Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study.

BACKGROUND: Strategies using oral arsenic trioxide (As2 O3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases. METHODS: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m2 /d, oral As2 O3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2 /d × 2) and cytarabine (100 mg/m2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As2 O3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features. RESULTS: The oral As2 O3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As2 O3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As2 O3 induction and non-As2 O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2 O3 induction cohort. CONCLUSIONS: The incorporation of oral As2 O3 into induction for newly diagnosed APL was safe and decreased relapses.

Transfusion of pathogen-reduced platelet components without leukoreduction.

BACKGROUND: Leukoreduction (LR) of platelet concentrate (PC) has evolved as the standard to mitigate risks of alloimmunization, clinical refractoriness, acute transfusion reactions (ATRs), and cytomegalovirus infection, but does not prevent transfusion-associated graft-versus-host disease (TA-GVHD). Amotosalen-ultraviolet A pathogen reduction (A-PR) of PC reduces risk of transfusion-transmitted infection and TA-GVHD. In vitro data indicate that A-PR effectively inactivates WBCs and infectious pathogens. STUDY DESIGN AND METHODS: A sequential cohort study evaluated A-PR without LR, gamma irradiation, and bacterial screening in hematopoietic stem cell transplant (HSCT) recipients. The first cohort received conventional PC (control) processed without LR, but with gamma irradiation and bacterial screening. The second cohort received A-PR PC (test) processed without: LR, bacterial screening, or gamma irradiation. The primary efficacy outcome was the 1-hour corrected count increment. The primary safety outcome was treatment-emergent ATR. Secondary outcomes included clinical refractoriness, and 100-day status for engraftment, TA-GVHD, HSCT-GVHD, infections, and mortality. RESULTS: Mean corrected count increment (× 103 ) of 33 test PC recipients was similar (18.9 ± 8.8 vs. 16.6 ± 8.4; p = 0.296) to that of 31 control PC recipients. Test recipients had a reduced, but nonsignificant, incidence of ATR (test = 9.1%, Control = 19.4%; p = 0.296). The frequencies of clinical refractoriness (0 of 33 vs. 4 of 31 patients) and refractory transfusions (6.6% vs. 19.3%) were lower in the test cohort (p = 0.05 and 0.02), respectively. No patient in either cohort had TA-GVHD. Day 100 engraftment, HSCT-GVHD, mortality, and infectious disease complications were similar between cohorts. CONCLUSIONS: This study indicated that A-PR PC without LR, gamma irradiation, or bacterial screening is feasible for support of HSCT.

Next-generation sequencing with a 54-gene panel identified unique mutational profile and prognostic markers in Chinese patients with myelofibrosis.

Current prognostication in myelofibrosis (MF) is based on clinicopathological features and mutations in a limited number of driver genes. The impact of other genetic mutations remains unclear. We evaluated for mutations in a myeloid panel of 54 genes using next-generation sequencing. Multivariate Cox regression analysis was used to determine prognostic factors for overall survival (OS) and leukaemia-free survival (LFS), based on mutations of these genes and relevant clinical and haematological features. One hundred and one patients (primary MF, N = 70; secondary MF, N = 31) with a median follow-up of 49 (1-256) months were studied. For the entire cohort, inferior OS was associated with male gender (P = 0.04), age > 65 years (P = 0.04), haemoglobin < 10 g/dL (P = 0.001), CUX1 mutation (P = 0.003) and TP53 mutation (P = 0.049); and inferior LFS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.04) and SRSF2 mutations (P = 0.008). In primary MF, inferior OS was associated with male gender (P = 0.03), haemoglobin < 10 g/dL (P = 0.002), platelet count < 100 × 109/L (P = 0.02), TET2 mutation (P = 0.01) and CUX1 mutation (P = 0.01); and inferior LFS was associated with haemoglobin < 10 g/dL (P = 0.02), platelet count < 100 × 109/L (P = 0.02), TET2 mutations (P = 0.01) and CUX1 mutations (P = 0.04). These results showed that clinical and haematological features and genetic mutations should be considered in MF prognostication.

Virtual blood banking in Hong Kong.

OBJECTIVE. To review our experience in virtual blood banking for intra-operative transfusion in Hong Kong. DESIGN. Retrospective study. SETTING. Three major acute hospitals and a specialised centre for joint replacement surgery with installation of an Operating Theatre Blood Transaction System. PATIENTS. Patients undergoing surgery under anaesthesia and requiring intra-operative transfusion for the period from the implementation of the system in individual institutes (Queen Elizabeth Hospital: June 1997; Princess Margaret Hospital: May 2001; Queen Mary Hospital: October 2009; and Hong Kong Buddhist Hospital: December 2010) till September 2011. RESULTS. Under the system, 58 923 units of red cells were released intra-operatively for 18 264 patients (11% of the total number of blood units issued by the blood banks in these institutes during the study period). About 1% of them (613 units) entailed unmatched red cells given to 183 patients for emergency transfusions during surgery. The mean time required for the issue of the first unit of red cells was less than 1 minute. A total of 1231 units of red cells were returned unused after being released. Among them, 95 units were deemed unfit for re-issue because they had left the temperature-monitored blood storage refrigerators in the operating theatres for more than 30 minutes. There was no delay in transfusion or postponement of surgery due to problems or downtime of the Operating Theatre Blood Transaction System. CONCLUSION. Our experience has shown that our virtual blood banking system was efficient and effective, and helped ensure that the right patient received the right amount of the right blood at the right time. The system can be implemented either locally in the same hospital with a central blood bank, or in a more remote and networked site without a nearby supporting blood bank.

Common association of haemolytic uraemic syndrome with invasive Streptococcus pneumoniae infection in five Chinese paediatric patients.

Haemolytic uraemic syndrome is an important cause of acute renal impairment in childhood. We review the incidence, and clinical and laboratory features of haemolytic uraemic syndrome in a Chinese population. Five patients were identified from 2006 to 2008. All patients were young children with associated invasive Streptococcus pneumoniae pulmonary infection. Serotypes 3, 14, and 19A were confirmed in four patients. The classical post-diarrhoeal form associated with Escherichia coli (O157:H7) infection was not seen. One patient died of acute respiratory failure. Streptococcus pneumoniae infection, as an associated condition in haemolytic uraemic syndrome, is important and relatively common in Chinese patients, especially among children. The acute clinical picture is similar to that reported in the western literature, except for an uncommon association with meningitis. The medium-term renal outcome of the Chinese population appears to be more favourable than the Caucasians. Widespread vaccination against Streptococcus pneumoniae may have resulted in changes in bacterial epidemiology and clinicians should be continuously aware of this severe disease. The use of washed blood components for transfusion in the acute stage requires further study.

Hepatitis C virus infection in adult Chinese hemophilia patients negative for the human immunodeficiency virus: treatment results with interferon and ribavirin.

Hepatitis C virus (HCV) eradication in hemophilia patients depends on viral and patient factors. We report the treatment results with interferon 3 (5 megaunits, 3 times per week) and ribavirin (1 g daily) for 1 year in 17 Chinese patients who were negative for the human immunodeficiency virus. The HCV genotype consisted of a mixture of Western (genotypes 1, 2, and 3) and Chinese (genotypes 1 and 6) patterns. Quasi species were common (29%). Seven patients (41%) stopped treatment because of complications. Sustained HCV eradication was achieved until the end of treatment or for 24 months in 7 of 17 patients, respectively. A sustained response occurred in 50% of the patients completing treatment and occurred only in patients with genotypes 1, 3, and 6 but not with quasi species.

Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia.

Two patients with pure red cell aplasia (PRCA) refractory to anti-thymocyte globulin, prednisolone, cyclophosphamide, fludarabine, mitoxantrone, dexamethasone and cyclosporine, were treated with alemtuzumab (anti-CD52 antibody). Case 1, a 35-year-old man with idiopathic PRCA, remitted completely with 130 mg of alemtuzumab. Case 2, a 42-year-old man with PRCA due to T-cell large granular lymphocyte (T-LGL) leukaemia, achieved complete remission of the PRCA with 490 mg of alemtuzumab, although the T-LGL leukaemia responded only transiently. There were no significant side effects, and normalization of erythropoiesis was durable. Alemtuzumab is active in PRCA that is idiopathic or secondary to T-cell lymphoproliferative diseases.

Therapy-related acute myeloid leukemia after single-agent treatment with fludarabine for chronic lymphocytic leukemia.

A 70-year-old man with B-cell chronic lymphocytic leukemia (CLL) received single-agent treatment with the purine analogue fludarabine, which led to complete remission. After 8 years, he presented with pancytopenia. Marrow examination showed acute myeloid leukemia (AML) with trilineage myelodysplasia (MDS). Cytogenetic analysis showed an unbalanced der(1;7)(p10;q10) that resulted effectively in deletion 7q; confirming the diagnosis of therapy-related AML (t-AML). No residual CLL was present. Together with previous reports of secondary cancers after fludarabine treatment and the association of monosomy 7/7q- with another purine analogue azathioprine, results suggest that t-AML might develop after fludarabine therapy.

A prospective, randomized, double-blind, placebo-controlled study of the platelet and global hemostatic effects of Ganoderma lucidum (Ling-Zhi) in healthy volunteers.

UNLABELLED: Ganoderma lucidum is a Chinese herbal medicine popular with cancer patients. Previous in vitro studies suggested that Ganoderma lucidum might impair hemostasis. In this prospective, randomized double-blind study, healthy volunteers received orally Ganoderma lucidum capsules 1.5 g (n = 20) or placebo (n = 20) daily for 4 wk. We monitored subjects before drug administration and at 4 and 8 wk thereafter by routine coagulation screen, fibrinogen concentration, von Willebrand ristocetin cofactor activity, platelet function analyzer PFA-100, and thrombelastography. There were no significant between-group differences and all measurements remained within the normal range. Ganoderma lucidum ingestion over 4 wk was not associated with impairment of hemostasis. IMPLICATIONS: Ingestion of Ganoderma lucidum does not cause impairment of hemostatic function in healthy volunteers, despite earlier in vitro reports that it may cause platelet inhibition and may have other antithrombotic and fibrinolytic activity. The use of Ganoderma lucidum preoperatively is unlikely to increase the risk of surgical bleeding in otherwise healthy patients.

Comparative host gene transcription by microarray analysis early after infection of the Huh7 cell line by severe acute respiratory syndrome coronavirus and human coronavirus 229E.

The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) at the cellular level is unclear. No human cell line was previously known to be susceptible to both SARS-CoV and other human coronaviruses. Huh7 cells were found to be susceptible to both SARS-CoV, associated with SARS, and human coronavirus 229E (HCoV-229E), usually associated with the common cold. Highly lytic and productive rates of infections within 48 h of inoculation were reproducible with both viruses. The early transcriptional profiles of host cell response to both types of infection at 2 and 4 h postinoculation were determined by using the Affymetrix HG-U133A microarray (about 22,000 genes). Much more perturbation of cellular gene transcription was observed after infection by SARS-CoV than after infection by HCoV-229E. Besides the upregulation of genes associated with apoptosis, which was exactly opposite to the previously reported effect of SARS-CoV in a colonic carcinoma cell line, genes related to inflammation, stress response, and procoagulation were also upregulated. These findings were confirmed by semiquantitative reverse transcription-PCR, reverse transcription-quantitative PCR for mRNA of genes, and immunoassays for some encoded proteins. These transcriptomal changes are compatible with the histological changes of pulmonary vasculitis and microvascular thrombosis in addition to the diffuse alveolar damage involving the pneumocytes.

Fludarabine, mitoxantrone and dexamethasone in the treatment of indolent B- and T-cell lymphoid malignancies in Chinese patients.

The treatment results of indolent lymphoid malignancies in Chinese are poorly reported. The efficacy of FND (fludarabine 25 mg/m2/d, x3; mitoxantrone 10 mg/m2/d, x1; dexamethasone 20 mg/d, x5; monthly cycles, x6) in 95 Chinese patients with indolent B-cell malignancies (at diagnosis: 55, relapse/refractory disease: 40) and nine Chinese patients with T-cell large granular lymphocyte leukaemia (T-LGL leukaemia) (at diagnosis: two, refractory disease: seven) was evaluated. For B-cell malignancies, the complete response (CR), partial response (PR) and overall response (OR) rates were 50.5%, 18% and 68.5% respectively. Better results were obtained for primary versus relapse/refractory disease (CR: 60% vs. 37.5%, P = 0.03; OR: 84% vs. 47.5%, P < 0.001; median progression-free survival (PFS): 44 months vs. 22 months; 2-year PFS: 66% vs. 47%, P = 0.039; overall survival (OS): not reached vs. 32%; 2-year OS: 92% vs. 58%, P < 0.001). Responsive patients (CR/PR) had a better median PFS (44 months vs. 5 months, P < 0.001) and OS (67 months vs. 13 months, P < 0.001) than unresponsive patients. For T-LGL leukaemia, the CR and molecular-remission rates were 56% and 67% (median follow-up: 23 months). FND is an active regimen for the treatment of indolent B- and T-cell malignancies in Chinese patients, with results comparable with Western patients with similar indolent lymphomas.

Plasmablastic transformation of multiple myeloma.

We describe morphological, immunophenotypic, and cytogenetic characterization of a case of multiple myeloma (MM) that showed plasmablastic transformation at the terminal phase with a picture resembling acute leukemia. The plasmablasts expressed monotypic cytoplasmic immunoglobulin together with myeloid and megakaryocytic markers at disease transformation. Conventional cytogenetic study of bone marrow cells showed coexistence of hypodiploid and hyperdiploid cells, with the former being the predominant clone as evidenced by an interphase fluorescence in situ hybridization study. The clinical course in our case shows that plasmablastic transformation should be considered in the differential diagnoses of disease progression in MM. Whether de novo plasmablastic myeloma and plasmablastic transformation can be distinguished as a progression from underlying MM merits further investigation, especially in terms of biologic features and relevance to prognosis.