Treatment of Adult Patients with Relapsed/Refractory B-Cell Philadelphia-Negative Acute Lymphoblastic Leukemia

The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very poor outcome. Allogeneic hematopoietic cell transplantation (HCT) still represents the only curative approach, but is not so frequently feasible, because of patient’s fitness, donor availability, and the ability to achieve a remission prior to HCT. The estimated remission rates with conventional cytotoxic agents are around 30%, but they are short-lived. These disappointing results led to the introduction of new immunologic-based treatments—blinatumomab and inotuzumab. They produced a substantial improvement in terms of response rates, with the ability, in most cases, to induce a minimal residual disease (MRD)-negative status. Similarly, T cells engineered to express a CD19-specific chimeric antigen receptor (CAR-T) have yielded sensational results among patients with relapsed/refractory B-ALL, with unexpectedly high MRD-negative complete remissions rates. However, the first studies looking at long-term outcomes after CAR-T infusions told us that a significant fraction of such responses are not durable, and may benefit from a consolidation approach such as an allogeneic HCT

A system of relational syllogistic incorporating full Boolean reasoning

We present a system of relational syllogistic, based on classical propositional logic, having primitives of the following form: Some A are R-related to some B; Some A are R-related to all B; All A are R-related to some B; All A are R-related to all B. Such primitives formalize sentences from natural language like `All students read some textbooks'. Here A and B denote arbitrary sets (of objects), and R denotes an arbitrary binary relation between objects. The language of the logic contains only variables denoting sets, determining the class of set terms, and variables denoting binary relations between objects, determining the class of relational terms. Both classes of terms are closed under the standard Boolean operations. The set of relational terms is also closed under taking the converse of a relation. The results of the paper are the completeness theorem with respect to the intended semantics and the computational complexity of the satisfiability problem.Comment: Available at http://link.springer.com/article/10.1007/s10849-012-9165-

Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15–20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents

Two-loop QCD Corrections to the Heavy Quark Form Factors: the Vector Contributions

We present closed analytic expressions of the electromagnetic vertex form factors for heavy quarks at the two-loop level in QCD for arbitrary momentum transfer. The calculation is carried out in dimensional regularization. The electric and magnetic form factors are expressed in terms of 1-dimensional harmonic polylogarithms of maximum weight 4.Comment: 79 pages, 3 figures. Version accepted by Nucl. Phys. B. All the results in Section 6 of the paper are available in an electronic form in the file formulas.in

Complex hyperbolic free groups with many parabolic elements

We consider in this work representations of the of the fundamental group of the 3-punctured sphere in ${\rm PU}(2,1)$ such that the boundary loops are mapped to ${\rm PU}(2,1)$. We provide a system of coordinates on the corresponding representation variety, and analyse more specifically those representations corresponding to subgroups of $(3,3,\infty)$-groups. In particular we prove that it is possible to construct representations of the free group of rank two \la a,b\ra in ${\rm PU}(2,1)$ for which $a$, $b$, $ab$, $ab^{-1}$, $ab^2$, $a^2b$ and $[a,b]$ all are mapped to parabolics.Comment: 21 pages, 11 figure

Spermatogenesis and sperm structure in the black-striped pipefish <i>Syngnathus abaster</i> (Teleostei, Syngnathidae) = Spermatogenesi e struttura degli spermatozoi in <i>Syngnathus abaster</i> (Teleostei, Synghathidae)

The gonads of adult males of the black-striped pipejish Syngnathus abaster were observed during the reproductive season to describe mature sperm both quantitativel/y and qualitatively. The results show that: a) the sperms number is always very low and, does not vary significantly during the reproductive season; b) all mature sperms observed may be assigned to the introsperm-like type. These data suggest that the unique and functional sperm of Syngnathids pertain to the introsperm type typical of internally fertilizing teleostean bony fishes