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Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard and curative treatment strategy for patients with hematologic malignancies. Recently, decitabine included regimens are investigated by several studies including ours, which may prevent relapse of primary malignant diseases. Methods: This study was to retrospectively evaluate a 7-day decitabine included regimen with reduced dose of idarubicin for patients with hematologic malignancies who underwent allo-HSCT. Results: A total of 84 patients were enrolled, including 24 cases in 7-day and 60 cases in 5-day decitabine groups, respectively. Patients conditioned with 7-day decitabine regimen showed accelerated neutrophil (12.05±1.97 versus 13.86±3.15; u = 9.309, P

Recently, the radius of neutron star (NS) PSR $\mathrm{J}0740+6620$ was measured by Neutron Star Interior Composition Explorer (NICER), and an updated measurement of neutron skin thickness of $^{208}\mathrm{Pb}$ (${R}_{\mathrm{skin}}^{208}$) was reported by the PREX-II experiment. These new measurements can help us better understand the unknown equation of state (EOS) of dense matter. In this work, we adopt a hybrid parameterization method, which incorporates the nuclear empirical parameterization and some widely used phenomenological parameterizations, to analyze the results of nuclear experiments and astrophysical observations. With the joint Bayesian analysis of GW170817, PSR $\mathrm{J}0030+0451$, and PSR $\mathrm{J}0740+6620$, the parameters that characterize the ultradense matter EOS are constrained. We find that the slope parameter $L$ is approximately constrained to ${70}_{\ensuremath{-}18}^{+21}\text{ }\text{ }\mathrm{MeV}$, which predicts ${R}_{\mathrm{skin}}^{208}=0.20{4}_{\ensuremath{-}0.026}^{+0.030}\text{ }\text{ }\mathrm{fm}$ by using the universal relation between ${R}_{\mathrm{skin}}^{208}$ and $L$. The bulk properties of canonical $1.4\text{ }\text{ }{M}_{\ensuremath{\bigodot}}$ NS (e.g., ${R}_{1.4}$ and ${\mathrm{\ensuremath{\Lambda}}}_{1.4}$) as well as the pressure (${P}_{2{\ensuremath{\rho}}_{\mathrm{sat}}}$) at two times the nuclear saturation density are well constrained by the data; i.e., ${R}_{1.4}$, ${\mathrm{\ensuremath{\Lambda}}}_{1.4}$, and ${P}_{2{\ensuremath{\rho}}_{\mathrm{sat}}}$ are approximately constrained to $12.3\ifmmode\pm\else\textpm\fi{}0.7\text{ }\text{ }\mathrm{km}$, ${330}_{\ensuremath{-}100}^{+140}$, and ${4.1}_{\ensuremath{-}1.2}^{+1.5}\ifmmode\times\else\texttimes\fi{}{10}^{34}\text{ }\text{ }\mathrm{dyn}\text{ }{\mathrm{cm}}^{\ensuremath{-}2}$, respectively. Besides, we find that the Bayes evidences of the hybrid star and normal NS assumptions are comparable, which indicates that current observation data are compatible with quarkyonic matter existing in the core of massive star. Finally, in the case of normal NS assumption, we obtain a constraint for the maximum mass of nonrotating NS ${M}_{\mathrm{TOV}}=2.3{0}_{\ensuremath{-}0.18}^{+0.30}\text{ }\text{ }{M}_{\ensuremath{\bigodot}}$. Based on this result and the current observational and theoretical knowledge about the NS population and its EOS, we find that a binary black hole merger scenario for GW190814 is more plausible. All of the uncertainties reported above are for 68.3% credible levels.

We perform a hierarchical Bayesian inference to investigate the population properties of the coalescing compact binaries involving at least one neutron star (NS). With the current gravitational-wave (GW) observation data, we can rule out none of the double Gaussian, single Gaussian, and uniform NS mass distribution models, though a specific double Gaussian model inferred from the Galactic NSs is found to be slightly more preferred. The mass distribution of black holes (BHs) in the neutron star–black hole (NSBH) population is found to be similar to that in the Galactic X-ray binaries. Additionally, the ratio of the merger rate densities between NSBHs and BNSs is estimated to be ∼3:7. The spin properties of the binaries, though constrained relatively poorly, play a nontrivial role in reconstructing the mass distribution of NSs and BHs. We find that a perfectly aligned spin distribution can be ruled out, while a purely isotropic distribution of spin orientation is still allowed. To evaluate the feasibility of reliably determining the population properties of NSs in the coalescing compact binaries with upcoming GW observations, we perform simulations with a mock population. We find that with 100 detections (including BNSs and NSBHs) the mass distribution of NSs can be well determined, and the fraction of BNSs can also be accurately estimated.

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in C57BL/6 mice. Single-cell transplantation and single-cell colony assay showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average eight megakaryocytes per colony) than did previously reported megakaryocyte progenitors (MkPs). Single-cell RNA-sequencing supported that these MgPs lie between HSCs and MkPs along the megakaryocyte differentiation pathway. Single-cell colony assay and single-cell RT-PCR analysis suggested the coexpression of CD41 and Pf4 is associated with megakaryocyte colony-forming activity. Single-cell colony assay of a small number of cells generated from single HSCs in culture suggested that MgPs are not direct progeny of HSCs. In this study, we propose a differentiation model in which HSCs give rise to MkPs through MgPs.

Gravitational-wave (GW) data can be used to test general relativity in the highly nonlinear and strong field regime. Modified gravity theories such as Einstein-dilation-Gauss-Bonnet and dynamical Chern-Simons can be tested with the additional GW signals detected in the first half of the third observing run of Advanced LIGO/Virgo. Specifically, we analyze gravitational-wave data of GW190412 and GW190814 to place constraints on the parameters of these two theories. Our results indicate that dynamical Chern-Simons gravity remains unconstrained. For Einstein-dilation-Gauss-Bonnet gravity, we find $\sqrt{\alpha_{\rm EdGB}}\lesssim 0.40\,\rm km$ when considering GW190814 data, assuming it is a black hole binary. Such a constraint is improved by a factor of approximately $10$ in comparison to that set by the first Gravitational-Wave Transient Catalog events., Comment: 9 pages, 4 figures, published in PRD

We develop a new nonparametric method to reconstruct the Equation of State (EoS) of Neutron Star with multimessenger data. As an universal function approximator, the Feed-Forward Neural Network (FFNN) with one hidden layer and a sigmoidal activation function can approximately fit any continuous function. Thus we are able to implement the nonparametric FFNN representation of the EoSs. This new representation is validated by its capabilities of fitting the theoretical EoSs and recovering the injected parameters. Then we adopt this nonparametric method to analyze the real data, including mass-tidal deformability measurement from the Binary Neutron Star (BNS) merger Gravitational Wave (GW) event GW170817 and mass-radius measurement of PSR J0030+0451 by {\it NICER}. We take the publicly available samples to construct the likelihood and use the nested sampling to obtain the posteriors of the parameters of FFNN according to the Bayesian theorem, which in turn can be translated to the posteriors of EoS parameters. Combining all these data, for a canonical 1.4 $M_\odot$ neutron star, we get the radius $R_{1.4}=11.83^{+1.25}_{-1.08}$ km and the tidal deformability $\Lambda_{1.4} = 323^{+334}_{-165}$ (90\% confidence interval).Furthermore, we find that in the high density region ($\geq 3\rho_{\rm sat}$), the 90\% lower limits of the $c_{\rm s}^2/c^2$ ($c_{\rm s}$ is the sound speed and $c$ is the velocity of light in the vacuum) are above $1/3$, which means that the so-called conformal limit (i.e., $c_{\rm s}^2/c^2, Comment: 11 pages, 3 figures, 2 tables, accepted for publication in ApJ

We develop a new method based on Gaussian process to reconstruct the mass distribution of binary black holes (BBHs). Instead of prespecifying the formalisms of mass distribution, we introduce a more flexible and nonparametric model with which the distribution can be mainly determined by the observed data. We first test our method with simulated data, and find that it can well recover the injected distribution. Then we apply this method to analyze the data of BBHs' observations from LIGO-Virgo Gravitational-Wave Transient Catalog 2. By reconstructing the chirp mass distribution, we find that there is a peak or a platform locating at $20-30\,M_{\odot}$ rather than a single-power-law-like decrease from low mass to high mass. Moreover, one or two peaks in the chirp mass range of $\mathcal{M}

Layered water injection development has become the main means to stabilize production and increase production. Through several years of research and field tests, a pre wired intelligent layered water injection technology has been formed which can be applied to the characteristics of high temperature and deep wells in Huabei Oilfield. Based on the characteristics of pre wired intelligent layered water injection technology and the demand of field production management, this paper optimizes the design and forms the intelligent allocation technology. Relying on the existing data transmission network of the oilfield, it can realize the real-time monitoring and remote control of the whole process of layered water injection well. Through the research of intelligent allocation technology of layered water injection well, we have achieved the following functions: Automatic adjustment of injection volume of underground intervals, keeping the qualified rate of separate injection at a high level for a long time, reducing invalid water injection cycle, improving water injection utilization efficiency; Regular automatic calibration of downhole flowmeter, improving the accuracy of flow test, and achieving accurate water injection;Optimize the flow automatic allocation program, and design the downhole automatic seal inspection program, meetting the requirements of remote control function; The efficiency of test allocation is greatly improved and the test process does not need to enter the instrument, which reduces the labor intensity and saves the production cost. These designs provide data support and technical support for reservoir analysis and evaluation, and promote the development of layered water injection technology in Huabei Oilfield to the direction of integration, intelligence and digitalization, which has broad application prospects.

The discovery of gravitational waves from compact objects coalescence opens a brand-new window to observe the universe. With more events being detected in the future, statistical examinations would be essential to better understand the underlying astrophysical processes. In this work we investigate the prospect of measuring the mass function of black holes that are merging with the neutron stars. Applying Bayesian parameter estimation for hundreds of simulated neutron star$-$black hole (NSBH) mergers, we find that the parameters for most of the injected events can be well recovered. We also take a Bayesian hierarchical model to reconstruct the population properties of the masses of black holes, in the presence of a low mass gap, both the mass gap and power-law index ($\alpha$) of black hole mass function can be well measured, thus we can reveal where the $\alpha$ is different for binary black hole (BBH) and NSBH systems. In the absence of a low mass gap, the gravitational wave data as well as the electromagnetic data can be used to pin down the nature of the merger event and then measure the mass of these very light black holes. However, as a result of the misclassification of BBH into NSBH, the measurement of $\alpha$ is more challenging and further dedicated efforts are needed., Comment: 12 pages, 6 figures, 2 tables, ApJ published

GW190425 is the second neutron star merger event detected by the Advanced LIGO/Virgo detectors. If interpreted as a double neutron star merger, the total gravitational mass is substantially larger than that of the binary systems identified in the Galaxy. In this work we analyze the gravitational-wave data within the neutron star$-$black hole merger scenario. For the black hole, we yield a mass of $2.40^{+0.36}_{-0.32}M_\odot$ and an aligned spin of $0.141^{+0.067}_{-0.064}$. As for the neutron star we find a mass of $1.15^{+0.15}_{-0.13}M_\odot$ and the dimensionless tidal deformability of $1.4^{+3.8}_{-1.2}\times 10^{3}$. These parameter ranges are for 90\% credibility. The inferred masses of the neutron star and the black hole are not in tension with current observations and we suggest that GW190425 is a viable candidate of a neutron star$-$black hole merger event. Benefitting from the continual enhancement of the sensitivities of the advanced gravitational detectors and the increase of the number of the observatories, similar events are anticipated to be much more precisely measured in the future and the presence of black holes below the so-called mass gap will be unambiguously clarified. If confirmed, the mergers of neutron stars with (quickly rotating) low-mass black holes are likely important production sites of the heaviest r-process elements., 7 pages, 4 figures, ApJL published

We analyze the LIGO/Virgo GWTC-2 catalog to study the primary mass distribution of the merging black holes. We perform hierarchical Bayesian analysis, and examine whether the mass distribution has a sharp cutoff for primary black hole masses below $65 M_\odot$, as predicted in pulsational pair instability supernova model. We construct two empirical mass functions. One is a piece-wise function with two power-law segments jointed by a sudden drop. The other consists of a main truncated power-law component, a Gaussian component, and a third very massive component. Both models can reasonably fit the data and a sharp drop of the mass distribution is found at $\sim 50M_\odot$, suggesting that the majority of the observed black holes can be explained by the stellar evolution scenarios in which the pulsational pair-instability process takes place. On the other hand, the very massive sub-population, which accounts for at most several percents of the total, may be formed through hierarchical mergers or other processes., Comment: Accepted for publication in ApJ (This manuscript incorporating the GWTC-2 data is to replace arXiv:2009.03854 that was based on the GWTC-1 data.)

Mitochondria are double-membrane organelles existing only in eukaryotic cells. Mitochondria perform various important functions，such as producing energy，regulating signal transduction，and contributing to stress response. Recent studies have highlighted an important role of mitochondria in the determination of hematopoietic stem cells （HSC） fate. Limited biogenesis or timely clearance of mitochondria is an important way against oxidative stress，which favors the quiescence of HSC. Accumulation of mitochondria may lead to proliferation of HSC，even the aging of HSC. Mitochondrial signaling regulates Ca

Background: CHOP is widely used for untreated PTCL patients (pts), although it has limited efficacy. Chidamide is an oral benzamide class of HDAC inhibitor with subtype specificity in inhibition of HDAC 1, 2, 3 and 10, approved in China for relapsed or refractory PTCL at 30 mg twice per week. A Phase 1b/2 study (NCT02809573) is evaluating the safety, pharmacokinetics and preliminary efficacy of chidamide in combination with CHOP (CHOP-chidamide) in the first-line treatment for PTCL pts. Results from the study are reported. Methods: This open-label, multicenter study enrolled pts (18~65 years) with previously untreated PTCL. Pts received one dose chidamide as the run-in treatment, and 4 days later the induction treatment of CHOP (6 cycles [each 21 days]) with chidamide on days 1, 4, 8 and 11. Pts who achieved a complete response or unconfirmed complete response (CR/CRu) at end of induction (EOI) received consolidation treatment with chidamide on days 1, 4, 8 and 11 every 21 days for 24 months maximum. A 3+3 design was employed in the chidamide dose-escalation stage with the starting dose at 20 mg. The first 21-day treatment cycle was a dose-limiting toxicities (DLTs) observation period (phase 1b; safety and pharmacokinetics), followed by a phase 2 cohort expansion stage. For pharmacokinetic (PK) evaluation, blood samples were collected at pre-dose and 1,2,4,8,12,24,48 and 72 h after the first dose of chidamide in the run-in period and in the first cycle of CHOP-chidamide. Primary endpoints were safety and tolerability of chidamide in combination with CHOP assessed by the incidence of adverse events (AEs) in both phase 1b and 2 and as DLTs during phase 1b. Secondary endpoint was efficacy as determined by the investigator. Results: Between Nov 15, 2016 and Aug 29, 2018, 30 pts were enrolled and received treatment. Pt demographics and disease characteristics are shown in Table 1. Fifteen pts were in the dose-escalation cohort and 15 in the expansion cohort (Table 2).One DLT with grade (Gr) 3 febrile neutropenia occurred in the first three enrolled pts in the 20 mg group, and 1 DLT with Gr 3 vascular access complication in the 35 mg group. Also, in the 35 mg group, 1 pt occurred Gr 2 neutropenia with sustained temperature >38℃, and the dose-escalation was stopped at this dose level. Serious AEs occurred in 7 (23.3%) of 30 pts during the combination treatment, including neutropenia (3 [10%]), leukopenia (2 [6.7%]), interstitial pneumonia (2 [6.7%]), thrombocytopenia (1 [3.3%]), febrile neutropenia (1 [3.3%]), pneumonia (1 [3.3%]), hyponatremia (1 [3.3%]), appendicitis (1 [3.3%]) and vascular access complication (1 [3.3%]). The most common (≥10%) Gr 3 or 4 treatment-related AEs were leukopenia (90%), neutropenia (83.3%), lymphocytopenia (40%), vomiting (13.3%), thrombocytopenia (10%) and febrile neutropenia (10%).No fatal AEs were reported. There were no apparently remarkable differences in frequency and intensity of AEs in pts between chidamide dose groups of 20 mg, 25 mg and 30 mg. Among 28 pts evaluable for response, 13 pts (46.4%) had a CR/CRu, 10 pts (35.7%) had a partial response, 1 pt (3.6%) had stable disease, and 4 pts (14.3%) had progressive disease (Table 3). Fifteen pts entered the consolidation phase (13 pts with CR/CRu, 1 pt with PR, 1 pt not evaluable), and the median treatment time was 189 days (35, 483). There was no AE leading to consolidation discontinuation. Progression-free survival (PFS) and overall survival (OS) at 12 months were 54.3% and 100%. At the data cutoff (Jan 8, 2019), median PFS was 14 months and median OS was not achieved. A total of 16 pts were evaluated in the PK analysis. Over the dose range from 20 to 35 mg, a linear and dose-dependent PK profile of chidamide was characterized in both monotherapy and combination treatment. In addition, co-administration of chidamide and CHOP did not significantly affect the plasma exposure of chidamide, with geometric mean ratio (combination vs monotherapy) values for Cmax and AUC were 97.6% (73.6%, 129.2%) and 97.9% (78.4%, 122.2%), respectively. Conclusions: The combination of 20mg to 30 mg chidamide to a standard 3-week cycle of CHOP chemotherapy showed a manageable safety profile and favourable antitumour activity in pts with previously untreated PTCL. This combination could be further explored in comparison to CHOP alone in a randomized trial. CHOP-chidamide did not significantly alter the chidamide pharmacokinetics. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Chidamideis an oral benzamide class of HDAC inhibitor with subtype specificity in inhibition of HDAC1, 2, 3 and 10, approved in China for relapsed or refractory PTCL at 30 mg twice per week. This Phase 1b/2 study (NCT02809573) is evaluating the safety, pharmacokinetics and preliminary efficacy of chidamide in previously untreated PTCL patients.

In this work we parameterize the Equation of State of dense neutron star (NS) matter with four pressure parameters of $\{\hat{p}_1, \hat{p}_2, \hat{p}_3, \hat{p}_4\}$ and then set the combined constraints with the data of GW 170817 and the data of 6 Low Mass X-ray Binaries (LMXBs) with thermonuclear burst or alternatively the symmetry energy of the nuclear interaction. We find that the nuclear data effectively narrow down the possible range of $\hat{p}_1$, the gravitational wave data plays the leading role in bounding $\hat{p}_2$, and the LMXB data as well as the lower bound on maximal gravitational mass of non-rotating NSs govern the constraints on $\hat{p}_3$ and $\hat{p}_4$. Using posterior samples of pressure parameters and some universal relations, we further investigate how the current data sets can advance our understanding of tidal deformability ($\Lambda$), moment of inertia ($I$) and binding energy ($BE$) of NSs. For a canonical mass of $1.4M_\odot$, we have $I_{1.4} = {1.43}^{+0.30}_{-0.13} \times 10^{38}~{\rm kg \cdot m^2}$, $\Lambda_{1.4} = 390_{-210}^{+280}$ , $R_{1.4} = 11.8_{-0.7}^{+1.2}~{\rm km}$ and $BE_{1.4} = {0.16}^{+0.01}_{-0.02} M_{\odot}$ if the constraints from the nuclear data and the gravitational wave data have been jointly applied. For the joint analysis of gravitational wave data and the LMXB data, we have $I_{1.4} = {1.28}^{+0.15}_{-0.08} \times 10^{38}~{\rm kg \cdot m^2}$, $\Lambda_{1.4} = 220_{-90}^{+90}$, $R_{1.4} = 11.1_{-0.6}^{+0.7}~{\rm km}$ and $BE_{1.4} = {0.18}^{+0.01}_{-0.01} M_{\odot}$. These results suggest that the current constraints on $\Lambda$ and $R$ still suffer from significant systematic uncertainties, while $I_{1.4}$ and $BE_{1.4}$ are better constrained., Comment: 12 pages, 5 figures, 6 tables, ApJ published. Corrected the typo error between source frame masses and detector frame masses in section 2.5

To investigate the relationship between early peak body temperature and neutropenia duration and its potential mechanism.A total of 111 patients with CR1 phase acute leukemia (AL) with neutropenia infection were enrolled in this study. The relationship between early peak body temperature and neutropenia duration was analyzed retrospectively, and the IL-6 serum level in patients with different peak of body temperature was detected, and the single cell culture system in vitro was established, the incorparation rate of EdU in vivo was detected, and the effect of IL-6 on mouse hematopoietic stem cells /progenitor cells was analyzed.Out of 111 patients with nentropenia, the body temperature38 °C and the neutropenia duration 9.5±3.69 d were observed in 44 patients, while the body temperature38 °C and neutropenia duration 7.33±4.20 d were observed in 69 patients, the differences between 2 groups was statistically signficant (P0.05). The EdU test showed that the number of EdUFor patients with neutropenic infection when initial body temperature peak is38 °C, the probability of neutropenia duration prolonging after chamotherapy increases, which may relate with promotive effect of pro-inflammatory cytokins on prliferation of hematopoietic stem cells/progenitor cells.

Cell-penetrating peptides provide a unique platform to create a new generation of cancer therapeutics with enhanced efficacy and diminished toxicity. In our study, enhanced expression of toll-like receptor 2 (TLR2) was observed in acute myeloid leukemia (AML) cells. Screening of a phage display peptide library using Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) identified a TLR2-binding peptide motif, Pep2. We show that the TLR2-binding peptide motif targeted and penetrated into leukemia cells in a TLR2-dependent manner. Moreover, a synthetic, chimeric peptide composed of the TLR2-binding motif linked to a programmed cell death-inducing sequence, D(KLAKLAK)2, induced apoptosis in AML cells with high TLR2 expression (TLR2(high)) but not in chronic myeloid leukemia (CML) cells with low TLR2 expression (TLR2(low)). The antileukemia activity of this chimeric peptide was confirmed in leukemia patient samples and an animal model of myeloid leukemia, as the development of leukemia was significantly delayed in mice with TLR2(high) AML compared to TLR2(low) CML NOD/SCID mice. TUNEL assays on bone marrow tissue slices revealed that the chimerical peptide induced leukemia cell apoptosis in a TLR2-dependent manner. Together, our findings indicate that TLR2 is a potential therapeutic target for the prevention and treatment of AML, and the prototype, Pep2-D(KLAKLAK)2, is a promising drug candidate in this setting.

To investigate the effect of microRNA-382 (miR-382) on the biological properties of human umbilical cord-derived mesenchymal stem cells (hUC-MSC).The mimics and inhibitor of miR-382 were transfected into hUC-MSC with lipo2000. Inverted microscopy was used to observe the morphology change of hUC-MSC. The proliferation of hUC-MSC was detected by CCK-8. Oil red O and alizarin red staining were applied to assess the adipogenic and osteogenic differentiation of hUC-MSC. Cetylpyridinium chloride was used to the quantitative analysis of osteogenic differentiation. The expression of Runx2 and some cytokines were detected by RT-PCR.miR-382 did not influence the morphology, proliferation and adipogenic differentiation of hUC-MSC miR-382 inhibited the expression of Runx2, thus could inhibit the osteogenesis of hUC-MSC, being confirmed by alizarin red stain; miR-382 could influence the expression of key cytokines secreted from hUC-MSC, such as IL-6, IDO1, G-CSF, M-CSF, GM-CSF.miR-382 decreases the expression of Runx2 and inhibites the osteogenesis of hUC-MSC. In addition, it also affects the expression of some key cytokines secreted from hUC-MSC.

Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML-RARα, which antagonizes myeloid differentiation and promotes APL-initiating cell self-renewal. Combined all-trans retinoic acid (ATRA) with arsenic trioxide (As2O3) or chemotherapy dramatically improves the prognosis of APL patients. Here we report that expression of pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARα and suppressing its sumoylation, ubiquitylation, and degradation. This represses PML nuclear body assembly, p53-mediated senescence, and cell differentiation, and supports cellular self-renewal. Genetically inhibiting TRIB3 expression or combination of a peptide disturbing TRIB3/PML-RARα interaction with ATRA/As2O3 eradicates APL by accelerating PML-RARα degradation. Our study provides insight into APL pathogenesis and a potential therapeutic option against APL.

To investigate the risk factors of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).The clinical data of 534 cases of 533 patients undergoing allo-HSCT during Jan 2004 and Sep 2012 were retrospectively analyzed. The effects of donor-recipient HLA mismatching, recipient age, donor age, donor-recipient sex combination, donor-recipient relationship, HSC source, conditioning regimen with or without total body irradiation (TBI) and HLA loci on intestinal aGVHD with different severity were analyzed by Logistic regression.Intestinal aGVHD occurred in 123(23.0%) cases, with 86(16.1%) cases of stage 1 intestinal aGVHD(16.1%) and 37(6.9%) cases of stage 2 to 4 intestinal aGVHD. Multivariate analysis showed that donor-recipient HLA mismatching (OR=2.519, P=0.002), increasing donor age (OR=1.034, P=0.003), female donor for male recipient (OR=1.855, P=0.007) were risk factors for intestinal aGVHD, HLA-B38 (OR=0.256, P=0.032) was its protective factor. Donor-recipient HLA mismatching (OR=2.799, P=0.011), increasing donor age (OR=1.045, P=0.012), HLA-A1 (OR=4.157, P=0.002), A30 (OR=3.143, P=0.005) were risk factors for stage 2 to 4 intestinal aGVHD.Occurrence of intestinal aGVHD and its severity are associated with donor-recipient HLA mismatching, donor age, donor-recipient sex relationships and some HLA loci.

To evaluate the efficacy and safety of antifungal prophylaxis of itraconazole in patients with acute myeloid leukemia (AML) to probe the relationship of the antifungal effect and the adverse events with serum concentration.From April 2009 to May 2011, a total of 310 courses from 112 patients referred to our institute were enrolled in this study; of them, 297 courses were eligible for analysis. Eligible cases were randomized into oral group and injection/oral group according to different chemotherapy of induction and consolidation. Blood samples were collected at different time points for measurements of serum itraconazole levels. The morbidity of IFI and the adverse events were analyzed.The morbidities of IFI in injection/oral and oral groups were 10.1% and 20.9%, respectively (P=0.010). 7 and 9 cases in injection/oral and oral groups, respectively were withdrawn from the study because of adverse events, and the difference between these two groups was of no significance. Serum itraconazole levels of injection/oral and oral groups were 672(299-1097) μg/L and 534(210-936) μg/L, respectively (P0.01).Antifungal prophylaxis with itraconazole in AML patients was effective and safe. Prophylactic effect with injection/oral itraconazole was superior to oral itraconazole solution; moreover, prophylactic effect of itraconazole was highly correlated with its serum level.

To investigate mesenchymal stem cells (MSCs) immunosuppressive activity in the presence of interferon-gamma (IFN-γ) to reveal synergistic immunomodulatory effects of IFN-γ and MSCs.① MSCs were cultured in the presence or absence of IFN-γ（100 ng/ml）, the supernatants were collected for measurements of PGE2、HGF and TGF-β1 by ELISA kits. ② MSCs were cultured in the presence or absence of IFN-γ （100 ng/ml）for 48 h. The cDNA was analysed for the expression of human indoleamine 2, 3-dioxygenase（IDO）mRNA by semiquantitative RT-PCR. ③ Mononuclear cells (MNCs) were extracted from peripheral blood of healthy donors. The T cell proliferation was tested in the co-culture system added with MSCs, recombinant human IFN-γ (100 ng/ml) and anti-IFN-γ mAb (5 μg/ml) by BrdU ELISA kit.①The immunosuppressive cytokines PGE2、HGF and TGF-β1 were detectable within 24-48 h in the supernatants. Their expressions were significantly up-regulated in the presence of IFN-γ. Concentrations of these cytokines were as of (1715.5±628.6) pg/ml vs (1344.5±709.4) pg/ml (P=0.001);(4031.8±1496.8) pg/ml vs (2452.4±1375.3) pg/ml（P=0.011）;(1753.5±413.8) pg/ml vs (1026.6±450.5) pg/ml（P0.001）,respectively. ②The expression of IDO mRNA was undetectable when MSCs were cultured alone. In contrast, The IDO mRNA expression was remarkably enhanced in the presence of IFN-γ. ③Bone marrow-derived MSCs remarkably suppressed allogeneic T cell proliferation in vitro. Addition of exogenous IFN-γ had no significant effect on the inhibitory capacity of MSCs, the inhibitory ratios of T cell proliferation were （40.4±10.9）% vs（36.7±7.4）% (P=0.272). By contrast, the inhibitory ratio of T cell proliferation was significantly decreased in the presence of anti-IFN-γ mAb[(40.4±10.9)% vs (23.9±7.6)%,P=0.002].①Human MSCs constitutively expressed immunosuppressive concentrations of PGE2, HGF and TGF-β1, and their expressions were significantly up-regulated by IFN-γ. ②IFN-γ-induced expression of IDO on MSCs involved in tryptophan catabolism. ③MSCs notably suppressed allogeneic T cell proliferation in vitro. IFN-γ promoted the immunosuppressive capacity of human MSCs, indicating the synergistic immunomodulatory effect of IFN-γ and MSCs.目的 探讨干扰素-γ（IFN-γ）对正常人骨髓间充质干细胞（MSC）免疫活性的影响,阐明IFN-γ与MSC在免疫抑制中的协同作用。方法 ① ELISA法检测IFN-γ（终浓度100 ng/ml）对正常人骨髓来源MSC前列腺素E2（PGE2）、肝细胞生长因子（HGF）和转化生长因子β1（TGF-β1）表达水平的影响。②RT-PCR法检测100 ng/ml IFN-γ作用下MSC内吲哚胺2,3-双加氧酶（IDO）基因表达水平变化。③ 体外刺激正常人外周血T细胞增殖,并与正常人骨髓来源MSC共培养,检测T细胞增殖水平;在共培养体系中分别加入重组人IFN-γ（100 ng/ml）及鼠抗人IFN-γ单克隆抗体（单抗,5 μg/ml）,检测T细胞增殖水平变化。结果 ①MSC单独培养24~48 h可检测到PGE2、HGF、TGF-β1三种细胞因子表达;IFN-γ可促进MSC上述细胞因子的表达[实验组及对照组PGE2、HGF、TGF-β1表达水平分别为(1715.5±628.6) pg/ml对(1344.5±709.4) pg/ml;(4031.8±1496.8) pg/ml对(2452.4±1375.3) pg/ml;(1753.5±413.8) pg/ml对(1026.6±450.5) pg/ml,P值分别为0.001、0.011及0.001]。②MSC单独培养48 h后,RT-PCR法未检测到IDO基因表达。与IFN-γ共培养后,IDO基因呈高水平表达。 ③在体外MSC可以显著抑制T细胞增殖,外源性IFN-γ不影响MSC对T细胞增殖的抑制作用[T细胞增殖抑制率分别为（40.4±10.9）%和（36.7±7.4）%,P=0.272];在反应体系中加入抗IFN-γ单抗后,MSC抑制T细胞增殖作用显著减弱[T细胞增殖抑制率分别为（40.4±10.9）%和（23.9±7.6）%,P=0.002]。结论 MSC组成性表达PGE2、HGF及TGF-β1等免疫抑制性细胞因子,在一定水平IFN-γ作用下,MSC分泌上述3种细胞因子水平明显上调,IDO mRNA表达水平显著增高,MSC免疫活性增强。骨髓MSC在体外可以显著抑制T淋巴细胞增殖,IFN-γ与MSC在免疫抑制中具有协同效应。

This study was aimed to observe the efficacy of autologous stem cell transplantation (ASCT) for adult patients with acute lymphoblastic leukemia (ALL), and investigate related prognostic factors.A total of 86 adult ALL patients underwent ASCT in Institute of Hematology and Blood Disease Hospital from November 2001 to January 2012 were followed up. Clinical characteristics and outcomes of all patients were retrospectively analyzed. Survival and univariate prognosis were analyzed by the Kaplan-Meier method and multivariate analysis by COX regression model.Outcomes were assessed in 81 cases, including 47 standard-risk and 34 high-risk patients. 1-, 3-, 5-, and 10-year leukemia-free survival (LFS) of standard-risk patients were (82.3±5.7)%, (76.9±6.5)%, (74.1±6.8)%, (67.4±8.9)% respectively,and relapse rates (RR) were as of (13.6±5.2)%, (21.6±6.4)%, (24.5±6.8)%, (31.3±9.0)% respectively. 1-, 3-, 5-, and 10-year LFS of high-risk patients were (55.8±8.9)%, (39.8±9.3)%, (39.8±9.3)%, (39.8±9.3)% respectively, and relapse rates (RR) were (38.8±9.2)%, (56.4±10.0)%, (56.4±10.0)%, (56.4±10.0)% respectively. T-ALL, white blood cell count(WBC) more than 30×109/L when first visited, increased LDH, positive fusion gene of TCR and bone marrow transplantation were the adverse prognostic factors. Multivariate analysis showed bone marrow transplantation was an independent adverse prognostic factor.ASCT was a choice for adult ALL patients when suitable donors were unavailable.目的 观察成人急性淋巴细胞白血病(ALL)患者行自体造血干细胞移植(auto-HSCT)的疗效,并探讨相关的预后危险因素。方法 对2001年11月至2012年1月行auto-HSCT的86例成人ALL患者进行随访,并对所有患者的临床特征及治疗转归进行回顾性分析,应用Kaplan-Meier法进行生存分析,用COX回归模型评估独立预后因素。结果 可评价疗效的81例auto-HSCT患者中标危47例,高危34例。标危组患者1、3、5、10年无病生存（LFS）率分别为（82.3±5.7）%、（76.9±6.5）%、(74.1±6.8)%、(67.4±8.9)%;累积复发（RR）率分别为(13.6±5.2)%、(21.6±6.4)%、(24.5±6.8)%、(31.3±9.0)%。高危组患者1、3、5、10年LFS率分别为（55.8±8.9）%、（39.8±9.3）%、（39.8±9.3）% 、（39.8±9.3）%;RR率分别为(38.8±9.2)%、(56.4±10.0)%、(56.4±10.0)%、(56.4±10.0)%。而疾病类型为T-ALL、初诊时WBC≥30×109/L、乳酸脱氢酶增高、TCR重排阳性及移植物来源于骨髓均为影响预后的不良因素,进一步应用COX多因素回归模型进行预后因素分析显示,移植物来源于骨髓是独立的预后不良因素。结论 成人ALL患者如果没有合适的供者,auto-HSCT也是治疗的一种有效手段。

Cell-penetrating peptides provide a unique platform to create a new generation of cancer therapeutics with enhanced efficacy and diminished toxicity. In our study, enhanced expression of toll-like receptor 2 (TLR2) was observed in acute myeloid leukemia (AML) cells. Screening of a phage display peptide library using Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) identified a TLR2-binding peptide motif, Pep2. We show that the TLR2-binding peptide motif targeted and penetrated into leukemia cells in a TLR2-dependent manner. Moreover, a synthetic, chimeric peptide composed of the TLR2-binding motif linked to a programmed cell death-inducing sequence, D(KLAKLAK)2, induced apoptosis in AML cells with high TLR2 expression (TLR2(high)) but not in chronic myeloid leukemia (CML) cells with low TLR2 expression (TLR2(low)). The antileukemia activity of this chimeric peptide was confirmed in leukemia patient samples and an animal model of myeloid leukemia, as the development of leukemia was significantly delayed in mice with TLR2(high) AML compared to TLR2(low) CML NOD/SCID mice. TUNEL assays on bone marrow tissue slices revealed that the chimerical peptide induced leukemia cell apoptosis in a TLR2-dependent manner. Together, our findings indicate that TLR2 is a potential therapeutic target for the prevention and treatment of AML, and the prototype, Pep2-D(KLAKLAK)2, is a promising drug candidate in this setting.

To explore the impact of IFN-γ + 874 polymorphisms on the outcome in HLA matched sibling HSCT.We used PCR-sequence-specific primer analysis (PCR-SSP) to analyze the polymorphisms of IFN-γ + 874 T/A in 80 recipient and donor pairs from October 2005 to March 2008.Recipients having donors who possessed IFN-γ + 874 A/A genotype had significantly earlier neutrophil recovery compared with those having donors with non-A/A genotype (15 (11 - 27) days vs 18 (12 - 30) days, P = 0.029). And IFN-γ + 874 A/A in both recipients and donors further facilitated neutrophil recovery compared with others (13 (11 - 25) days and 19 (12 - 31) days, P = 0.019). Besides, IFN-γ + 874 A/A in recipients increased the probability of grade II-IV acute graft versus disease (aGVHD) and cytomegalovirus viraemia compared with IFN-γ + 874 T/A or T/T genotype (20% vs 4% P = 0.041, 43.6% vs 16.0% P = 0.032), which lead to increased 5-year transplant-related mortality (TRM) (33.7% ± 6.8% vs 12.0% ± 6.5%, P = 0.050) and decreased 5-year event free survival (EFS) \[(58.2 ± 6.7)% vs (84.0 ± 7.3)%, P = 0.032\] compared with the latter. IFN-γ + 874 A/A in both recipients and donors also significantly increased the probability of grade II-IV aGVHD and cytomegalovirus viraemia compared with the other (21.7% vs 5.9%, P = 0.050; 45.7% vs 20.6%, P = 0.020), which caused increased 5-year TRM \[(31.6 ± 7.5)% vs (13.6 ± 6.5)%, P = 0.048\] and decreased 5-year EFS \[(56.8 ± 7.3)% vs (79.4 ± 6.9)%, P = 0.037\] compared with the other.In HLA-matched sibling HSCT setting, the presence of IFN-γ + 874 T allele in recipients or in both recipients and donors significantly decreased the risk of grade II-IV aGVHD and CMV infection and increased EFS. While IFN-γ + 874 A/A in donors or in both recipients and donors was associated with shorter duration to neutrophil recovery.

Summary BACKGROUND: The alloreactivity of natural killer cell and certain subsets of T lymphocyte are regulated by the interaction between killer immunoglobulin-like receptors (KIRs) of donor cells and human leukocyte antigen (HLA)class I molecules on target cells. The interaction has been shown to influence the outcome of allogeneic haematopoietic stem cell transplantation (HSCT). Homozygous C1 or C2 and heterozygous C1/C2 were divided by HLA-Cw typing and they influenced the outcome of HSCT. OBJECTIVE: The purpose of the study was to analyse the impact of interaction between recipient HLA-Cw and donor KIR on outcome. METHODS: The genotypes of recipient HLA-Cw ligands and donor KIRs were correlated with the clinical outcomes of 52 patients who received HLA-matched, sibling donor HSCT for myeloid malignancies. RESULTS: The incidence of chronic graft versus host disease (GVHD) was significantly lower in C1 or C2 homozygotes than in C1/C2 heterozygotes (p = 0.000). Higher overall survival (OS) and disease-free survival (DFS) rates were observed in C1 or C2 homozygotes than in C1/C2 heterozygotes (OS, 81% ± 8% vs 54% ± 10%, p = 0.034; DFS, 81% ± 8% vs 54% ± 10%, p = 0.024). A lower incidence of chronic GVHD and higher OS and DFS were observed in the HLA-KIR mismatched group (chronic GVHD, p = 0.007; OS, 84% ± 7% vs 47% ± 13%, p = 0.003; DFS, 84% ± 7% vs 47% ± 13%, p = 0.002). CONCLUSION: The interaction between recipient HLA ligand and donor KIR had a significant impact on the outcome of patients receiving matched sibling HSCT. C1/C2 heterozygotes or HLA-KIR matched patients may benefit from additional intensified therapy with better outcome.

To evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for severe aplastic anemia (SAA).The clinical data of 41 SAA patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28 patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24 received allogeneic peripheral blood stem cell (PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) + anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+ cytarabine (Ara-C) ± busulfan (Bu)/melphalan (Mel). Prophylaxis for graft-versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short-term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused CD34(+) cells were 3.48 (2.39 - 4.80)×10(6)/kg in allo-BMT and 2.95 (1.27 - 5.98)×10(6)/kg in allo-PBSCT, respectively.Hematopoietic reconstitution was observed in all 41 patients (100%). The median time of neutrophils (ANC) reached to 0.5×10(9)/L and platelets (PLT) reached to 20×10(9)/L were 14 (10 - 23) days and 19 (8 - 38) days, respectively. 12 patients developed acute GVHD (aGVHD), out of which 11 developed grade I-II aGVHD, and one developed grade IV. 2 patients occurred chronic GVHD (cGVHD), out of which one with local cGVHD and the other with extensive. 4 patients occurred graft rejection (GR), all of them recovered haemopoiesis and survived after donor PBSC infusion. 5 patients (12.2%) died, out of which one died of extensive cGVHD, and 4 died of invasive fungal infections (IFI). Median follow-up time was 23 (3 - 79) months. 36 patients survived. 5-year estimated overall survival (OS), disease free survival (DFS), and transplant-related mortality (TRM) was (81.1 ± 9.0)%, (68.4 ± 11.0)%, and (18.9 ± 9.0)%, respectively. Univariate analysis showed that lover OS had significant correlation with receiving PBSCT, occurrence of aGVHD, the number of infused CD34(+) cells no more than 2.5×10(6)/kg, the number of red blood cell (RBC) transfusion before transplant more than 30 U and occurrence of IFI after transplantation (P = 0.034, 0.001, 0.006, 0.000, 0.001, respectively). Occurrence of aGVHD had significant correlation with the disparity between donor and recipient ABO blood groups, the number of PLT transfusion more than 100 U, and the number of RBC transfusion more than 30 U before transplantation, the number of infused CD34(+) cells no more than 2.5× 10(6)/kg (P = 0.019, 0.038, 0.005, 0.005, respectively). The occurrence of GR had significant correlation with the number of PLT transfusion more than 100 U before transplantation (P = 0.038).MSD allo-HSCT is an effective therapy for patients with SAA. Lower number of blood transfusion before transplantation, use of BMT, more number of infused CD34(+) cells can effectively prevent and treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD allo-HSCT for SAA.

The study was purposed to investigate the effect of alloreactive natural killer (alloNK) cells on immune reconstitution in murine haploidentical bone marrow transplantation (BMT). The murine model of haploidentical BMT was established by using (C57BL/6×BALB/c)BCF(1)(H-2(d/b)) mouse as the donor, and BALB/c (H-2(d)) mouse as the recipient. Recipient mice were divided into BMT group, non-allo-reactive NK (non-alloNK) cell group and alloNK cell group according to different transfusion. The effect of adding alloNK cells to transfusion was assessed by thymus pathology, the proportion of spleen NK cells, the spleen cell proliferation, the IFN-γ and IL-4 concentrations product at 24 and 48 h of recipient spleen cell culture supernatant at 2 months after BMT. The results showed that there were no obvious difference in thymus tissue among 3 groups under the optical microscope. The proportion of recipient spleen NK cells in non-alloNK group was significantly lower than that in BMT group (P0.05). There was no significant difference in proliferation of the recipient spleen cells among 3 groups at 2 months after BMT. The IFN-γ concentration product at 24 and 48 h of recipient spleen cell culture supernatant in alloNK group was significantly lower than that in other 2 groups at 2 months after BMT (P0.05). The IL-4 concentration in each group was not significantly different (P0.05). It is concluded that alloNK cells do not damage the thymus structure and may induce Th2 immune response in murine haploidentical BMT.

To study the clinical characteristics and antimicrobial resistance of bloodstream infections caused by Gram positive bacteria, so as to provide reference for the rational use of antimicrobial agent.One hundred and eight patients with bloodstream infections of Gram positive bacteria in our hospital from January 2009 to December 2009 were retrospectively reviewed. The clinical manifestations, pathogen types and antimicrobial susceptibility results of pathogens isolated from bloodstream were analyzed.All patients had fever and 31.89% with rigor, 22.41% of the patients had no local infection lesions, 77.59% had clear infection lesions, including oral infections, respiratory tract infections and soft tissue infections. The pathogen testing showed that 12.82% were staphylococci aureus, 50.42% coagulase-negative staphylococci, 24.8% streptococci, 9.4% enterococci and 2.56% Listeria monocytogenes. Antibiotics resistance of staphylococcus and enterococci in our hospital was severe. The percentage of methicillin-resistant staphylococcus aureus in this investigation was 68.92%. The resistant rates of methicillin-resistant coagulase-negative staphylococci (MRCNS) to the most antimicrobial agents were higher than that methicillin-sensitive coagulase-negative staphylococci. One strain of MRCNS was found resistant to teicoplanin and linezolid, and 1 strain of enterococci resistant to teicoplanin and linezolid.Gram positive bacteria shows serious drug resistance, but still keeps highly sensitive to vancomycin, linezolid, teicoplanin and quinupristin/dalfopristin.

To investigate the incidence, risk factors, prognosis and high risk patients of invasive fungal infections (IFI) in patients with hematological diseases.: Over 2-week hospitalized patients from January 2007 to December 2008 were retrospectively reviewed. Logistic regression was used to analyze the risk factors of IFI, and recursive partitioning to reveal high risk patients. Incidence of IFI was estimated by cumulative incidence function, and the prognosis by Kaplan-Meier method.A total of 1048 assessable treatment cycles were recorded and 93 cases of IFI were diagnosed, with an incidence of 8.87 per 100 treatment cycles. Multivariate logistic regression revealed the following risk factors: age (OR 1.025, 95% CI 1.010-1.041, P = 0.002), duration of neutropenia (OR 1.028, 95% CI 1.014-1.042, P0.0001) and uncontrolled underlying diseases (OR 2.620, 95% CI 1.608-4.268, P = 0.0001). Recursive partitioning found two groups of high risk patients: (1) patients with uncontrolled underlying diseases and neutropenia durationor = 58 days (7/12, 58.3%), (2) patients with uncontrolled underlying diseases and ageor = 33 years (40/208, 19.2%). At the end of follow-up, 111 cases of IFI were recorded in 451 patients, with a 1-year cumulative incidence of 27.1%. In patients with established IFI, overall survival rate and IFI related mortality rate at 12 weeks after diagnosis were 83.4% and 13.5% respectively.Age, duration of neutropenia and uncontrolled underlying diseases are risk factors of IFI; patients with uncontrolled underlying diseases and ageor = 33 years were at high risk of IFI and need major concern. IFI has a better prognosis and a lower related mortality in this study.

The objective of this study was to investigate the correlation between the gene polymorphisms of drug metabolizing enzymes and the outcome of the first induction chemotherapy in patients with de novo acute myeloid leukemia (AML). 113 de novo AML patients were enrolled in this study. The genotypes of 11 single nucleotide polymorphisms (SNP) in drug metabolizing enzymes were detected by the SNPstream(®) Genotyping System. The correlation between the distribution of genotypes and the complete remission rate of first induction chemotherapy was analyzed by logical regression. The results showed that patients with variant genotype of CYP2D6 (rs16947) had a lower complete remission (CR) rate, as compared to those with wild type (p = 0.033, OR = 0.32, 95%CI 0.112 - 0.915); meanwhile the patients with variant genotype of GSTO2 (rs156697) had a higher CR rate as compared to those with wild type (p = 0.011, OR = 3.023, 95%CI 1.289 - 7.089). Combined analysis of the above polymorphisms, showed that patients with variant genotype of CYP2D6 and wild genotype of GSTO2 (V + W) had lower CR rates in comparison to patients with wild genotypes of both polymorphisms (p = 0.017, OR = 0.183, 95%CI 0.045 - 0.735). It is concluded that CYP2D6 (rs16947) and GSTO2 (rs156697) polymorphisms are independent factors influencing CR rates of the first induction chemotherapy in de novo AML patients.

Chronic myeloid leukemia (CML) at advanced and blastic phase is a disease with poor prognosis, for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment choice with curative potential. This study was purposed to investigate the therapeutic efficacy of allo-HSCT and prognosis of advanced CML patients. The 28 cases of CML in accelerated phase or blast crisis received allo-HSCT were analysed retrospectively in terms curative efficacy, basic characteristics before transplant and prognosis, therapeutic strategy before transplant and prognosis, events after transplant and prognosis. The results indicated that 10 out of 28 patients were in complete remission, showing a 3-year overall survival and disease-free survival rate of 34.9% and 35.7% respectively; 18 patients died. Univariate analysis revealed that the clonal evolution and blast amount are baseline risk factor of poor prognosis, and combination of them can be used to predict the outcome of patients; application of imatinib before transplant and achievement of complete hematologic remission could not improve the prognosis; severe aGVHD among post-transplant events was proven to be a negative prognostic factor. It is concluded that for advanced CML patients received allo-HSCT, clonal evolution and blast percentage are prognostic factors, and the pre-transplant use of imatinib did not influence the outcome.

To investigate the prognosis and hepatitis B serologic marker changes in patients with HBV infection or with HBV infected donors after allogenic hematopoietic stem cell transplantation (allo-HSCT).The clinical outcomes of 79 patients receiving allo-HSCT, including 55 with HBV infection and 24 from HBV infected donors were analyzed retrospectively.(1) HBV infection did not interfere with the clinical outcome of allo-HSCT. (2) In 20 HBsAg(+) patients, 13(65.0%) developed HBV reactivation between 0.5 and 10 months after transplantation, 9(45.0%) developed HBV-related hepatitis. (3) For the 35 HBsAg(-) and HBcAb/HBeAb positive patients, 4 (11.4%) occurred HBV seroconversion, 1 of the 4 complicated with severe chronic graft-versus-host disease (cGVHD). (4) There was a significant difference in HBV reactivation rate between the HBsAg(+) and HBsAg-groups (P0.01). The incidence of hepatitis occurred within 100 days after HSCT was high in HBsAg(+) patients (P0.05). (5) Clearance of HBsAg was observed in 2 HBsAg(+) patients, both of whom received graft from HBsAb positive donors.Donors or recipients infected with HBV is not considered an absolute contraindication for HSCT, but HBsAg positivity is a high risk factor for HBV reactivation and prophylactic lamivudine treatment may be helpful. For patients with HBcAb/HBeAb positivity, seroconversion can be observed, especially after immunosuppressant withdrawal. Adoptive immunity is effective in clearing HBV in these patients.

Despite its widespread use in the management of HIV-related cytomegalovirus (CMV) infection, there have been surprisingly few reports of the use of valganciclovir (VGC) in the post-allotransplant setting. So far, no multi-center, non-crossover trial data have been available with the use of this drug as the primary pre-emptive. The present study evaluated the efficacy and safety of VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT).From January to April 2007, VGC was adopted in eleven centers in mainland China for pre-emptive therapy of CMV infection in consecutive patients undergoing allogeneic HSCT. Allogeneic HSCT recipients were followed weekly via CMV pp65 antigenemia assay or real-time quantitative polymerase chain reaction (PCR) for detection of CMV-DNA. Patients with a positive assay were treated with VGC, 900 mg P.O. twice a day for 14 days followed by 900 mg P.O. once a day for 14 days after a negative result or the CMV-DNA load was lower.A total of 54 patients (15 siblings, 28 mismatched related donors, 11 unrelated donors) had a positive assay treated with oral VGC. The seroconversion rate was 89% (48/54) as confirmed by a negative assay; six patients failed oral VGC. No significant toxicity was encountered. No case of CMV disease was diagnosed in the responding patients with a median follow-up of 5.3 months after the drug administration.Pre-emptive therapy of CMV viraemia with oral VGC is safe and effective in allogeneic HSCT.

This study was purposed to investigate the effect of prostaglandin E2 (PGE2) on proliferation of peripheral blood T lymphocytes, and to evaluate the regulatory role of PGE2 on immunological balance between Th1/Th2 and Tc1/Tc2 lymphocytes. The peripheral blood mononuclear cells (PBMNC) were stimulated by anti-human CD3 monoclonal antibody (mAb) and anti-human CD28 mAb, and were cultured in the presence of different concentration of PGE2 for 120 hours. The proliferation of peripheral blood T lymphocytes was assayed according to the manufacture protocol of BrdU Kit; the IFN-gamma and IL-4 levels in supernatants cultured for 24, 48, 72 and 120 hours were detected by ELISA; the ratios of CD4+IL-4+ T cells/CD4+ IFN-gamma+ T cells and CD8+IL-4+ T cell/CD8+IFN-gamma+ T cells were determined by flow cytometry. The cells cultured without PGE2 were used as control. The results indicated that (1) with the raising of concentration of PGE2, the inhibitory rate of T cell proliferation in vitro significantly increased (p=0.001). There was significant positive correlation between inhibitory rate of T cells and PGE2 concentration (correlation coefficient=0.889, p=0.000). (2) the difference between the IFN-gamma concentrations in supernatant cultured for 120 and 72 hours in test groups had no statistical significance (p=0.917). The IFN-gamma concentration increased continually with prolonging of culture time in control group (p=0.046). The IFN-gamma concentrations produced at different times in test group were significantly lower compared with those in control group (p0.05). The IL-4 concentrations produced at different time had no significant change in test groups (p=0.400). The IL-4 concentration in 24 hours in control group was significantly higher than that at 48, 72 and 120 hours in control group (p=0.007, 0.003 and 0.002). After cultured for 24 hours the IL-4 concentration in test group was significantly lower than that in control group (p=0.037), but after cultured for 48, 72 and 120 hours, the IL-4 concentration in test group did not show statistical difference in comparison with control group (p0.05). (3) the proportions of CD4+IFN-gamma+T cells in test group and in control group had no significant difference (p=0.767). The proportion of CD4+IL-4+T cells in test group was slightly higher than that in control group (p=0.051). The ratio of CD4+IL-4+T cells to CD4+IFN-gamma+ T cells in test group was significantly higher than that in control group (p=0.011). The proportions of CD8+IFN-gamma+ T cells in test group and in control group had no statistical difference (p=0.441). The proportion of CD8+IL-4+T cells in test group was significantly higher than that in control group (p=0.015). The ratio of CD8+IL-4+ T cells to CD8+IFN-gamma+ T cells in test group were obviously higher than that in control group(p=0.038). It is concluded that the PGE2 inhibits the proliferation of T lymphocytes in vitro. PGE2 influences the production of IFN-gamma and IL-4, and significantly influences peak appearance of IFN-gamma produced by T lymphocyte. PGE2 can continuously inhibit the production of IFN-gamma, but its continuous effect on IL-4 is no significant. PGE2 enhances the ratio of CD4+IL-4+T lymphocytes to CD4+IFN-gamma+T lymphocytes and the ratio of CD8+IL-4+T lymphocytes to CD8+IFN-gamma+T lymphocytes, and regulates development of T cells toward Th2/Tc2 cells.

This study was purposed to evaluate the outcome of patients with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in complete remission, and to study the prognostic factors. 75 cases of AML in complete remission receiving allo-HSCT from January 2000 to December 2007 were retrospectively analyzed. Major end points of study included overall survival (OS), disease free survival (DFS), relapse rate and transplantation related mortality (TRM). The results showed that 3-year OS and DFS of the study population reached to 58.4% and 53.9% respectively, and the relapse rate and TRM leaded to 16.9% and 29.9% respectively. Incidence of acute GVHD was 59.6%, with 18.7% II-IV aGVHD. Different prognosis was observed between HSCT recipients of alternative donor and HLA-matched related donor (MRD) (3-year DFS was 34.3% vs 60.0%, p = 0.019), between patients of refractory leukemia and the control (3-year DFS was 35.7% vs 58.2%, p = 0.048), between recipients with and without severe aGVHD (3-year DFS was 35.7% vs 54.4%, p = 0.059). Further analysis revealed significantly high TRM in recipients receiving allo-HSCT of alternative donor (p = 0.033) and high rate of severe aGVHD (p = 0.010). Multivariate analysis revealed three negative prognostic factors: donor availability (alternative vs MRD) (p = 0.049, RR = 2.09, 95%CI 1.01 - 4.36), refractory leukemia (p = 0.038, RR = 2.33, 95%CI 1.05 - 5.20) and severe aGVHD (p = 0.040, RR = 2.33, 95%CI 1.04 - 5.20). It is concluded that allo-HSCT is a choice for the AML case at complete remission and TRM is the major cause of the transplantation failure. Donor availability, refractory leukemia and severe aGVHD are confirmed as risk factors of poor prognosis for allo-HSCT patients with AML in CR.

The study was aimed to compare the efficiency of cytomegalovirus (CMV) quantitative PCR and CMV-pp65 antigen test for detection of CMV infection and their clinical significance in patients received allogeneic hematopoietic stem cell transplantation (HSCT). 84 patients received allogeneic HSCT were enrolled in study. Anticoagulant blood samples were obtained from the recipients before and after transplantation and in the convalescence. CMV quantitative PCR and CMV-pp65 antigen test were performed weekly. The results showed that out of 84 patients, 26 cases were positive (30.95%) by CMV quantitative PCR method. Of the 26 cases, 9 cases were CMV antigenemia and 13 cases were CMV disease, the median positive time was 37.1 (7 - 105) days after HSCT. 22 cases were positive (26.19%) by CMV-pp65 antigen test method, the median positive time was 46.6 (10 - 128) days after HSCT. All the 22 positive cases detected by CMV-pp65 antigen test were also positive by CMV quantitative PCR method. Nevertheless, 4 positive cases detected by CMV quantitative PCR but negative detected by CMV-pp65 antigen test method did not develop CMV disease. The CMV disease was found in the cases either with moderate to high copies of CMV quantitative PCR or moderate to high level CMV antigenemia by CMV-pp65 antigen test method. The clearance median time was 17.5 (11 - 28) days by CMV quantitative PCR method after receiving antiviral therapy and was 10.0 (7 - 21) days by CMV-pp65 antigen detection method. It is concluded that both CMV quantitative PCR and CMV-pp65 antigen test can detect the infection of CMV early and effectively in patients received HSCT. CMV quantitative PCR is more sensitive, and CMV-pp65 is more specific. It can be more effective to guide the antiviral treatment and evaluate its efficacy when combining the two methods.