Background: Although neurologic manifestations often complicate the course of patients with multiple myeloma (MM), direct central nervous system invasion is rare.Objective: To describe the neurologic symptoms and signs, imaging, cerebrospinal fluid findings, and the clinical course of patients with central nervous system myeloma invasion, all of whom had leptomeningeal myelomatosis.Design and Participants: Review of 23 patients with MM and leptomeningeal myelomatosis proven by malignant plasma cells in their cerebrospinal fluid.Setting: Tertiary-care university medical center.Results: Twenty-one patients had advanced-stage MM. Leptomeningeal myelomatosis was diagnosed up to 29 months (median, 13 months) after diagnosis of MM.
Thin film deposits of Cu, Ni, and Rh were obtained by hydrogen reduction of normalCufalse(normaltfa)2 , normalCufalse(normalhfa)2·H2O , normalNifalse(normalhfafalse)2·2H2O , and normalRhfalse(normaltfa)3 from the gas phase (tfa = trifluoroacetylacetonate anion; hfa = hexafluoroacetylacetonate anion). The chelates are well suited for gas plating purposes by virtue of their high volatility and ease of reduction by hydrogen. The deposition process can be conducted at atmospheric pressure and at temperatures as low as 250°C. The process is potentially cyclic, free chelating agent being regenerated by the reduction reaction.
vestigation of the p-ray strength function as a function of A. Therefore, it should be possible, in a series of experiments such as this, to differentiate between the Asls and A'~d ependen. ce of (I'~p/D) predicted by the single-particle and giant-resonance models, respectively.The data-taking rates for this experiment can be improved by a factor of at least j.000 with the best equipment available with existing technology. '8 It is therefore reasonable to expect this technique to become a fruitful source of information for many other properties of nuclei other than those investigated here. for his encouragement. We also wish to thank Capt. R. L. Van Hemert for assistance in the reduction of the data; E.M. Lent for calculations of the bremsstrahlung energy dependence and intensity; J. Nutter and the mechanical technicians for construction and assembly of the equipment required for this experiment; and E. Dante, Jr. and the accelerator operators for the good performance of the machine under unusual operating conditions. We also are indebted to Dr. R. C. Block of the Rensselaer Polytechnic Institute for sending us his high-resolution neutroncapture cross-section data on Fe" prior to publication. PHYSICAL REVIEWThe Beg (y,n) Be' cross section was measured as a function of photon energy from less than 1 to about 40 keV threshold, by the threshold photoneutron technique. The cross section rises sharply to a maximum of 1.6 mb at 6 keV above threshold and then decreases slowly to 1.2 mb at 40 keV. An attempt was made to fit these data, and earlier data obtained from monoenergetic y-ray source measurements, with a curve of the Breit -Wigner form in order to examine the possibility that the shape of the cross section is influenced primarily by a single level near threshold. The results show that such a curve is inadequate to explain the data, and thus indicate that a more complex theory and even better data are needed to understand fully the nature of the cross section near threshold for the Be&(y,n) reaction.
A442 (1964), indicate that at H= 0 there is no temperature range in which the specific heat has a singularity of the form (la) with a measurable a. 3 B. Mo McCoy and T. T. Wu, Phys. Rev. 176, 631 (1968), and Phys. Rev. Letters 21, 549 (1968). 4 B. M. McCoy, to be published. This work relies onExtensive studies on stellar processes have produced strong evidence that neutron capture plays the dominant role in the synthesis of elements heavier than iron. 1,2 However, the specific nature of the source of the neutrons needed for these processes still is uncertain. The most likely sources appear to be the reaction 1,3 * 4 Ne 21 (o?,w)Mg 24 and the reaction 5 Ne 22 (a?,n)Mg 25 (see also Reeves 6 and Peters 7 ). This paper reports the discovery of a resonance in the Mg 26 compound system which might enhance significantly the neutron production from the latter reaction.The resonance was observed with the threshold photoneutron technique. This technique, which has been described in detail elsewhere, 8 ' 9 was used to measure the photoneutron cross section for Mg 26 just above the neutron separation energy of 11.1 MeV. It consists of a high-resolution time-of-flight measurement of the spectrum of neutrons photoejected from a nuclear sample by a bremsstrahlung beam, when the bremsstrahlung end-point energy is limited so that the state of the residual nucleus is known. The sample consisted of 85.5 g of MgO enriched to 99.7% Mg 26 . The Mg 26 (y,n)Mg 25 cross-section data presented here were taken at an electron beam energy of 13.3 MeV and with an angle of 135° between the incident beam direction and the neutron flight tube. Additional measurements were made at several lower beam energies to measure background and to determine the correspondence between the peaks in the photoneutron spectrum and the states of the residual nucleus. Also, a measurement was made at 90° in order to help identi-that of B. M. McCoy and T. T. Wu, to be published. 5 A related lack of analyticity of the bulk magnetization at H= 0 has been discovered in another random two-dimensional Ising model by R. Griffiths, Phys. Rev. Letters 2£, 17 (1969). 6 R 0 Griffiths, J. Math. Phys. 8, 478 (1967). fy the spin and parity assignments of the prominent levels. A new neutron detector 10 was used, located 17 m from the sample. Its efficiency ranges from about 12% at 2 keV to 4% at 2 MeV, and its response time was comparable with the 30-nsee beam-burst width.The measured differential photoneutron cross section at 135° as a function of photon energy E y and of laboratory neutron energy E L is shown in Fig. 1. The energies of the peaks of the most prominent resonances are at E L = 54. 3, 63.2, 182, 224, 358, 392, 617, and 1109 keV. Peak energies that correspond to neutron emission to the first excited state (rather than the ground state) of Mg 25 occur at £^ = 432 and 737 keV. The areas under the curves for the resonances whose peaks are at E £ = 617 and 1109 keV (E y = 11.752 and 12.268 MeV, respectively) are identical to those obtained with monoenergetic photons...
Introduction The iliac crest is the usual sampling site for minimal residual disease (MRD) monitoring in Multiple Myeloma (MM). However, the disease distribution in the bone marrow (BM) is often heterogeneous. Functional imaging can be used to complement MRD detection at a single site, thereby accounting for asymmetrically distributed disease. Diffusion weighted MRI with background suppression (DWIBS) is a novel functional imaging method that can detect disease in a higher proportion of newly diagnosed MM (NDMM) patients than 18F-fluorodeoxyglucose positron emission tomography (PET), as it is independent of the tumor metabolism. Yet, its performance for monitoring of residual disease has not been described. The aims of this study were 1) to compare DWIBS to PET for the detection of residual disease in patients achieving complete remission (CR), and 2) to test whether DWIBS and PET could complement MRD flow cytometry with a sensitivity of 1x10-5. To address these aims, we investigated 168 NDMM and 33 relapsed patients for whom DWIBS, PET, and MRD were available at the onset of CR during first-line and salvage therapy, respectively. Methods All patients signed written consent in accordance with the Declaration of Helsinki. Residual focal lesions (FLs) were defined as well delineated focal intensities above the surrounding BM background. For DWIBS FLs were considered if restriction could be confirmed on ADC maps. 8-color MRD flow cytometry with a limit of detection of 1x10-5 was available for 83 NDMM and all 33 salvage therapy patients. The Kaplan-Meier method was used for survival analyses. PFS time was measured from onset of CR to relapse or death from any cause or censored at the date of last contact. Paired-end whole exome sequencing of CD138-enriched MM cells was performed on an Illumina HiSeq 2500. Mutations were called from BWA aligned sequencing reads using MuTect. Subclonal reconstruction was done using SciClone. Results Compared to PET, DWIBS detected more CR patients with residual FLs (21% vs. 6%), and the concordance between PET and DWIBS was low. Only 6 of the DWIBS-positive patients also presented with FLs in PET. Yet, 5 patients had PET+/DWIBS- FLs, suggesting that the two techniques are complementary. Both, DWIBS+ and PET+ FLs negatively impacted PFS (p<0.05). For 83 patients MRD data were available. Combining MRD and imaging, residual disease was detectable in 53 patients (64%). The best outcome was seen for 30 double negative (MRD-/Imaging-) patients (3 events with a median follow-up of 3.6 years), the worst outcome was seen for 10 double positive (MRD+/Imaging+) patients (median PFS: 2.1 years). Only 4 of 86 patients were MRD-/Imaging+, indicating that residual FLs are rare in MRD-negative NDMM patients at a sensitivity of 1x10-5. A heterogeneous disease distribution is a common feature of late-stage patients. To test if this increased heterogeneity confounded MRD, we investigated a set of 33 heavily pretreated patients who achieved CR during salvage therapy. Combining MRD and imaging data, we detected residual disease in 25 patients (76%). Of note, the proportion of patients, who were MRD-negative but had residual FLs on functional imaging was significantly higher compared to NDMM (8/16 vs 4/34 patients, p=0.01). At the same time, 10 patients (30%) were MRD+ but Imaging-, supporting the idea that a combined MRD/Imaging approach can improve detection of residual disease and should be used in late-stage patients. To obtain insights in the underlying biology, we performed longitudinal multi-region sequencing of a subset of these CR patients. Our findings support the concept of persistence and progression of multiple spatially separated clones in the BM irrespective of being in an MRD-negative CR. Thereby, focal residual disease could be shown to contribute to relapse. Conclusion DWIBS is a promising tool for detection of residual disease and complements PET. The combination of MRD diagnostics and functional imaging improves prediction of outcome, with double-negativity and double positivity defining groups with excellent and dismal PFS, respectively. Prospective trials using this information to tailor therapy are warranted. From a biological perspective, this study highlights the confounding effects of spatial heterogeneity and limited dissemination of clones within the BM on MRD diagnostics. This may especially be true for patients achieving deep responses during salvage therapies. Disclosures Roy Choudhury: University of Arkansas for Medical Sciences: Employment, Research Funding. Epstein:University of Arkansas for Medical Sciences: Employment. Barlogie:International Workshop on Waldenström's Macroglobulinemia: Other: travel stipend; Millenium: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Other: travel stipend; ComtecMed- World Congress on Controversies in Hematology: Other: travel stipend; Myeloma Health, LLC: Patents & Royalties: : Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC; European School of Haematology- International Conference on Multiple Myeloma: Other: travel stipend; Celgene: Consultancy, Research Funding; Dana Farber Cancer Institute: Other: travel stipend. Davies:Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Morgan:Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding.
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