Sporadic Lateral Ventricular Hemangioblastoma presenting with Intraventricular and Subarachnoid Haemorrhage

Intraventricular hemangioblastoma (HB) is very rare; few cases of intraventricular HB have been reported in the literature, either sporadically or in association with von Hippel-Lindau disease. Furthermore, the incidence of ventricular haemorrhage from HB seems to be uncommon. We report a unique case of sporadic HB of the right lateral ventricle presenting with intratumoural and intraventricular haemorrhage in addition to multifocal intracranial superficial siderosis, indicating the presence of a subarachnoid haemorrhage (SAH) as well. Such a combination has not been reported before. In the future, the detection of an intraventricular mass in association with ventricular haemorrhage, with or without SAH, should include HB as a differential diagnosis, particularly when the imaging appearances are not typical of the more common intraventricular tumours

PA038 Down syndrome patients with acute lymphoblastic leukemia have an intermediate prognosis with high infectious morbidity

Purpose: Even with modern therapy the outcome of ALL in children with Down’s syndrome (DS) remains inferior to non-DS patients. The higher incidence of infections in this group of patients may result not only in toxic-mortality, but may also impact on leukemia-related outcomes due to therapy omissions and delays.Method: This retrospective analysis looks at the outcome of DS patients with ALL diagnosed between 1997 and 2009 at our institution.Results: Of 24 patients, 14 were males with a median age of 4.8 years (mean5.0þ0.53 years; range 1.4–12.8 years) at diagnosis. Two patients had corrected congenital cardiac defects. The mean WBC count was 35.8 x 109/L (SEMþ24.66; range 0.89–500). All patients had precursor B-cell phenotype, two had CNS disease and none had any risk-associated cytogenetic features. Two patients received 3-druginduction and 21 were started on a 4-drug induction. There were three early deaths during induction; one patient died of parainfluenza-related ARDS, one with multi-organism sepsis and H1N1 influenza infection and the third with disseminated aspergillosis. Of 22 patients who were evaluated for BM response at day 14 only one had residual leukemia, with 50% blasts. All 21 patients who completed induction achieved CR. OS at a median follow-up of 3 years is 69% compared to 81% for non-DS pre-B ALL patients treated during the same time period with similar protocols. Five relapsed (2 BM, 2 CNS, 1 BM+CNS) at a median of 11.8 months; RFS is 73.2%at a median of 3.1 years. Infectious toxicity was high during induction and intensification phases of therapy compared to other phases.Conclusion: ALL patients with DS need to be treated with fairly intensive therapy in order to improve disease related outcomes; however, one has to balance this with the increased risk of infections, particularly during induction and intensification phases

Does high dose cytosine arabinoside improves disease free survival for down syndrome acute myelocytic leukemia patients?

Acute myelocytic leukemia (AML) in Down Syndrome (DS) children is characterized by a young age of onset (\u3c 2 years), a low white blood cell count and high frequency of Megakaryocytic leukemia. DS children with AML have higher disease free survival (DFS) rates as compared to non DS AML patients. Previous studies have suggested that intensification chemotherapy may not be necessary for the treatment of DS children with AML. The objective of this study was to clarify the effectiveness and toxicities of using high dose Cytosine Arabinoside (HD AraC) intensification in the treatment of DS AML. Clinical data for children (\u3c14 years) with DS AML, diagnosed between September 2000 to May 2005, were retrieved from the hospital data base. Patients were divided into two groups; Group A patients received chemotherapy containing HD AraC, while Group B patients did not. A total of 15 patients were included, eight in Group A and seven in group B. The median age at diagnosis was 22 months (A=23 months, B=22 months). The two groups were matched regarding their clinical and laboratory parameters. There was no significant difference in DFS between groups A and B, 75% and 85% respectively (P = 0.82) at a mean observation period of 42.9 months for group A and 23.12 months for group B. The median time to relapse was 6 months for group A and 8 months for group B. The overall treatment related toxicity was higher in Group A patients but achieved only borderline significance (P = 0.06). However, when toxicity was assessed separately for induction and post induction phases of chemotherapy there were significantly more infectious events (17 v. 2; p=0.0006) in the post induction phase which includes HD AraC intensification in Group A. Even when only serious infections (bacteremia, fungal infection, sepsis) were included in the evaluation this difference persisted (7 v. 1; p=0.0339), with less toxicity for Group B patients. No such difference was noted between the two groups during induction chemotherapy. In conclusion the use of HD AraC in post-induction intensification phases for DS AML children does not improve DFS and is associated with more treatment related toxicity

PB005 Treatment of DS-AML without HDARAC does not impact on disease outcome

Purpose: Disease related outcome for DS children with AML is higher than non-DS patients, but with more toxicity. Optimally intensive therapy for DS-AML needs to be determined.Method: We retrospectively reviewed the outcome of DS-AML at our institution between 2000 and 2009 treated on two different protocols; Group A utilized HDARAC post-induction and Group B was treated without HDARAC.Results: Twenty patients were treated; 10 patients in each group. There were 15 boys, and the median age was 27.7 months (mean 43.2+6.9; 8\u3c2 yrs, 9 2–4 years and3\u3e4 years). The clinical characteristics of patients in the two groups were similar (median age 29.5 v. 24.2 mo; mean WBC 27.5 v. 13.8 X 109/L; Hg 74.4 v. 80.1 g/L; plt54 v. 18 X109/L, p\u3e0.5 for all). Seven patients had M7 and 8 M2 subtype. Two had CSF positivity. Eight patients had congenital cardiac abnormalities and one dysplastic kidney. One patient in each Arm failed to achieve CR following 2 induction cycles, but both achieved CR following HDARAC. Six have relapsed (Group A¼3, GroupB¼3) at a median of 4.2 months from CR. 5-year OS is 80.4% and RFS is 67.7%. There was no difference in OS or RFS between the two groups (OS 78.8% v. 80%, p=0.7; RFS 70% v. 62.2%, p=0.9). No difference was found for induction-phase toxicity, however there was significantly more infectious toxicity with Group A postinduction (9 v. 3 patients, p=0.02). Specifically, 13 v. 1 episode of F/N (p=0.001), 4v. 0 invasive fungal infections (p=0.082), 3 v. 1 non-BS bacterial infections(p=0.12) and 4 v. 2 BS bacterial infections (p=0.6). Three patients in Group B developed subclinical reduction in cardiac function.Conclusion: Treatment of DS-AML is feasible without HD-ARAC for most DS-AML patients. HDARAC is associated with increase infectious toxicity without improving disease free survival

Prevalence of Bleeding Symptoms among Adolescents and Young Adults in the Capital City of Saudi Arabia

Background. Bleeding disorders vary in prevalence. While some are rare, some can be common in both sexes. Most bleeding disorders manifest as chronic bleeding tendencies or as an increase in bleeding during surgical procedures or trauma. The consequences of bleeding can be as simple as iron deficiency or catastrophic, resulting in severe morbidity and mortality. Bleeding disorders typically affect both sexes except hemophilia A and B, which mainly affects males. Method. We conducted a questionnaire-based survey among adolescents and young adults (1901 [49%] boys, 1980 [51%] girls) in Riyadh city regarding bleeding symptoms. Of these, 1849 (47.6%) responded “Yes/Positive” for at least one question about the bleeding symptoms. Results. The most common bleeding symptom was epistaxis (19.7% of the sample population) detected in Phase I of the study. A tandem survey was conducted among 525 adolescents who had responded “Yes/Positive” to any one of the questions inquiring about bleeding symptoms. Conclusion. In this study, we report for the first time the prevalence of bleeding symptoms in a representative sample of Saudi adolescents and young adults

Degree of concordance between peripheral blood leukemic blast count and mid induction bone marrow in childhood acute lymphoblastic leukemia

While different Pediatric ALL study groups have used varying definitions of early response (BM vs. PB, prophase vs. day 7 vs. day 14), all agree that it provides critical prognostic information. Bone Marrow aspiration and biopsy (BMA/B) is an invasive procedure requiring sedation or anesthesia, and an early/mid induction specimen may be difficult to interpret even by experienced hematopathologists. In this study we attempted to determine if there was a concordance between peripheral blood blast (PBB) clearance and the findings of the day 14 BMA/B, and whether day 7 PBB count could reliably replace a mid induction BMA/B. Clinical data for newly diagnosed pediatric (\u3c14 years) ALL patients between January 1999 and December 2001 were retrieved from our prospective database. Day 14 BMA/B slides were reviewed independently by two hematopathologist. For the total 165 patients, median age was 4 years, 53.9% were boys. Complete information was available for 151 of these patients and further analysis is based on this number. 124 (82.1%) were treated with 4 agents while the remainder received a 3-drug induction. 23 (18.5%) had positive PBB on D7, and 21 (13.9%) had \u3e5% blasts in the D14 BMA/B. The D7 PBB count could positively and negatively predict the D14 BMA/B 71.9% and 89.4% of the times, respectively. In conclusion, when the D14 BMA/B is used as a measure of early response, an absence of D7 PBB can reliably predict a negative BM, however persistence of PBB does not necessarily predict a sub-optimal BM response to early therapy. Therefore, patients without PBB on D7 may not require BMA/B on D14, therefore avoiding an invasive procedure for this group of patients

Assessing the Performance of Extended Half-Life Coagulation Factor VIII, FC Fusion Protein by Using Chromogenic and One-Stage Assays in Saudi Hemophilia A Patients

Background. The one-stage assay is the most common method to measure factor VIII activity (FVIII : C) in hemophilia A patients. The chromogenic assay is another two-stage test involving purified coagulation factors followed by factor Xa-specific chromogenic substrate. Aim. This study aimed to assess the discrepancy and correlation between the chromogenic and one-stage assays in measuring FVIII : C levels in hemophilia patients receiving Extended Half-Life Elocta® as a recombinant extended half-life coagulation factor. Methods. We performed a study comparing the measurements of FVIII : C levels by the chromogenic versus the one-stage assays at different drug levels. Data of FVIII : C levels, dosage, and the time interval from administration to measurement were retrieved from the hospital records. The correlation, mean differences, and discrepancy between the two assays were calculated. The linear regression analysis was used to predict the time interval till reaching 1% FVIII : C. Results. Fourteen patients with 56 samples were included in the study. Of them, 13 patients were receiving Elocta® as a prophylactic, while one was receiving Elocta® on demand. One-third of these samples showed a discrepancy between the chromogenic and one-stage assays. The two assays were well correlated. Mean differences were significant at the individual and the time interval level. The time since the last Elocta® injection could significantly predict FVIII : C levels (β = 0.366, P<0.001). Conclusion. Our findings suggested a significant difference between both methods; the FVIII : C levels measured by the one-stage assay were less than those estimated by the chromogenic assay. However, the measurements of FVIII levels by the two assays were well correlated but discrepant in one-third of the samples. The levels of FVIII : C reach 1% after 5.4 days since the last Elocta® administration

Effective treatment of biphenotypic acute leukemia in children with chemotherapy alone

Biphenotypic acute leukemia (BAL) is now a well-defined entity. However, the outcome of this rare type of acute leukemia is variable and the treatment strategies are controversial. This is a retrospective review analyzing the clinical features and the outcome of BAL cases diagnosed and treated at our institution between January 1999 and December 2004. The diagnosis was based on morphological and cytochemical evaluation, supported with extensive immunophenotyping. The European Group for Immunophenotyping in Leukemia (EGIL) scoring system was utilized to diagnose the BAL. 17 patients (4.1% of 411 ALL patients) were classified as BAL. Of these 15 were B-lymphoid/myeloid and two were T/B-lymphoid. Median age at diagnosis was 7.23 years (range 1.3–14.4 years). Nine patients were male, four had WBC count \u3e100 × 109/L, and 6 (35.3%) had CNS disease. Cytogenetic analysis was available in 14 cases of which three (21.4 %) had a normal karyotype. The most frequent abnormalities were MLL gene rearrangement (n=4; 28.6%) followed by abnormality at the 14q32 locus (n=3; 21.4%; two patients with add(14)(q32) and one t(8:14)(q21:q32)). All patients were treated uniformly, on a modified St Jude TXIII-B high-risk protocol, with agents known to be effective against both lymphoid and myeloid leukemia. They received a 6-drug induction with prednisone, vincristine, daunomycin, asparaginase, etoposide and cytosine arabinoside, followed by consolidation using high-dose methotrexate (2gm/m2) and mercaptopurine. Post remission all patients were eligible for allogeneic bone marrow transplantation (BMT) if a full matched related donor was available. If none was available, patients received continuation therapy consisting of weekly administration of non cross-resistant drug pairs for 120 weeks. All patient achieved remission post induction. Five patients underwent BMT in first remission (CR1), and 12 were treated with chemotherapy (CTX) alone. Two patients in the CTX arm relapsed. Both relapses were extramedullary (isolated CNS in one and lacrimal duct in the other). These patients were reinduced and underwent BMT in CR2. There were no relapses in the BMT arm. No serious acute therapy-related toxicity or infections were noted in the CTX arm. One patient died of BMT- related complications in CR1. With a median follow-up of 2.6 years, the actuarial OS and EFS at 4 years are 71.6 % and 79.5%, respectively. OS and EFS comparing BMT with CTX are 82% v. 74.1% (p=0.5) and 80% v. 79.5% (p=0.84), respectively. We conclude that this chemotherapy protocol is effective and safe in treating BAL. BMT in CR1 may not be needed for these patients.. Presence of CVL and prolonged use of broad spectrum antibiotics are major risk factor for candidaemia

The outcome of children with T-cell acute lymphoblastic leukemia: A single institution experience

Background: T-cell acute lymphoblastic leukemia (T-ALL) constitutes 10% to 15 % of childhood ALL cases in the Western literature. However, higher proportions, up to 40%, have been reported in certain developing countries. While the outcome of childhood T-ALL has improved dramatically over the last decades, by using intensive multi-agent chemotherapeutic regimens, about 30% to 40% of these patients still experience relapses.Patients and methods: Medical records of the 411 pediatric patients (0–13 years old) diagnosed with ALL and treated at our institution between January 1999 and December 2004 were retrospectively reviewed.Result: Fifty-three (12.9%) of the patients had T-ALL. 52 of these were treated according to a multi-drug chemotherapy protocol, based on a modification of the St. Jude Total XIII-B protocol, including high-dose methotrexate (HD-MTX), at 2gm/m2, and non-cross-resistant drug pair administered weekly during the continuation phase. The remaining one patient received a standard ALL therapy with a single delayed intensification and anti-metabolite based maintenance therapy. Early response to induction chemotherapy was assessed using a bone marrow (BM) evaluation at Day-14 of induction. The mean age was 7.1 years and 36 patients (68%) were males. Twenty (39%), out of 51 patients with available results, had CNS involvement. Of these eight (15.5%) were categorized as CNS-3, while 12 (23.5%) were CNS-2. 50% of the patients presented with mediastinal mass. Nine (18%) of the patients with available initial WBC (n=49) had hyperleukocytosis with a WBC \u3e100 × 109/L. 8 out of the 51 patients with a Day-14 evaluation had \u3e5% blasts in the BM. All patients subsequently achieved remission at the end of induction. The 5-year event-free survival (EFS) and overall survival (OS) rates were 63.9% and 76.4%, respectively. 13 (24.5%) patients relapsed at a median time of one year. Six relapses occurred in the BM, 5 isolated-CNS relapses, one CNS+BM and one in the skin+BM. Only 2 of these relapsed patients are long-term survivors. The disease-related and treatment toxicity-related deaths occurred in 11(20.7%) and 2(3.7%) patients, respectively. The initial WBC count, mediastinal mass, CNS status or the Day-14 BM results were not found to impact negatively on the outcome, by multivariate analysis.Conclusion: Our current treatment strategy has resulted in potential cure for about two-thirds of the patients with childhood T-ALL. However, a significant number of patients do fail treatment and novel strategies need to be devised for them. Unfortunately, as specific clinical features that could determine outcome have not as yet been identified, risk stratification, similar to that utilized for precursor-B cell ALL, is not feasible. Further study into risk determining variables at the molecular level, such as activating NOTCH1 mutations, may be promising in predicting outcome and determining treatment intensity in children with T-ALL