Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: a single center experience of 10 years.

BACKGROUND: Data on mature T-cell and natural killer (NK)-cell lymphomas diagnosed with the World Health Organization (WHO) classification scheme are scarce. They are regarded to be more common in Asian populations. METHODS: Consecutive T-cell and NK-cell lymphomas classified according to the WHO scheme within 10 years in a Chinese population were reviewed. RESULTS: There were 148 cases, constituting 16.6% (T-cell, n=90, 10.1%, NK-cell, n=58, 6.5%) of all non-Hodgkin lymphomas in this period. There was a male predominance (male:female = 2.5), young age at diagnosis (median age 50 years, range 8-86) and frequent extranodal presentation. Commonest T-cell lymphomas included anaplastic large cell lymphoma (ALCL, n=25, median age 35 years, nodal 60%, stage I/II 60%), peripheral T-cell lymphoma, unspecified (PTCL, n=24, median age 54 years, nodal 42%, stage I/II 42%), and angioimmunoblastic T-cell lymphoma (AILT, n=19, median age 67 years, nodal 95%, stage I/II 26%). Overall frequencies of T-cell lymphomas were comparable to Western patients. AILT, PTCL and ALCL were aggressive with a poor outcome. NK-cell lymphomas were predominantly extranodal (96%) and aggressive, with a frequency much higher than Western patients. CONCLUSIONS: The apparent high prevalence of T-cell and NK-cell lymphomas in the Chinese was due to more frequent NK-cell but not T-cell lymphomas.

Two novel factor X gene mutations in a Chinese family with factor X deficiency.

We report a factor X (FX)-deficient Chinese family with two novel FX gene (F10) mutations. Two sibling probands had a bleeding tendency since childhood. Both had very low FX:C (<0.01 IU/ml) and FX:Ag (5-6%) levels and were heterozygous for two novel F10 mutations, a 2-bp GC deletion involving nucleotides 33 and 34, leading to premature chain termination at residue 45, and a T237-->C mutation, leading to Phe71-->Ser. A family study confirmed that the mother had the 2-bp GC deletion and a type I FX deficiency. The father had the Phe71-->Ser mutation. Interestingly, a type I FX deficiency was also observed, suggesting that Phe71-->Ser, occurring at a site sandwiched between two Gla residues, might perturb FX protein stability.

Successful treatment of acquired factor VIII inhibitor with cyclosporin.

Acquired factor VIII inhibitor causes a rare but life-threatening form of bleeding disorder, owing to the formation of auto-antibodies against FVIII. Treatment modalities include the use of immunosuppressive drugs such as cyclophosphamide and corticosteroids, plasmapheresis and i.v. immunoglobulin. A patient with idiopathic acquired FVIII inhibitor presented with serious bleeding complications resistant to all the above therapeutic modalities. Treatment with cyclosporin, however, resulted in a prompt and complete response. The lack of side-effects and the relatively quick response suggest that cyclosporin may be tried as front line treatment for patients with acquired FVIII inhibitors.

Two factor XI mutations in a Chinese family with factor XI deficiency.

We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713-->T mutation resulting in Gln263-->Term, and an exon-10 C979-->A mutation resulting in Tyr351-->Term. Two daughters were heterozygous for the Gln263-->Term mutation and two for the Try351-->Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263-->Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351-->Term mutation is novel.

Prevalence and specificity of clinically significant red cell alloantibodies in Chinese women during pregnancy--a review of cases from 1997 to 2001.

Guidelines for the prevention and management of red cell alloantibodies during pregnancy, related to anti-D in particular, are well established in Caucasian populations. However, because of the racial difference of the blood group distribution, applicability to Chinese is unknown as a result of insufficient data on the prevalence and their outcome. In a retrospective review of 28,303 (21,327 Chinese) antenatal attendances from 1997 to 2001, 213 (0.79%) women were found to have a total of 230 irregular antibodies. About 137 (0.64%) were ethnic Chinese, and a total of 160 irregular antibodies were identified in their blood samples. About 58 of these Chinese women (0.27%) were found to have 66 clinically significant antibodies. There was only one case of anti-D detected in an Rh(D)-negative subject. Our study shows the overall prevalence of clinically significant antibodies in Chinese women, which was not different from that of the Western population. However, the specificities of the antibodies differ with the commonest antibodies encountered; these being anti-Mi (57.6%), anti-E (19.7%), anti-S (10.6%) and anti-c (7.6%). Neonatal jaundice was observed in 37 babies and 10 of them required phototherapy. The findings support the previous recommendation that routine antenatal antibody screening for Chinese women may not be worthwhile except in Rh(D)-negative subjects or those with an antecedent history of haemolytic disease of the newborn (HDN). The relative high incidence of anti-Mi in the present study and the local population, in general, may warrant a large-scale prospective study of pregnancy outcome in these subjects, especially in the light of the previous case reports of HDN because of anti-Mi.

Anti-thymocyte globulin treatment of marrow aplasia associated with paroxysmal nocturnal haemoglobinuria (PNH) resulted in haematological improvement due to an expansion of the PNH clone.

A patient with aplastic anaemia developed paroxysmal nocturnal haemoglobinuria (PNH) 4 years after diagnosis, with an ensuing haematopoietic improvement. The PNH clone subsequently declined, leading to pancytopenia again. Anti-thymocyte globulin had to be administered 14 years later, which resulted in haematopoietic improvement once more. Flow cytometric analysis showed that this was attributable to expansion of the PNH clone, owing probably to alleviation of its suppression by immune-mediated mechanisms. PIG-A gene analysis showed that the same PNH clone had waned and waxed in the clinical course. Our results suggest that the PNH clone might rarely be an immune target as well.

Atypical blasts and bone marrow necrosis associated with near-triploid relapse of acute promyelocytic leukemia after arsenic trioxide treatment.

The pathologic features of acute promyelocytic leukemia (APL) with t(15;17)(q22;q21) are highly characteristic, which with few exceptions enable a firm diagnosis to be made on morphologic grounds. An APL patient in first relapse presented with large, bizarre circulating blasts and bone marrow necrosis 2 weeks after chemotherapy consolidation for an arsenic trioxide-induced remission. Although a morphologic diagnosis could not be reached, cytogenetic investigations showed a near-triploid clone with t(15;17), confirming APL in second relapse. This case showed that clonal evolution with additional karyotypic aberrations might alter the blast morphology and pathologic features in APL.

In vivo effect of haemodilution with saline on coagulation: a randomized controlled trial.

BACKGROUND: Previous studies have shown that 10-30% haemodilution with crystalloid may induce a hypercoagulable state demonstrable by using the Thrombelastograph (TEG). While most are in vitro studies, the few in vivo studies are limited by confounding surgical or 'environmental' factors. We conducted this randomized controlled study to evaluate the coagulation changes associated with in vivo haemodilution. METHODS: Twenty patients undergoing major hepatobiliary surgery were randomly allocated to one of two study groups. Group H (n = 10) had 30% blood volume withdrawn over 30 min and replaced with saline. Group C (n = 10) did not have any blood withdrawn. Blood samples were taken in both groups at 10, 20 and 30 min. Native TEG, complete blood count, coagulation profile, fibrinogen, antithrombin III, protein C and thrombin-antithrombin complex concentrations were measured. RESULTS: Compared with Group C, Group H patients had significantly greater shortening of r-time at 30 min (-30% vs +36%), greater shortening of k-time at all time points (-36% vs +17% at 10 min; -37% vs +44% at 20 min; -45% vs +49% at 30 min), and greater widening of alpha at 30 min (+71% vs +4%). The decrease in antithrombin III and other natural procoagulants and anticoagulants closely followed that of haematocrit, with the exception of thrombin-antithrombin complex. CONCLUSION: In vivo haemodilution of up to 30% with saline can induce a hypercoagulable state. The mechanism remains unclear as disproportionate dilution of natural anticoagulants was not detected. Thrombin-antithrombin complex concentration remained stable despite haemodilution in Group H, which may suggest increased thrombin generation.