for suspicion of GI-aGVHD. GI-aGVHD grading was I (n=5), II (n=39), III (n=23), and IV (n=12). GI biopsy confirmed aGVHD in 49 (62%) patients and results were negative in 30 (38%). Thirty-two (40%) patients started treatment based on clinical criteria before procedure. Twenty-four out of 79 patients had a change in therapy because of biopsy results. Treatment change was significantly more common in patients who had a positive biopsy results compared with those with negative results (24/49 vs. 4/30, P=0.02). Comparing patients who started therapy before the biopsy results (n=32) and the remaining patients (n=47) who were not started on therapy, the biopsy results had more impact in altering/starting therapy in these patients (24/47 vs. 0/32, P<0.00001). For the 32 patients who started therapy before the procedure, the biopsy confirmed aGVHD diagnosis in 20 of them (63%). Only 1 patient (1.25%) had duodenal hematoma and needed prolong GI rest and ultimately recovered. GI endoscopy and biopsy was safe and useful in guiding therapy for GI-aGVHD.

Intrapericardial steroid treatment for recurrent pericardial effusion in a patient with acute lymphoblastic Leukaemia

Intrapericardial corticosteroid therapy for pericardial effusion is an uncommon practice. We had an initial experience with this therapeutic measure but this was our first attempt in the context of malignant diseases and paraneoplastic syndrome. A patient with relapsed Acute Lymphoblastic Leukemia and recurrent pericardial effusion presented. She had been treated by pericardiocenthesis and systemic corticosteroids on two occasions. Following the second pericardiocenthesis and pericardial drainage, methylprednisolone was injected into the pericardium prior to withdrawal of the draining catheter. The patient had a dramatic clinical improvement with a short hospital stay and a lower dose of systemic steroids. We conclude that Intrapericardial steroids injection may be beneficial for patients with paraneoplastic syndrome and pericardial effusion. Copyright

Successful hematopoietic stem cell transplantation for osteopetrosis using reduced intensity conditioning

Infantile malignant osteopetrosis (IMO) is an autosomal recessive condition characterized by defective osteoclast activity, with hematopoietic bone marrow transplant being the only available cure. Over the past several years, new conditioning regimes and donor options have emerged, thus extending the possibility of cure to a greater number of patients and improving the outcomes of bone marrow transplant. Here we detail the outcomes of bone marrow transplant in a cohort of 31 patients treated with a combination of fludarabine, treosulphan, thiotepa, and antithymocyte globulin.