1,888 research outputs found
Tregs combined with mature donor T cells hasten immune reconstitution without triggering GvHD in HLA haploidentical transplantation
Young pregnant woman with mild dysphagia: Diagnostic and treatment workup predicting laryngeal schwannoma.
Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype–mismatched hematopoietic transplants
AbstractIn human leukocyte antigen haplotype–mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4– and IL-10–producing CD4+ cells not expressing the IL-12 receptor β2 chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12–producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4+ cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4+ cell counts increased in significantly less time. Finally, elimination of G-CSF–mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell–depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery
Z-extremization and F-theorem in Chern-Simons matter theories
The three dimensional exact R symmetry of N=2 SCFTs extremizes the partition
function localized on a three sphere. Here we verify this statement at weak
coupling. We give a detailed analysis for two classes of models. The first one
is an SU(N)_k gauge theory at large k with both fundamental and adjoint matter
fields, while the second is a flavored version of the ABJ theory, where the CS
levels are large but they do not necessarily sum up to zero. We study in both
cases superpotential deformations and compute the R charges at different fixed
points. When these fixed points are connected by an RG flow we explicitly
verify that the free energy decreases at the endpoints of the flow between the
fixed points, corroborating the conjecture of an F-theorem in three dimensions.Comment: 28 pages, 3 figures, JHEP.cls, minor corrections, references adde
The Large N Limit of Toric Chern-Simons Matter Theories and Their Duals
We compute the large N limit of the localized three dimensional free energy
of various field theories with known proposed AdS duals. We show that
vector-like theories agree with the expected supergravity results, and with the
conjectured F-theorem. We also check that the large N free energy is preserved
by the three dimensional Seiberg duality for general classes of vector like
theories. Then we analyze the behavior of the free energy of chiral-like
theories by applying a new proposal. The proposal is based on the restoration
of a discrete symmetry on the free energy before the extremization. We apply
this procedure at strong coupling in some examples and we discuss the results.
We conclude the paper by proposing an alternative geometrical expression for
the free energy.Comment: 40 pages, 7 figures, using jheppub.sty, references adde
Risk assessment in diffuse large cell lymphoma at first relapse. A study by the Italian Intergroup for Lymphomas.
BACKGROUND AND OBJECTIVES: Our aim was to identify risk factors in adults with diffuse large cell lymphoma at first relapse. DESIGN AND METHODS: We studied 474 patients observed at 45 centers in Italy. Median time from diagnosis to relapse was 395 days, median age at relapse was 55 years and median follow-up from relapse was 3.3 years. Salvage therapy consisted of polychemotherapy in 79% of patients, monochemotherapy and/or radiotherapy and/or surgery alone in 16%, and palliative therapy in 5%. Salvage treatment was intensified with high-dose chemotherapy + stem cell transplant in 20% of patients. OS and PFS were compared by sex, International Prognostic Index at diagnosis, histology, B/T phenotype, initial treatment, salvage therapy, and features at relapse: time from diagnosis, LDH, stage, performance status and bone marrow involvement. Cox models, adjusted for salvage therapy, were performed with factors related to overall survival (OS) and progression-free survival (PFS). RESULTS: Overall response (complete + partial) was 63%, OS at 3 years 35% and PFS at 3 years 26%. Relapse within 12 months from diagnosis, elevated serum lactic dehydrogenase (LDH), advanced stage and poor performance status were independent adverse factors for OS and PFS. The cumulative number of adverse factors is proposed as prognostic index for DLCL at first relapse since it identifies risk groups (p<0.0001) and has been validated (p=0.01). Moreover, it predicts OS and PFS in the selected group of patients with a responsive relapse (p<0.0001). INTERPRETATION AND CONCLUSION: Delay from initial diagnosis, LDH, stage and performance status at relapse should be balanced in comparative studies of salvage therapy of adults with DLCL. Patients with more than 2 adverse factors are one third of all cases and deserve more effective salvage treatments
Targeting the leukemic stem cell: the Holy Grail of leukemia therapy
Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological
properties have been elucidated, including their distinct replicative properties, cell surface
phenotypes, their increased resistance to chemo-therapeutic drugs and the involvement of growthpromoting
chromosomal translocations. Of particular importance is their ability to transfer
malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice.
Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at
the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we
will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In
addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include
the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with smallmolecule
inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with
effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a
variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding
cassette transporter proteins are being extensively studied, as they are important in drug resistance
â a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field,
it is a highly promising battleground that may reveal the Holy Grail of cancer therapy. Originally published Leukemia, Vol. 23, No. 1, Jan 200
Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study
To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P=.0002), equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH) value at normal levels or above (P<.0001), performance status (PS) equal to or more than 2 (Pless than or equal to.0001), stage III or higher (P=.0001), and bone marrow involvement (P=.0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4,3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (Pless than or equal to.0001; log-rank, 66.79)
Induction chemotherapy stategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients.
BACKGROUND AND OBJECTIVES: This multinational retrospective study compares the outcomes of patients with primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis after first-generation (dose-intensive regimens), third-generation (alternating regimens) and high-dose chemotherapy strategies, frequently with adjuvant radiation therapy. DESIGN AND METHODS: Between August 1981 and December 1999, a total of 426 previously untreated patients with confirmed diagnosis were enrolled in 20 institutions to receive combination chemotherapy with either first generation (CHOP or CHOP-like) regimens, third generation (MACOP-B, VACOP-B, ProMACE CytaBOM) regimens or high-dose chemotherapy (HDS/ABMT). RESULTS: With chemotherapy, complete response (CR) rates were 49% (50/105), 51% (142/277) and 53% (23/44) with first generation, third generation and high-dose chemotherapy strategies, respectively; partial response (PR) rates were 32%, 36% and 35%, respectively. All patients who achieved CR and 124/142 (84%) with PR had radiation therapy on the mediastinum. The final CR rates became 61% for CHOP/CHOP-like regimens, 79% for MACOP-B and other regimens, and 75% for HDS/ABMT. After median follow-ups from attaining CR of 48.5 months for CHOP/CHOP-like regimens, 51.7 months for MACOP-B type regimens and 32.4 months for HDS/ABMT, relapses occurred in 15/64 (23%), 27/218 (12%) and 0/33 (0%) patients, respectively. Projected 10-year progression-free survival rates were 35%, 67% and 78%, respectively (p=0.0000). Projected 10-year overall survival rates were 44%, 71% and 77%, respectively (p=0.0000), after median follow-ups from diagnosis of 52.3 months, 54.9 months and 35.8 months, respectively. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, MACOP-B plus radiation therapy may be a better strategy than other treatments; these retrospective data need to be confirmed by prospective studies. The encouraging survival results after high dose chemotherapy require confirmation in selected high-risk patients
Refined Checks and Exact Dualities in Three Dimensions
We discuss and provide nontrivial evidence for a large class of dualities in
three-dimensional field theories with different gauge groups. We match the full
partition functions of the dual phases for any value of the couplings to
underpin our proposals. We focus on two classes of models. The first class,
motivated by the AdS/CFT conjecture, consists of necklace U(N) quiver gauge
theories with non chiral matter fields. We also consider orientifold
projections and establish dualities among necklace quivers with alternating
orthogonal and symplectic groups. The second class consists of theories with
tensor matter fields with free theory duals. In most of these cases the
R-symmetry mixes with IR accidental symmetries and we develop the prescription
to include their contribution into the partition function and the extremization
problem accordingly.Comment: 38 pages, 3 figure, using jheppu
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