Search

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 10^7/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0–85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 10^9/L on day 60 was 80.6% (68.2–88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 10^9/L and platelets ≥ 50 × 10^9/L on day 100 were 75.8% (62.6–84.9%) and 72.6% (59.4–82.1%), respectively, with median time to platelets ≥ 20 × 10^9/L and platelets ≥ 50 × 10^9/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II–IV and III–IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.

Objective A central venous catheter (CVC) is often needed to treat hematologic diseases, but it is accompanied by many complications. Ultrasound guidance (USG) or a peripherally inserted central venous catheter (PICC) can reduce such complications. Meterials We collected data of patients with attempted CVC placement in our hematology unit in 2012 (before introduction of USG and PICC) and 2018 (after introduction) and compared both periods. Results In total, 187 CVC insertions were attempted in 2018 and 198 in 2012. USG was used 154 times (82%) in 2018 and 4 times (2%) in 2012 (p

A novel method to fabricate undulator magnets of a-few-millimetre-period length is being explored. Plate-type magnets, 100 mm-long with 4 mm-period length, have been successfully fabricated. They produce an undulator field of approximately 3 kG at a gap of 1.6 mm. Prototype undulators based on this technology have been constructed. Field measurements and characterization show that the quality of the undulator field of these plate magnets is sufficient for an undulator light source, and the calculated spectrum shows that the fundamental radiation emitted from this field is quite satisfactory. Test experiments for light generation using a real electron beam have been carried out at a test accelerator at the Research Center for Electron Photon Science (ELPH), Tohoku University, Japan, which is able to realize optics conditions to accept a very short gap of ∼1.6 mm. First observation and characterization of blue light was successfully accomplished.

Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced-intensity conditioning without anti-thymocyte globulin (ATG). The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. Cord blood (CB) cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia. Full donor engraftment rate was 86.8%. The cumulative incidence of neutrophil and platelet engraftment was 86.4% and 85.5%, respectively. The median time to neutrophil (>0.5 × 109 /L) and platelet (2.0 × 109 /L) recovery was 17.5 and 44 days, respectively. The probability of severe acute graft-vs-host disease (GVHD) was 47.5%. The cumulative incidence of extensive chronic GVHD was 3.0%. The probability of relapse and non-relapse mortality was 30.4% and 28.0%, respectively. The survival rate at 3 years was 45.6%, although most patients were at an advanced stage. These results suggest that our intrabone marrow-CBT procedure without using ATG improves hematopoietic recovery and decreases the incidence of chronic GVHD, but does not decrease the incidence of acute GVHD.

The aim of this randomized phase II study was to improve the treatment delays and discontinuations associated with bendamustine use by comparing the effect of Benda-14 (intravenous bendamustine, 120 mg/m

As the potent, selective Fms-Like Tyrosine Kinase 3 (FLT3) inhibitor gilteritinib has only been approved for use for a few years, its efficacy and complications remain incompletely understood. We herein report an elderly patient with FLT3 internal tandem duplications (FLT3-ITD) mutated acute myeloid leukemia (AML) who developed natural killer cell large granular lymphocytes (NK-LGL) in the bone marrow and peripheral blood during gilteritinib treatment. Case: A 79-year-old Japanese female had been diagnosed with FLT3-ITD-mutated AML. The patient received hydroxycarbamide 2000 mg daily for induction chemotherapy but did not achieve remission at day 28 postinduction. The treatment was then changed to gilteritinib 120 mg daily. Although the reduction of blasts in peripheral blood occurred immediately, it was revealed abnormal lymphocytes with large granules developed in bone marrow and peripheral blood. These lymphocytes were analyzed by flow cytometry, which revealed that these cells were NK-LGL because they expressed CD2, CD7, CD16, and CD56 and did not express CD3, CD19, and CD20. The patient achieved partial remission (PR) in a month with gilteritinib treatment. Leukemia eventually could not be controlled, but PR persisted for about 4 months and leukemia was controlled for 4 months after progression disease (PD) with gilteritinib treatment alone. Conclusion: Gilteritinib may induce the NK-LGL. The exact mechanism and effect of LGL in patients with FLT3 mutated AML treated with gilteritinib warrants further investigation.

Dose intensity (DI) of chemotherapy affects prognosis of diffuse large B cell lymphoma (DLBCL). Myelotoxicity is the major dose-limiting toxicity (DLT) of most cytotoxic agents for hematological malignancies, whereas DLT of vincristine (VCR) is mainly neurological toxicity. Although VCR is a key drug and its combination with other cytotoxic agents needs consideration, studies focused on relative DI (RDI) of VCR have not been done before. We retrospectively analyzed 86 cases of DLBCL that received six or more cycles of cyclophosphamide (CPM), doxorubicin (DXR), VCR, prednisolone, and rituximab [R-CHOP] and calculated RDI of each cytotoxic agent to analyze its influence on treatment outcome. The median RDI of CPM, doxorubicin, and VCR was 80.0, 81.7, and 78.4 %, respectively (p = 0.002). The average RDI (ARDI) of these three agents was 80.0 %. The overall survival was significantly worse in the low ARDI (85 %) than in the high ARDI (85 %) group (2-year survival rate 67.2 vs 93.4 %, p = 0.011). The survival rate with low RDI VCR (85 %) was lower than that with high RDI VCR (85 %), even when the remaining two agents had high ARDI (2-year survival rate 74.3 vs 95.8 %, p = 0.047). In conclusion, VCR dose tended to be reduced compared with CPM and DXR in R-CHOP. Lower ARDI of cytotoxic agents and lower RDI of VCR could lead to poor prognosis in the treatment of DLBCL with R-CHOP. We thought these observations should be confirmed in a prospective study.

High quality intense relativistic electron beams are generated by the interaction of two colliding laser pulses to inject plasma electrons into a wakefield excited by one of the laser pulses. The mechanism of the injection is analyzed theoretically and the generation of a high quality electron beam is verified by the numerical simulation. An electron beam has a small energy spread of 1%, ultrashort pulse duration less than 10 fs and normalized transverse emittance less than 1 π mm mrad.

By utilizing a pulsed laser beam of TEM(1,0)+TEM(0,1) mode, it was found numerically for the first time that an electron bunch can be effectively trapped by the transverse ponderomotive force in the transverse direction and at the same time accelerated by the longitudinal ponderomotive force to about 378 MeV at the laser peak intensity of I∼5.48×1018 W/cm2. In addition, the electron bunch size is preferably small: at this laser intensity the electron bunch thickness is ∼10λ in the longitudinal direction and the bunch radius is about 625λ in the transverse direction.

Laser wakefield acceleration (LWFA) experiment using 100TW laser is planned at JAERI-Kansai. High quality short pulse electron beams and the precise electron-laser synchronization are necessary to accelerate the electron beam by the laser. A microtron with a photocathode rf-gun was developed as a high quality electron injector. The quantum efficiency(QE) of the photocathode was measured to be 2 × 10 −5 . Emittance and a pulse width of the electron beams were 6π mm-mrad and 10ps, respectively. In order to produce a short pulse electron beam, and to synchronize between the electron beam and the laser pulse, the inverse free electron laser (IFEL) is planed. A gas jet was set up and a density of the gas was measured by Mach-Zehnder interferometer. In order to overcome a short acceleration length of the LWFA, the Z-pinch plasma waveguide has been developed for 1 GeV laser wakefield acceleration.

The coherent wakefield excited by 2 TW, 50 fs laser pulses in a gas-jet plasma around 1018 cm−3 is measured with a time-resolved frequency domain interferometer. The density distribution of the helium gas is measured with a time-resolved Mach–Zehnder interferometer to search for the optimum laser focus position and timing in the gas jet. The results show an accelerating wakefield excitation of 20 GeV/m with good coherency, which is useful for ultrahigh gradient particle acceleration in a compact system. This is the first time-resolved measurement of laser wakefield excitation in a gas-jet plasma.

Yoshio Mizuta, Tomonao Hosokai, Shinichi Masuda, Alexei Zhidkov, Nobuhiko Nakanii, Zhan Jin, Hiroki Nakahara, Tomohiro Kohara, Kenta Iwasa, Masaki Kando, Sergei Bulanov, and Ryosuke Kodama 1 Graduate School of Engineering, Osaka University,2-1 Yamada-oka, Suita, Osaka, 565-0871, Japan 2 Photon Pioneers Center, Osaka University, 2-8 Yamada-oka, Suita, Osaka, 565-0871, Japan 3 Japan Science and Technology Agency (JST), CREST 4 Kansai Photon Science Institute, Japan Atomic Energy Agency, 8-1-7 Umemidai, Kidugawa, Kyoto 619-0215, Japan 5 Institute of Laser Engineering, Osaka University, 2-6 Yamada-oka, Suita, Osaka, 565-0871, Japan

[Background] Bendamustine has demonstrated high response rates in non-Hodgkin lymphomas (NHL). However, standard administration schedule frequently shows delayed hematological recovery resulting in the discontinuation of treatment. Here we designed a novel treatment schedule that could be more tolerable and conducted randomized phase II study (UMIN000008702). [Methods] Patients (pts) with relapsed/refractory(R/R) indolent B-cell NHL and mantle cell lymphoma were randomly assigned to standard arm (120mg/m2 on day1 and 2, every 3 weeks) or Benda-14 arm (120 mg/m2 on day1 and 15, every 4 weeks) of bendamustine monotherapy. Each arm was repeated to 6 cycles and the accomplishment rate (AR) of all scheduled treatment was analyzed as primary end point. [Results] A total of 46 pts were enrolled into the study. Baseline characteristics were: median age 64 years (range 46-78); 48% male; 76% follicular lymphoma; 33% ECOG PS ≥1; 50% having one previous regimen. 65% stage III/IV. 24% bone marrow positive. 33% with bulky mass (>6cm). Using random allocation, twenty two and 24 pts were assigned to standard and Benda-14 arm and the AR of 6 cycles in each arm was 41 and 38%, respectively. The median number of cycles was 4.5 in both arms. Eleven (50%) in standard and 10 (42%) in Benda-14 arm withdrew from protocol due to mainly prolonged hematological toxicities. Three withdrew due to disease progression. Two withdrew due to adverse events (AE). Grade 4 non-hematological AE was observed in one. Overall response rate (ORR) in the standard arm was 77% (95% confidence interval [CI], 59 to 95), including a 50% complete response (CR) compared with 83% (95% CI, 68-99), including a 46% CR in Benda-14 arm. After a median follow-up time of 16 months, the median event-free survival (EFS) in the standard arm and Benda-14 arm was 14.6 months (95% CI, 8-26) and 15 months (95% CI, 11 - not reached), respectively. There was no significant difference between two arms in AR and in EFS (p=0.431). The overall survival (OS) in both arms was the same of 89% at 15 months. [Conclusions] Although this study did not confirm the superiority of Benda-14 to complete 6 cycles of treatment, Benda-14 arm appears to be equally tolerable and active as the present standard therapy. Benda-14 could be a study arm of next trial that determines better practical strategy for this disease population. Disclosures Igarashi: Zenyaku-Kogyo Inc.: Research Funding. Tsukasaki:Daiichi Sankyo Co., Ltd.: Consultancy; Takeda: Research Funding.

Interaction of relativistically intense axisymmetrically polarized (radially or azimuthally polarized) laser pulses (RIAPLP) with underdense plasma is shown experimentally and theoretically to be essentially different from the interaction of conventional Gaussian pulses. The difference is clearly observed in distinct spectra of the side-scattered laser light for the RIAPLP and Gaussian pulses, as well as in the appearance of a spatially localized strong side emission of second harmonic of the laser pulse in the case of RIAPLP. According to our analysis based on three-dimensional particle-in-cell simulations, this is a result of instability in the propagation of RIAPLP in uniform underdense plasma.

We retrospectively analyzed the bone mineral density (BMD) of postmenopausal Japanese women taking an aromatase inhibitor (AI), exemestane, anastrozole or letrozole, and calculated the decrease rate constant of BMD in each individual to compare the influence of the three AIs on BMD. We also aimed to evaluate the preventive effect of bisphosphonates (BPs) on the AI-induced decrease in BMD. The decrease rate constant of BMD (k(e)) in each individual was determined as a slope of linear regression of the relationship between time and logarithm of BMD value in each patient during the AI therapy. To compensate for the age-related change in BMD level, we estimated the age-related decrease rate constant of BMD (ke,0) in healthy Japanese postmenopausal women from the literature. AIs decreased BMD with a ke value of -0.0329 yr(-1), which was 4.7-fold larger than the k(e,₀) value of -0.00699 yr(-1). No significant difference was detected in the influence on BMD among AIs. Co-administration of BP ameliorated the ke value to -0.0117 yr(-1), a value similar to k(e,₀). The influence of AIs on BMD was quantitatively evaluated by using the decrease rate constant of BMD (k(e)). The present study also suggests that BPs may be useful to prevent the decrease in BMD induced by AIs.

Background; The number of non-Hodgkin's lymphoma (NHL) patients in the elderly has been increasing due to the long-lived society. It is not rare to treat elderly NHL patients aged over 85 years old. Individualizing the doses of cancer chemotherapy agents and progress in supportive therapy has improved the prognosis for elderly patients with NHL. Prolonged hospitalization elderly patients have adverse effects, which include dementia, difficulty in walking, and depression. Optimal treatment for these patients is unknown. Patients and Methods; In our hospital between April 2012 and December 2014, we treated 19 elderly patients (85 and over 85 years) with NHL as outpatients with VDS 3mg (day 1) and Dexa. (day 1-4) which repeated every 3 weeks for as long as possible. Results; Complete remission was achieved in 5 patients and partial remission in 6; the median duration of survival was 14 months. Adverse effects included leukopenia in 1 patient ( Disclosures No relevant conflicts of interest to declare.

We investigate a laser wakefield excited by intense laser pulses, and the possibility of generating an intense bright electron source by an intense laser pulse. The coherent wakefield excited by 2 TW, 50 fs laser pulses in a gas‐jet plasma around 1018 cm−3 is measured with a time‐resolved frequency domain interferometer (FDI). The results show an accelerating wakefield excitation of 20 GeV/m with good coherency. This is the first time‐resolved measurement of laser wakefield excitation in a gas‐jet plasma. The experimental results agree with the simulation results and linear theory. The pump‐probe interferometer system of FDI will be modified to the optical injection system as a relativistic electron beam injector. In 1D particle in cell simulation we obtain results of high quality intense electron beam generation.

A plasma lens experiment is planned at SLAC with high energy electron beams and high plasma density. We have developed a PIC code, SPLASH (Simulation of Plasma Lens and Synchrotron-radiation in Hybrid), for computer simulations of this experiment. The plasma lens focusing effects are simulated for the beam energy at 30 and 50 GeV and the plasma density between np/nb=0.1 and 100. The original bunch size is 3 and 5 μm in radius. Due to plasma focusing, the beam size is reduced, which is progressively more effective when the relative plasma density increases from the “underdense” regime to the “overdense” one. However, field compensation due to the plasma return current renders the plasma focusing effect suppressed when the plasma density further increases to the “superdense” regime. The beam waist is located between ±20 mm around the original focal point. In the most effective case, the beam is focused from 5 μm to 2 μm and from 3 μm to 1 μm.

Successful combination treatment with bevacizumab, thalidomide and autologous PBSC for severe POEMS syndrome

Successful engraftment by second cord blood transplantation with reduced-intensity conditioning after graft rejection due to hemophagocytic syndrome following initial CBT

Background: POEMS syndrome is a rare plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes associated with multiorgan involvement and monoclonal plasma cell dyscrasia. The pathogenesis of POEMS syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF) probably secreted by plasma cells is considered to be responsible. High-dose melphalan (Mel) with autologous stem cell transplantation (ASCT) has been recently considered to be an effective strategy, but its treatment related mortality is considered to be high. Here, we report the results of ASCT for POEMS syndrome. Methods: Between January 2004 and June 2008, twelve patients with POEMS syndrome underwent ASCT at Chiba University Hospital and were retrospectively analyzed in the study. Conditioning treatment for ASCT was Mel 200 mg/m2, while Mel dose was reduced to 140 mg/m2 if a patient had poor performance status (PS). Results: Ten out of twelve patients were male and their median age was 48 years (range 34–61). Median time from first symptom and diagnosis to ASCT was 21 and 10 months, respectively. Seven patients received induction therapy before preparation of ASCT, thalidomide-dexamethasone in four, intravenous Mel in two, and bevacizumab followed by thalidomide in one patient. Peripheral blood stem cells were mobilized by cyclophosphamide/G-CSF in nine cases and G-CSF alone in three. Median serum VEGF level before ASCT was 2835 pg/ml (range; 334–5300). Median number of infused CD34+ cells was 2.3 × 106/kg (range; 2.1–4.3 × 106/kg). Eleven patients were conditioned with Mel 200 mg/m2, while one patient with poor PS (Karnofsky score 30%) received Mel 140 mg/m2. Median time to neutrophil recovery (>500/mm3) was 13 days post transplant (range 9–17 days). Only two patients developed respiratory distress during neutrophil engraftment period. Both cases were successfully treated with corticosteroid therapy, none of them required intubation. During a median follow up period of 16.5 months (range 2–54), there was no transplant related death. Neurologic improvement was significantly observed in all patients and median post transplantation serum VEGF level was decreased to 330 pg/ml (range 87–3250). Only one patient experienced relapse of polyneuropathy at 43 months post transplant following reincrease of serum VEGF level. Conclusions: ASCT is an effective therapy for POEMS syndrome. Despite previous published reports arousing potential risk of life-threatening engraftment syndrome, treatment related mortality and periengraftment pulmonary complications were significantly low in our patient series. We speculate that stabilization of serum VEGF level by induction therapy before ASCT could play a potential role for reducing the risk of peritransplant complications.