ISSN / EISSN : 25729241 / 25729241
Current Publisher: Ovid Technologies (Wolters Kluwer Health) (10.1097)
Total articles ≅ 2,716
Latest articles in this journal
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000337
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000309
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000355
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000346
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000351
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000349
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000352
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000302
While classical nodal mantle cell lymphoma (cMCL) is often associated with involvement of multiple extranodal sites, isolated extranodal disease (ED) at the time of diagnosis is a rare event; data on the outcome of these forms are lacking. On behalf of the European MCL Network, we conducted a retrospective analysis on the clinical characteristics and outcomes of MCL presenting with isolated or predominant ED (MALT MCL). We collected data on 127 patients with MALT MCL diagnosed from 1998 to 2015: 78 patients (61%) were male with a median age of 65 years. The involved sites include: upper airways + Waldeyer ring (40; 32%), gastrointestinal tract (32; 25%), ocular adnexa (17; 13%), oral cavity and salivary glands (17; 13%) and others (13; 1%); 7 patients showed multiple extranodal sites. The median follow-up was 80 months (range: 6-182), 5-year progression-free survival (PFS) was 45% (95% CI: 35-54) and 5-year overall survival (OS) was 71% (95% CI: 62-79). In an explorative setting, we compared MALT MCL with a group of 128 cMCL patients: MALT MCL patients showed a significantly longer PFS and OS compared with nodal cMCL; with a median PFS of 4.5 years vs 2.8 years (p = 0.001) and median OS of 9.8 years vs 6.9 years (p = 0.018), respectively. Patients with MALT MCL at diagnosis showed a more favorable prognosis and indolent course than classical nodal type. This clinical variant of MCL should be acknowledged to avoid possible over-treatment.
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000312
Aberrant activation of key signaling-molecules is a hallmark of acute myeloid leukemia (AML) and may have prognostic and therapeutic implications. AML summarizes several disease entities with a variety of genetic subtypes. A comprehensive model spanning from signal activation patterns in major genetic subtypes of pediatric AML (pedAML) to outcome prediction and pre-clinical response to signaling inhibitors has not yet been provided. We established a high-throughput flow-cytometry based method to assess activation of hallmark phospho-proteins (phospho-flow) in 166 bone-marrow derived pedAML samples under basal and cytokine stimulated conditions. We correlated levels of activated phospho-proteins at diagnosis with relapse incidence in intermediate (IR) and high risk (HR) subtypes. In parallel, we screened a set of signaling inhibitors for their efficacy against primary AML blasts in a flow-cytometry based ex vivo cytotoxicity assay and validated the results in a murine xenograft model. Certain phospho-signal patterns differ between genetic subtypes of pedAML. Some are consistently seen through all AML subtypes such as pSTAT5. In IR/HR subtypes high levels of GM-CSF stimulated pSTAT5 and low levels of unstimulated pJNK correlated with increased relapse risk overall. Combination of GM-CSF/pSTAT5high and basal/pJNKlow separated three risk groups among IR/HR subtypes. Out of 10 tested signaling inhibitors, midostaurin most effectively affected AML blasts and simultaneously blocked phosphorylation of multiple proteins, including STAT5. In a mouse xenograft model of KMT2A-rearranged pedAML, midostaurin significantly prolonged disease latency. Our study demonstrates the applicability of phospho-flow for relapse-risk assessment in pedAML, whereas functional phenotype-driven ex vivo testing of signaling inhibitors may allow individualized therapy.
HemaSphere, Volume 4; doi:10.1097/hs9.0000000000000317
The overall prognosis of patients with follicular lymphoma has substantially improved over the last decades with a 10-year overall survival of around 80% for the majority of patients. However, for most patients follicular lymphoma it is still a relapsing and remitting disease. Furthermore, certain subsets of patients still have much shorter survival. Currently, there is no established standard how to treat high-risk follicular lymphoma. With advances in the understanding of the biology and pathogenesis of B cell malignancies, a plethora of new compounds have been investigated in FL. These compounds have the potential to increase efficacy if added to current regimens or even replace them. The implementation of these compounds in treatment algorithms is another unsolved issue. This overview highlights major controversies in the treatment of follicular lymphoma and discusses the most recent and relevant clinical trials.