Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis.

Four women and three men after allogeneic (n=4) and autologous (n=3) haematopoietic SCT (HSCT) were observed to have an increase in T-cell large granular lymphocytes (T-LGLs) of CD3+CD8+ phenotype for a median of 41 (15-118) months. Clonal rearrangement of the T-cell receptor gene was verified by two PCR techniques and direct DNA sequencing, confirming that the cases were neoplastic and therefore classifiable as T-LGL leukaemia. In the allogeneic HSCT cases, T-LGL leukaemia was derived from donor T cells in three patients, as shown by DNA chimerism analysis, and recipient T cells in one patient who had graft failure previously. None of the patients showed cytopenia, autoimmune phenomenon or organ infiltration, which were features typical of de novo T-LGL leukaemia. Six patients had remained asymptomatic with stable large granular lymphocyte counts. One patient died from cerebral relapse of the original lymphoma. T-LGL leukaemias occurring post-HSCT are distinct from de novo T-LGL leukaemia and may have a different pathogenesis and clinical course. Patients did not require specific treatment, and the disease remained stable for long periods.

Task factor usability ratings for different age groups writing Chinese.

This study evaluated how different task factors affect performance and user subjective preferences for three different age groups of Chinese subjects (6-11, 20-23, 65-70 years) when hand writing Chinese characters. The subjects copied Chinese character sentences with different settings for the task factors of writing plane angle (horizontal 0 degrees , slanted 15 degrees ), writing direction (horizontal, vertical), and line spacing (5 mm, 7 mm and no lines). Writing speed was measured and subjective preferences (effectiveness and satisfaction) were assessed for each of the task factor settings. The result showed that there was a conflict between writing speed and personal preference for the line spacing factor; 5 mm line spacing increased writing speed but it was the least preferred. It was also found that: vertical and horizontal writing directions and a slanted work surface suited school-aged children; a horizontal work surface and horizontal writing direction suited university students; and a horizontal writing direction with either a horizontal or slanted work surface suited the older adults.

Glucose-6-phosphate-dehydrogenase deficiency and haematopoietic stem cell transplantation in Chinese patients.

Deficiency in glucose-6-phosphate dehydrogenase (G6PD), an X-linked recessive red cell enzymopathy, is endemic in Southern Chinese. Universal screening of newborn is done in Hong Kong, Taiwan and Singapore, among other places. In Hong Kong, 4.8% of males are affected and seven common G6PD alleles account for over 99% of all defects. Male hemizygotes suffer from severe deficiency, while female heterozygotes may also be affected. Deficiency of G6PD may affect haematopoietic stem cell transplantation (HSCT) recipients and donors, before and after HSCT. Female patients with clonal erythropoiesis (eg myelodysplasia/myeloproliferative diseases) will have the male population incidence of G6PD. Quantitative enzyme level screening is prudent for donors and recipients, and should be repeated after engraftment. Cotrimoxazole prophylaxis should be avoided in known male and female carriers, including those with low-normal G6PD enzyme levels. Our experience suggested that G6PD-deficient marrow, stem cell and cord blood donor units have no engraftment problems. Post-engraftment G6PD levels correlate with those in donors. An acquired change in G6PD status may serve as a surrogate marker for engraftment. For female heterozygote donors with normal G6PD levels, skewing of lyonized X-chromosome ratio during engraftment may result in over-expression of the deficient allele. This can result in unexpected significant G6PD deficiency. Hence, a repeat G6PD screening at stable engraftment is recommended, especially before commencement of oxidative medications.

Explaining coronary heart disease trends in Hong Kong: creation of a model for policy and planning.

1. The largest contribution of coronary heart disease (CHD) mortality reductions was from medical treatment. 2. A smaller contribution was estimated to be due to risk factors changes. 3. Improvement of treatment uptake levels can have a substantial effect in reducing CHD mortality.

G6PD deficiency from lyonization after hematopoietic stem cell transplantation from female heterozygous donors.

To determine whether during hematopoietic stem cell transplantation (HSCT), X-chromosome inactivation (lyonization) of donor HSC might change after engraftment in recipients, the glucose-6-phosphate dehydrogenase (G6PD) gene of 180 female donors was genotyped by PCR/allele-specific primer extension, and MALDI-TOF mass spectrometry/Sequenom MassARRAY analysis. X-inactivation was determined by semiquantitative PCR for the HUMARA gene before/after HpaII digestion. X-inactivation was preserved in most cases post-HSCT, although altered skewing of lyonization might occur to either of the X-chromosomes. Among pre-HSCT clinicopathologic parameters analyzed, only recipient gender significantly affected skewing. Seven donors with normal G6PD biochemically but heterozygous for G6PD mutants were identified. Owing to lyonization changes, some donor-recipient pairs showed significantly different G6PD levels. In one donor-recipient pair, extreme lyonization affecting the wild-type G6PD allele occurred, causing biochemical G6PD deficiency in the recipient. In HSCT from asymptomatic female donors heterozygous for X-linked recessive disorders, altered lyonization might cause clinical diseases in the recipients.

Comparison of computed radiography and film/screen combination using a contrast-detail phantom.

The purpose of this work is to compare computed radiography (Kodak CR 400) and film/screen combination (Speed 400) systems in regards of patient dose, technique settings, and contrast-detail detectability. A special contrast-detail phantom with drilled holes of varying diameter (detail) and varying depth (contrast) was utilized. Various thicknesses of the Lucite sheets were utilized to simulate scattering tissues. Images of the phantom were acquired using a range of 60-120 kVp for film/screen and CR with a conventional x-ray tube and then for CR with additional 2 mm aluminum added filtration to the x-ray beam. The patient entrance skin dose was measured while maintaining 1.6 o.d. for film/screen images and 1900 Exposure Index for CR images. CR phantom images were displayed on the diagnostic workstation for soft copy reading as well as printed on films for hard copy reading on viewbox. Four physicists evaluated the images by scoring the threshold target depth along the row of the same target diameter. Detection ratio was calculated by counting the number of detectable targets divided by the total number of targets in the phantom. The overall score was related to the patient entrance skin dose, kVp, and the thickness of the scattering material. The patient entrance skin dose was reduced as the additional aluminum filter was added to the x-ray beam. Our findings suggested using a higher kVp setting and additional added filtration would reduce the patient entrance skin dose without compromising the contrast-detail detectability, which was compensated by the contrast manipulation on soft-copy display workstations.

Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon.

To look for subtle evidence of marrow involvement in nasal NK cell lymphoma at diagnosis, we retrospectively studied trephine biopsy specimens from 25 consecutive patients by 2 sensitive techniques: CD56 immunohistochemistry and Epstein-Barr virus-encoded RNA in situ hybridization (EBER ISH). Only 2 patients had marrow involvement by NK cell lymphoma at diagnosis. In 3 additional patients, marrow involvement developed during or after systemic recurrence. All 5 positive cases were revealed by EBER ISH, but only 3 cases showed CD56 immunoreactivity. Among the 5 cases, only 2 were recognized by morphologic assessment. All 5 patients died, often within a short period, compared with a mortality of 50% for patients without demonstrable marrow involvement. Marrow involvement is distinctly uncommon in nasal NK cell lymphoma at diagnosis, and EBER ISH is the most sensitive technique for the demonstration of occult NK cell lymphoma. Despite the low frequency of marrow involvement in nasal NK cell lymphoma, EBER ISH is worthwhile to identify the minor subgroup of patients with a high likelihood of early death due to disease and when autologous bone marrow or peripheral blood stem cell transplantation is contemplated.

Mantle cell lymphoma in leukemic phase: characterization of its broad cytologic spectrum with emphasis on the importance of distinction from other chronic lymphoproliferative disorders.

BACKGROUND: Mantle cell lymphoma is a mature, virgin B-cell neoplasm characterized immunologically by a panB+, CD5+, CD23-, cyclin D1+ phenotype and genetically by t(11;14)(q13;q32) with overexpression of the cyclin D1 (bcl-1) gene. It usually presents as advanced stage disease, involving lymph nodes, spleen, bone marrow, and extranodal sites, particularly the gastrointestinal tract. However, frank leukemic presentation with high white cell counts is uncommon and can be difficult to distinguish from other chronic lymphoproliferative disorders. The aim of this study was to characterize the morphologic spectrum of leukemic mantle cell lymphoma. METHODS: During the period July 1994 through October 1998, 14 patients with mantle cell lymphoma in leukemic phase were diagnosed at the Department of Pathology, Queen Elizabeth Hospital, Hong Kong. The diagnosis of mantle cell lymphoma was based on histologic and immunocytochemical findings and was confirmed by cyclin D1 immunoreactivity in all cases. The clinical records and laboratory results were reviewed. Peripheral blood smears, bone marrow, and other tissue biopsies were examined, with particular attention to the cytologic features of the leukemic mantle cells. RESULTS: Mantle cell lymphoma in leukemic phase showed a very aggressive clinical course. Eight patients died at a mean of 13 months, and only 1 patient was disease free. Morphologically, the leukemic mantle cells exhibited a broad morphologic spectrum, with several cytologic patterns identified: 1) mixed small and medium-sized cells, 2) predominantly medium-sized cells, 3) predominantly large cells, and 4) giant cells. Despite variations in the size and nuclear shape, the leukemic mantle cells could usually be recognized by the nuclear irregularity and clefting, moderately dense but evenly distributed chromatin, small nucleoli, and scant cytoplasm. CONCLUSIONS: Recognition of the characteristic cytologic features of leukemic mantle cells can help to distinguish them from other chronic lymphoproliferative disorders. In contrast to the latter, the clinical course is aggressive and response to conventional chemotherapy is poor.

Isolated extramedullary relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia.

Relapse of chronic myeloid leukemia (CML) as extramedullary granulocytic sarcoma (GS) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. We report two patients who developed spinal GS as the first indication of relapse after allogeneic BMT for CML. In both cases, the marrow was in morphologic and karyotypic remission. However, fluorescence in situ hybridization (FISH) successfully demonstrated the presence of a minor Ph-positive clone in the marrow, as well as an occult clone with an additional Ph chromosome detected in one case. The results indicated a stronger graft-versus-leukemia effect in the marrow than in the peripheral tissues.

Comparison of haemoglobin H inclusion bodies with embryonic zeta globin in screening for alpha thalassaemia.

AIMS: To compare the haemoglobin (Hb) H inclusion test with immunocytochemical detection of embryonic zeta chains in screening for alpha thalassaemia. METHODS: Blood samples from 115 patients with relevant clinical history and hypochromic microcytic indexes were screened using the HbH inclusion test and the Variant Hemoglobin Testing System (BioRad, Hercules, CA, USA). RESULTS: The HbH inclusion test was positive in 61 of 115 cases, three of whom had HbH disease confirmed by electrophoresis. The remaining 58 had alpha thalassaemia 1. All three HbH cases and 56 of 58 cases of alpha thalassaemia 1 expressed embryonic zeta chains, giving a specificity of 96.7%. Fifty four of 115 cases had a negative HbH inclusion test, of whom 50 had beta thalassaemia trait and three had iron deficiency. No diagnosis was reached for the remaining patient. CONCLUSION: The immunocytochemical test is as sensitive as the HbH inclusion test in screening for alpha thalassaemia. The presence of zeta chains is highly specific for alpha thalassaemia 1 incorporating the (--/SEA) deletion. The specificity and simplicity of the immunocytochemical test make it the test of choice in screening for alpha thalassaemia.