L-asparaginase induced intracranial haemorrhage in acute lymphoblastic leukemia.

A 20-year-old national serviceman with acute lymphoblastic leukaemia, developed a large left parieto-occipital haemorrhage 7 days after completion of induction chemotherapy. Severe hypofibrinogenemia had been noted while he was receiving L-asparaginase. The haemorrhage could not be attributed to thrombocytopenia, disseminated intravascular coagulopathy, arterio-venous malformation, berry aneurysm or leukaemic infiltration because each of these causes was carefully investigated into and excluded. We conclude that the intracranial haemorrhage was likely L-asparaginase induced, an uncommon but recognised complication associated with L-asparaginase therapy.

Use of ondansetron in the control of emesis in autologous peripheral blood stem cell transplant (APBSCT) for solid tumours.

AIM: The use of autologous peripheral blood stem cell transplant (APBSCT) for solid tumours have increased exponentially in the last 5 years. While the use of 5-hydroxytryptamine 3 (5HT3) receptor antagonists has been shown to improve control of emesis in patients receiving conventional dose chemotherapy, similar literature in APBSCT is more limited. We report our experience in the use of ondansetron in APBSCT. METHOD: Twenty-three patients with solid tumours receiving high-dose chemotherapy with APBSCT were studied. All were started on intravenous ondansetron at 24 mg/day before commencement of the conditioning regimen and continued till vomiting had ceased for 24 hours. The conditioning regimen used was dependent on the tumour type and the duration ranged from 4 to 6 days. Control of emesis was assessed by the number of vomiting episodes in each 24-hour period, monitored throughout conditioning till discharge from hospital. RESULTS: Complete or major protection from vomiting was achieved in 83% of patients on day 1. During the entire conditioning period, 52% of patients achieved complete or major response to ondansetron. After the conditioning period (delayed emesis), 44% of patients achieved complete or major response. CONCLUSIONS: The control of emesis for patients undergoing high-dose chemotherapy with APBSCT is fair with ondansetron. Research on more effective combinations to further improve emetic control in this selected group of patients is needed.

Comparison of peripheral blood CD34+ concentration, colony-forming units granulocyte-macrophage and mononuclear cells in leukapheresed product for the prediction of peripheral blood CD34+ cell yield harvest.

The aim of this study was to evaluate reliability of parameters which may be used to guide peripheral stem cell harvests in cancer patients prior to myeloablative chemotherapy. Each leukapheresed product was analysed for CD34-positive (CD34+) cell count, mononuclear cell (MNC) count and the number of colony-forming units granulocyte-macrophage (CFU-GM). Each patient's peripheral blood (PB) taken before leukapheresis was analysed for CD34+ concentration. We evaluated whether the CD34+ yield from leukapheresis correlated with any of the three parameters. A total of 119 procedures were performed in 33 patients. The yield of CD34+ cells by leukapheresis correlated weakly but significantly with the peripheral blood CD34+ cell count (R = 0.4 P < 0.05), the MNC cells (R = 0.4, P < 0.05), and CFU-GM (R = 0.4, P < 0.05). When a PB CD34+ count of 50 x 10(6)/L was used as a cut-off value, the accuracy for prediction of adequate leukapheresis (> 1 x 10(6) CD34+ cells/kg) was 78%.

Splenic lymphoma with villus lymphocytes--an uncommon cause for lymphocytosis.

We describe the clinical and laboratory features of four patients who presented with mild to moderate lymphocytosis but with no peripheral lymphadenopathy. These patients in the past, would have been classified as chronic lymphocytic leukaemia (CLL). However, it is now realised that chronic lymphoproliferative disorders are very heterogeneous and the clinical and laboratory features of our patients would support a diagnosis of splenic lymphoma with villus lymphocytes (SLVL) with characteristic morphological features. SLVL usually runs a benign clinical course but symptoms related a benign clinical course but symptoms related to splenomegaly or hypersplenism may be a problem. Splenectomy is considered the treatment of choice in these patients. Two of our patients had splenectomy and the other two patients are on regular follow-up without any specific treatment. It is therefore important to recognise this uncommon condition and also to differentiate it from CLL.

Treatment of acute promyelocytic leukaemia in first relapse with all-trans retinoic acid.

A 27-year-old Chinese woman with acute promyelocytic leukaemia in first relapse after the initial conventional induction chemotherapy 18 months earlier was treated with all-trans retinoic acid (ATRA) at an initial dose of 45 mg/m2 and subsequently increased to 65 mg/m2 on day 15. Complete remission was achieved after a total of 40 days of ATRA alone. Serial marrow examinations during induction showed progressive maturation of myelopoiesis without bone marrow hypoplasia. There was a significant reduction in number of cells with the t(15;17) translocation when complete remission was achieved. ATRA was very well-tolerated. The symptoms of dry skin and intermittent headache were self-limiting.

Multiple myeloma: the National University Hospital (NUH) experience.

The aim of this retrospective study was to define the characteristics of local patients with multiple myeloma. Twenty-nine de novo cases were accrued from October 1986 to January 1992 at the National University Hospital of Singapore. Features like median age of presentation, sex distribution, the incidence of IgG, IgA and light chain subtypes were similar to published data. However IgD myeloma appeared to be more common here and it tended to be more advanced at presentation. Objective response rate to treatment with the melphalan-prednisolone combination was about 40% with a median survival of 18 months.

Feasibility and efficacy of maintenance chemotherapy following autologous bone marrow transplantation for first remission acute lymphoblastic leukaemia.

Thirty-eight patients with poor risk ALL in first remission received maintenance chemotherapy following ABMT. Patients were conditioned for ABMT with high-dose melphalan and single fraction total body irradiation. Maintenance chemotherapy was commenced in a total of 26 patients and was tolerated to a median daily dose of 6-mercaptopurine of 40.5 mg/m2 and a median weekly dose of MTX 8.3 mg/m2. Twenty patients remain alive in first remission with a projected disease-free survival of 50% and a median follow-up in survivors of 200 weeks (range 48-387 weeks). Eleven patients have relapsed at a median of 4.5 months from ABMT. These patients were compared with remission patients with ALL receiving conventional chemotherapy on the United Kingdom Medical Research Council trials UKALL X and XA. After stratifying for major risk factors and allowing for the delay from remission to transplant, we have shown a significant reduction in the risk of relapse after ABMT (p = 0.04). Disease-free survival was not significantly increased due to transplant-related toxicity. This study suggests that maintenance chemotherapy to prevent relapse after ABMT for ALL is well tolerated and warrants assessment in a formal controlled trial.

Acute deep vein thrombosis in hospital practice.

A recent cross sectional study on symptomatic acute deep vein thrombosis at the National University Hospital (NUH) in Singapore found a frequency rate of 0.79 per 1000 patient admissions. A total of 39 patients were accrued over 18 months, 36 with deep vein thrombosis alone and three complicated by pulmonary embolism. No sex or ethnic predilection was observed in this cohort of hospitalised patients. Twenty-eight (71.8%) patients were 40 years or older. Majority (89.7%) of patients had at least two predisposing factors. While prolonged bedrest and operative procedures featured equally frequently in patients above and below 40 years, neoplasms were predominantly associated with the former and protein C or S deficiency primarily with the latter. The exhaustive laboratory confirmation of an inherent thrombotic tendency is recommended only for patients below 40 years of age.

Alpha-thalassaemia and beta-thalassaemia traits: biological difference based on red cell indices and zinc protoporphyrin.

alpha-thalassaemia and beta-thalassaemia traits are two commonly encountered haemoglobinopathies in South East Asia. Both present with hypochromia and microcytosis. The use of modern electronic or optical cell counters which measure accurately the red cell parameters has allowed for an initial quick screening for the presence of thalassaemia. Seven red cell parameters were measured by the Technicon H1 cell analyser--red cell count, Hb, MCV, MCH, red cell distribution width (RDW) and haemoglobin distribution width (HDW). Discriminant analysis of these parameters and zinc protoprophyin (ZP) indicates that in healthy individuals, alpha-thalassaemia can be differentiated from beta-thalassaemia with an accuracy of 86% when analysed as a group. In hospitalized patients the accuracy dropped to 71% due to biases of concomitant illness. The two most important parameters for indicating differences between alpha- and beta-thalassaemia are MCV and ZP. The results confirm further that though alpha- and beta-thalassaemia have the same phenotypic expression they differ in their biology.

Diagnosis of leukocyte disorders with an automated haematology counter (Technicon H-1 analyser).

The differential leukocyte count is very important in the diagnosis of various leukocyte disorders. Newer automated haematology counters can now perform differential leukocyte count, thus reducing the dependence on experienced medical technologists. The Technicon H.1 analyser (Technicon Instruments Corp., New York, USA) can perform even more complicated tasks like flagging abnormal cells, generating cytograms based on cell size and cytochemistry. In this paper we report on the useful cellular characteristics of the various leukocyte disorders as measured by the Technicon H.1 analyser.

Incidence of thrombocytopenia in an acute care hospital.

Our recent survey recorded thrombocytopenia in 1 per 105.5 adults inpatients in an acute care hospital. Less than 30% of these patients demonstrated any bleeding manifestations. The high pickup rate of asymptomatic thrombocytopenia is a spin off from the current practice of recording the platelet count with every full blood count request. 46.6% of our thrombocytopenic patients had an underlying infection. The high association between thrombocytopenia and infection justifies a search for an infective process when one encounters an unexpected or unexplained reduction in the platelet count.

Agranulocytosis and anaemia induced by sulfametopyrazine in a sulfametopyrazine-trimethoprim combination.

We report a case of prolonged fever, agranulocytosis, and anaemia associated with the long acting sulphametopyrazine-trimethoprim combination (Kelfiprim). A woman of 23 years took an overdose of 13 tablets over five days for presumed cystitis. One day after the last dose the patient developed fever and a generalised rash. The fever persisted and her previously normal leukocyte count decreased to 1.8 x 10(9)/1. After treatment with paracetamol the fever settled briefly, and then recurred for another 16 days. A later peripheral blood leukocyte count of 0.77 x 10(9)/1, haemoglobin of 10.8 g/dl, and a hypocellular bone marrow with depressed granulopoiesis and haemopoiesis suggested marrow suppression induced by sulfametopyrazine. Since the IgM antibody against the Epstein-Barr virus capsid antigen was detected, the adverse drug reaction might have been aggravated by this virus. The case highlights the risk of severe haematological adverse reactions associated with sulphonamide treatment, and argues for the use of trimethoprim alone for uncomplicated cystitis.