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Introduction Lenalidomide plus dexamethasone is effective and well tolerated in relapsed/refractory multiple myeloma (RRMM). In this observational, noninterventional European post-authorization safety study, the safety profile of lenalidomide plus dexamethasone was investigated and compared with that of other agents in the treatment of RRMM in a real-world setting. Patients and Methods Patients had received ≥ 1 prior antimyeloma therapy; prior lenalidomide was excluded. Treatment was per investigator’s routine practice. Adverse events were analyzed by incidence rates per 100 person-years to account for differences in observation length and treatment duration. Results In total, 2150 patients initiated lenalidomide, and 1479 initiated any other antimyeloma therapy, predominately bortezomib (80.3%), which was primarily administered intravenously (74.3%). The incidence rate of neuropathy was lower with lenalidomide (10.5) than with bortezomib (78.9) or thalidomide (38.7). Lenalidomide also had a lower incidence rate of infections (68.7) versus bortezomib (95.9) and thalidomide (76.0). Conversely, the incidence rate of neutropenia was higher with lenalidomide (38.0) than with bortezomib (18.2) or thalidomide (25.7). The incidence rates of thrombocytopenia were 24.4, 40.4, and 14.4 with lenalidomide, bortezomib, and thalidomide, respectively. Conclusion No new safety signals for lenalidomide were identified in this study, which is the largest prospective real-world European study of lenalidomide in patients with RRMM to date. These results confirm that the safety profile of lenalidomide plus dexamethasone in RRMM in a real-world setting is comparable to that reported in clinical trials.

Eddy current heating with synchronized thermography (ST) is utilized for the contactless characterization of flexible hybrid electronics. A proposed approach is used for analyzing the uniformity of large area electronics being the basis for the quality assurance of hybrid electronics manufacturing. Flexible polymer substrate with printed conductors, bonded conventionally manufactured light-emitting diode (LED) chips and current regulators were used as test samples. Obtained results show that ST with eddy current heating is an effective and roll-to-roll compatible measurement tool for in-situ quality monitoring of hybrid electronics manufacturing.

The predominant expense for the manufacturing cost of new generation photovoltaic devices including perovskite solar cells (PSC) emanate from the use of indium tin oxide (ITO) as transparent electrodes and is due to its limited supply and patterning costs. The PSC devices also struggle with low lifetime, and thus it has a high potential of generating rapid end-of-life (EOL) products resulting in surged photovoltaic wastes. In addition, the PSC devices contain unfavorable toxic elements such as lead and thus any effort to tackle the problem would help the environmental sustainability. In this article, the aforementioned issues were solved by the quality recovery of patterned ITO substrates from old devices through “top-down” approach, which essentially stripped out the unsought component layers present on ITO and subsequently reused for fresh devices. The PSC recycling and ITO recovery was done by treating EOL device with a single non-volatile inexpensive alkaline solvent. The appropriately recovered ITO had shown (optical, surface and electrical) properties close to the reference and was found to be suitable for direct reuse as the best power conversion efficiency (PCE) of recycled PSC varied only 0.85% less than the initial device.

This paper investigates the possibility of detecting defects in photovoltaic (PV) cell and panels under harsh outdoor environmental conditions with the help of synchronized thermography (ST). Infrared (IR) images are obtained under changing solar radiation levels, moderate wind speeds and ambient temperatures below zero degree Celsius with the help of a portable IR-camera. We demonstrate that IR-images obtained under harsh environmental conditions provide the same information as IR-images recorded under common environmental conditions. We elaborate the differences in parameters such as measurement time and region-of-interest (ROI) which need to be adjusted when carrying out measurements under harsh conditions. Our technique allows maintenance staff to carry out measurements, both, during summertime and wintertime, on the site of a PV power plant to identify PV panels with potential defects.

OBJECTIVE: We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma.METHODS: This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 → 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86).RESULTS: Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections.CONCLUSION: In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.

This paper investigates opportunities to rapidly detect defects in photovoltaic (PV) panels. It is worth noting that a defect in a single PV cell can significantly reduce the output power of a PV panel and, thereby, of an entire PV array. Hence, it is crucial to detect faults in PV panels and replace them within PV power plants. In this paper, we utilise synchronized thermography (ST) to obtain infrared (IR) images under outdoor environmental conditions. We illustrate how IR-images obtained under changing irradiation and different angles can be analysed to rapidly detect defects in PV panels. Our technique allows maintenance staff to quickly identify PV panels with defects on the site of a PV power plant.

This paper investigates defects in photovoltaic (PV) panels, more precisely, the location of defects in PV panels. With the help of electrical verification, it is possible to verify the impact of defects on output performances. However, it is not possible to determine the location of defects in order to address the origin of problems, for example, in the manufacturing process of PV panels. In this paper, the focus lies on finding similarities in the location of defect areas in PV panels. Samples were characterized with the help of synchronized thermography and time-resolved thermography in order to obtain infrared (IR) images of PV panels. IR images are helpful to obtain a visual image on the health of PV panels, identify the position of defects, and estimate the influence of defects on the output power. This information can be useful, for example, for improving the fabrication process of PV panels.

Capability of high-speed and low-cost manufacturing makes the printing techniques a very promising approach for large-area flexible electronics mass manufacturing. Due to fast and intensive technology development, the lack of knowledge about the reliability and lifetime of printed electronics is obvious, requiring further investigation. Especially, the effect of torsional bending on lifetime is a mostly unexplored field of reliability testing. In this article, a torsional bending test of parallel printed silver conductors (0.3-, 0.5-mm pitch) on polymer substrate (polyethylene terephthalate, 125- \mu \text{m} thickness) was conducted and analyzed. According to the experimental results, torsional bending causes wear-out type failures in conductors and the length-to-width (LTW) ratio of the sample's substrate was observed to have a significant impact on reliability. If the LTW ratio is smaller than 3, the lifetime of printed conductor seems to collapse and samples lasted for approximately only 17 bending cycles on average. Lifetime was improved by increasing the LTW ratio and samples withstood over hundreds of cycles with LTW ratio of higher than 15. However, the distance of a conductor from the edge of the substrate was not observed to have any significant influence on the reliability under torsional bending.

Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to β2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.

This paper investigates the ways to detect defects in photovoltaic (PV) cells and panels. Here, two different methods have been used. First, the output behavior was characterized by measuring the amount of current at different voltage levels to obtain the current–voltage and power–voltage curves. Second, infrared emissions of forward-biased nonilluminated PV cells and panels were measured by the use of synchronized thermography. From these measurements, temperature maps can be derived, which indicate that the temperature within a given PV cell unevenly rises due to the defects in the cell. Uneven temperature distribution indicates defects and reduced output power.

BACKGROUND Autologous stem cell transplantation is a standard treatment in multiple myeloma (MM). Blood grafts are usually collected after mobilization with granulocyte–colony-stimulating factor (G-CSF) alone or in a combination with cyclophosphamide (CY). There is limited knowledge of the possible effects of different mobilization regimens on blood graft characteristics and posttransplant outcomes. STUDY DESIGN AND METHODS Thirty-eight patients with MM were included in this study. The patients were randomly assigned at registration to mobilization with either low-dose CY plus G-CSF (Arm A) or G-CSF alone (Arm B) and received three cycles of lenalidomide, bortetzomib, and dexamethasone induction. Flow cytometry analysis of lymphocyte subsets in the blood grafts after cryopreservation was performed. Hematologic and immune recovery were evaluated up to 12 months posttransplant. RESULTS The blood grafts in Arm A contained significantly more CD34+ cells but in Arm B there was a greater proportion of CD34+CD38– cells and higher numbers of T and B lymphocytes as well as natural killer (NK) cells. The engraftment was comparable but lymphocyte count at 15 days posttransplant was higher in Arm B (0.8 × 109/L vs. 0.5 × 109/L, p = 0.033). At 3 and 6 months posttransplant the total number of NK cells was also higher in G-CSF–mobilized patients. There was no difference in progression-free survival between the study arms. CONCLUSION CY plus G-GSF yields more CD34+ cells but seems to diminish lymphocyte and NK cell counts in the grafts and hampers immune recovery after transplantation. Thus G-CSF alone might be a preferred mobilization method due to more rapid immune recovery posttransplant.

Synchronized thermography (ST) is utilized in the characterization of a flexible hybrid electronics. ST is used for both in the analysis of the structural uniformity and electrical functionality. Flexible lighting foils combining conventionally manufactured light-emitting diode (LED) chips and current regulators with a printed wiring on polyethylene terephthalate (PET) substrate were used as test samples. The measurement results proves that ST measurement method is a feasible method for the uniformity and electrical functionality characterization of large-area printed thin films with conventional electronics. ST is an interesting option to be used as a measurement tool for online quality monitoring of hybrid electronics manufacturing.

Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data. Methods: We carried out a retrospective, observational study using data from the national Finnish Hematology Registry (FHR) to provide real-world evidence of outcomes for all adult patients diagnosed with and treated for MM between 2009-2013 at one of the six regional hospitals, with at least six months of recorded follow-up. Patients were identified within the FHR by applying eligibility criteria of a diagnosis of MM and verifiable records of medical treatment and lines of treatment during the study period. Patients receiving allogenic stem cell transplantation were excluded from the cohort, as were individuals who only had monoclonal gammopathy of undetermined significance diagnosis and patients who had not initiated treatment during this period. Kaplan Meier curves were used to calculate overall survival and time to next treatment. Stratification was carried out by drug status (conventional/novel) and by autologous stem cell transplant (ASCT) status. Results: A total of 321 patients met the inclusion criteria and were included in this study. Overall survival (OS) was longest in patients who received first-line novel therapy and ASCT (median not reached during 60-month follow-up) versus 46.2 months for novel first-line therapy without ASCT and 25.6 months for first-line conventional therapy without ASCT. Similarly, median time to next treatment were 33.9 months, 12.6 months and 7.8 months, respectively. Conclusions: The adoption of novel treatments in MM in Finland has had substantial impact on patient outcomes. Given the reality of complex treatment combinations for MM and relatively low patient numbers, assessing individual treatment effectiveness will require substantial cohort sizes and advanced, collaborative analytics on an international scale.

This paper investigated the applicability of thermal annealing to be used for the color conversion of organic light-emitting diodes (OLEDs) made of a blend of light-emitting polyfluorenes. Blue-light-emitting polyfluorene poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) was used as the host material and green-light-emitting polyfluorene poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)] (F8BT) as the dopant material. Annealing treatment was conducted at the temperatures of 150 °C and 270 °C, before top contact deposition. Both nonannealed OLEDs and those annealed at 270 °C showed green color emission, implying that emission was taking place via the dopant material F8BT. Instead, the light emission color of the OLEDs annealed at 150 °C was shifted to white upon a rise of a blue spectral component. The origin of the blue light emission was attributed to PFO and indicated considerable phase separation between PFO and F8BT. This paper showed that thermal annealing can be applied to modify the light emission color of polyfluorene-blend OLEDs.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common first-line treatment for patients with multiple myeloma (MM) under 65 years of age. A second ASCT at first relapse is frequently used but is challenged by the use of novel drugs. We retrospectively studied the outcome of second-line treatment in MM patients from the Nordic countries with relapse after first-line HDT and ASCT. Patients that underwent a second ASCT (n=111) were compared with patients re-treated with conventional cytotoxic drugs only (n=91) or with regimens including novel drugs (proteasome inhibitors and/or immunomodulatory drugs) (n=362) without a second ASCT. For patients receiving a second ASCT median overall survival was 4.0 years compared with 3.3 years (P

The effect of thermal annealing on electroluminescent (EL) properties of polyfluorene-based organic light-emitting diodes (OLEDs) was studied. Two types of light-emitting layers were investigated: undoped layers made of poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) and doped layers consisting of 95 wt% of PFO and 5 wt% of poly[(9,9-di-n-octylfluorenyl-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)] (F8BT). Thermal annealing at 190 °C and 290 °C was performed prior to top contact thermal deposition. The experiments indicated that the annealing treatment results in significant changes of EL properties in both types of the considered OLEDs. However, the annealing affects them differently. For the undoped OLEDs, the devices annealed at 190 °C presented the highest luminance and current density. In the case of doped OLEDs, the highest luminance was observed in the non-annealed devices and the highest current density in the devices annealed at 190 °C. Remarkably, the annealing was noticed to affect the EL spectra of both types of OLEDs. In the undoped OLEDs the purest blue emission was observed from the OLEDs annealed at 190 °C, whereas the OLEDs annealed at 290 °C and the non-annealed OLEDs in particular had pronounced undesired green emission, a common problem for the polyfluorene-based blue light-emitting polymers. Green emission originating from F8BT was observed for the doped OLEDs in the case of non-annealed devices and the devices annealed at 290 °C, whereas the spectrum of the similar devices annealed at 190 °C had an additional blue component corresponding to PFO emission.

We present here the first MS-case where rituximab-treatment led to grade IV neutropenia, with hospitalization and treatment of a serious infection with broad-spectrum antibiotics. The neutropenia resolved promptly with granulocyte-colony stimulating factor-treatment and the patient recovered well. Due to risk of recurring neutropenia rituximab-treatment was not re-administered. We discuss the mechanisms and occurrence of neutropenia as a side effect to rituximab-treatment of MS, and remind of the importance of monitoring rituximab-treated MS-patients for this rare but potentially dangerous side effect.

This paper investigates defects in photovoltaic (PV) panels, more precisely, the location of defects in PV panels. With the help of electrical verification, it is possible to verify the impact of defects on output performances. However, it is not possible to determine the location of defects in order to address problems, for example in the manufacturing process of PV panels. In this paper, the focus lies on finding similarities in the location of defect areas in PV panels. Samples were characterised with the help of synchronized thermography (ST) in order to obtain infrared (IR) images of PV panels. IR-images are helpful to get a visual image on the health of PV panels and identify the position of defects. This information can be useful, for example to improve the fabrication process of PV panels.

Testing and characterization techniques intended for traditional electronics production are rarely compatible with modern large-area, thin film electronics manufacturing processes such as roll-to-roll fabrication. Online quality monitoring of conductive thin films is necessary for upscaling and maintaining high-yield production. Thermography has already shown its usefulness in these kinds of applications, but has suffered from the lack of proper non-contact electrical heating. Now a fully contactless quality inspection technique based on thermal imaging and induction heating is implemented and evaluated. This approach is capable of discovering defected areas and estimating conductivity degradation online with full coverage over conductive thin films.

We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation.

Objective Infections and graft-versus-host disease (GVHD) are the main causes of transplant-related mortality (TRM) of patients undergoing allo-SCT. The role of iron overload (IO) has been debated in this context. Studies, performed with non-specific surrogate markers of iron, suggest that IO predicts poor outcome after allo-SCT. Methods In this prospective study, we quantified pretransplant IO with MRI-based hepatic iron concentration (HIC) measurement; the degree of IO was used to predict infections, GVHD, and mortality after allo-SCT. Logistic univariate, multivariate, and Cox's regression analyses were performed. Results Iron overload was present in 78% of the patients (HIC>36 μmol/g). The median HIC was 98 μmol/g (range 5–348). There were no cases of cardiac iron excess. IO was significantly associated with severe infections during the early post-transplant period (for every 10 μmol/g increase OR: 1.15, 95% CI 1.05–1.26, P = 0.003). The odds for severe infections increased 6.5- (>125 μmol/g OR: 6.5, P = 0.013) to 14-fold (>269 μmol/g OR: 14.1, P = 0.040) with increasing HIC. IO was found to be associated with reduced risk of acute and chronic GVHD. Although TRM was due to infection-related deaths, IO was not associated with TRM or OS. Conclusion Pretransplant IO, measured with a direct MRI-based measurement, predicts severe infections in the early post-transplant period.

The consumption of platelet products in Finland is exceptionally high. For the most part, platelets are transfused pre-operatively to thrombocytopenic patients in order to prevent hemorrhage. Most of the minor procedures could, however, be conducted even if the patients'platelet levels would be lower than usual. In cardiac surgery, platelets are used because of the hemorrhagic diathesis associated with platelet inhibitors. Platelet inhibitors will, however, also bind to transfused platelets, whereby instead of prophylactic platelet transfusions it would be more sensible to leave the thorax open and not carry out ineffective platelet transfusions until the effect of the inhibitors has run out. We outline the prophylactic use of platelets based on recent international clinical practice guidelines.

This paper investigates defects in photovoltaic cells and panels which cause notable losses in output performances. Here, the focus lies on the impact of hairline cracks which result in a remarkable drop of the available output current and, thus, the available output power. Firstly, samples were characterised with the help of synchronized thermography (ST) in order to localise and analyse the defects. Secondly, samples were measured with the help of electrical verification to obtain the characteristic I-V (Current-Voltage) curve. Finally, the geometric area of PV cells was calculated which corresponds to the effective area for energy production due to the presence of a defect. Results show the correlation between the available power of PV cells with temperature variations in IR-emissions. Proposed methods are capable of detecting defects in PV cells and quantise the impact on output performances.

The most common means of mobilizing autologous stem cells is G-CSF alone or combined with cyclophosphamide (CY) to obtain sufficient CD34(+) cells for one to two transplants. There are few prospective, randomized studies investigating mobilization regimens in multiple myeloma (MM), especially after lenalidomide-based induction. We designed this prospective, randomized study to compare low-dose CY 2 g/m(2)+G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up-front induction in MM. Of the 80 initially randomized patients, 69 patients were evaluable, 34 and 35 patients in arms A and B, respectively. The primary end point was the proportion of patients achieving a yield of >= 3x10(6)/kg CD34(+) cells with 1 - 2 aphereses, which was achieved in 94% and 77% in arms A and B, respectively (P = 0.084). The median number of aphereses needed to reach the yield of >= 3x10(6)/kg was lower in arm A than in arm B (1 vs 2, P = 0.035). Two patients needed plerixafor in arm A and five patients in arm B (P = 0.428). Although CY-based mobilization was more effective, G-CSF alone was successful in a great majority of patients to reach the defined collection target after three cycles of lenalidomide-based induction.

Purpose Patients with Richter's syndrome (RS) have a poor prognosis with conventional chemotherapy. The aim of this study was to evaluate the outcome after autologous stem-cell transplantation (autoSCT) or allogeneic stem-cell transplantation (alloSCT) in RS. Patients and Methods A survey was sent to all European Group for Blood and Marrow Transplantation centers assessing transplantations performed for RS. Eligibility criteria included a diagnosis of RS or secondary lymphoma before SCT, age ≥ 18 years, and SCT performed from 1997 to 2007. Data were analyzed by descriptive statistics and methods from survival analysis. Results Fifty-nine patients were registered. Thirty-four patients had received autoSCT, mostly because of chemotherapy-sensitive disease, and 25 had received alloSCT, with 36% being refractory to chemotherapy at SCT. In 18 allograft recipients (72%), reduced-intensity conditioning (RIC) was used. Three-year estimates of the probabilities of overall survival and relapse-free survival (RFS) and the cumulative incidences of relapse and nonrelapse mortality were 36%, 27%, 47%, and 26% for alloSCT and 59%, 45%, 43%, and 12% for autoSCT, respectively. Taking into account the limitations set by the low number of events and age younger than 60 years, chemotherapy-sensitive disease and RIC were found to be associated with superior RFS after alloSCT in multivariate analysis. Factors with a significant impact on autoSCT could not be identified. Conclusion Patients with RS who are sensitive to induction chemotherapy appear to benefit from consolidation with transplantation strategies, and prolonged survival was observed in a proportion of patients.

Biologic and clinical observations suggest that combining imatinib with IFN-α may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-α2b (Peg–IFN-α2b) 50 μg weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg–IFN-α2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg–IFN-α2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg–IFN-α2b treatment (< 12-week MMR rate 67%, > 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg–IFN-α2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg–IFN-α2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.

Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P

Imatinib, a small molecule inhibitor of ABL, PDGFR and C-KIT, has revolutionized treatment of chronic myeloid leukaemia (CML). However, resistance to treatment is of increasing importance and often is due to point mutations in the Abl kinase domain (Abl KD). Here, we analysed clinical outcome and mutation status in two independent Nordic populations (n = 77) of imatinib-resistant CML patients. We detected BCR-ABL transcripts containing point mutations of residues in the P-loop, A-loop and other kinase domain residues in 32 patients (42%). In contrast to previous data, mutations in BCR-ABL were as frequently found in patients with primary resistance (56%) as with secondary resistance (53%). No T315I mutations were found in the study cohort. BCR-ABL splice variants were identified in a significant number of our cases (19%): BCR-ABL transcripts of variable length; a variant fusion transcript joining BCR exon 14 sequences to ABL exon 4; partial, in-frame-deletion of exon 4 due to induction of a cryptic splice site by the L248V and finally, alternative splicing of ABL exon 7 sequences. Though the majority of splice variants observed in this study do not encode functional proteins, alternative splicing appears to represent a common phenomenon in the biology of CML. We conclude that Abl KD point mutations represent a major mechanism of imatinib resistance. Other sequence irregularities were also detected, but their significance in conferring resistance is unclear. Diagnostic strategies looking for imatinib-resistant clones should be designed to detect a broader profile of BCR-ABL variants than just point mutations.

Background and study design. Reduced intensity conditioning transplantation (RICT) is a commonly applied treatment option for AML patients >50 years of age. Prospective, controlled studies comparing RICT with standard chemotherapy are warranted. In this study, we aimed to prevent selection biases. Thus, patients were included prior to HLA typing of potential sibling donors, and statistical analyses were based on an intention-to-transplant, donor versus no-donor approach. Hence, the analyses also include events occurring during the donor search period and also the transplantation procedures along with post-transplant events. Patients and procedures. Between 2003 and 2016, 163 patients with AML in CR1 were included in Canada (n=69), Sweden (n=63), and Germany/Finland/Norway/New Zealand (n=31). Eighteen patients were excluded due to enrolment after the start of donor typing (n=14), lack of data (n=1), low-risk AML (n=2) or withdrawn consent (n=1). Thus, results from 145 patients with high (n=48) or intermediate (n=97) risk disease were available for analysis. Included patients were a median of 63 (50-70) years old, deemed fit for RICT and had at least one willing and healthy but not yet HLA typed sibling. The ensuing HLA typings thus yielded one RICT group including patients with ≥1 confirmed matched sibling donor (MSD), and one control group with no MSD. Date of inclusion was defined as date of HLA typing of the first potential MSD. The protocol-specified conditioning regimen for RICT was fludarabine (150-180 mg/m2) and busulfan (8 mg/kg orally or 6.4 mg/kg i.v., used in 95% of patients). Immunosuppression was ciclosporin alone (9%), with methotrexate (53%) or with MMF (35%). Peripheral blood stem cells were used in 95% of transplantations. Control patients received consolidation chemotherapy as per local routines. Statistics. Baseline factors were compared between study groups using Fisher´s exact test and rank sum tests. The primary endpoint was overall survival (OS) with secondary endpoints of relapse-free survival (RFS), relapse incidence (RI) and non-relapse mortality (NRM). Kaplan-Meier curves were used to estimate OS and RFS and cumulative incidence functions were used to estimate NRM and RI considering competing risks. The logrank test was employed for group comparisons of event rates with time censored at 5 yrs post inclusion. Results. The median follow-up time of surviving patients was 7.9 (0.24-14) yrs. Age, AML risk group and time from CR to inclusion did not differ between the study groups. Time lag from diagnosis to study inclusion was 65 (32-256) days (Controls) and 64 (29-319) days (RICT), P=0.74, Mann-Whitney test. Time from CR1 to inclusion was 22 (0-218) days (Controls) and 19 (0-131) (RICT). Excluding conditioning, patients in the RICT group received fewer chemotherapy cycles than controls. The time from start of last chemotherapy to transplant was median 63 (36-212) days. The incidence of acute (grade 2-4) and chronic extensive GvHD in transplanted patients was 25% and 39%, respectively. The non-relapse mortality at 3 years post inclusion (Table) was 12% (RICT group) and 4% (Controls). Causes of death was primarily AML, accounting for 73% and 88% of all deaths in the RICT and control groups, respectively. Twenty pts with an identified donor did not reach RICT due to relapse (n=12), co-morbidities (n=5), death (n=2), other (n=1). Total mortality at time of analysis was slightly lower in the RICT group (66% vs 75%). Overall survival (primary endpoint) at 3 years was 45% (CI 33-56) and 48% (36-60), in RICT and control groups, respectively. At 10 years after inclusion, OS in study groups were similar; RICT 27% (CI 15-41), Control 25% (CI 15-36). There were no significant differences between study groups with respect to primary or secondary endpoints (OS: P=0.27, RFS:P=0.98, RI: P=0.50, NRM: P=0.10, logrank tests. Figure). Conclusions. Applying an intention-to-treat analysis we did not demonstrate clinical benefit of sibling donor search and stem cell transplantation after a reduced intensity busulfan/fludarabine based regimen in AML patients ≥50 years in CR1. Early relapse was the main reason for preventing transplants in patients with an identified donor. Support from study groups: Canadian BMT Group, Australasian Leukaemia and Lymphoma Group, Norwegian/Swedish BMT Group, Swedish AML group Disclosures Kiss: Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees, Research Funding. Wallhult:Jazz Pharmaceuticals: Speakers Bureau; Amgen: Speakers Bureau; Daichii-Sankyo: Speakers Bureau. Finke:Riemser: Consultancy, Honoraria, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding. Sabloff:Celgene: Membership on an entity's Board of Directors or advisory committees.

Achievement of complete response (CR) is a new goal of therapy for multiple myeloma (MM). By sensitive methods, the depth of response can be measured even among the patients in CR. We used a sensitive real-time quantitative polymerase chain reaction by allele-specific primers (qASO-PCR) to assess the level of minimal residual disease (MRD) in bone marrow of 37 patients with myeloma who had achieved CR/near-to-CR after autologous or allogeneic stem cell transplantation (SCT). Allele-specific primers could be successfully designed for 86% of patients. Three to six months after autotransplantation, the PCR target was not detectable in 53% of patients (16/30 patients), and the respective figure after allotransplantation was 71 % (5/7 patients); the median sensitivity of PCR assay was

Udgivelsesdato: 2010-May-3 SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial very unlikely may challenge chemotherapy plus r-metHuG-CSF priming in candidates for high-dose therapy.Bone Marrow Transplantation advance online publication, 3 May 2010; doi:10.1038/bmt.2010.84.

Central nervous system immune reconstitution inflammatory syndrome (IRIS) after hematopoietic SCT