The Prevalence of Sensorineural Hearing Loss in ß-thalassaemia patient treated with Desferrioxamine.

OBJECTIVE: This study aimed to evaluate the prevalence of sensorineural hearing loss (SNHL) in ß-thalassaemia patients treated with Desferrioxamine (DFO) and determine the correlation of SNHL with average daily DFO dosage, serum ferritin level and Therapeutic index (T.I). METHODS: This is a cross sectional descriptive study carried out for a period of 14 months and 54 patients were recruited. The recruited patients are transfusion dependant ß- thalassaemia patient aged 3 years and above treated with DFO. An interview, clinical examination and hearing assessment, which included tympanogram, and Pure Tone Audiometry (PTA) or behaviour alaudiometry were performed. The data on age started on DFO, average daily DFO, duration of DFO intake, serum ferritin past 1 year and Therapeutic Index (T.I) were obtained from patients' case notes. RESULTS: The prevalence of SNHL was 57.4% and majority has mild hearing loss (93.6%). Fourteen patients (25.9%) have bilateral ear involvement and as many as 17 patients (31.5%) have SNHL in either ear. A total of 23 patients (42.6%) have normal hearing level. Although the prevalence of SNHL was 57.4%, only a small percentage of the patient noticed and complained of hearing loss (11.1%). There is no association between age started on DFO, average daily DFO and duration of DFO intake with normal hearing group and those patients with SNHL. Positive correlation was seen between average daily DFO with 2000 and 4000Hz on PTA in the left ear and between serum ferritin level past 1 year with 4000 and 8000Hz in the right ear and 8000Hz in the left ear. No significant correlation was seen between T.I on PTA. CONCLUSION: The prevalence of SNHL from hearing assessment is high in ß-thalassaemia patients in this study. However, it is manifested clinically in a smaller percentage. We suggest a baseline hearing assessment should be carried on all ß-thalassaemia patients prior to DFO chelation therapy.

Spectrum of infections in splenectomised thalassaemia patients.

Splenectomised thalassaemia patients are at risk of developing sepsis. As the infection may be life-threatening, treatment should be sought and given promptly. A retrospective study was performed amongst our thalassaemia major patients who were splenectomised. The vaccination status of each patient and the types of infections seen were reviewed to obtain a local perspective. In our cohort of 49 splenectomised patients, 25 patients required hospitalization for the treatment of infection. There were a total of 40 febrile episodes within this hospitalised group of which 27.5% were microbiologically documented infection with bacteraemia. The predominant causative organisms were gram negative rods and three patients succumbed to overwhelming septicaemic shock as a result of delayed presentation. Sixty percent of the febrile episodes were clinically documented infection and comprised mainly upper respiratory tract infections. Based on the spectrum of infections seen, there is a need to improve the patients' awareness level so that early treatment is sought. There is also a need to re-address the approach towards vaccination in this immunocompromised group of patients by administering a booster pneumococcal and influenza vaccination in an attempt to reduce morbidity.

Juvenile myelomonocytic leukaemia: a case series.

Juvenile myelomonocytic leukaemia (JMML), previously known as juvenile chronic myeloid leukaemia (JCML) is a rare, myelodysplastic - myeloproliferative disease typically presenting in early childhood. This disorder is difficult to distinguish from other myeloproliferative syndrome such as chronic myeloid leukaemia (CML) because of the similarities in their clinical and bone marrow findings. However, because of its unique biological characteristics such as absolute monocytosis with dysplasia, absence of Philadelphia chromosome or BCR-ABL fusion protein, hypergammaglobulinaemia and raised fetal haemoglobin level, this disorder does not satisfy the criteria for inclusion in the CML or chronic myelomonocytic leukaemia (CMML) group, as seen in adult patients. We describe a series of three patients with JMML, who had almost similar clinical and laboratory findings, and discuss the difficulty in the classification and treatment of the disease.

Growth velocity in transfusion dependent prepubertal thalassemia patients: results from a thalassemia center in Malaysia.

Growth impairment is commonly seen in children with thalassemia despite regular blood transfusions and desferrioxamine treatments. We investigated the growth velocity of 26 prepubertal patients with beta-thalassemia or HbE-beta thalassemia who were transfusion dependent aged between 2 and 13 years. The prevalence of impaired growth velocity (ie, growth velocity less than the third percentile) amongst the transfusion dependent prepubertal thalassemics was 57.7% compared to 19.2% in the control group. The mean height velocity of the thalassemics was 11.1% less than controls but this difference was not statistically significant (4.23cm/year vs 4.76cm/year, p = 0.08). The mean serum ferritin level of the thalassemics with a height < 3rd percentile was higher compared to those with a height > 3rd percentile (4,567.0 vs 2,271.0, p = 0.01). Our study showed that there was a high prevalence of impaired growth velocity amongst our transfusion dependent prepubertal thalassemics. This highlights the problem of inadequate chelation therapy, and compliance with chelation therapy amongst our patients. This study emphasizes the importance of monitoring growth parameters and optimal iron chelation therapy in these patients.

Audit of newborn screening programme for congenital hypothyroidism.

Newborn screening for congenital hypothyroidism (CH) was implemented in Hospital UKM in December 2004 using cord blood sample. From the audit over a period of 25 months, a total of 13,875 newborn babies were screened with a coverage of 98.8%. From this cohort, the mean recall rate was 0.32%; unfortunately the mean percentage of recalled babies that came for retesting was only 79.5%. In addition, the mean sample rejection rate was high, i.e. 2.2%. Two babies were diagnosed to have CH. These findings implied that whilst the coverage of screening was good, there is a need for regular surveillance of performance of both clinical and laboratory personnel. In addition, a more concerted effort should be carried out to promote community awareness of such a programme.

Assessment of P-gp and MRP1 activities using MultiDrugQuant Assay Kit: a preliminary study of correlation between protein expressions and its functional activities in newly diagnosed acute leukaemia patients.

Multidrug resistance (MDR) is believed to be responsible for poor response of patients towards chemotherapy particularly patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The best-characterized resistance mechanism is the one mediated by permeability-glycoprotein (P-gp) encoded by MDR1 gene, which is responsible for drug efflux. We studied P-gp and multidrug resistance-associated protein 1 (MRP1) expression and functional activities in 43 newly diagnosed acute leukemia cases (19 paediatric ALL cases and 24 adult AML cases). The expression and functional activities were examined using flow cytometry and MultiDrugQuant assay kit (involving calcein AM uptake and efflux). P-gp and MRP1 expression and its functional activities were observed in 68.4% of paediatric ALL. In adult AML cases, all cases expressed MRP1 and its functional activities but only 58.3% were positive for P-gp and its functional activities. We were able to show a significant correlation between the expression of the multidrug resistant protein (P-gp and MRP1) and their functional activity in adult AML and paediatric ALL samples.

Amelanotic spitzoid melanoma in a prepubescent boy.

The diagnosis of malignant melanoma (MM) in children is difficult due to its uncommon occurrence as well histological similarities to Spitz nevus. A case of MM of the foot in an 11-year-old boy is reported illustrating the histological overlap between Spitz nevus and MM. In our patient, both the primary foot lesion and the regional inguinal metastases were amelanotic, further increasing the diagnostic difficulty. The literature on MM in children is limited and the documentation of such unusual cases is necessary to improve the knowledge on this disease.

Malignant pancreatic carcinoid tumour.

Pancreatic carcinoid tumours are rare, particularly within the paediatric population. The clinical presentation is largely dependent on the functionality of the tumour. Although the tumour is generally slow-growing, surgical resection is still the mainstay of curative treatment. Morbidity is, however, significantly contributed by secretion of excess hormones; in view of this, biotherapy is an important treatment strategy. Octreotide, a somatostatin analogue, has been shown to be successful in both symptomatic control and stability of tumour progression. We report a 12-year-old girl, who presented with hypertensive crisis, and showed good response to a combination of chemotherapy and octreotide.

Cefepime plus amikacin as an initial empirical therapy of febrile neutropenia in paediatric cancer patients.

INTRODUCTION: We evaluated the efficacy of cefepime in association with amikacin in the initial empirical therapy of febrile neutropenic children. METHODS: The study was an open-labelled, non-randomised prospective trial to assess the efficacy and safety of this association, from January 2003 to December 2003. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received cefepime (50 mg per kg per dose every 8 hours for children weighing less than or equal to 40 kg; and 2 g every 8 hours for those weighing more than 40 kg) plus a single daily dose of amikacin at 15 mg per kg per day, up to a maximum 250 mg. If fever persisted, a second-line therapy with carbapenem was administered. Amphotericin B was added at 96 hours if fever and neutropenia persisted. RESULTS: 103 episodes of fever and neutropenia were evaluated in 54 patients. 18.4 percent of the episodes were microbiologically-documented infections, 24.3 percent were clinically documented, and 57.3 percent were episodes with unexplained fever. 54.4 percent of the episodes responded to cefepime plus amikacin without a need for treatment modification. A higher success rate (74.6 percent) was observed in episodes with unexplained fever. In all cases of persistent fever, the antibiotics were changed to carbapenem within 72 hours and all patients survived. One patient died because of culture-negative septic shock within 24 hours of admission. A mild gastrointestinal intolerance occurred in three patients. CONCLUSION: This study suggests that cefepime plus amikacin presents a satisfactory efficacy and a good tolerance as an initial empirical therapy for febrile neutropenic children.

Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias.

The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.

Recurrent gastric inflammatory myofibroblastic tumour in a 13-year-old male.

A 13-year-old boy who had epigastric pain and pallor for 2 months and found to have an ulcerative mass in the stomach and underwent partial gastrectomy. A diagnosis of inflammatory myofibroblastic tumour (IMT) of the stomach was made on histological examination. Three years later, recurrence in the stomach, with invasion into the pancreas and hilum of the spleen was noted and was managed by wide wedge resection of the stomach, distal pancreatectomy and splenectomy. The patient has been recurrence-free for the past 2 years. Gastric IMT is an uncommon tumour in children with unpredictable prognosis.

Transient abnormal myelopoeisis in newborns with Down syndrome.

Transient abnormal myelopoeisis (TAM) is a haematological phenomenon commonly seen in newborns with Down syndrome. Although the majority show spontaneous resolution, this condition should not be dismissed too readily as there have been associated fatalities. Furthermore, even for those who do show spontaneous resolution, a significant percentage will develop acute megakaryoblastic leukaemia within the next few years of life. We report a series of four patients with TAM who presented with hepatosplenomegaly and leucocytosis detected on preliminary investigations.

Unbalanced chromosomal translocation: a cause of recurrent spontaneous abortion.

Recurrent spontaneous abortion, defined as three consecutive abortions, occurs in approximately 1% to 2% of couples. Although the cause is unknown in up to 50% of cases, about 5% of these couples are found to be a balanced translocation carrier. We report a case in which the mother was identified to be a translocation carrier following the birth of a baby with multiple congenital abnormalities.

Case report post-splenectomy sepsis in thalassemic patients.

Thalassemia is the commonest hemoglobinopathy in Malaysia. Patients with thalassemia major are transfusion dependent, and a large proportion of them will require splenectomy. As this particular group of patients is immunocompromized, overwhelming sepsis is a recognized complication. We report a series of three patients who all developed intra-abdominal abscesses following splenectomy.