Significant advances in diagnosis and management have cured the majority of children with cancer. In the leukaemias, the commonest childhood malignancy, intensive induction-consolidation is important to ensure a lasting cure in about 65-80% and to eliminate the traditionally bad prognostic risk factors associated with less intensive treatment. Bone marrow transplantation (BMT) has a curative role in the minority who relapse particularly while on treatment. With few exceptions, most paediatric solid tumours are curable. Although the multimodal approach is responsible for the progress made, chemotherapy has emerged to play a dominant role. It has, in several tumours, obviated or reduced the need for radiotherapy and/or surgery. In Wilms' tumour and Hodgkin's disease, refinement of treatment is now in progress to reduce therapy-related morbidity while not sacrificing efficacy.
Gaucher Disease may now be treated with enzyme replacement therapy (ERT) or bone marrow transplantation (BMT). Both have their advantages and disadvantages. Results with BMT are curative when successful but limited by the scarcity of an appropriate donor. ERT offers very good relief of symptoms but treatment is lifelong and cost of treatment exorbitant. Patients in developing countries are particularly disadvantaged and management remains a dilemma for both doctor and patient.
We prospectively studied the type, frequency and outcome of infections in 513 patients with 762 consecutive episodes of febrile neutropenia (FN) over a five-year period between 1995 and 1999 in a single paediatric oncology unit. The findings were then compared with a similar study carried out in our unit between 1990 and 1994. The types of bacterial isolates and sensitivity patterns were also studied to identify trends and to gauge the suitability of antibiotics chosen for empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although 70% of patients did not have an obvious site of sepsis. The majority of isolates (61.9%) were gram-negative bacteria, a consistent finding throughout the study period. Resistance to ceftazidime, amikacin and imipenem among gram-negative bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were encountered. There were 36 sepsis-related deaths. Factors associated with a fatal outome were prolonged capillary refill time, hypotension, fever above 39 degrees C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis. A change to our current choice of empirical antibiotics for FN, comprising ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively high resistance rates found.
A 25-month-old boy with beta-thalassaemia major was presented with an opportunity for umbilical cord blood transplantation when his unborn sibling was diagnosed in utero to be a beta-thalassaemia carrier and also human leucocyte antigen compatible. A barely adequate amount of cord blood was collected at the birth of his sibling and infused into the patient after appropriate chemo-conditioning. Engraftment occurred without major complications. The subject is now alive and well 9 months post-transplant, thus marking our first success in umbilical cord blood transplantation.
Haemophagocytic Lymphohistiocytosis (HLH) is a rare clinical illness with a high mortality. There are reported effective treatment and a favourable outcome if diagnosed early. Five cases of childhood non-familial HLH seen over a 3 year period in our hospital are presented. The diagnosis was not suspected in the referring hospitals even after a bone marrow biopsy examination in two cases. Delay in referral was between 2 weeks to 2 months. A viral trigger was detected in only two cases. There were two deaths. Cause of death in both cases were cytomegalovirus pneumonitis and disseminated intravascular coagulopathy. Respond to treatment was better if started earlier. One case spontaneously resolved. Earlier diagnosis will lead to prompt treatment and a better outcome.
Campylobacter Jejuni is being increasingly recognised as a cause of bacteraemia enteritis and two infants with this condition are described. Awareness of the organism. as a possible cause of septicaemia is important because it has special growth requirements and delay in the diagnosis can be detrimental in a disease which usually only responds to erythromycin, gentamicin and chloramphenicol.
We report the occurrence of X-linked lymphoproliferative disease (XLP) in two brothers in a Malaysian family. In this disorder, a primary Epstein-Barr virus (EBV) infection is followed by an abnormal proliferation of transformed B-cells that cannot be controlled by suppressor T-cells, leading to the development of deranged immune function. This results in fatal infectious mononucleosis, acquired hypogammaglobulinaemia, virus-infected haemophagocytic syndrome and non-Hodgkin's lymphoma. The diagnosis should be considered when there is a family history of any male having a fulminant course of infectious mononucleosis, an otherwise benign disease. Early diagnosis is important as bone marrow transplantation is the only curative option in this disorder.
Distal renal tubular acidosis (RTA) and hereditary elliptocytosis (HE) are apparently distinct, genetic conditions. We report a family with 3 children having both hereditary elliptocytosis and distal renal tubular acidosis. The simultaneous occurrence of these two conditions in three siblings could be due to covariations in the same family, although a possible contiguous gene syndrome for distal RTA and HE cannot be excluded. This report emphasises the importance of excluding a renal tubular defect in any child who presents with elliptocytosis and failure to thrive.
Formerly thought to have a constant incidence rate throughout the world, Wilms' tumour (nephroblastoma) has been shown to be less common among Asian children. A retrospective demographic and morphological study of Wilms' tumour histologically diagnosed over a 22-year period at the Department of Pathology, University Hospital, Kuala Lumpur was conducted to assess for inherent demographic and morphological differences between tumours in Malaysian children and those of Western populations. Thirty-seven cases of histologically proven Wilms' tumour qualified for inclusion in this study. 19 patients were Chinese, 13 Malay, 4 Indian and 1 Anglo-asian. 21 were male and 16 were female (M:F ratio = 1.3:1). Their ages ranged from 1 month to 4 years. 70.3% of the patients were below 2 years of age. 36 cases had unilateral and 1 bilateral tumours. Of unilateral tumours, 19 involved the left kidney and 17 the right. Histological assessment, based on criteria of the National Wilms' Tumor Study Group, revealed 20 (52.6%) tumours with a mixed pattern while 8 (21.1%) showed epithelial, 7 (18.4%) blastemal and 3 (7.8%) stromal-predominant patterns. Anaplasia was observed in only 2 tumours (5.3%). There was no obvious difference in age range and sex distribution, laterality of tumours and incidence of anaplasia between this and Western studies. No ethnic predilection was observed. A notably larger percentage of cases were below 2 years of age. Also, a larger proportion of epithelial-predominant and a lower proportion of blastemal-predominant tumours was observed compared with patterns reported from Western populations.
Clear cell sarcoma of kidney (CCSK) is a rare but distinct tumor of childhood frequently confused with Wilms' tumor (nephroblastoma). It has a characteristic histology, a marked predilection for metastasis to bone, and an aggressive clinical course with a high relapse rate in spite of surgical excision, chemotherapy and radiotherapy. We report the first histologically proven CCSK in a Malaysian patient. This was an 8-mth-old Malay boy who was clinically diagnosed to have stage I Wilms' tumor. Despite treatment, he developed multiple metastases 10 mths after initial presentation and died soon after. Emphasis is placed on recognizing this entity in view of (1) its naturally aggressive behaviour and (2) the prospect of improving prognosis with currently recommended intensified chemotherapeutic regimes. Its immunohistochemical profile of vimentin-positivity and negativity for epithelial membrane antigen, cytokeratin and Factor-8 related antigen is more in favour of a mesenchymal or glomerular origin than a tubular or vascular origin.
Eight cases of clear cell sarcoma of kidney were seen in the Department of Pathology, University Hospital, Kuala Lumpur, Malaysia over the 16-year period from 1973 to 1989. Five of the patients were males. Six patients were Malay, one Chinese and one Indian. The patients' ages ranged from 8 months to 3 years. Clear cell sarcoma was the original diagnosis in two patients while six were diagnosed as blastemal-predominant Wilms' tumours at presentation. Metastases developed in five patients. Metastatic sites included the thoracic vertebra, skull, orbit, humerus, radius, ulna, shoulder, lung and liver. The prolonged survival, of 9 years and 9 months, seen in one patient despite omission of Adriamycin (doxorubicin) from the chemotherapeutic protocol is highlighted. We also emphasise the histological factors which are of help in differentiating clear cell sarcoma from Wilms' tumour.
Vulvar ulceration is a rare manifestation of histiocytosis X. A 13-year-old girl had a nonhealing vulvar ulcer for 1 year. She had been in remission from histiocytosis X and the ulcer was not recognised as a sign of disease recurrence until tissue biopsy was obtained for histopathological and immunohistochemical studies. This article stresses the importance of establishing an accurate diagnosis when chronic vulvar ulcers are encountered and reviews the literature on this uncommon presentation of histiocytosis X.
The simultaneous expression of both lymphoid and myeloid phenotypic features in acute leukaemia is rare. We report 3 cases of biphenotypic hybrid acute leukaemia seen in our institution. All 3 patients achieved remission with treatment for acute lymphoblastic leukaemia but two subsequently relapsed while on treatment. The hybrid acute leukaemias are important areas for further research both for delineation of basic biology and choice of optimal treatment.
Malignant lymphoma constitutes the third most common childhood malignancy seen at the University Hospital, Kuala Lumpur and can be categorised into Hodgkin's disease and non-Hodgkin's lymphoma. Both diseases demonstrate a higher preference for Chinese males. The majority of patients presented with stage IV disease. High default rate and poor compliance to treatment were associated with poor overall cure rates but encouraging results have been obtained in those who adhered to therapy. There is an obvious need to educate the public on the improved outlook 'or childhood malignancies and 'or earlier referral to help reduce the higher mortality and morbidity associated with advanced disease.
A report is presented of seven patients with acute septicaemic melioidosis seen at the University Hospital, Kuala Lumpur, Malaysia, during 1976-1979. All had associated disorders which rendered them more susceptible to infection. As prognosis depends on early diagnosis it is important that this disease be considered in the differential diagnosis of a septicaemic illness in such patients from endemic areas. The treatment of choice is a combination of tetracyclines and chloramphenicol, initially used in massive doses, and continued for at least six month to prevent relapses.
One hundred four children with acute lymphoblastic leukaemia were diagnosed at the University Hospital, Kuala Lumpur, Malaysia, between 1976 and 1982; 87 were evaluable with respect to treatment. They were divided into good prognosis (GP) and bad prognosis (BP) groups based on their initial total white cell count, their treatment differing only during the maintenance phase. Remission was achieved in 82 patients (94%) of whom ten (12%) subsequently died in remission from infection. Twenty-eight (34%) relapsed while on treatment and three while off therapy. Eleven patients ceased treatment after 3 yr of continuous complete remission (CCR). Three of these later relapsed, two within the first year. Survival in CCR was significantly better in the GP group up to 30 months, after which the difference diminished. There was no difference in survival between boys and girls. The overall disease-free survival at 3 yr and 5 yr was 40% and 25%, respectively, with a median follow-up period of 20 months (range 4-69 months). The reasons for the relatively low survival rates as compared with those in developed countries are discussed.
A 13-year old boy with acute lymphoblastic leukemia on chemotherapy developed neutropenia and acute cellulitis progressing to fulminating septicemia due to Pseudomonas pseudomallei. Septicemic melioidosis should be considered in the differential diagnosis of a febrile illness in children who are susceptible to infections.
A review of all cases of nephroblastoma admitted to the University Hospital over a 10 year period reveals that its incidence relative to the other childhood tumours and epidemiological features are similar to other centres. The majority of patients presented with either stage III or IV disease. During the period 1968·1972 the number of defaulters was high and survival was poor. Following the introduction of treatment protocol, default rate has fallen and 5 of 7 patients have survived more than 2 years. Earlier referral and education of the parents should help improve the outcome for children with Wilms' tumour in Malaysia.