Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma

BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancerrelated deaths worldwide.Transarterial chemoembolization(TACE)is the best treatment of intermediate hepatocellular carcinoma(HCC).Doxorubicin is the most commonly used drug despite a low level of evidence.AIM To compare the objective response rate of idarubicin-based TACE(Ida-TACE)against doxorubicin-based TACE(Dox-TACE)in intermediate stage HCC.METHODS Between January 2012 and December 2014,all patients treated with TACE at our academic hospital were screened.Inclusion criteria were patients with Child-Pugh score A or B,a performance status below or equal to 1,and no prior TACE.Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin.Each patient treated with idarubicin was matched with two doxorubicin-treated patients.The TACE response was assessed by independent radiologists according to the mRECIST criteria.RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin.There were 93%and 87%of cirrhotic patients and 87%and 70%of Child-Pugh A in the doxorubicin and idarubicin groups,respectively.The median number of HCC per patient was two in both groups with 31%and 26%of single nodules in doxorubicin and idarubicin groups,respectively.Objective response rate after first TACE was 76.7%and 73.3%(P=0.797)with 41.7%and 40.0%complete response in doxorubicin and idarubicin groups,respectively.Progression-free survival was 7.7 mo in both groups,and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups,respectively.Safety profiles were similar in both groups,with grade 3-4 adverse events in 35%of Dox-TACE and 43%of Ida-TACEs.CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety.Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.     

Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases

This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra‐nodal disease (9/9), including hepato‐splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10⁹/l, with 12–90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T‐cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first‐line therapy and 3/4 relapsed. Four patients are alive with a median follow‐up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high‐risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed.     

Identification of a new chemical class of antimalarials

The increasing spread of drug-resistant malaria strains underscores the need for new antimalarial agents with novel modes of action (MOAs). Here, we describe a compound representative of a new class of antimalarials. This molecule, ACT-213615, potently inhibits in vitro erythrocytic growth of all tested Plasmodium falciparum strains, irrespective of their drug resistance properties, with half-maximal inhibitory concentration (IC(50)) values in the low single-digit nanomolar range. Like the clinically used artemisinins, the compound equally and very rapidly affects all 3 asexual erythrocytic parasite stages. In contrast, microarray studies suggest that the MOA of ACT-213615 is different from that of the artemisinins and other known antimalarials. ACT-213615 is orally bioavailable in mice, exhibits activity in the murine Plasmodium berghei model and efficacy comparable to that of the reference drug chloroquine in the recently established P. falciparum SCID mouse model. ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potential.     

No Association of Phenotypic ABO Blood Group and Malaria during Pregnancy

Abstract. In a few small studies an association between blood group O and placental malaria has been described. The relationship between blood group and malaria in pregnancy (Plasmodium vivax and Plasmodium falciparum) was analyzed in 1,468 women from three longitudinal cohort studies in which weekly malaria screening was done systematically during pregnancy. One-third of women (447 of 1,468) had at least one malaria infection in pregnancy. The ABO blood group phenotype was not associated with the species of infection, frequency of malaria attacks, symptoms of malaria, hematocrit, or parasitemia during pregnancy.     

Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa)

Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that γδ T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (FcγRIIIA) was specifically expressed by the majority of HCMV-induced γδ T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate γδ T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16(+)γδ T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFNγ when incubated with IgG-opsonized virions. This CD16-induced IFNγ production was greatly enhanced by IL12 and IFNα, 2 cytokines produced during HCMV infection, and conferred to γδ T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for γδ T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients.     

Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM

Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow-CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.