The value and practicality of granulocyte transfusion: a single oncology centre experience.

There is an increased risk of infection in patients with neutropaenia, especially in those with neutrophil counts of less than 0.5 x 10(9)/L, and neutropaenia-associated infection remains a limiting factor in treating malignancy especially of haematopoietic origin. Transfusing donor neutrophils is a logical approach to these problems, but granulocyte transfusion (GTx), a practice first advocated in the 1960s, is underused and although now enjoying resurgence, remains controversial. The aim of this study was to determine the practical aspects of GTx and clinical responses in patients receiving them. This is an observational retrospective review of GTx in patients undergoing therapy for predominantly haematological malignancies. We reviewed blood bank records and identified patients who received therapeutic granulocytes procured by leukapheresis and linked these recipients with their granulocyte donors. We determined the reasons for GTx and their clinical and relevant haematological responses to the transfusions. We identified 22 patients receiving at least three continuous days of GTx and who had adequate clinical and haematological data. Most donors were relatives and ABO matched with their respective recipients. Mean age of the patients was 28.8 years. Severe aplastic anaemia was the most common diagnosis, occurring in 9 patients (40.9%), followed by acute myeloid leukaemia in 6 (27.3%). Disseminated fungal infection was the most common reason for GTx, occurring in 16 patients (73%), followed by febrile neutropaenia in 7 patients. Fifteen (68.2%) patients showed clinical improvement. This uncontrolled retrospective observational study provides some evidence that procurement and use of GTx is safe for both donors and recipients and is probably an effective supportive therapy for patients with febrile neutropaenia.

Extramedullary myeloid cell tumours localised to the mediastinum: a rare clinicopathological entity with unique karyotypic features.

Extramedullary myeloid cell tumour (EMMT) localised to the mediastinum is a rare manifestation of acute myeloid leukaemia, forming less than 4% of all cases of EMMT. In contrast to other types of EMMT, cytogenetic characteristics of this rare entity are relatively unknown. This report describes a patient with EMMT who had evidence of superior vena cava syndrome and normal peripheral blood counts at diagnosis. The results from an initial biopsy specimen were consistent with a diagnosis of mediastinal large B cell lymphoma. A diagnosis of acute myeloid leukaemia was made three months after initial diagnosis by bone marrow examination. Review of the initial biopsy specimen showed strong positivity for myeloperoxidase, revealing that the patient had been initially misdiagnosed as having large B cell lymphoma. Cytogenetic studies revealed a near triploid and near tetraploid karyotype with structural abnormalities in 12 and three metaphases, respectively. Review of the literature showed that a near tetraploid or triploid karyotype is found in most of the reported cases of mediastinal EMMT. Thus, the presence of a near triploid/tetraploid karyotype and mediastinal EMMT may represent a specific subset of EMMT. The biological relevance of this observation is discussed.

Cerebral fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI, and clinical observations in a patient with infantile G(M1) gangliosidosis.

The clinical, biochemical, pathological and neuroradiological findings of a 2-year-old Saudi boy with infantile G(M1) gangliosidosis are reported. The patient had a progressive neurologic deterioration, manifesting with developmental regression, sensorimotor and psychointellectual dysfunction and generalized spasticity that started at 4 months of age. Cherry-red macula, facial dysmorphia, hepatomegaly, exaggerated startle response to sounds, skeletal dysplasia, and vacuolated foamy lymphocytes that contain finely fibrillar material in addition to lamellar membranes and electron-dense rounded bodies were seen. MRI of the brain demonstrated mild diffuse brain atrophy and features of delayed dysmyelination and demyelination. Brain FDG PET scan revealed a mild decrease in the basal ganglia uptake, and moderate to severe decrease in thalamic and visual cortex uptake, and an area of increased glucose uptake in the left frontal lobe, probably representing an active seizure focus. The functional changes indicated by FDG PET scan and the structural abnormalities shown on MRI were found to be complementary in the imaging evaluation of infantile G(M1) gangliosidosis.

Systemic lupus erythematosus presenting with haemorrhagic manifestation.

A 26-year-old female presented with an episode of severe mucus membrane bleeding. Investigations revealed prolonged prothrombin time (PT), and partial thromboplastin time (PTT), normal thrombin time (TT) and reptilase time, thrombocytopenia, a positive test for lupus anticoagulant (LA), as well as anti-cardiolipin antibodies (ACL). A toxicology screen for toxic drugs and coumadin was negative. Coagulation factor assays revealed low levels for factor II and XII. Low level inhibitor to factor II was demonstrated. Patient had a negative VDRL test and positive anti-nuclear antibodies (ANA). The diagnosis of acquired hypoprothrombinaemia secondary to circulating inhibitor induced by LA was made, and then the patient was started on prednisone, which led to cessation of the bleeding and normalization of PT and PTT, as well as an increase of factor II and factor XII levels. A few months later, the patient developed arthralgia and alopecia, and antibodies against double-stranded DNA were detected, and the diagnosis of systemic lupus erythematosis (SLE) was confirmed. The patient continued to have mild prolongation of PT and PTT while on a low dose of prednisone, but she had no bleeding symptoms. A computed tomography scan of the brain was carried out for unexplained central nervous system (CNS) symptoms, and it revealed mild hydrocephalus, which was thought to be part of the CNS manifestations of SLE. It was concluded that patients with SLE may present with haemostatic defects that are a result of either platelet-related causes (quantitative or qualitative) or coagulation factor deficiency secondary to circulating inhibitor, or both, in the absence of other features of SLE which may appear later.

Wolman's disease: The King Faisal Specialist Hospital and Research Centre experience.

BACKGROUND: Wolman's disease is a rare autosomal recessive lysosomal storage disease. A recent review indicates that approximately 50 patients have been reported in the world. Reports of patients from the Arabian peninsula are rare due to lack of awareness among pediatricians. PATIENTS AND METHODS: We retrospectively reviewed the clinical, radiological, biochemical and histopathological findings of four Saudi patients diagnosed with Wolman's disease at King Faisal Specialist Hospital and Research Centre. The diagnosis was confirmed by deficient acid lipase activity in the leukocytes and fibroblasts, which was measured using 4-methylumbelliferyl palmitate. RESULTS: All patients were failing to thrive with progressive hepatosplenomegaly. Abdominal x-ray revealed calcifications which were confirmed on abdominal CT scan. Peripheral blood film showed vacuolated lymphocytes and the bone marrow aspiration showed foamy histiocytes. Liver biopsy in one patient showed marked steatosis and elliptical empty clefs predominantly in the Kupffer cells, indicating cholesterol storage in the reticulo-endothelial cells. The acid lipase activity was less than 6% in all patients. CONCLUSION: In all suspected cases of Wolman's disease, a plain abdominal x-ray should be obtained to check for the typical pattern of adrenal calcification characteristic of the disease, especially in any young infant with failure to thrive and progressive hepatosplenomegaly.

Bone marrow morphologic findings in patients with human immunodeficiency virus (HIV) infection.

The hematologic, histologic and morphologic bone marrow findings of 18 patients with human immunodeficiency virus (HIV) infection were reviewed. The mean age of the patients studied was 27 years; age range was six to 63 years. The main bone marrow morphologic finding was hypercellularity (72%), which was mainly due to megakaryocytic hyperplasia with or without granulocytic or erythrocytic hyperplasia. Naked (denuded) megakaryocytic nuclei, which are considered an indicator of HIV infection, were present in 72% of the bone marrows examined. Reticuloendothelial iron blockade was identified in 78% of cases. Other less frequent findings included erythrocytic dysplasia (44%), plasmacytosis (28%), nonspecific granulomas (17%), Hodgkin's and non-Hodgkin's lymphoma (17%), lymphocytic aggregates (11%) and histiocytosis (6%) . The bone marrow findings in this series of HIV patients appear to be similar to what has been previously reported from other countries.

Apoliprotein B polymorphism: Application to monitoring early bone marrow transplantation in Saudi population.

Seventy-three unrelated Saudi individuals and seven consecutive bone marrow transplant donor-recipient pairs were studied to characterize and determine the frequency of 3' apolipoprotein B alleles by polymerase chain reaction. The samples analyzed were either peripheral blood or bone marrow aspirates. Eleven different alleles were detected. The index of heterozygosity was 0.66. Apolipoprotein B analysis was informative in 57% of the studied donor-recipient pairs. Engraftment was detected as early as day three post-transplantation. The threshold of detection of this allele was up to 0.01x106/ml. Mixed chimerism of the order of 1% could be detected. We concluded that apolipoprotein B is a highly polymorphic allele among the Saudi population and this makes the region a useful marker for monitoring engraftment following allogeneic bone marrow transplantation.

Glanzmann's thrombasthenia with mild von Willebrand's disease.

A Saudi Arabian family is reported in which Glanzmann's thrombasthenia and von Willebrand's disease occurred simultaneously. The daughter presented with menorrhagia and gave a history of gastrointestinal bleeding and a strong family history of bleeding disorder. Full haematological investigations were performed on the propositus, parents, and siblings, including complete blood count, bleeding time, prothrombin time, partial thromboplastin time, factor VIII:C, von Willebrand factor, ristocetin cofactor, platelet aggregometry, platelet glycoprotein Ib and IIb/IIIa and platelet antigen PLT-1 (Coulter Clone). The propositus had Glanzmann's thrombasthenia, both parents had mild von Willebrand's disease and were carriers of Glanzmann's thrombasthenia. Three symptomatic brothers had both Glanzmann's thrombasthenia and von Willebrand's disease; two asymptomatic brothers had von Willebrand's disease only and one had completely normal results. Those family members with both diseases were more severely affected than those with just one disease. In areas where consanguineous marriage is common, such as Saudi Arabia, multiple haemostatic abnormalities may occur, and investigation should not stop with the discovery of a single abnormality. The increased clinical severity of bleeding, including haemarthroses, in those patients having both congenital defects emphasises the importance of von Willebrand factor in glycoprotein Ib-mediated platelet adhesion.