Kent Stobart

Leukemia and Lymphoma Incidence in Children in Alberta, Canada: A Population-Based 22-Year Retrospective Study

There is a paucity of published literature on the epidemiology of childhood acute leukemias and lymphomas in Canada. This study was designed to describe children and youth (age <20 years) diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in Alberta, Canada, during 22 fiscal years. The Alberta Cancer Registry was used to extract data all ALL, AML, HL, and NHL cases diagnosed between April 1, 1982, and March 31, 2004. Population data for Alberta were also obtained. Descriptive statistics and cluster detection tests were used. During 22 years, 525, 117, 257, and 111 children (total = 1010) were diagnosed with ALL, AML, HL, and NHL, respectively. The median ages at diagnosis were 4, 11, 16, and 12 years for ALL, AML, HL, and NHL, respectively. The majority were male for ALL (287/525, 55%), AML (64/117, 55%), and NHL (81/111, 73%), and female for HL (133/257, 52%). The crude rates per 100,000 children were variable, without significant trends, over time and for each diagnosis; the median annual rates, per 100,000 children, were 3.00 (ranging from 1.87 to 3.75) for ALL, 0.62 (ranging from 0.26 to1.27) for AML, 1.42 (ranging from 0.76 to 2.67) for HL, and 0.54 (ranging from 0.24 to 1.40) for NHL. A few potential spatiotemporal clusters were identified. They are likely due to small number of cases and plausibly clinically insignificant. Overall, childhood leukemia and lymphoma rates in Alberta have remained relatively stable, with no clear epidemiological trends and no significant spatiotemporal clustering. Further investigations are warranted to see if such stability continues and if spatiotemporal patterns arise from longer studies and studies in larger geographic regions with a larger sample size, whilst analyzing for other causal/associated factors, individual susceptibilities, and disease outcomes.

A case of Sotos syndrome with neuroblastoma.

transplantation. He was class I thalassemic by Pesaro classification. He was conditioned with busulfan and cyclophosphamide. He received cyclosporine and methotrexate as graft-versus-host disease prophylaxis. Posttransplant he was on fluconazole prophylaxis. On day +3 posttransplant, purulent discharge was noted from double lumen Hickman catheter insertion site and redness along the tunneled course of the catheter and mild pain. He had no associated fever. He was started on broad spectrum antibiotics after taking pus culture and blood culture. Yeast was isolated for pus culture and identified as Trichosporon asahii (Fig. 1). Blood culture was negative. The minimal inhibitory concentrations of voriconazole (VCZ), amphotericin B, fluconazole, and caspofungin against the T. asahii isolate were 0.04, 0.25, 3, and >32mg/mL, respectively. Oral VCZ was included in the therapy and his Hickman catheter was removed. His line site healed after 5 days and had no further purulent discharge. His neutrophils engrafted on day +16 and platelets on day +22 posttransplant. He continued to receive VCZ for next 3 months. Child is alive and thalassemia-free at 18 months posttransplant. Trichosporon spp. are emerging as opportunistic agents that cause systemic diseases in immunocompromised hosts. Trichosporonosis carries a poor prognosis in neutropenic patients.1 Only 5 cases of Trichosporon infection after bone marrow transplant have been reported.1–3 Four had systemic infection and 3 died, whereas 1 had catheter infection and he survived. In addition, T. asahii, the most common of the Trichosporon spp. in systemic Trichosporon infection, seems less susceptible to amphotericin B.4 New extended spectrum triazoles, especially VCZ, posaconazole, and ravuconazole, have been shown to have good activity against Trichosporon spp. in vitro.5 Both VCZ and amphotericin B exhibited low minimal inhibitory concentrations and minimal fungicidal concentrations in vitro.6 Although an optimal therapy for trichosporonosis is yet to be identified, our observations in this case provide encouraging evidence of the utility of VCZ for treatment of trichosporonosis.

Childhood cancer trends in a Western Canadian province: a population-based 22-year retrospective study.

The objective of this study was to describe children and youth <20 years of age diagnosed with malignant cancer in Alberta, Canada over 22 years. We consider both temporal and geographical variations.

Second Bacteremia During Antibiotic Treatment in Children With Acute Myeloid Leukemia: A Report From the Canadian Infections in Acute Myeloid Leukemia Research Group

BACKGROUND The risk of second bacteremia during antibiotic treatment for initial bacteremia is unknown in high-risk populations. Our objectives were to describe the prevalence of second bacteremia during treatment and identify risk factors in children with acute myeloid leukemia (AML). METHODS We conducted a retrospective, population-based cohort study that included children and adolescents with de novo, non-M3 AML who were diagnosed and treated between January 1, 1995 and December 31, 2004 at 15 Canadian centers. Patients were monitored for bacteremia during chemotherapy until completion of treatment, hematopoietic stem cell transplantation, relapse, refractory disease, or death. RESULTS There were 290 episodes of bacteremia occurring in 185 (54.3%) of 341 children. Eighteen (6.2%) had a second bacteremia while receiving antibiotic treatment. Two episodes of second bacteremia were complicated by sepsis; there were no infection-related deaths. Eleven episodes (61.1%) had either an initial Gram-positive and subsequent Gram-negative bacteremia or initial Gram-negative followed by Gram-positive bacteremia. Days receiving corticosteroids (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07-1.12; P < .0001), cumulative dose of corticosteroids (OR, 1.04; 95% CI, 1.00-1.08; P = .035), and days of neutropenia from start of course to initial bacteremia (OR, 1.07; 95% CI, 1.02-1.12; P = .007) were significantly associated with second bacteremia. CONCLUSIONS In pediatric AML, 6% of patients will experience a second bacteremia during antibiotic treatment; duration of corticosteroid exposure and neutropenia are risk factors. These patients remain at high risk for second bacteremia after identification of the initial bacteremia and warrant continued broad-spectrum treatment during profound neutropenia.

Clear cell variant of embryonal rhabdomyosarcoma: report of an unusual retroperitoneal tumor--case report and literature review.

Case Report A 4-year 8-month-old female presented with 5 months history of emesis, abdominal pain, night sweats, weight loss (5 pounds, 2267.96 g), and fullness of left upper abdominal quadrant noted by parents on the day of admission. On examination, the abdomen showed a large firm 10 10 cm mass in the above area with another 4 4 cm mass in the right upper quadrant. Further systemic examination was normal. Complete blood counts were normal. Alanine transaminase (470 U/L), aspartate transaminase (470 U/L), amylase (417 U/L), lipase (564 U/L), and bilirubin (89 g/L) were elevated. Urinary catecholamines, α-fetoprotein (AFP), and βhuman chorionic gonadotropin (hCG) values were normal. Magnetic resonance imaging (MRI) of the abdomen showed a large retroperitoneal mass 10 13 14 cm in size intimately associated with the left lobe of the liver, encasing the hepatic artery origin. There was a tumor thrombus in the common bile duct causing enlargement of the gall bladder as well (►Fig. 1). A solitary nonocclusive thrombus was also seen in the portal vein. Bone marrow aspiration and biopsy were clear of malignancy. Full body bone scan showed no evidence of tumor involvement. A laparoscopy with biopsy of the tumor was performed 4 days after admission. Intraoperatively, extensive dissemination of tumor throughout abdomen along with omental seeding was noted. Histopathology showed nodules and sheets of clear cells and minimal spindle cells as well as undifferentiated basophilic cells admixed with focal round strap and tadpoleshaped eosinophilic rhabdomyoblasts. Aberrant mitoses and karyorrhexis were present. Immunohistochemistry showed desmin positivity and a proliferation activity (MIB1 or Ki67) of 40% with negativity of neuron-specific enolase, pankeratin markers for epithelial cell differentiation, AFP, hCG, and chromogranin A for endocrine differentiation. Myogenin (MYF4) was positive (►Fig. 2a–d). The Childrens Hospital follows strict criteria of quality assurance and the diagnosis was reviewed and confirmed according to Childrens Oncology Group protocols in the North-American Review Panel for pediatric tumors. Electron microscopy showed loose array of fusiform cells in a collagenous-likematrix. Tumor cells showed sarcomatoid formation with contractile filaments (alternating thick and thin filaments with Z-bands) substantiating the light microscopy features. Cells also contained a large amount of glycogen and dilated cisterns of rough endoplasmic reticulum. No alveolar pattern of rhabdomyosarcoma was detected (►Fig. 2e, f). At the pediatric tumor board therapy options for this stage IV metastatic embryonal rhabdomyosarcoma, clear cell variant were discussed. The child was started on intensive multiagent chemotherapy with dose compressed 2 weekly alternating cycles of vincristine, doxorubicin, cyclophosphamide, and etoposide/ ifosfamide. This was continued for 16 weeks. Interim assessment with reimaging showed a lack of major response to therapy and absence of significant tumor shrinkage. Thereafter, the patient received weekly vincristine along with

Can evidence harm? Certainly not hemophilia treatment and community.

*Institute of Internal & Cardiovascular Medicine, University of Perugia, Perugia, Italy; Department of Paediatrics, University of Alberta,Edmonton, Canada; and Departments of Clinical Haematology and Molecular Diagnostics, Manchester Royal Infirmary, Manchester, UKTo cite this article: Iorio A, Stobart K, Bolton-Maggs P. Can evidence harm? Certainly not hemophilia treatment and community. J ThrombHaemost 2006; 4: 505–6.See also Mannucci PM. Need for randomized trials in hemophilia. This issue, pp 501–2; Aledort L, Ljung R, Blanchette V on behalf of theInternational Prophylaxis Study Group. Are randomized clinical trials the only truth? Not always. This issue, pp 503–4; Srivastava A; Konkle B;Blanchette V; Makris M. Uncertain times for research on hemophilia and allied disorders. This issue, pp 680–3.