(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email email@example.com.
Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1,546 patients, Barta et al.
In this week’s issue of Blood, Barta and colleagues address three controversial issues of HIV-associated non-Hodgkin lymphoma (HIV-NHL) based on an analysis of pooled data from more than 1,500 patients in 19 clinical trials. They first evaluated the efficacy of a combination regimen of cyclophosphamide, infusional doxorubicin, infusional vincristine, and prednisone (CHOP) when compared to more intensive therapy, most notably a combination of etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH), and demonstrated that EPOCH yielded better overall survival in diffuse large B-cell lymphoma. Investigators next addressed the safety and efficacy of rituximab, which is known to potentially increase infections in immunocompromised hosts, and concluded that the therapy was both safe and improved patient survival. As a final step, investigators examined the impact of combination antiretroviral therapy (cART) on treatment outcomes and report that cART was associated with better complete response rates, with a trend toward improved survival. While there are limitations to the study, as it is based on combining results of selected clinical trials, this study begins to define the optimal treatment approach for HIV-NHL.
CMV serostatus has still an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT, Schmidt-Hieber et al.
The advent of cytomegalovirus (CMV) monitoring has allowed for the preemptive treatment of allogeneic stem cell transplant recipients with ganciclovir and has led to a decreased frequency of frank CMV-related disease in these patients. Despite this success, the majority of patients still require therapy upon reactivation of their disease. While diagnosis and treatment have improved, controversy remains about the prognostic impact of CMV on hematopoietic stem cell transplant. In this week’s issue of Blood, Schmidt-Hieber and colleagues report on the impact of CMV serostatus after allogeneic stem cell transplantation in 16,628 acute leukemia patients. They demonstrate that despite improvements in diagnosis and treatment, CMV seropositivity in either donor or recipient decreased leukemia-free and overall survival and increased non-relapse mortality.
Robust ZFN-Mediated Genome Editing In Adult Hemophilic Mice, Anguela et al.
In this week’s issue of Blood, Anguela and colleagues report the successful gene editing of a defective Factor IX gene in adult mice through adeno-associated virus-mediated delivery of a zinc finger nucleas and a corrective donor template. While previously successful in neonatal animals and in a mouse model of hemophilia B, the accomplishment of gene editing in adult quiescent liver cells represents a major advance toward the success of this approach in somatic gene therapy. These data help further demonstrate the potential utility of gene editing as a strategy for correcting monogenic diseases in non-replicating tissues.
Autocrine TNF-α production supports CML stem and progenitor cell survival and enhances their proliferation, Gallipoli et al.
While tyrosine kinase inhibitors have proven effective in treatment of chronic myeloid leukemia (CML), this therapy is generally not curative. In most cases, disease resistance can be attributed to the persistence of CML stem cells that do not depend on BCR-ABL to survive and presumably have a kinase-independent survival mechanism. In this week’s issue of Blood, Gallipoli and colleagues report that CML stem cells produce more TNF-α than normal stem cells, supporting a mechanism that promotes survival of leukemic stem cells through NFkB/P65 activity and expression of the common b-chain of interleukin 3 and GM-CSF. In the manuscript investigators report that treatment with the TNF-α small molecule inhibitor induced apoptosis of CML stem cells, a response that significantly increased with the addition of nilotinib. This outcome suggests that the TNF-α pathway may be an important therapeutic target for the eradication of CML.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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