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In this paper, an MQTT based protocol is designed and implemented for control, management and monitoring of HVAC in a cloud platform in real time. The MQTT protocol is a two-way messaging protocol, and has the generality, flexibility, light weighted, quickness with reliability and security. In the implemented system, performance and reliability of the communication protocol is considered for data acquisition and control between the CCU and the cloud server. Control and monitoring for the cloud server is performed in real time in conjunction with CCU and the MQTT server.

JXTA does not need to be managed by the central server, and has the property that can communicate with any device that is connected to the network. Thus, JXTA can be applied to the communication between heterogeneous P2P systems. This paper deals with the design of a data exchange system utilizing the JXTA’s foregoing property, which is able to connect P2P systems with different protocols and APIs.

The prognostic impact of extramedullary plasmacytomas (EMPs) on newly diagnosed symptomatic multiple myeloma (MM) was evaluated in the context of treatment approach including autologous stem cell transplantation (ASCT) and chemotherapy alone. A total of 275 consecutive patients with newly diagnosed MM were included, and 54 patients (19.6 %) had EMPs at diagnosis. Patients with initial EMPs were more likely to have myeloma bone disease but favorable laboratory parameters in hemoglobin and β2-microglobulin. Patients were treated with different schemas based on transplant eligibility (154 in ASCT-eligible vs. 121 in ASCT-ineligible). After a median follow-up of 24.6 months (range, 0.2-56.3 months) in survivors, patients with initial EMPs had significantly worse progression-free survival (PFS) (P = 0.035) and overall survival (OS) (P = 0.006) compared to those without initial EMPs. In the multivariate analyses, the presence of initial EMPs was an independent prognostic factor for PFS (relative risk (RR) of 2.24, P = 0.024) and OS (RR of 2.47, P = 0.027) in the transplant-ineligible patients, whereas it did not significantly influence PFS (P = 0.341) or OS (P = 0.499) in the transplant-eligible patients. However, the adverse impact of EMPs observed in transplant-ineligible patients was attenuated among the patients treated with bortezomib. These data suggest that ASCT can overcome the negative impact of EMPs and highlight the potential efficacy of bortezomib on EMPs in the non-transplant setting.

The current definition of complete response (CR) in multiple myeloma (MM) includes negative serum and urine immunofixation (IFE) tests and (P=0.005). Patients with (P=0.050)or ≥5% BMPCs + serologic non-CR(P=0.001). Interestingly, the prognostic impact of BMPCs was more apparent for patients who did not achieve a serologic CR(P=0.042)compared to those with a serologic CR(P=0.647). We concluded that IFE negativity and

In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in Western countries. Only a few studies of CLL have been conducted in Korea, and no long-term clinical outcome data are available. We assessed the frequency of common chromosomal aberrations in Korean CLL patients using interphase fluorescence in situ hybridization (FISH) and investigated their relationship to clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were performed in 58 patients, and FISH results were available in 48 patients. We used six DNA probes for the detection of del(13q14), trisomy 12, del(11q22), del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were identified in 15 of 58 patients (26%) with conventional cytogenetic studies and in 25 of 48 patients (52%) with interphase FISH, including six patients with complex karyotypes. In contrast with the results of Western studies, trisomy 12 was the most common aberration, followed by IGH rearrangement, del(13q14), del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated del(13q14) was less frequent than in Western studies. Compared with the other types of chromosomal aberrations, patients with del(11q22) and del(17p13) were more likely to be Rai stage 3-4 and Binet stage C, resulting in poor responses to chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and isolated del(13q14) showed better responses and superior survival outcomes. The incidence of CLL is lower in Korea than in Western countries, and the frequency of chromosomal aberrations differs, perhaps reflecting differences in the pathogenic mechanism between ethnicities. Large prospective studies are needed to further assess the prognostic value of these results in Korean CLL patients.

Several criteria to define fitness for induction chemotherapy in elderly acute myeloid leukemia (AML) have been proposed; however, no studies have reported outcomes according to the application of a risk-adapted approach. We treated 256 consecutive patients with elderly AML (≥60 years) with a risk-adapted approach based on age, comorbidity score (CS), and performance status (ECOG). Eighty-five low-risk patients (age ≤ 65 years and ECOG 0-1 with CS2), 86 intermediate-risk patients (age65 years or ECOG = 2 with CS2), and 85 high-risk patients (ECOG2 or CS ≥ 2) were treated with induction chemotherapies, including standard intensive regimens, abbreviated-scheduled regimens, and modified low-dose cytarabine with oral etoposide (mLDAC), respectively. Overall response rates (ORR; complete response and complete response with incomplete recovery) for these three groups were 71.8%, 60.5%, and 41.2%, respectively, without a significant difference in early death rate (17.6%, 25.6%, 23.5%, P = 0.415). Among three abbreviated-scheduled regimens, a gemtuzumab ozogamicin (GO)-containing regimen (n = 43) showed a similar ORR rate (72.1%) to the intensive regimen. After achieving remission, 142 patients went on postremission treatments, including reduced-intensity allogeneic transplantation (RIC, n = 41), standard consolidation (n = 71), and repeated mLDAC (n = 30) according to donor availability, age, ECOG, and CS. Multivariate analyses revealed that not only RIC, but also repeated mLDAC, resulted in significantly superior survival outcomes to standard consolidation independent of age, ECOG, and CS. Clinical benefits of mLDAC for high-risk patients and abbreviated induction with GO for intermediate-risk patients should be confirmed with further studies. Our results also suggest that RIC should be actively considered in elderly AML as a postremission treatment.

No consecutive analysis of BAALC and WT1 expressions associated with core-binding factor AML (CBF-AML) from diagnosis to hematopoietic stem cell transplantation (HSCT) has yet been reported. We investigated BAALC and WT1 expressions using a method of real-time quantitative polymerase chain reaction (RQ-PCR) at diagnosis, after induction chemotherapy, at pre-HSCT, and at post-HSCT period in 45 consecutive patients [t(8,21) (n = 28), inv(16) (n = 17)], who received HSCT as a post-remission treatment. BAALC and WT1 RQ-PCR decrement ratio (DR) was also calculated at post-induction chemotherapy, at pre-HSCT, and at post-HSCT compared with the diagnostic level. Higher BAALC expression at diagnosis showed significantly inferior OS (P = 0.031), EFS (P = 0.011), and higher CIR (P = 0.002) rates. At post-HSCT, both higher BAALC and WT1 expressions showed significantly inferior OS (P = 0.005, 0.016), EFS (P = 0.002, 0.006), and higher CIR (P = 0.001, 0.003) rates. A subgroup of t(8;21) showing higher BAALC and WT1 expressions at post-HSCT were also associated with inferior OS (P = 0.018, 0.015) and higher CIR rates (P = 0.019, 0.011). While BAALC DR showed no significant results on outcomes, WT1 DR more than 2-log at post-HSCT showed significantly lower CIR rate (P = 0.028). This study showed that higher post-HSCT BAALC and WT1 expressions in patients with CBF-AML may be good markers of minimal residual disease for the prediction of survival and relapse after HSCT.

Karyotype analysis in acute myeloid leukemia (AML) is one of the powerful prognostic factors for complete remission (CR), relapse, and overall survival (OS). Cytogenetic mosaicism is considered to be one of the important characteristics in expression of phenotypic manifestations. However, it has not come into focus due to emerging molecular biological approaches and the results of a number of mutation studies. Clinical correlates and prognostic relevance of mosaicism were evaluated in 163 AML patients [adverse-risk karyotypes (n = 72) and undefined karyotypes (n = 91)]. All patients were treated by induction and consolidation chemotherapies and finally went on hematopoietic stem cell transplantations (HSCT). Patients were divided into two subgroups, either with or without normal karyotype (NK) mosaicism. Seventy patients exhibited NK mosaicism and 93 did not. There were no significant differences in age, gender, chemotherapy cycles to achieve CR, HSCT donor type, source or intensity properties between the two subgroups. We found that NK mosaicism remaining in adverse-risk and undefined karyotype at diagnosis significantly correlates with better OS (p = 0.001) and lower CIR (p = 0.021) rate after HSCT. Our data show that the poor prognostic properties of unfavorable risk karyotype can be overcome to a great extent by allogeneic HSCT and chronic GVHD, especially in the subgroup with NK mosaicism. Cytogenetic mosaicism at initial diagnosis can be an influential factor for survival outcomes, even after HSCT.

The aim of this study was to evaluate the impact of marrow blasts at transplant in adult acute myeloid leukemia (AML) patients. We analyzed 478 patients who underwent allogeneic stem cell transplantation (SCT). All patients were divided into five subgroups according to the percentage of blasts:2 % (n = 361), ≥2 to3 % (n = 64), ≥3 to5 % (n = 28), ≥5 to12 % (n = 11), and ≥12 % (n = 4). After a median follow-up of 59.5 months (range 3.3-125.9 months) for survivors, patients with higher marrow blasts at transplant showed lower overall survival (OS) and disease-free survival (DFS). In multivariate analyses, OS and DFS did not show significant differences with blast counts up to 12 %, compared with blast counts of2 %; by contrast, the presence of12 % marrow blasts was associated with significantly poorer OS and DFS. In the separate multivariate analyses by cytogenetic risk group, the impact of12 % marrow blast on survival outcomes was observed in all risk groups. Thus, pre-transplant bone marrow status is an important prognostic factor for AML patients. In addition, the higher relapse rate in patients with12 % marrow blasts may provide insights into the tolerable blast cell burden that can be overcome by the graft-versus leukemia effect.

Background Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-γ), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. Methods Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. Results Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. Conclusion This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2-yr disease-free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G-COR (group of continuous response, n = 19), G-NoC (group of no change, n = 15), G-LOR (group of loss of response, n = 6), and G-DP (group of disease progression, n = 4), respectively. When dichotomized as G-COR/G-NoC versus G-LOR/G-DP, significantly different 2-yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G-LOR/G-DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G-LOR/G-DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher-risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G-COR showed a trend of better DFS compared with G-NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS.

Objective: The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation-comorbidity index score ≤3). Methods: Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced-intensity conditioning (RIC; n = 14), intensified RIC by adding low-dose total body irradiation (iRIC; n = 15), and myeloablative conditioning (MAC; n = 17). Results: After a median follow-up of 73.7 months, RIC had a better 4-yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, P = 0.022] because of a lower transplant-related mortality (TRM) (RR, 0.08, P = 0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, P = 0.689) because of similarly high TRM (RR of 0.41, P = 0.480). Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) after RIC was higher, but GVHD-specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, P = 0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients. Conclusion: This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC–SCT should be considered for relative healthy lower-risk MDS patients.

IL-17 is involved in inducing and mediating pro-inflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels during the peri-transplant period may affect alloreactive responses after allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA before conditioning and on day 0, +7, and +14 after transplantation. With a median follow-up of 17 months, the overall survival, disease-free survival, non-relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%, respectively. Ten patients relapsed within 180 days (early relapse, 10.5%) post-transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180 days had higher sIL-17 levels, whereas no association existed between sIL-17 levels and other clinical outcomes, including acute GVHD. Receiver operating characteristic curve analyses also revealed that sIL-17 levels were available for the prediction of early relapse and that patients with higher sIL-17 levels at each time point had a significantly higher early relapse. Multivariate analyses and subgroup analyses with only standard disease status suggest the association of sIL-17 levels with subsequent early relapse independent of disease status at transplantation. This study is the first one demonstrating the early change in sIL-17 during the peri-transplant period and the association with early relapse in humans.

Although reduced-intensity conditioning (RIC) has been increasingly used in patients with myelodysplastic syndrome (MDS) to reduce transplant-related mortality, a high relapse rate in RIC remains an unresolved problem. Considering the additive antileukemic effect of low-dose total body irradiation (TBI), we evaluated the feasibility of combining RIC regimens with low-dose TBI in de novo MDS. The RIC regimen combined with low-dose TBI in this study consisted of fludarabine (150 mg/m2), intravenous busulfan (6.4 mg/kg), and TBI (400 cGy). Antithymocyte globulin was used to overcome HLA mismatching. A total of 31 subjects were recruited with a median age of 39 years (range 19–63). The patients received transplants from siblings (n = 20) or unrelated donors (n = 11). All patients rapidly achieved full-donor chimerism. At a median follow-up for survivors of 35 months (range 6.0–54.9), the 3-year overall survival, event-free survival, transplantation-related mortality, and relapse rates were 67.6, 63.2, 20.5 and 11.4%, respectively. The 3-year cumulative incidence of acute (grades II–IV) and chronic extensive graft-versus-host disease in patients who survived at least 100 days was 39.2 and 44.6%, respectively. These results suggest that an RIC combined with low-dose TBI may be a feasible therapeutic approach for treating de novo MDS.

Osteolytic lesions with activated osteoclast (OC) and suppressed osteoblast (OB) activity are characteristics of myeloma bone lesion. Recently, it has been shown that bortezomib treatment enhances OB function. To evaluate the effect of bortezomib on myeloma bone lesions, we performed bone scans, where increased uptake of the radiopharmaceutical by OBs is associated with re-building activity. Bortezomib treatment markedly enhanced bone metabolic activity and increased alkaline phosphatase levels, and decreased monoclonal protein levels. These findings suggest that bortezomib has potent anti-myeloma activity and bone-protecting effects, with enhanced OB function.

Techflex®, a polypropylene-lined, multilayer infusion bag, was studied for its compatibility with diazepam, in comparison to the conventional infusion bag, Safeflex®, which is comprised of poly(vinyl chloride) (PVC). Diazepam was diluted in 0.9% sodium chloride isotonic solution and stored in the infusion bags for 24 h. To evaluate the sorption of diazepam into the infusion bags during storage, the concentration of the drug remaining in the bag was measured using gas chromatography-mass spectroscopy. The PVC bags exhibited a marked sorption of diazepam, with a drug loss reaching up to 90% of the initial concentration after 24 h of contact, whereas Techflex® inhibited the drug sorption, showing approximately 10%, under the same conditions. The differences in the sorption behaviors of the bags are discussed in terms of solubility parameters and crystallinities of the polymers.

In understanding student achievement from teaching English through movies, some quantitative studies yield positive results. However, paucity of...

Aim: The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system. Methods: We retrospectively analyzed registered data from 3,209 patients since 1999. Results: The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20–54.06 months). Patients ≤40 years demonstrated a longer OS than patients >65 years of age (median OS 71.13 vs. 36.73 months, p < 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p < 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT. Conclusions: We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis.

Background: The prevalence of AIDS-related lymphoma (ARL) is increasing in South Korea. The aim of this study is to identify the clinical features of ARL in South Korea. Methods: From 1998 through 2006, we retrospectively analysed a total of 23 cases of ARL from seven institutions. Results: The patients consisted of 20 males and 3 females at a median age of 40 (range, 20–72) on diagnosis of AIDS. ARL developed at their median age of 41 (range, 24–72). The histological diagnosis was aggressive B cell lymphoma in the majority, but rare T cell and NK/ T cell lymphoma were also included. Ten of 23 (43.5%) was receiving highly active anti-retroviral therapy (HAART) before the diagnosis of ARL. Fifteen of twenty-three patients were given combination chemotherapy with/without radiation, four were given radiation alone, and four did not receive any treatment against medical advice. Of 20 patients followed-up, nine were alive in remission, two alive in disease, one died of treatment related complication, four died of progressive lymphoma, four died of AIDS related causes. The response to treatment included CR in eight (44.4%), PR in four (22.2%) and PD in three (16.7%). The response to HARRT was evaluable in 13 patients based on CD4þ cell count and HIV viral load, among which nine (69.2%) responded. Estimated median survival time was 43.9 months. Conclusions: Although the population of patients is small, this is the first clinical data analyses of Korean ARL patients. As a substantial portion of the patients remains alive disease free, the impact of HAART on the clinical course of ARL needs further follow-up and evaluation.

A nationwide survey on the status of plasma exchange in Korea was performed during the 2 year period 2001–02. Data from 496 patients were collected from 15 major hospitals. The most common indication was myasthenia gravis (15.3%), followed by thrombotic thrombocytopenic purpura (14.5%) and hemolytic uremic syndrome (9.7%). Clinical improvement was noted in 70.1% of the 415 cases. Plasma exchange by centrifugation alone accounted for 92.4%. Postcentrifugal filtration was carried out in 5.6% and double filtration in 2.0% of treatments. The most common instruments for the centrifugation were Cobe Spectra (71.3%) and Fenwal CS3000 (15.8%). Filtration was performed by either Kuraray KM8300 or Kuraray KM8800. The overall frequency of complications was 11.1% (293/2647 cases), of which symptomatic hypocalcemia was the most common (2.3%).

In a continuation of our previous studies on blood compatibility profiles of anion-substituted poly(vinyl alcohol) (PVA) membranes, in which hydroxyl groups have been replaced with carboxymethyl (C-PVA) and sulfonyl groups (S-PVA), we have studied the activation of complement components and the changes in white cell and platelet countin vitro and compared them with those of unmodified PVA, Cuprophane, and low-density polyethylene. Complement activation of fluid phase components, C3a, Bb, iC3b, and SC5b-9, and of bound phases, C3c, C3d, and SC5b-9, were assessed by enzyme-linked immunosorbent assay (ELISA) and immunoblot, respectively. The changes in the number of white cells and platelets following complement activation were counted using a Coulter counter. C-PVA and S-PVA activated C3 to a lesser extent than did PVA, which we attribute to the diminished level of surface nucleophiles of the samples. In addition, C- and S-PVA exhibit increased inhibition of Bb production, resulting in a decrease in the extent of C5 activation. Consequently, because of the reduced activation of C3 and C5, C- and S-PVA samples cause marked decreases in the SC5b-9 levels in plasma. We also found that the negatively charged sulfonate and carboxylate groups of the samples cause a greater extent of adsorbtion of the positively charged anaphylatoxins, C3a and C5a, because of strong electrostatic attraction, which in turn provides an inhibition of chemotaxis and activation of leukocytes. The ability to inhibit complement production, together with the binding ability of anaphylatoxins of the C- and S-PVA samples, leads to a prominent decrease in lysis of leukocytes as well as activation of platelets.

Anion-substituted poly(vinyl alcohol) (PVA) membranes, carboxymethylated PVA (C-PVA), and sulfonated PVA (S-PVA) were prepared and the effects of these substitutions on the plasma protein adsorption were studied by one- and two-dimensional gel electrophoresis and immunoblotting. When Cuprophane was used as a negative control, the amount of total proteins bound to samples decreased in the order Cuprophane > PVA > C-PVA > S-PVA, which we attribute to the effects of the surface characteristics of the samples, such as their surface tensions and electrostatic properties, on the adsorption of proteins to the surfaces of the materials. The results revealed that albumin was the most abundant protein in all the samples. The proportion of adsorbed fibrinogen to S-PVA exceeded those of PVA and C-PVA, whereas S-PVA exhibited the lowest IgG adsorption affinity among the samples we studied.

In this article, we present, design, and implement a software and hardware for an embedded RAID system. The merits and drawbacks of our system are presented by performance evaluation. The proposed hardware system consists of three fibre channel controllers for the interface with fibre channel disks and hosts. Embedded Linux in which a RAID software is implemented is ported to the hardware. A SCSI target mode device driver and a target mode SCSI module are designed for that our RAID system is considered as a block device to a host computer. Linux Multi-device is used as RAID functions of this system. A data cache module is implemented for high performance and the interconnection between Linux Multi-device and the target mode SCSI module. The RAID 5 module of Multi-device is modified for improvement of read performance. The benchmark shows that the new RAID 5 module is superior to the original one in overall performance.

Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is a major concern in myelodysplastic syndromes (MDS), but the role of Wilms tumor gene 1 (WT1) as a predictive marker for post-HSCT relapse remains to be validated. We measured WT1 transcript levels by real-time quantitative PCR from marrow samples of 82 MDS patients who underwent transplantation between 2009 and 2013. Pre-HSCT WT1 expression weakly correlated with marrow blast counts or International Prognostic Scoring System scores and failed to predict post-transplantation relapse. Regarding post-HSCT WT1, transcript levels of relapsed patients were significantly higher in comparison to those in remission. Further analysis using receiver operating characteristics curves showed that higher (>154 copies/104ABL) 1-month post-HSCT WT1 resulted in a higher 3-year relapse rate (47.2% versus 6.9%, P < .001) with poorer disease-free survival (DFS) and overall survival at 3 years (41.7% versus 79.0% and 54.3% versus 82.1%, P = .003 and P = .033, respectively). Multivariate analysis after adjusting for pre-HSCT karyotype and chronic graft-versus-host disease (GVHD) also revealed that higher 1-month post-HSCT WT1 was an independent predictive marker for subsequent relapse (P = .002) and poorer DFS (P = .010). In the higher 1-month post-HSCT WT1 subgroup, patients with chronic GVHD showed lower relapse rate and favorable survival outcome. One month post-HSCT WT1 expression was a useful marker for minimal residual disease and relapse prediction in association with chronic GVHD in the context of HSCT for MDS.

We analyzed the outcome of stem cell transplantation (SCT) for 59 acute myeloid leukemia (AML) patients with t(8;21). The 5-year overall and disease-free survival (OS and DFS) were 70.2 and 68.4%, respectively. The 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality were 16.9 and 13.6%, respectively. OS and DFS in the reduced-intensity conditioning (RIC)-SCT group (70.4%) were not different from in the autologous SCT (ASCT) group (72.4 and 69.0%, respectively). Age was a factor affecting OS (p = 0.007) and DFS (p = 0.008) in the ASCT group, but not in the RIC-SCT group. In the ASCT group, lack of the X chromosome (-X) and an age of >50 years were associated with inferior survival; however, these differences disappeared in the RIC-SCT group. CIR was significantly higher in patients with -X than in those without -X only in the ASCT group (p = 0.038), i.e. not in the RIC-SCT group. ASCT and RIC-SCT are equally effective for the intensification of postremission treatment of AML patients with t(8;21). The subgroups with advanced age or -X should be preferentially considered for RIC-SCT, rather than ASCT. Further investigations with randomized prospective trials of a sizeable study population are warranted. © 2014 S. Karger AG, Basel

Eighty adult patients with acute myeloid leukemia (AML) received peripheral blood T cell–replete HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Disease status at transplantation was either first or second complete remission (CR, n = 69) or relapse/refractory (n = 11). Identical transplant-related procedures with conditioning regimen consisting of fractionated 800 cGy total body irradiation (TBI), fludarabine (30 mg/m2/day for 5 days), busulfan (3.2 mg/kg/day for 2 days), and antithymocyte globulin (1.25 mg/kg/day on days −4 to −1) and graft-versus-host disease (GVHD) prophylaxis with tacrolimus and methotrexate were used in all patients. Recovery of neutrophil (median, 11 days) and platelet (median, 10 days) counts was achieved in all patients with full donor chimerism (≥99%), and no delayed engraftment failure was observed. The cumulative incidence of grades III to IV acute GVHD and moderate to severe chronic GVHD was 11.2% and 26.3%, respectively. A donor CD8+ and CD4+ T cell dose above the median value was significantly associated with the incidences of grades II to IV acute GHVD and moderate to severe chronic GVHD, respectively. After a median follow-up of 28 months for survivors, the 2-year cumulative incidences of relapse (n = 20) and nonrelapse mortality (n = 10) were 26.6% and 12.2%, respectively. Although all but 1 patient in relapse/refractory status died, the 2-year overall and progression-free survival of patients in first CR was 82.5% and 75.1%, respectively. We suggest the strategy of fractionated 800 cGy TBI-based conditioning with unmanipulated peripheral blood stem cell grafts seems feasible with favorable outcomes for adult patients with AML undergoing haplo-HSCT in CR.

Karyotype is a powerful prognostic factor for complete remission (CR) and overall survival (OS) in acute myelogenous leukemia (AML). Adverse-risk karyotype AML is now treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) to overcome relapse. We attempted to stratify patients with this disease using a combination of known factors. We evaluated clinical correlates in 211 adults with AML and adverse-risk karyotypes. We divided the patients into several subgroups based on the number of chromosomal aberrations (NCAs), normal karyotype (NK) mosaicism, and monosomal karyotype (MK) status. CR rates and survival outcomes were compared among the subgroups, and the relapse rate was calculated in the allo-HSCT subgroup. The cutoff of NCA ≥5 showed the worst OS (P

Summary The major limitation of autologous stem cell transplantation (auto-SCT) in non-Hodgkin lymphoma (NHL) is relapse. Although autologous graft contamination may be a potential cause, prior purging of the autograft remains controversial. Therefore, we retrospectively analysed 56 consecutive patients with NHL receiving auto-SCT at complete (n = 41) or partial remission (n = 15). Among them, 24 patients underwent autograft manipulation with positive selection of CD34+ cells using a CliniMACS device (purged group). Twenty-five patients had received ≥2 previous chemotherapy regimens before auto-SCT. After a median follow-up of 41·4 months, transplant-related mortality was observed only in unpurged group (n = 2; 3·6%). The 3-year overall survival (91·7% vs. 56·1%, P = 0·009) and progression-free survival (78·7% vs. 53·1%, P = 0·034) favoured CD34+ purification. While neutrophil recovery was similar, platelet recovery was delayed in the purged group. Cytomegalovirus reactivation was predominantly observed in the purged group, although no other clinically unmanageable infectious complications occurred. Although this study has the inevitable limitations of heterogeneity in previous treatment and NHL subtypes, and a small number of patients analysed, the high survival rate in the purged group may suggest the need for prospective randomized trials to determine the role of CD34+ purification in auto-SCT for NHL.

In Asia, the incidence of chronic lymphocytic leukaemia (CLL) is lower than in Western countries. Only a few studies of CLL have been conducted in Korea, and no long-term clinical outcome data are available. We assessed the frequency of common chromosomal aberrations in Korean CLL patients using interphase fluorescence in situ hybridization (FISH) and investigated their relationship to clinical outcomes. Between 2000 and 2011, conventional cytogenetic studies were performed in 58 patients, and FISH results were available in 48 patients. We used six DNA probes for the detection of del(13q14), trisomy 12, del(11q22), del(17p13), IGH rearrangement and del(6q23). Chromosomal aberrations were identified in 15 of 58 patients (26%) with conventional cytogenetic studies and in 25 of 48 patients (52%) with interphase FISH, including six patients with complex karyotypes. In contrast with the results of Western studies, trisomy 12 was the most common aberration, followed by IGH rearrangement, del(13q14), del(11q22) and del(17p13). Deletion of 6q23 was not observed, and isolated del(13q14) was less frequent than in Western studies. Compared with the other types of chromosomal aberrations, patients with del(11q22) and del(17p13) were more likely to be Rai stage 3-4 and Binet stage C, resulting in poor responses to chemotherapy and worse outcomes. In contrast, patient with trisomy 12 and isolated del(13q14) showed better responses and superior survival outcomes. The incidence of CLL is lower in Korea than in Western countries, and the frequency of chromosomal aberrations differs, perhaps reflecting differences in the pathogenic mechanism between ethnicities. Large prospective studies are needed to further assess the prognostic value of these results in Korean CLL patients.

The aim of this study was to evaluate the impact of the response to induction therapy on the long-term prognosis of multiple myeloma (MM) after autologous stem cell transplantation (ASCT) in the era of novel agents (NAs). A total of 171 patients who were newly diagnosed with MM and underwent early ASCT were analyzed. One hundred ten had a NA-based induction therapy, and 61 patients had a non-NA-based induction therapy. After a median follow-up of 45.4 months, the 4-year overall survival (OS) and progression-free survival (PFS) from transplantation were 60.5 and 25.5 %, respectively, for the NA-based induction group and 54.6 and 15.6 %, respectively, for the non-NA-based induction group. Multivariate analyses revealed that the patients who had NA-based induction had a significantly shorter OS (P < 0.001) and PFS (P < 0.001) when at least a partial response (PR) was not achieved. In patients who did not receive NAs before ASCT, lack of at least a PR to induction therapy was not associated with a survival disadvantage. These findings suggest that, unlike pretransplantation induction before NAs, patients who do not respond to induction treatment using NAs may not derive a benefit from ASCT. The relevance of induction failure differs for corticosteroid- and NA-based induction.

The aim of this study was to estimate the prognostic factors for the outcomes of chronic myeloid leukemia (CML) patients receiving allogeneic stem cell transplantation (SCT) in chronic phase (CP) in the era of tyrosine kinase inhibitors (TKIs). Ninety-seven patients who underwent allogeneic SCT in CP were analyzed. Forty-seven were TKI-naive at the time of transplant, and 50 received TKI(s) treatment before transplantation. After a median follow-up of 115.8 months, the 4-year overall survival and event-free survival were 80.4 and 58.8%, respectively. Multivariate analysis showed that there were no differences in survival outcomes based on prior TKI therapy. Older age was a prognostic factor for higher treatment-related mortality (TRM), and the type of graft source and younger age were associated with relapse, but prior TKI therapy and disease status at the time of transplant were not associated with either TRM or relapse. Additionally, a major molecular response at 1 month and an MR(4.5) at 3 months were important predictors of favorable long-term outcomes. This study demonstrates the prognostic factors for the outcomes of allogeneic SCT in CP CML and shows that survival outcomes were not affected by the administration of long-term multi-TKI treatment prior to transplantation.

Data for 125 patients with cytogenetically normal acute myeloid leukemia (CN-AML) regarding BAALC and combinatorial molecular markers at diagnosis were evaluated. Fewer patients with higher BAALC expression at diagnosis achieved a complete remission (CR) (49.2 vs. 75.8%, p = 0.002) after the first cycle of chemotherapy, and there were more primary refractory cases (37.3 vs. 18.2%, p = 0.017). In a combinatorial analysis, FLT3-ITD-positive patients with higher BAALC showed more refractoriness and the worst overall survival (OS) (p0.001) and disease-free survival (DFS) (p0.001) in CN-AML. When NPM1-mutated CN-AML was combined with either FLT3-ITD mutation or higher BAALC expression, both OS (p = 0.043) and DFS (p = 0.008) were worse; when combined with both, it showed the worst OS (p0.001) and DFS (p = 0.004). Higher BAALC expression and FLT3-ITD mutation, both individually and in combination, were associated with worse survival outcomes in CN-AML, and this was also applicable in NPM1-mutated CN-AML, known as a favorable-risk group.

Background Novel agents (NAs) such as thalidomide and bortezomib have been administered in combination with autologous stem-cell transplantation (ASCT) to effectively treat multiple myeloma (MM). However, whether NAs perform better as induction treatments prior to transplantation, or as post-transplant maintenance therapies remains unclear. Methods We retrospectively analyzed 106 consecutive patients with MM who underwent ASCT within 1 year of diagnosis as first-line therapy. Results Eighty-seven (82.1%) patients received NAs before ASCT, whereas 68 (64.2%) received NAs after ASCT. NAs were administered to each patient as follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT were significantly higher for patients who received NAs as induction treatment compared to those who did not receive pre-transplant NAs. At a median follow-up of 37.9 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and P=0.04, respectively), but not in those with NAs as pre-transplant induction treatment. The PFS of patients with NAs before and after ASCT was higher than that of the patients with NAs as induction therapy alone (P=0.05). Age, serum β2-microglobulin level, complete response after ASCT, and NA use post-ASCT independently predicted survival outcomes. Conclusion These findings suggest that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT. Induction therapy using NAs also improves high-quality response rates before and after ASCT.

Objectives For patients with acute myeloid leukemia in first complete remission (AML CR1) lacking HLA-matched sibling donors (MSD), 8/8-matched unrelated donors (URD) are mostly used in cases with poor-risk features. For AML CR1 with intermediate cytogenetics, however, the benefit of 8/8-matched URD should be compared with non-allogeneic therapies as well as MSD. Methods To address this issue, we assessed the transplantation outcomes of 8/8-matched URD (n = 54) compared with MSD (n = 145) or autologous transplantation (n = 89) for AML CR1 with intermediate cytogenetics. Results In multivariate analyses, 8/8-matched URD had comparable 6-yr overall survival (OS, P = 0.997), disease-free survival (DFS, P = 0.951), and relapse (P = 0.672) to MSD, whereas 8/8-matched URD had a higher OS (P = 0.070) and DFS (P = 0.035) with lower relapse (P = 0.009) than autologous transplantation. No difference in non-relapse mortality was observed according to donor type. Notably, these equivalent or superior outcomes of 8/8-matched URD compared with MSD or autologous transplantation, respectively, were particularly evident in patients without poor-risk features (n = 200), such as older age, hyperleukocytosis at diagnosis, and myelodysplasia-related changes, who are not usual candidates for URD transplantation. Conclusions These results indicate that 8/8-matched URD are feasible next option in AML CR1 with intermediate cytogenetics, when lacking MSD, even in patients without poor-risk features.

The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P

Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-6-stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT–PCR showed that anti-IL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.

Iron overload due to regular transfusions of packed red cells can cause multiple organ damage. Iron chelation therapy (ICT) is important in patients with aplastic anemia (AA) who require blood transfusions as supportive management. With the introduction of the oral iron chelator deferasirox, ICT has become more widely available and feasible. We studied 4 adult AA patients who had transfusion-induced iron overload and showed hematological improvement after ICT with oral deferasirox. Following deferasirox treatment, hemoglobin increased and serum ferritin levels decreased, and the patients subsequently became transfusion independent. Our experience raises the possibility of the potential benefit of ICT on hematopoiesis. Further long-term studies in larger patient cohorts are needed to clarify the effect of the restoration of hematopoiesis after iron chelation therapy.

Cytomegalovirus gastrointestinal (CMV-GI) disease in GI graft-versus-host disease (GI-GVHD) has not been properly evaluated in the era of preemptive therapy for CMV infection. We investigated 103 patients with GI-GVHD who underwent endoscopic biopsies with immunohistochemical staining for CMV. All recipients and/or donors were seropositive for CMV and monitored with a strategy of preemptive therapy based on real-time quantitative polymerase chain reaction. Twenty-six patients (25 %) developed CMV-GI disease, especially in HLA-mismatched transplants (P = 0.023) and with initial gut involvement of GVHD (P = 0.009). The CMV-GI diseases were diagnosed at follow-up endoscopies (n = 10, 39 %), comprising 19 % of 52 patients who underwent follow-up endoscopies, as well as initial endoscopies (n = 16, 61 %), comprising 16 % of all GI-GVHD patients. In seven cases, either at initial (n = 5) or follow-up endoscopies (n = 2), CMV-GI disease was diagnosed in the absence of histopathologic evidence for GI-GVHD. Notably, only 11 patients (42 %) had prior CMV DNAemia before the diagnosis of CMV-GI disease, while 12 (46 %) and three (12 %) had concurrent and no CMV DNAemia, respectively. Sixty-five percent of CMV-GI disease was resolved by additional antiviral therapies, but CMV-GI disease (P = 0.032) as well as severity of GVHD (P = 0.001) negatively affected GVHD-specific survival. In conclusion, our data demonstrate that CMV-GI disease was a cause of initial or persistent GI manifestations after the initiation of therapy in a considerable proportion of GI-GVHD. These suggest the necessity of novel strategies to reduce CMV-GI disease as well as an effort to confirm CMV with repeated endoscopies.

Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA) ineligible for allogeneic stem cell transplantation. Recently, rabbit ATG with cyclosporine A has been used as a first-line IST regimen in patients with SAA because of unavailability of horse ATG. We retrospectively analyzed adult SAA patients who were treated with horse ATG (n=46) or rabbit ATG (n=53) between Feb 2001 and May 2010 to compare hematologic response and survival. Overall response rates at 3, 6, 12, and 18 months were similar in both the horse and rabbit ATG groups: 28.3 versus 35.8 % (P=0.421), 39.1 versus 45.3 % (P=0.537), 45.7 versus 49.1 % (P=0.735), and 47.8 versus 50.9 % (P=0.757), respectively. The complete response (CR) rate at 6 months in the horse ATG was significantly superior in comparison with the rabbit ATG (13.0 versus 1.9 %, P=0.031). But CR rates became similar in both groups after 6 months: 17.4 versus 11.3 % (P=0.387) at 12 months and 21.7 versus 22.6 % (P=0.914) at 18 months. Lymphocyte depletion after ATG was more profound and protracted in the rabbit ATG group compared to the horse ATG group. Overall survival (P=0.460) and failure-free survival (P=0.911) were not significantly different between the two groups. Our retrospective study demonstrated that the efficacy of first-line IST with rabbit ATG is similar to that with horse ATG. However, the time from treatment to CR was longer with rabbit ATG than with horse ATG, partly due to more profound and protracted lymphocyte depletion.

Background aims The aim of this study was to investigate the correlation between infused lymphocyte populations and lymphocyte subsets at engraftment, and the early clinical implications of lymphocyte subset recovery after autologous stem cell transplantation (ASCT) in multiple myeloma (MM). Methods We examined the lymphocyte populations of infused autografts and the lymphocyte subsets of peripheral blood at engraftment from 50 patients using flow cytometry. Each subset was grouped as low (below median) and high (above median) to examine the correlation with mucositis of grade 3 or more and the occurrence of infections and cytomegalovirus (CMV) reactivation. Results Using Spearman correlation coefficients, we found that cell doses of infused CD8 + ( P =0.042) and CD19 + cells ( P =0.044) were significantly associated with the absolute lymphocyte count (ALC) at engraftment. The dose of infused CD34 + cells was not associated with the change of lymphocyte subsets except for an inverse correlation with CD4 + cells ( P =0.006). After adjusting for potential variables in univariate analysis, multivariate analyzes revealed that the lower ratio of infused CD4 + to CD8 + cells ( P =0.030) was an independent factor for severe mucositis. Of lymphocyte subsets at engraftment, a higher frequency of CD3 + ( P =0.024) and a lower frequency of CD56 + ( P =0.020) were independent predictors for infections after engraftment. A higher frequency of CD8 + cells ( P =0.041) and a lower ratio of CD4 + to CD8 + ( P =0.021) were independent predictors for CMV reactivation. Conclusions Our data suggest that lymphocyte subset analysis of infused autograft and peripheral blood at engraftment may provide new predictors for early complications after ASCT in patient with MM.

To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed.

The aim of this study was to determine the optimum conditioning intensity for allogeneic stem cell transplantation (SCT) in young (age ≤50), lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without significant comorbidities (hematopoietic cell transplantation-comorbidity index score ≤3).Transplant outcomes from 46 consecutive patients were retrospectively analyzed according to the conditioning intensity: reduced-intensity conditioning (RIC; n = 14), intensified RIC by adding low-dose total body irradiation (iRIC; n = 15), and myeloablative conditioning (MAC; n = 17).After a median follow-up of 73.7 months, RIC had a better 4-yr overall survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate analysis showed that RIC was associated with improved OS compared with the MAC [relative risk (RR) of 0.08, P = 0.022] because of a lower transplant-related mortality (TRM) (RR, 0.08, P = 0.035). iRIC failed to show survival benefits over the MAC (RR of 0.77, P = 0.689) because of similarly high TRM (RR of 0.41, P = 0.480). Cumulative incidence of acute and chronic graft-versus-host disease (GVHD) after RIC was higher, but GVHD-specific survival was significantly better (RIC 100% vs. iRIC 45.7% vs. MAC, P = 0.018). Relapse rate was not different among the three groups, but in the RIC group, azacitidine was available and useful for inducing remission in two patients.This study shows that RIC improved OS by directly lowering TRM and indirectly giving an additional chance for relapsed MDS in the era of hypomethylating treatment. RIC-SCT should be considered for relative healthy lower-risk MDS patients.