The impact of hepatitis B virus (HBV) infection on clinical outcomes of patients with diffuse large B-cell lymphoma.

We performed a retrospective study to analyse the characteristics and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) patients with hepatitis B virus (HBV) infection and compare with those without HBV infection. The occurrence of hepatitis after withdrawal of prophylactic antiviral treatment on completion of chemotherapy was also assessed. The HBsAg-positive patients were given prophylactic antiviral treatment until 6 months after finishing chemotherapy. A total of 81 patients were recruited with 16 in the HBsAg-positive group and 65 in the HBsAg-negative group. The clinical characteristics were similar in both groups of patients. There was no significant difference in complete remission rate between the two groups (63% in HBsAg-positive group vs. 54% in HBsAg-negative group, P = 0.59). There was also no statistically significant difference in overall survival between the two groups (P = 0.23). Four of the 16 HBsAg-positive patients (25%) had hepatitis after cessation of chemotherapy and prophylactic lamivudine. The mean time of onset of hepatitis was 3 months after stopping lamivudine. In conclusion, HBV infection did not appear to affect the prognosis of DLBCL patients given antiviral prophylaxis. It is reasonable to consider prophylactic antiviral therapy to extend to at least one year on completion of chemotherapy.

Mental health recovery for psychiatric inpatient services: perceived importance of the elements of recovery.

OBJECTIVES. To develop a questionnaire for measuring the perceived importance of the elements of mental health recovery in psychiatric inpatients in Hong Kong and to test the psychometric properties of the questionnaire. METHODS. Thematic content analysis of identified literature on mental health recovery was performed to identify the elements related to mental health recovery. A questionnaire was developed to assess the perceived importance of the identified elements. An expert panel was set up to evaluate the content validity and patient focus group's face validity of the questionnaire. Participants were recruited from medium-stay and rehabilitation wards of Castle Peak Hospital. RESULTS. A total of 101 psychiatric inpatients completed the questionnaire, the majority of whom suffered from schizophrenia (75%). Having meaning in life was rated by 91% of the participants as an important element of recovery, followed by hope (86%) and general health and wellness (85%). Cronbach's alpha for internal consistency was 0.91. Explorative factor analysis yielded 7 factors and intraclass correlation coefficients revealed a fair-to-good test-retest reliability. CONCLUSIONS. The results supported the psychometric properties of the questionnaire for measurement of mental health recovery and serve as a basis for the future development of recovery-oriented services in the psychiatric inpatient settings in this locality.

BCR-ABL mutational studies for predicting the response of patients with chronic myeloid leukaemia to second-generation tyrosine kinase inhibitors after imatinib failure.

Imatinib is the standard treatment for chronic myeloid leukaemia. BCR-ABL kinase domain mutation is the commonest mechanism implicated in imatinib resistance. In in-vitro studies, kinase domain mutations are variably resistant to second-line agents. We performed BCR-ABL kinase domain mutational studies in 25 patients in five institutions who failed imatinib and were treated with either nilotinib or dasatinib, to see if their mutational status would predict their clinical responses. Kinase domain mutations involving 11 amino acid substitutions were found in 12 (48%) patients. Most patients showed single kinase domain mutations. There was some concordance between reported drug sensitivity patterns and patient responses. Discordant responses could be related to drug dosage variations and unknown BCR-ABL independent mechanisms. The response prediction for patients with multiple kinase domain mutations was challenging and their mutational patterns could change after tyrosine kinase inhibitor therapy. Although BCR-ABL kinase domain mutational analysis has limitations as a means of predicting the clinical response to second-line tyrosine kinase inhibitors, it helps inform therapy decisions in the management of chronic myeloid leukaemia after imatinib failure.

Organ-specific hemosiderosis and functional correlation in Chinese patients with thalassemia intermedia and hemoglobin H disease.

We performed MRI assessment in 37 adult Chinese patients with thalassemia intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*, only 5% of patients had cardiac hemosiderosis. The two patients with reduced ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI values. Prospective data with serial functional and imaging monitoring is needed to verify the utility for chelation to improve cardiac and endocrine function in this group of patients.

Arsenic trioxide in comparison with chemotherapy and bone marrow transplantation for the treatment of relapsed acute promyelocytic leukaemia.

BACKGROUND: The best overall treatment strategy for patients with acute promyelocytic leukaemia (APL) in relapse with chemotherapy, bone marrow transplantation (BMT) or arsenic trioxide (As(2)O(3)) based therapy remains undefined. PATIENTS AND METHODS: We reviewed the clinical course and treatment outcome of 143 APL cases seen in four major hospitals in Hong Kong over a 10-year period. RESULTS: Complete remission (CR) was attained in 113 cases (79%) with all-trans retinoic acid (ATRA) and chemotherapy. Relapse occurred at a median of 16 months in 54 cases, with a 3-year disease free survival of 56%. Post-relapse treatment was successful in 41 cases (76%), giving an actuarial 3-year overall survival (OS) of 81% from CR1. Three different protocols were used: chemotherapy alone (n = 19), allogeneic BMT (n = 14) and an As(2)O(3)-based regimen (n = 21). Chemotherapy was associated with the highest treatment-related mortality (TRM) at 53%, giving a CR2 rate of 47%. TRM was 36% for BMT. The CR2 rate for the As(2)O(3)-based regimen was 100%, with no TRM. However, 38% of As(2)O(3) treated patients had subsequent relapses, which were further salvaged in 75% by combined As(2)O(3) plus ATRA. The actuarial OS for the three protocols leveled off by 2 years at 82% for As(2)O(3), 43% for BMT and 23% for chemotherapy (P = 0.0004). CONCLUSIONS: Our results suggest that As(2)O(3) may be superior to chemotherapy and BMT for the treatment of APL in relapse.

Cytomegalovirus infection associated with clonal proliferation of T-cell large granular lymphocytes: causal or casual?

Clonal proliferation of T-cell large granular lymphocytes (LGL) is an indolent disorder characterized by splenomegaly, lymphocytosis and frequent manifestations of immune disturbances. The LGL are CD3(+) CD4(-) CD8(+) CD56(-). The clonality of the tumor cell population is often only demonstrable by T-cell receptor (TCR) gene rearrangement study because chromosomal abnormality is distinctly rare. We describe a case of T-cell LGL leukemia that presented initially as cytomegalovirus infection. The leukemic LGL are shown to be clonal by both TCR gene rearrangement and chromosomal studies. They persist after subsidence of the cytomegalovirus infection.

Fatal diffuse alveolar damage complicating acute myeloid leukemia with abnormal eosinophils and trisomy X.

We describe a case of acute myeloid leukemia (AML) with abnormal eosinophils in a 44-year-old Chinese woman that was complicated by diffuse alveolar damage (DAD) and pulmonary hemorrhage (PH) shortly after induction chemotherapy. Cytogenetic study of bone marrow cells at diagnosis showed a rare aberration of trisomy X (+X) as the sole acquired karyotypic abnormality. We speculate that tissue damage by cellular constituents of the abnormal eosinophils that were released on cell lysis after chemotherapy might be etiologically linked to the occurrence of fatal pulmonary complications.

Two balanced and novel chromosomal translocations in myeloid malignancies. characterization by multiplex fluorescence in situ hybridization.

We describe two novel chromosomal translocations in two cases of leukemia in which these translocations were further characterized as the sole acquired karyotypic abnormality by mutliplex fluorescence in situ hybridization (M-FISH). They comprised a case of acute myeloid leukemia with t(6;10)(q21;p12) and a case of chronic myelomonocytic leukemia with t(5;12)(q34;q24). To the best of our knowledge, these two balanced translocations are novel and are hitherto unrecognized in hematologic malignancies. While the clinical and pathogenic significance of these translocations remains to be defined, the present report illustrates that M-FISH technology contributes to the exclusion of subtle or cryptic translocations in sole karyotypic aberrations and the confirmation of novel chromosomal arrangements in neoplastic disorders.

Diagnosis of concurrent hemoglobin H disease and heterozygous beta-thalassemia.

Definitive diagnosis of concurrent hemoglobin (Hb) H disease and heterozygous beta-thalassemia cannot be made from Hb analysis alone, but necessitates genotype analysis and family study. Interactions between alpha- and beta-thalassemia must be considered when investigating moderate to severe hypochromic microcytic anemia of uncertain cause in adult patients from areas with a high prevalence of globin gene mutations.

Acute myeloid leukaemia with giant granules: association with t(10; 11)(p13; q14) and disseminated intravascular coagulation.

A 16-year-old Chinese girl presented with AML-M5a. A bone marrow examination showed that the myeloblasts which were overwhelming the marrow contained giant granules (pseudo-Chediak-Higashi anomaly). Her karyotype showed a rare translocation t(10; 11)(p13; q14). Molecular delineation of the translocation breakpoints was not possible. Nonetheless, this case further demonstrates the morphological and phenotypic heterogeneity of acute leukaemia with this translocation. In this girl it was associated with disseminated intravascular coagulation.

Molecular characterization of der(15)t(11;15) as a secondary cytogenetic abnormality in acute promyelocytic leukemia with cryptic PML-RAR alpha fusion on 17q.

A case of acute promyelocytic leukemia (APL) with cryptic PML-RAR alpha fusion on 17q and add(15p) as a secondary abnormality was characterized using molecular cytogenetic techniques. Spectral karyotyping (SKY) showed that chromosome 11 material was added to 15p, forming a der(15)t(11;15), which was refined to der(15)t(11;15)(q13.2;p13) with information obtained by comparative genomic hybridization (CGH). Interstitial insertion of chromosome 15 material into chromosome 17q was found by fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes. This study illustrates the necessity of a combination of molecular cytogenetics to decipher complex karyotypic abnormalities and cryptic translocations in leukemia.

A simple surgical treatment for upper lid trichiasis.

The authors report the results of a simple surgical treatment in 24 lids of 19 patients. The most common cause of the trichiasis was trachoma (83.3%). The operation involved splitting the lid margin, fracturing the tarsal plate, and everting sutures. The anatomic success rate was 62.5% and the functional success rate was 75%. Recurrent cilia were mostly isolated and symptomatic improvement was achieved in all but one patient. The authors conclude that this is a cost-effective procedure.

Intensive consolidation chemotherapy for newly diagnosed acute myeloid leukemia using a regime containing moderate dose cytosine arabinoside and mitoxantrone.

Fifty patients with previously untreated acute myeloid leukemia were treated with an induction regimen consisting of cytosine arabinoside 100 mg/m2 per day by 18 h i.v. infusion for 7 days, daunorubicin 50 mg/m2 per day by i.v. bolus injection for 3 days and etoposide 75 mg/m2 per day by 1 h i.v. infusion for 7 days. Thirty seven of them (74%) went into complete remission (CR) and they all then received two consecutive courses of consolidation chemotherapy consisting of cytosine arabinoside 500 mg/m2 per day by 1 h i.v. infusion every 12 h for 4 days (total eight doses) and mitoxantrone 12 mg/m2 daily by 30 min i.v. infusion for 3 days. They were followed by maintenance chemotherapy with cytosine arabinoside and thioguanine 2 monthly. With a median follow up time of 24 months, 20 of the 37 complete responders had relapsed (54%). The disease-free survival (DFS) of 37 CR patients and the overall survival of all patients at 24 months were 37 and 44%, respectively. Age of patients and number of courses of induction chemotherapy to achieve CR were significant factors predicting DFS. Myelosuppression was the major toxic side effects. Ten patients had prolonged marrow suppression following consolidation chemotherapy. In conclusion, despite the significant myelosuppression observed, overall improvement in treatment outcome was not demonstrable with the use of this intensive consolidation therapy.