Secondary Plasma Research Articles

Poor outcome despite modern treatments: A retrospective study of 99 patients with primary and secondary plasma cell leukemia.

Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL). We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 109/L. We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression-free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4-9.2) and 18.3 months (95% CI, 0.0-39.0) for pPCL and 0.8 (95% CI, 0.5-1.1) and 1.2 months (95% CI, 0.9-1.5) for sPCL (both p < 0.001). We observed no improvement in OS over time (2005-2012 vs. 2013-2020, p = 0.629 for pPCL and p = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high-risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities). This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high-risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options.

An Approach to Identify a Biomarker for Secondary Plasma Cell Leukemia Development

An Approach to Identify a Biomarker for Secondary Plasma Cell Leukemia Development

Leucémie à plasmocytes secondaire : à propos d’un cas rare et revue de littérature Secondary plasma cell leukemia: a rare case report and review of the literature

Plasma cell leukemia is a hematological malignancy characterized by monoclonal proliferation of plasma cells in the peripheral blood and bone marrow. It is defined by a blood plasma count greater than 2 × 109/L (2G/L) and/or the presence of more than 20% plasma cells in the white blood cell count. There are two forms: the primary or de novo form, which manifests itself immediately as leukemia, and the secondary form , which corresponds to the evolution of a known multiple myeloma. It is a highly aggressive form of plasma cell neoplasm, with a poor prognosis despite therapeutic advances. In this context, we present a rare case of secondary plasma cell leukemia in a 56-year-old female patient, diagnosed at the hematology laboratory of the Hassan II University Hospital in Fez. The patient was being followed for multiple myeloma, for which she was put on chemotherapy according to the Velcade + Thalidomide + Dexamethasone protocol. Six months later, the patient presented with a febrile hemorrhagic syndrome. The blood count showed hyperleukocytosis at 39.4 G/L and bicytopenia (Hemoglobin = 7.9 g/dl, Platelets = 58 G/L). Blood smear showed a 36% plasma cell count suggestive of secondary plasma cell leukemia. At the end of this observation, we underline the crucial importance of regular monitoring by careful cytological examination of the blood smear in all patients followed for multiple myeloma.

Secondary Plasma Cell Leukemia with Blastoid Morphology Mimicking Acute Leukemia: the First Case Report in Korea

Secondary Plasma Cell Leukemia with Blastoid Morphology Mimicking Acute Leukemia: the First Case Report in Korea

Experimental and numerical simulation research on shock wave rock-breaking by high voltage electric pulse

High-voltage electric pulse(HVEP) drilling technology has the advantages of high rock-breaking efficiency, green and non-polluting. Aiming at the importance of HVEP drilling technology in generating plasma channels, plasma shock waves, and rock-breaking pits, this paper carries out multi-physics field numerical simulations and indoor electric pulse breakdown experiments. This paper first constructs a two-dimensional numerical model of rock electric breakdown. The simulation of HVEP rock breaking, plasma channel and plasma shock wave is realized from the five-field coupling and combined with the wave control equations. The effects of different electrode shapes on the plasma channel, breakdown channel and shock wave are analyzed. Then, this paper designed an indoor HVEP rock-breaking experiment to investigate the influence of different electrode shapes on rock breakdown and plasma shock waves. The simulation and experimental results show that the indoor electric pulse breakdown experiment results are consistent with the simulation results; The plasma channels are formed by the ‘electrical damage’ through each other, and the secondary plasma channel is often generated inside the rock. The generation of the secondary plasma channel means that the rock fragmentation depth and the fragmentation area will be increased; The larger the contact area of the electrode bit with the rock, the larger the radius (volume) of the plasma channel and the smaller the amplitude of the plasma shock wave; The quadrangular electrode bits have the best rock-breaking effect and are recommended; The conical electrode bit has the most excellent dispersion in the statistical analysis of the electric pulse rock-breaking effect, and the stability of the rock-breaking effect is poor, so it is recommended to use it together with the composite drill bit; The cylindrical electrode bit has the best aggregation degree of electric pulse rock-breaking and the most stable rock-breaking effect.

Decoding the Nature of Coherent Radio Emission in Pulsars I: Observational Constraints

Radio observations from normal pulsars indicate that the coherent radio emission is excited by curvature radiation from charge bunches. In this review, we provide a systematic description of the various observational constraints on the radio emission mechanism. We have discussed the presence of highly polarized time samples where the polarization position angle follow two orthogonal well-defined tracks across the profile that closely match the rotating vector model in an identical manner. The observations also show the presence of circular polarization, with both the right and left handed circular polarization seen across the profile. Other constraints on the emission mechanism are provided by the detailed measurements of the spectral index variation across the profile window, where the central part of the profile, corresponding to the core component, has a steeper spectrum than the surrounding cones. Finally, the detailed measurements of the subpulse drifting behaviour can be explained by considering the presence of non-dipolar field on the stellar surface and the formation of the partially screened gap (PSG) above the polar cap region. The PSG gives rise to a non-stationary plasma flow that has a multi-component nature, consisting of highly energetic primary particles, secondary pair plasma, and iron ions discharged from the surface, with large fragmentation resulting in dense plasma clouds and lower-density inter-cloud regions. The physical properties of the outflowing plasma and the observational constraints lead us to consider coherent curvature radiation as the most viable explanation for the emission mechanism in normal pulsars, where propagation effects due to adiabatic walking and refraction are largely inconsequential.

Weak oxidant fraction in the microwave plasma influencing the evolution of nanocrystalline-diamond–imbedded diamond–like carbon network at low temperatures and its orbital hybridization dependent wide optical band gaps

The diamond-like carbon (DLC) thin films having intrinsic nanocrystalline diamond (NCD) components were synthesized on bare glass substrates at 300 °C, employing a (C2H2/CO2/H2/) gas mixture in MW-PECVD. Relevant influence of the weak oxidant fraction [F = CO2/(CO2 + C2H2)] in the plasma on the specific hybridized constituents (sp3 and sp2) in the C-network, optical transmission characteristics of the film, and its accomplished degree of nanocrystallinity were investigated. A substantial segment of the NCD was achieved in the DLC matrix. An optimized diamond-phase component corresponding to the minimized bond angle disorder in the matrix was accounted from the manifestation of the maxima of IDia/IG and IDia/ID simultaneous to the minimum of ID/IG ratio in Raman response, along with an allied diamond peak appearing near 1332 cm−1. The optimal DLC film at F = 0.23 revealed a wide optical band gap (Eg) of ∼3.60 eV, ∼59% sp3-hybridized C component of the diamond phase, and a significant sp3/sp2 ratio of ∼2.1. The film microstructure seemed homogeneous with uniformly distributed NCDs of average diameter ∼7.5 nm and dominant 〈111〉 crystallographic orientation. The sp3/sp2 fraction in the film matrix has been correlated directly to the IDia/IG and IDia/ID, and inversely to ID/IG ratios of the Raman data. Atomic-O, including atomic-H, remains instrumental in chemical reactions, facilitating the etching of graphitic and a-C phases while preserving the superior sp3-hybridized NCD component growing uninterruptedly in the DLC network that subsists shielded from the high-energy ion impact within secondary plasma under the shadow mask.

Nonthermal Plasma Synthesis of Metallic Ti Nanocrystals

Nanoscale metallic titanium (Ti) offers unique energetic and biocompatible characteristics for the aerospace and biomedical industries. A rapid and sustainable method to form purified Ti nanocrystals is still in demand due to their high oxygen affinity. Herein, we report the production of highly purified Ti nanoparticles with a nonequilibrium face center cubic (FCC) structure from titanium tetrachloride (TiCl4) via a capacitively coupled plasma (CCP) route. Furthermore, we demonstrate a secondary H2 treatment plasma as an effective strategy to improve the air stability of a thin layer of nanoparticles by further removal of chlorine from the particle surface. Hexagonal and cubic-shaped Ti nanocrystals of high purity were maintained in the air after the secondary H2 plasma treatment. The FCC phase potentially originates from small-sized grains in the initial stage of nucleation inside the plasma environment, which is revealed by a size evolution study with variations of plasma power input.

Influence of a Secondary Plasma Cloud on the Ablation of Pellets in Magnetic Confinement Devices

The analysis of experimental data on the structure of hydrocarbon pellet clouds on the LHD stellarator has allowed one to estimate the relative contributions of neutral and plasma shielding at the ablation of macroparticles (pellets) in a high-temperature magnetized toroidal plasma. A method for the self-consistent calculation of the pellet ablation rate, the characteristic size of the pellet cloud, and the electron density in its singly ionized part including neutral gas and plasma shielding is described. This calculation for polystyrene pellets injected into the LHD plasma gives the results that agree with the experimental data obtained during the early ablation phase, when the ablation rate is determined by thermal electrons and the contribution of the superthermal component of the hot plasma to ablation can be neglected.

PROPERTIES OF A SECONDARY DISCHARGE PLASMA SUPPORTED BY A ROTATING GLIDING DISCHARGE

In this work, the results of an experimental study of plasma parameters of a secondary discharge at atmospheric pressure, sustained by a low-power (~ 100 W) rotating gliding discharge in an air stream under conditions of a significant excess of the plasma channel length of the secondary discharge over the length of the self-sustained discharge channel in the range of 1...100, are presented. Plasma parameter determination was carried out using emission spectroscopy of the plasma with the SpecAir program. The assessment of the electric field intensity in the secondary discharge plasma was based on the dependencies between the discharge voltage drop and the length of the discharge current channel.

Paired Circulating Tumor DNA in Cerebrospinal Fluid and Peripheral Blood: Reliable Technology for Diagnosing and Monitoring Primary and Secondary Central Nervous Lymphoma

Objective: This research delineates the temporal alterations of cell-free circulating tumor DNA (ctDNA) in the plasma and cerebrospinal fluid (CSF) of patients harboring primary and secondary central nervous system (CNS) lymphoma. The aim is to establish that CSF serves as a superior reservoir of ctDNA compared to plasma, thereby aiding in diagnostic processes and monitoring therapeutic efficacy. Concurrently, this study underscores the enhanced response and survival rates in patients administered Bruton's tyrosine kinase (BTK) inhibitors over an extended period exceeding three months. Methods: Data including cranial-enhanced magnetic resonance imaging (MRI) scans, leukocyte and protein concentrations in the CSF, exfoliated CSF cytology, flow cytometry, interleukin-10 to interleukin-6 ratios, ctDNA in plasma and CSF, were gathered from patients presenting primary and secondary CNS lymphoma（7 PCNSL,9 SCNSL）. The temporal ctDNA modifications in plasma and CSF during the patient's disease progression-initial onset, remission, and relapse-were scrutinized. Additionally, the implications of BTK inhibitor usage on patient response rates and survival rates were assessed. Results: Within the cohort of primary CNS lymphoma patients, ctDNA was detected in the CSF and plasma of 2 and 5 patients, respectively. Conversely, in patients with secondary CNS lymphoma, CSF and plasma ctDNA were discovered in 8 and 4 cases, respectively. The detection rate was contingent upon the central lesion's magnitude and position and the patient's surgical history related to the brain. Four patients, including two from each group, underwent cranial-enhanced MRI to appraise tumor burden at various disease stages, simultaneously with the monitoring of ctDNA in plasma and CSF. It was revealed that ctDNA levels in the CSF were in synchrony with the tumor burden, whereas plasma ctDNA levels remained relatively static. This indicates that CSF ctDNA may serve as a viable tool to assess therapeutic responses in CNS lymphoma patients. In two patients where surgical biopsy was unfeasible and both CSF exfoliation cytology and flow cytometry returned negative results, CSF ctDNA was positive, thereby underscoring its auxiliary role in diagnosing CNS lymphoma. Furthermore, the study indicated improved response and survival rates in patients subjected to BTK inhibitors for over three months. Conclusion: CSF ctDNA demonstrates potential in detecting CNS lymphoma and in the dynamic monitoring of therapeutic responses. Compared to cranial-enhanced MRI, exfoliated CSF cytology, and flow cytometry, CSF ctDNA testing offers superior sensitivity. For patients for whom brain surgical biopsy is not an option, CSF ctDNA testing emerges as a valuable supplementary diagnostic tool. CSF ctDNA allows for dynamic monitoring of therapeutic responses in CNS lymphoma patients, enabling the detection of residual lesions, and thereby guiding the formulation and duration of the treatment regimen. Patients administered oral BTK inhibitors for more than three months demonstrate higher treatment response and survival rates.

Primary and Secondary Plasma Cell Leukemia Risk Stratification By Circulating Plasma Cells

Plasma cell leukemia (PCL) is a rare plasma cell dyscrasia associated with poor outcomes. PCL can present de novo as primary PCL (pPCL) or from preceding multiple myeloma as secondary PCL (sPCL). The International Myeloma Working Group (IMWG) in 2021 updated the diagnostic criteria for pPCL using circulating plasma cells (CPC) to ≥5% instead of ≥20% as both carry similar survival. In this single center retrospective analysis, we compared clinical features and overall survival (OS) for 104 patients: with pPCL ≥5% CPC ( N = 35), sPCL 5-19% CPC (sPCL-A) ( N = 11), sPCL ≥20% CPC (sPCL-B) ( N = 38), and spillover group 1-4% CPC regardless of newly diagnosed or secondary status ( N = 20). Mean ages were 57 - 59 years old for all groups (range: 25 - 84) with no difference in age between groups ( p = 0.90). There was a slight predominance of females (54.8%) over males and blacks (53.9%) over non-blacks. More patients with pPCL were black (65.7%) compared to sPCL and spillover groups, although this difference was not statistically significant ( p = 0.35). pPCL patients presented with the highest mean WBC at diagnosis (23.4 x10 9/L) compared to sPCL-A (5.5 x10 9/L), sPCL-B (12.2 x10 9/L), and spillover (7.2 x10 9/L) groups ( p &amp;lt;0.001). Patients in all groups were anemic (hemoglobin 7.8 - 9.3 g/dL), thrombocytopenic (platelets 60.2 - 101.2 x 10 9/L), and had abnormal renal function (creatinine 1.4 - 2.7 mg/dL), elevated LDH (918.7 - 1515.5 units/L, highest in sPCL-A), and elevated uric acid levels (5.9 - 8.2 mg/dL). sPCL patients and spillover group had more lytic lesions on skeletal survey ( p = 0.009) and positron emission tomography (PET) ( p = 0.02) compared to patients with pPCL. sPCL-A patients had higher incidences of lymphadenopathy ( N = 5/11, 62.5%, p = 0.02) and central nervous system invasion ( N = 4/11, 36.4%, p = 0.02) compared to other groups. There was no difference in incidence of extramedullary disease ( p = 0.29) between groups. Over 90% of patients with PCL had high-risk cytogenetics with 63% carrying a complex karyotype. Hypodiploidy was seen more often in patients with pPCL and sPCL-B compared to sPCL-A and spillover ( p = 0.005). There was no difference between groups in incidence of deletion 17p ( p = 0.53). All patients benefited in terms of OS from daratumumab (HR 0.44, 95% CI 0.25 - 0.76; p = 0.004), IMiDs (HR 0.13, 95% CI 0.08 - 0.23; p &amp;lt;0.001), PIs (HR 0.43, 95% CI 0.25 - 0.75; p = 0.003), chemotherapy (HR 0.56, 95% CI 0.32 - 0.98; p = 0.04), and autologous hematopoietic stem cell transplantation (HR 0.33, 95% CI 0.16 - 0.71; p = 0.004). DVT-PACE type regimens (dexamethasone-bortezomib-thalidomide-cisplatin-doxorubicin-cyclophosphamide-etoposide) are used for pPCL and may be less effective in sPCL and spillover patients who have been heavily pretreated. We noted no benefit in OS for all patients including pPCL, sPCL-A, sPCL-B, and spillover groups who received DVT-PACE (HR 0.97, 95% CI 0.62 - 1.50, p = 0.88). The lack of OS benefit in pPCL patients receiving DVT-PACE persisted on multivariate analysis when adjusting for PCL group alone (HR 0.79, 95% CI 0.50 -1.26; p = 0.33) and PCL group, age, platelet count, and presence of high-risk cytogenetics (HR 1.11, 95% CI 0.63 - 1.94; p = 0.72). After median follow-up of 6.70 months, median OS was 7.14 months for the entire cohort with 92.3% ( N = 96) deceased. On univariate analysis, male sex, age &amp;gt;58 years old, high-risk cytogenetics, LDH &amp;gt;604 units/L, creatinine &amp;gt;1.40 mg/dL, hemoglobin &amp;lt;8.3 g/dL, platelets &amp;lt;53.5 x10 9/L, lytic lesions on skeletal survey and on PET, extramedullary disease on PET, and plasmacytoma were associated with inferior median OS (Table 1). pPCL had higher median OS (13.1 months) compared to sPCL-A (3.1 months, p = 0.03) and sPCL-B (3.5 months, p = 0.003) (Figure 1). There was no statistically significant difference in median OS between pPCL (13.1 months) and spillover patients (10 months) ( p = 0.48) as well as sPCL-A (3.1 months) and sPCL-B (3.5 months) ( p = 0.80). Although the spillover group was associated with a trend towards better OS compared to sPCL-A and sPCL-B groups, this was not statistically significant, which may be due to low N which is a limitation of the study. Further research is required to better understand the clinical features, treatment responses, and outcomes of pPCL, sPCL, and spillover group (1-4% CPC).

Primary or Secondary Plasma Cell Leukemia: Dismal Outcome Despite Modern Treatments

BACKGROUND Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia, associated with short survival. This disease is usually divided into primary PCL (pPCL), when occurring de novo, or secondary PCL (sPCL), when a patient previously diagnosed with multiple myeloma (MM) undergoes leukemic transformation. Because of the very low incidence of PCL, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand PCL, particularly in regard to the characteristics of MM before leukemic transformation and the outcomes following modern treatments in both pPCL and sPCL. METHODS We performed a retrospective, multicenter study of patients diagnosed with PCL between January 2005 and December 2020 in eight institutions in the Province of Québec, Canada. Patients were identified through digital medical records. The 2013 International Myeloma Working Group (IMWG) diagnostic criteria for PCL (circulating plasma cells ≥ 20% and/or ≥ 2 x 10 9/L) were used to determine eligibility. Patients were excluded if they received treatment for another malignancy after the diagnosis of PCL. RESULTS We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. Among significant clinical characteristics, both pPCL and sPCL patients showed a high frequency of thrombocytopenia, splenomegaly, and light chain isotype (Table I). At MM diagnosis, patients who eventually progressed to sPCL were much younger (median 61.8 years) than a typical MM cohort and many of them already demonstrated markers of poor prognosis, including elevated lactate dehydrogenase (LDH), elevated ß 2-microglobulin and complex cytogenetics (Table I). The median time between initial MM diagnosis and leukemic progression was 27.3 months (IQR, 12.7 - 41.6). The median number of lines of treatment prior to transformation was 2 (range 1 - 7). Overall, autologous stem cell transplant (ASCT; n = 28) or tandem ASCT-allogeneic stem cell transplant (ASCT-alloSCT; n = 4) did not result in longer time to PCL progression when compared to those who received chemotherapy alone (31.6 vs 22.9 months, p = 0.164). Median overall survival (OS) for pPCL and sPCL were respectively 18.3 months (95% CI, 0.0 - 39.0) and 1.2 months (95% CI, 0.9 - 1.5) (p &amp;lt; 0.001). When considering survival from MM diagnosis to death, the median OS for sPCL was 30.2 months (95% CI, 24.1 - 36.2). Patients with pPCL who underwent ASCT or tandem ASCT-alloSCT had a significantly longer OS than patients treated with chemotherapy alone (HR 0.27, 95% CI 0.11 - 0.64, p = 0.003). The impact of stem cell transplant on sPCL survival could not be assessed, as only one of 66 sPCL patients received this type of treatment. The median number of lines of treatment was 2 (range 1 - 9) for pPCL and 1 (range 0 - 5) for sPCL. Interestingly, patients receiving more recent regimens (2013-2020) did not have a better OS than patients receiving earlier treatments (2005-2012) (p = 0.391). When analysed separately, OS for pPCL or sPCL did not improve significantly in the later period (Figure 1). Clinical characteristics independently associated with poor outcomes were sPCL subtype and elevated LDH (respectively, HR 4.9, 95% CI 2.2 - 11.9, p &amp;lt; 0.001 and HR 2.4, 95% CI 1.0 - 5.7, p = 0.049). Although expression of CD19 and/or CD20 was not statistically significant in multivariable analysis, a trend towards improved survival was observed in patients expressing these markers (HR 0.4, 95% CI 0.1 - 1.1, p = 0.062). CONCLUSION This retrospective, multicenter study is one of the largest PCL cohorts reported and we are, to our knowledge, the first to investigate characteristics of MM patients before their transformation into sPCL. Although this subgroup is often described as a late-stage complication of heavily pretreated MM, our data suggest that sPCL originates from an already high-risk MM population rather than being the result of long-term selection of an aggressive clone. More information is however needed for early identification of MM patients at risk of PCL transformation. Finally, despite the use of newer chemotherapy regimens, we observed no improvement in OS in recent years, highlighting the urgent need for better treatment options for both pPCL and sPCL.

Influence of a Secondary Plasma Cloud on the Ablation of Pellets in Magnetic Confinement Devices

Influence of a Secondary Plasma Cloud on the Ablation of Pellets in Magnetic Confinement Devices

Plasma cell leukemia in a 34-year-old male: rare scenario case report

Introduction: Plasma cell leukaemia is an uncommon plasma cell dyscrasia with a very poor prognosis. It is more common among males and usually presents between 55 and 65 years of age. Case presentation: A 34-year-old male presented to Al-Assad hospital with unremitting back pain. He was given analgesics but his pain was unresponsive to treatment, and due to the COVID-19 pandemic, he refused a computed tomography scan in the hospital. Later that year, he presented again with weight loss, nausea, abdominal pain, melena, and ascites. He was pale with a moderately distended abdomen. Laboratory tests revealed anaemia, thrombocytopenia, hypercalcemia, increased total proteins, and elevated lactate dehydrogenase. Flow cytometry findings of the bone marrow aspirate showed the presence of 30% of plasma cells, positive for CD38, CD56, and kappa light chains. He was diagnosed with secondary plasma cell leukaemia and started on chemotherapy; however, he could not continue his treatment due to myeloid inhibition. He passed away 5 months later. Clinical discussion: Multiple myeloma was not suspected in the patient due to his young age. The diagnosis was delayed even further due to the COVID-19 pandemic. His multiple myeloma progressed into secondary plasma cell leukaemia and had uncommon features like small intestinal polyps. Even though there has been groundbreaking advancements in chemotherapy, plasma cell leukaemia still possesses a fatal prognosis. Conclusion: This report showcases a rare age presentation with unique manifestations of secondary plasma cell leukaemia. Multiple myeloma should be a differential diagnosis for cases with unexplained back pain despite an unclassical age.

Clinical and cytogenetic characteristics of primary and secondary plasma cell leukemia under the new IMWG definition criteria: a retrospective study

ABSTRACTBackgroundPlasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, exhibiting a more unfavorable prognosis than multiple myeloma. PCL is classified into pPCL and sPCL. Recently, the IMWG has recommended new PCL definition criteria, which require the presence of ≥5% circulating plasma cells in peripheral blood smears. Due to its low incidence, research on pPCL and sPCL is limited.MethodsWe conducted a retrospective study and analyzed clinical and cytogenetic data of pPCL and sPCL patients. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method, and survival distributions were compared using the log-rank test.ResultsThis is a small cohort comprising 23 pPCL and 9 sPCL patients. Notably, sPCL patients showed a higher incidence of extramedullary infiltration and a higher percentage of bone marrow plasma cells (p = 0.015 and 0.025, respectively). Although no significant difference was found between the two groups in OS and PFS, a trend emerged suggesting a superior survival outcome for pPCL patients, with a higher cumulative 1-year PFS rate (38.3% vs. 13.3%) and a lower early mortality rate (mortality rate at 3 months: 15% vs. 33%). We also suggested that pPCL patients carrying t(11;14) may have a longer median survival time than individuals with other cytogenetic abnormalities, but this was not confirmed due to the small sample size.ConclusionOur study revealed clinical and cytogenetic features of pPCL and sPCL patients according to the new diagnostic criteria. The findings suggested a generally better prognosis for pPCL than sPCL and the likelihood of t(11;14) translocation acting as a favorable prognostic factor in pPCL. It is important to note that our study had a limited sample size, which may lead to bias. We hope well-designed studies can be conducted to provide more results.

BCLXL PROTAC degrader DT2216 targets secondary plasma cell leukemia addicted to BCLXL for survival.

Secondary plasma cell leukemia (sPCL) is a rare form of aggressive plasma cell malignancy arising mostly at end-stage refractory multiple myeloma and consequently presenting limited therapeutic options. We analyzed 13 sPCL for their sensitivity to BH3 mimetics targeting either BCL2 (venetoclax) or BCLXL (A1155463) and showed that 3 sPCL were efficiently killed by venetoclax and 3 sPCL by A1155463. Accordingly, BH3 profiling of 2 sPCL sensitive to BCLXL inhibition confirmed their high BCLXL primed profile. While targeting BCLXL using BH3 mimetics induces platelets on-target drug toxicity, the recent development of DT2216, a clinical-stage BCLXL proteolysis targeting chimera PROTAC compound, provides an alternative strategy to target BCLXL. Indeed, DT2216 specifically degrades BCLXL via VHL E3 ligase, without inducing thrombocytopenia. We demonstrated in human myeloma cell lines and sPCL that sensitivity to DT2216 strongly correlated with the sensitivity to A1155463. Interestingly, we showed that low doses of DT2216 (nM range) were sufficient to specifically degrade BCLXL after 48 hours of treatment, consistent with VHL expression, in all cell lines but irrespectively to DT2216 sensitivity. In myeloma cells, DT2216 induced apoptotic cell death and triggered BAX and BAK activation. In conclusion, our study demonstrated that patients with sPCL addicted to BCLXL, a small but a very challenging group, could potentially receive therapeutic benefit from DT2216. Clinical trials of DT2216 in this subset of sPCL patients are warranted.

Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia

To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

Plasma cell leukemia: A rare case

Plasma cell leukaemia is an extremely rare haematological malignancy with a poor prognosis. It is defined by the presence in the circulating blood of a number of plasma cells greater than 2 giga/L or greater than 20% of the leukocytes. It presents in two forms: secondary plasma cell leukaemia complicating a known multiple myeloma, and primary plasma cell leukaemia, which is leukaemic in origin. We report the observation of a 52-year-old Moroccan patient who presented with bone pain and general deterioration 3 months before hospitalisation. The haemogram revealed normocytic normochromic anaemia at 8.1 g/dL and hyperleukocytosis. The blood smear showed the presence of 38% of plasma cells. The myelogram confirmed the diagnosis of APL by showing a rich marrow with 63% dystrophic plasma cells. In this case, we emphasise the importance of careful cytological examination of the blood smear.

Study of the electric arc dynamics in a cascaded-anode plasma torch

In plasma spraying process, the plasma jet stability depends on the electric arc movement inside the plasma torch. For conventional plasma torches with rod cathode and a large anodic surface, arc roots are free to move along the anode wall, leading to high plasma jet fluctuations. To overcome these instabilities, cascaded-anode plasma torches have been developed, reducing considerably the electric arc movement and thus the plasma jet fluctuations. Unfortunately, a small number of studies reports on the behaviour of theses torches including the arc instabilities and on electrode erosion process as well. In this work, several diagnostics have been set up to further understand the cascaded-anode plasma torch behaviour under different sets of operating conditions. Influence of plasma forming gas composition on the electric arc dynamic has been studied through anodic imaging. The issue of the intense plasma radiation masking is discussed since the light emitted by the arc column interferes with anodic arc roots observations. Multiple constricted arc roots have been observed and a preferential site for anodic arc root has been identified for all experimental conditions. The addition of a secondary plasma forming gas promotes a higher number of reattachments. The influence of the electric arc movement on plasma jet stability is also studied by following the plasma jet brightness fluctuations. The low voltage fluctuation frequency is also observed on brightness spectra, which means that these fluctuations could have an impact on in-flight particle treatment.