Tk Chan

CD56 ˛ NK lymphomas: clinicopathological features and prognosis

The surface molecule CD56 marks a category of malignant lymphoma of putative natural killer (NK) cell origin. We conducted a retrospective analysis of 24 cases of CD56+ NK lymphoma/leukaemia to define the clinicopathologic and prognostic features of this specific group of lymphomas. 56 cases of nasal lymphomas and 204 cases with an initial diagnosis of peripheral T‐cell lymphoma were retrospectively analysed. To specifically examine lymphomas of putative NK origin, only those that were negative for surface expression of CD3 but positive for CD56 were analysed. 24 cases were identified. The initial predominant sites of involvement were nasal (n =18), palate (n = 1), nodal (n = 1) and multi‐organ (n =4). Clinically, in patients with disease localized to one anatomical site (n = 20), most had symptoms confined to the nose, with a high percentage in early stage (I: 91%; IV: 9%). The marrow was not involved in any of these cases. However, patients with multi‐organ involvement at presentation (n = 4) behaved differently. All presented acutely with pancytopenia, hepatosplenomegaly, and marrow infiltration with haemophagocytosis. A leukaemic phase was observed in one case. Anthracycline containing combination chemotherapy resulted in complete remission in 75% of patients with localized disease, but only in 25% with multi‐organ involvement. The median survival of patients with localized disease was 12 months, compared with 2 months in the multi‐organ group (P =0.06); the disease‐free survival was significantly better in the former (P <0.01). The overall median survival of all patients was still poor at 11 months.

Genetic and clinical features of hemoglobin H disease in Chinese patients

BACKGROUND Normally, one pair of each of the two alpha-globin genes, alpha1 and alpha2, resides on each copy of chromosome 16. In hemoglobin H disease, three of these four alpha-globin genes are affected by a deletion, a mutation, or both. We studied the alpha1-globin gene abnormalities and the clinical and hematologic features of Chinese patients with hemoglobin H disease in Hong Kong. METHODS We assessed the clinical features, hematologic values, serum ferritin levels, and liver function of 114 patients with hemoglobin H disease. We also performed echocardiography and magnetic resonance imaging of the liver and examined the two pairs of alpha-globin genes. RESULTS Hemoglobin H disease in 87 of the 114 patients (76 percent) was due to the deletion of three of the four alpha-globin genes (--/-alpha), a combination termed the deletional type of hemoglobin H. The remaining 27 patients (24 percent) had the nondeletional type of hemoglobin H disease, in which two alpha-globin genes are deleted and a third is mutated (--/alphaalphaT). All 87 patients with the deletional type of hemoglobin H were double heterozygotes in whom there was a deletion of both alpha-globin genes from one chromosome, plus a deletion of the alpha1 or alpha2 gene from the other chromosome (--/alpha- or --/-alpha). A variety of mutated alpha-globin genes was found in the patients with nondeletional type of hemoglobin H disease. Patients with the nondeletional type of the H disease had more symptoms at a younger age, more severe hemolytic anemia, and larger spleens and were more likely to require transfusions than patients with deletional hemoglobin H disease. The severity of iron overload was not related to the genotype. CONCLUSIONS Chinese patients in Hong Kong with the nondeletional type of hemoglobin H disease have more severe disease than those with the deletional type of the disease. Iron overload is a major cause of disability in both forms of the disease.

Molecular defects in Hb H hydrops fetalis

The molecular defect in two unique cases of Hb H hydrops fetalis has been characterized. Both cases are due to co‐inheritance of a ‘non‐deletion’ defect affecting the α2 gene: at codon 30 (ΔGAG, Glu) and codon 59 (G  →  A, Gly →  Asp) respectively, and a ζ‐α thalassaemia (thal) 1 or α thal 1 genotype. These two non‐deletion defects, unlike previously described cases, resulted in severe anaemia of the fetuses and emphasize the importance of performing prenatal diagnosis for these families.

Nasal lymphoma: A retrospective analysis of 60 cases

Sixty cases of nasal lymphomas were reviewed. There were 42 men and 18 women. the median age was 49 years. the histologic types were low grade in four cases, intermediate grade in 33, high grade in seven, and unclassifiable in 16. Thirteen cases had features of polymorphic reticulosis. the immunophenotype was available in 18 cases and a majority of 67% of them were T‐cell. Forty‐one of them (68%) had clinically localized (Stage I and II) disease which often spread locally to neighboring tissues and they presented predominantly with nasal symptoms. Nasal lymphoma appeared to carry a poor prognosis. Although our patients with clinically localized disease had significantly better prognosis than those with advanced disease, the 5‐year survival of Stage I and II patients was only 55%. Chemotherapy did not appear to be more effective than radiotherapy alone in preventing relapses but the patient number was too small to allow a firm conclusion to be made. Patients with advanced disease had even poorer prognosis with a 5‐year survival of only 17%. Innovative therapy has to be developed for these patients.

A reverse dot-blot method for rapid detection of non-deletion α thalassaemia

A reverse dot blot method based on membrane‐bound allele‐specific oligonucleotides as hybridization targets for amplified α‐gene fragments has been developed for the rapid detection of four non‐deletion α thalassaemia defects found in the Chinese. Since these non‐deletion defects account for 22.8% of haemoglobin H disease, a sensitive, specific and rapid screening method should be of value.

Deep Vein Thrombosis and Changes in Coagulation and Fibrinolysis after Gynaecological Operations in Chinese: the Effect of Oral Contraceptives and Malignant Disease

Of 154 Chinese patients who underwent gynaecological operations, four showed a positive 125I fibrinogen leg scan for venous thrombosis, an overall incidence of 2.6%. In those who were on oral contraceptives and had major pelvic surgery for benign conditions, the incidence was 10.5%; in those who had Wertheim hysterectomy for carcinoma of cervix, it was 6.7%. This confirms the rarity of post‐operative thromboembolism in the Chinese. Fragment E showed a biphasic rise after major operation due to tissue injury and venous thrombosis. In patients with malignancy, the postoperative ‘fibrinolytic shutdown’, represented by decreased plasminogen activator together with increased α1, antitrypsin and C inhibitor levels, was more marked. In addition, α2 macroglobulin level was lower and fell significantly after operation. In patients on oral contraceptives, fragment E levels were higher after surgery and there was no decrease in plasminogen activator levels. Antithrombin III levels did not fall except in three of the four patients with venous thrombosis. A marked increase in fragment E level and a decrease in antithrombin III level might be useful diagnostic markers for postoperative venous thrombosis.

A thalassaemia array for Southeast Asia

The α and β thalassaemias are the commonest genetic disorders worldwide. The homozygous state is associated with high morbidity and mortality, thus screening of at‐risk pregnancies and prenatal testing are strongly advocated. A thalassaemia (thal) array has been designed using allele‐specific arrayed primer extension (AS‐APEX) for the simultaneous analysis of 15 non‐deletion α‐gene defects and 23 β‐gene mutations commonly found in southeast Asian countries, where thalassaemias are highly prevalent. This overcomes the problem of using multiple reverse dot blot analysis. The array showed 100% sensitivity and specificity in the detection of 120 β‐thal mutants and 35 non‐deletion α‐thal mutants. It is robust enough to be produced in a single place and shipped to other laboratories for use. The production cost of the array is low, each slide can be used for three different test samples and is therefore amenable to large scale antenatal screening in southeast Asian countries.

Organization of the ζ‐α genes in Chinese

Summary. Analysis of α and ζ genes in 101 healthy normals and hospitalized patients with non‐haematological diseases revealed a 3% incidence of α thalassaemia in the local Chinese population of Hong Kong. Triple α genes were found in only one person while triple ζ genes were more prevalent, occurring in 13 subjects. Studies of 28 unselected patients with Hb H disease indicated a predominance of the rightward χ gene deletion. The extent of α gene deletion in homozygous α thalassaemia 1 was at least 18.1 kb, beginning from the BamH I site 3’to the ζ1 gene and includes the Φα, α2 and α1 genes. Nineteen of the 20 chromosomes bearing the α thalassaemia 1 deletion had identical ζ‐intergenic hypervariable region suggesting a common origin of this mutation. The co‐inheritance of α thalassaemia in β thalassaemia subjects was 8%, but did not ameliorate the clinical features of those with homozygous β thalassaemia

Characteristics and distribution of β thalassemia haplotypes in South China

SummaryEleven restriction site polymorphisms in the β-globin gene cluster were determined in 48 Chinese with homozygous β-thalassemia and their parents. Seven haplotypes were identified as associated with the βthal chromosome and 25 with the βA chromosome. The distribution of the various βthal haplotypes in different regions of South China was mapped and discussed in relation to prenatal diagnosis and migration of the Chinese people.

Essential thrombocythemia with BCR/ABL rearrangement

Essential thrombocythemia (ET) was diagnosed clinically in three patients Karyotypic analysis and reverse transcription polymerase chain reaction for the bcr-abl chimeric transcript showed that two were Philadelphia chromosome (Ph) positive, bcr-abl positive, whereas the third was Ph negative, bcr-abl positive. The first patient received an allogeneic bone marrow transplantation but relapsed as localized blastic transformation, thus behaving similarly to chronic myeloid leukemia (CML). However, the other patients showed clinical courses more in keeping with ET. Essential thrombocythemia with BCR rearrangements may resemble CML but there are clinical differences. These may be due to genetic changes in addition to the BCR rearrangement.