Characteristics, primary treatment, and survival of MDS/MPN with neutrophilia:a population-based study

Myelodysplastic and myeloproliferative neoplasms (MDS/MPN) with neutrophilia, until recently called atypical chronic myeloid leukemia (aCML), being part of the MDS/MPN is a very rare disease with poor prognosis. Although emerging data reveal its cytogenetic and molecular profile, integrated survival and treatment data remain scarce. We analyzed a cohort of 347 adult patients diagnosed with MDS/MPN with neutrophilia, registered in the Netherlands Cancer Registry between 2001 and 2019. Our demographic baseline data align with other cohorts. We observed cytogenetic aberrations exclusively in patients aged &gt;65 years, with trisomy 8 being the most common abnormality. We identified 16 distinct molecular mutations, with some patients (16/101) harboring up to 3 different mutations; ASXL1 being the most frequent one (22%). In a multivariable Cox regression analysis, only age, hemoglobin level and allogeneic hematopoietic stem cell transplant (alloHSCT) were associated with overall survival (aged &gt;65 years; hazard ratio [HR] 1.85; P = .001 and alloHSCT HR, 0.51; P = .039). Because no other treatment modality seemed to affect survival and might cause toxicity, we propose that all patients eligible for alloHSCT should, whenever possible, receive an allogeneic transplant. It is imperative that we strive to improve outcomes for patients who are not eligible for alloHSCT. Tackling this challenge requires international collaborative efforts to conduct prospective intervention studies.</p

Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma

The efficacy of daratumumab depends partially on CD38 expression on multiple myeloma (MM) cells. We have previously shown that all-trans retinoic acid (ATRA) upregulates CD38 expression and reverts daratumumab-resistance ex vivo. We therefore evaluated the optimal dose, efficacy, and safety of daratumumab combined with ATRA in patients with daratumumab-refractory MM in a phase 1/2 study (NCT02751255). In part A of the study, 63 patients were treated with daratumumab monotherapy. Fifty patients with daratumumabrefractory MM were subsequently enrolled in part B and treated with daratumumab (reintensified schedule) combined with ATRA until disease progression. The recommended phase 2 dose of ATRA in combination with daratumumab was defined as 45 mg/m2. At this dose, the overall response rate (ORR) was 5%, indicating that the primary endpoint (ORR $15%) was not met. However, most patients (66%) achieved at least stable disease. After a median follow-up of 43 months, the median progression-free survival (PFS) for all patients was 2.8 months. Patients who previously achieved at least a partial response or minimal response/stable disease with prior daratumumab monotherapy had a significantly longer PFS compared with patients who immediately progressed during daratumumab as single agent (median PFS 3.4 and 2.8 vs 1.3 months). The median overall survival was 19.1 months. The addition of ATRA did not increase the incidence of adverse events. Flow cytometric analysis revealed that ATRA temporarily increased CD38 expression on immune cell subsets. In conclusion, the addition of ATRA and reintensification of daratumumab had limited activity in patients with daratumumab-refractory MM, which may be explained by the transient upregulation of CD38 expression. This trial was registered at www.clinicaltrials.gov as #NCT02751255

Centrality dependence of charged hadron production in deuteron+gold and nucleon+gold collisions at sqrt(s_NN)=200 GeV

We present transverse momentum (p_T) spectra of charged hadrons measured in deuteron-gold and nucleon-gold collisions at \sqrts = 200 GeV for four centrality classes. Nucleon-gold collisions were selected by tagging events in which a spectator nucleon was observed in one of two forward rapidity detectors. The spectra and yields were investigated as a function of the number of binary nucleon-nucleon collisions, \nu, suffered by deuteron nucleons. A comparison of charged particle yields to those in p+p collisions show that the yield per nucleon-nucleon collision saturates with \nu for high momentum particles. We also present the charged hadron to neutral pion ratios as a function of p_T.Comment: 330 authors, 15 pages text, 16 figures, 3 tables. Submitted to Phys. Rev. Lett. v2 has minor changes to reflect revisions during review process. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

High-pT pi^zero Production with Respect to the Reaction Plane in Au + Au Collisions at sqrt(s_NN) = 200 GeV

Measurements of the azimuthal anisotropy of high-\pT neutral pion neutral pion production in Au+Au collisions at sqrt(s_NN) = 200 GeV by the PHENIX experiment are presented. The data included in this paper were collected during the 2004 RHIC running period and represent approximately an order of magnitude increase in the number of analyzed events relative to previously published results. Azimuthal angle distributions of pi^0s detected in the PHENIX electromagnetic calorimeters are measured relative to the reaction plane determined event-by-event using the forward and backward beam-beam counters. Amplitudes of the second Fourier component (v_2) of the angular distributions are presented as a function of pi^0 transverse momentum p_T for different bins in collision centrality. Measured reaction plane dependent pi^0 yields are used to determine the azimuthal dependence of the pi^0 suppression as a function of p_T, R_AA (Delta phi,p_T). A jet-quenching motivated geometric analysis is presented that attempts to simultaneously describe the centrality dependence and reaction plane angle dependence of the pi^0 suppression in terms of the path lengths of hypothetical parent partons in the medium. This set of results allows for a detailed examination of the influence of geometry in the collision region, and of the interplay between collective flow and jet-quenching effects along the azimuthal axis.Comment: 344 authors, 35 pages text, RevTeX-4, 24 figures, 8 tables. Submitted to Physical Review

Cold Nuclear Matter Effects on J/Psi as Constrained by Deuteron-Gold Measurements at sqrt(s_NN) = 200 GeV

We present a new analysis of J/psi production yields in deuteron-gold collisions at sqrt(s_NN) = 200 GeV using data taken by the PHENIX experiment in 2003 and previously published in [S.S. Adler et al., Phys. Rev. Lett 96, 012304 (2006)]. The high statistics proton-proton J/psi data taken in 2005 is used to improve the baseline measurement and thus construct updated cold nuclear matter modification factors R_dAu. A suppression of J/psi in cold nuclear matter is observed as one goes forward in rapidity (in the deuteron-going direction), corresponding to a region more sensitive to initial state low-x gluons in the gold nucleus. The measured nuclear modification factors are compared to theoretical calculations of nuclear shadowing to which a J/psi (or precursor) break-up cross-section is added. Breakup cross sections of sigma_breakup = 2.8^[+1.7_-1.4] (2.2^[+1.6_-1.5]) mb are obtained by fitting these calculations to the data using two different models of nuclear shadowing. These breakup cross section values are consistent within large uncertainties with the 4.2 +/- 0.5 mb determined at lower collision energies. Projecting this range of cold nuclear matter effects to copper-copper and gold-gold collisions reveals that the current constraints are not sufficient to firmly quantify the additional hot nuclear matter effect.Comment: 453 authors from 59 institutions, 15 pages, 13 figures, 5 tables. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Observation of charge-dependent azimuthal correlations and possible local strong parity violation in heavy ion collisions

Parity-odd domains, corresponding to non-trivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the orbital momentum of the system created in non-central collisions. To study this effect, we investigate a three particle mixed harmonics azimuthal correlator which is a \P-even observable, but directly sensitive to the charge separation effect. We report measurements of this observable using the STAR detector in Au+Au and Cu+Cu collisions at $\sqrt{s_{NN}}$=200 and 62~GeV. The results are presented as a function of collision centrality, particle separation in rapidity, and particle transverse momentum. A signal consistent with several of the theoretical expectations is detected in all four data sets. We compare our results to the predictions of existing event generators, and discuss in detail possible contributions from other effects that are not related to parity violation.Comment: 17 pages, 14 figures, as accepted for publication in Physical Review C

Studying Parton Energy Loss in Heavy-Ion Collisions via Direct-Photon and Charged-Particle Azimuthal Correlations

Charged-particle spectra associated with direct photon ($\gamma_{dir}$) and $\pi^0$ are measured in $p$+$p$ and Au+Au collisions at center-of-mass energy $\sqrt{s_{_{NN}}}=200$ GeV with the STAR detector at RHIC. A hower-shape analysis is used to partially discriminate between $\gamma_{dir}$ and $\pi^0$. Assuming no associated charged particles in the $\gamma_{dir}$ direction (near side) and small contribution from fragmentation photons ($\gamma_{frag}$), the associated charged-particle yields opposite to $\gamma_{dir}$ (away side) are extracted. At mid-rapidity ($|\eta|<0.9$) in central Au+Au collisions, charged-particle yields associated with $\gamma_{dir}$ and $\pi^0$ at high transverse momentum ($8< p_{T}^{trig}<16$ GeV/$c$) are suppressed by a factor of 3-5 compared with $p$ + $p$ collisions. The observed suppression of the associated charged particles, in the kinematic range $|\eta|<1$ and $3< p_{T}^{assoc} < 16$ GeV/$c$, is similar for $\gamma_{dir}$ and $\pi^0$, and independent of the $\gamma_{dir}$ energy within uncertainties. These measurements indicate that the parton energy loss, in the covered kinematic range, is insensitive to the parton path length.Comment: submitted to Phys. Rev. Lett, 6 pages, 4 figure

Charged and strange hadron elliptic flow in Cu+Cu collisions at sNN\sqrt{s_{NN}} = 62.4 and 200 GeV

We present the results of an elliptic flow analysis of Cu+Cu collisions recorded with the STAR detector at 62.4 and 200GeV. Elliptic flow as a function of transverse momentum is reported for different collision centralities for charged hadrons and strangeness containing hadrons $K_{S}^{0}$, $\Lambda$, $\Xi$, $\phi$ in the midrapidity region $|eta|<1.0$. Significant reduction in systematic uncertainty of the measurement due to non-flow effects has been achieved by correlating particles at midrapidity, $|\eta|<1.0$, with those at forward rapidity, $2.5<|\eta|<4.0$. We also present azimuthal correlations in p+p collisions at 200 GeV to help estimating non-flow effects. To study the system-size dependence of elliptic flow, we present a detailed comparison with previously published results from Au+Au collisions at 200 GeV. We observe that $v_{2}$($p_{T}$) of strange hadrons has similar scaling properties as were first observed in Au+Au collisions, i.e.: (i) at low transverse momenta, $p_T<2GeV/c$, $v_{2}$ scales with transverse kinetic energy, $m_{T}-m$, and (ii) at intermediate $p_T$, $2<p_T<4GeV/c$, it scales with the number of constituent quarks, $n_q$. We have found that ideal hydrodynamic calculations fail to reproduce the centrality dependence of $v_{2}$($p_{T}$) for $K_{S}^{0}$ and $\Lambda$. Eccentricity scaled $v_2$ values, $v_{2}/\epsilon$, are larger in more central collisions, suggesting stronger collective flow develops in more central collisions. The comparison with Au+Au collisions which go further in density shows $v_{2}/\epsilon$ depend on the system size, number of participants $N_{part}$. This indicates that the ideal hydrodynamic limit is not reached in Cu+Cu collisions, presumably because the assumption of thermalization is not attained.Comment: 18 pages, 14 figure