Role of genetics in prognostication in myeloma

As in other hematological malignancies, cytogenetics is becoming a major prognostic parameter in myeloma. Myeloma differs from other hemopathies particularly in technical aspects related to low proliferation and partial infiltrates. Thus, fluorescence in-situ hybridization (FISH) is probably the best method for cytogenetic assessment in myeloma, but it requires the identification of the malignant cells (morphologically, immunologically or through sorting). Several chromosomal abnormalities have been identified. Among them, the t(4;14) and t(14;16) translocations and the del(17p) are the most important for outcome prediction, all of them predicting a short overall survival. However, even in these genetically defined subgroups, an outcome heterogeneity is observed, suggesting the role of other factors (genetic or otherwise) in disease evolution.     

Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics,predictive factors and impact on post‐transplant outcome

This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post‐transplant outcome. Ninety‐four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post‐transplant dates, using a real‐time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post‐transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5‐6/6, P < 0·001) increased the probability of post‐transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15–30 post‐transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft‐versus‐host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT.     

In vitro photochemical inactivation of cell-associated human T-cell leukemia virus Type I and II in human platelet concentrates and plasma by use of amotosalen

BACKGROUND: Human T-cell leukemia virus Types I and II (HTLV-I and HTLV-II), blood-borne retroviruses found worldwide, can cause leukemia, immunosuppression, and severe neurologic diseases. In most countries, HTLV-I and -II screening is not performed systematically for blood donations. A new photochemical treatment (PCT) with a synthetic psoralen was developed to inactivate most pathogens in platelet (PLT) concentrates or plasma and to improve the safety of blood donations. STUDY DESIGN AND METHODS: Cell-associated HTLV-I or -II (10(6)/mL) was inoculated in full-size fresh PLT concentrates or fresh frozen plasma and treated with 150 micromol per L amotosalen (S-59) and different doses of long-wavelength ultraviolet A (UVA) light. The residual viral titer in the treated samples was assessed by a cocultivation assay on indicator cells. RESULTS: The inactivation obtained at a 3.0 J per cm2 UVA dose was greater than 5.2 log foci-forming units (FFUs) per mL for HTLV-I and 4.6 log FFUs per mL for HTLV-II in presence of human PLT concentrates and greater than 4.5 log FFUs per mL for HTLV-I and 5.7 log FFUs per mL for HTLV-II in the presence of human plasma. The residual infectivity was very low and shown as the limit of detection of the cocultivation assay. CONCLUSION: In human plasma or PLT concentrates, the retroviruses HTLV-I and -II were strongly sensitive to the PCT with 150 micromol per L amotosalen (S-59) and a 3.0 J per cm2 UVA dose. This high efficiency for photoinactivation of these retroviruses opens a possibility of improving the safety of PLTs or plasma transfusion in the future.     

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study

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Is a Cementless Dual Mobility Socket in Primary THA a Reasonable Option?

Background  

Dislocation after THA continues to be relatively common. Dual mobility sockets have been associated with low dislocation rates, but it remains unclear whether their use in primary THA would not introduce additional complications.     

High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty-two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication.     

Detection of Toxoplasma gondii DNA and specific antibodies in high-risk pregnant women

Primary maternal infection with toxoplasmosis during pregnancy is frequently associated with transplacental transmission to the fetus. This study was conducted to test the utility of a polymerase chain reaction (PCR) assay to detect recent infections with Toxoplasma in pregnant women. One hundred forty-eight women with high-risk pregnancies who had abnormal pregnancy outcomes (cases) and 100 with normal pregnancies (controls) were tested for the presence of Toxoplasma DNA in their blood by a nested PCR and specific antibodies to Toxoplasma by an enzyme-linked immunosorbent assay. The IgG results of the cases differed significantly from those of the controls (54% and 12%, respectively; P < 0.02). Four (2.7%) of the cases were IgM positive, but none of the controls were positive. Detection of Toxoplasma DNA in 20 (8.1%) of the IgG-positive cases suggests a recent infection. The risk factors associated with the infection were eating raw meat and contact with soil. The diagnostic serology of recent infection in early pregnancy could be confirmed by a positive Toxoplasma-specific PCR result in blood samples collected in the first half of pregnancy, even in the presence of serologic results difficult to interpret due to the lack of sequential follow-up during pregnancy.     

Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.     

Focal nodular hyperplasia occurring after blunt abdominal trauma

Focal nodular hyperplasia of the liver is a benign neoplasm. The pathogenesis is unknown, but it was hypothesized that focal nodular hyperplasia may be a response to a vascular abnormality. We report on a case of focal nodular hyperplasia that developed in a young patient 1 year after a blunt hepatic injury.