Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Efficacy and prognostic analysis of orthopedic surgery in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To evaluate the efficacy and prognosis of orthopedic surgical resection surgery in patients with newly diagnosed multiple myeloma (NDMM). Methods: This retrospective cohort study collected clinical data of patients with NDMM who underwent surgery due to spinal cord compression or pathological long-bone fractures at the Peking Union Medical College Hospital from 1 January 2003 to 31 December 2021. Patients who received biopsy or vertebroplasty/kyphoplasty were excluded and patients with the same degree of bone disease and who did not undergo any surgical intervention were selected as controls. Visual analogue scale (VAS) and physical status (ECOG) scores, progression-free survival (PFS), and overall survival (OS) were compared. Statistical analysis included the χ2-test, t-test, and Kaplan-Meier methods. Results: Baseline data were compared between the surgical group (n=40 with 43 interventions) and the non-surgical group (n=80), and included sex, age, paraprotein type, International Staging System (ISS), number of lytic lesions, cytogenetic abnormalities, first-line treatment, and the proportion of patients receiving autologous stem cell transplantation (ASCT) (all P>0.05). Serum M protein levels in the surgical group were significantly lower than those of the non-surgical group [(21.95±16.44) g/L vs. (36.18±20.85) g/L, P=0.005]. The surgical lesions involved the axial skeleton (79.1%, 34/43) or the extremities (20.9%, 9/43). VAS and ECOG scores improved significantly after surgery (VAS: 2.30±0.80 vs. 6.60±1.50, P<0.001; ECOG: 2.09±0.59 vs. 3.09±0.73, P<0.001). The median follow-up time was 51 months. Kaplan-Meier survival analysis suggested that the median PFS (25 vs. 29 months) and OS (46 vs. 60 months) were comparable between the surgical and non-surgical intervention groups (both P>0.05). Subgroup analysis showed that among patients with ISS Ⅰ or those who had received ASCT, PFS in the surgical group was similar to that of the non-surgical intervention group (both P>0.05), while OS was worse (P=0.005, 0.017). Patients with ISS Ⅱ/Ⅲ scores or without ASCT had similar PFS and OS between the surgical and non-surgical intervention groups (all P>0.05). Cox multivariate analysis suggested that ISS and ASCT were independent prognostic factors for OS (ISS: HR=0.42, 95%CI 0.19-0.93, P=0.031; ASCT: HR=0.41, 95%CI 0.18-0.97, P=0.041), while orthopedic surgery did not influence survival (P=0.233). Conclusion: For patients with NDMM, orthopedic surgical resection decreased bone-related complications and improved quality of life, but did not affect survival.

Prognostic Value of CD56 Expression in Newly Diagnosed Multiple Myeloma Patients and Its Related Factors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effect of CD56 expression on the prognosis of newly diagnosed multiple myeloma (MM) patients and explore the relationship between CD56 with clinical characteristics.@*METHODS@#In this retrospective study, the clinical data and laboratory parameters of 175 newly diagnosed MM patients from February 2015 to December 2020 in the Second Hospital of Anhui Medical University were collected. The patients were divided into CD56+ and CD56- groups based on the expression of CD56, and the general data and laboratory parameters of the two groups were compared. The patients were followed up to June 30, 2021, and progression-free survival (PFS) and overall survival (OS) were recorded. PFS and OS curves of the two groups were plotted respectively, and the survival differences were compared. Univariate and multivariate Cox regression analyses were performed to analyze the effect of CD56 on the prognosis of newly diagnosed MM patients.@*RESULTS@#In 175 newly diagnosed MM patients, 57(32.6%) cases were in the CD56-group and 118 (67.4%) cases in the CD56+ group. There was significant correlation between CD56 expression and ISS stage, ECOG score, platelets, β2-microglobulin, creatinine, and extramedullary disease (all P <0.05). The incidence of extramedullary disease in the CD56- group was significantly higher than that in the CD56+ group (29.8% vs 12.7%, P =0.006). The median follow-up time of the whole cohort was 23.6 (1.0-78.6) months. The median PFS of patients in CD56+ group and CD56- group were 18.6 (1.2-77.6) and 12.2 (1.0-49.0) months, respectively, and the median OS of the two groups were 27.6 (1.4-77.7) and 19.7 (1.0-78.6) months, respectively. The 2-year PFS rate in the CD56+ group was significantly higher than that in the CD56- group (57.6% vs 36.8%, P =0.010), and the 2-year OS rate in the CD56+ group was higher than that in the CD56- group, but it didn't reach statistical significance (74.6% vs 64.9%, P =0.158). The results of univariate Cox regression analysis showed that the PFS was significantly shorter in newly diagnosed MM patients with advanced age, type IgG, high ECOG score, decreased platelet count, increased lactate dehydrogenase level, extramedullary disease, and CD56- (all P <0.05), the OS was significantly shorter in patients with high ECOG score, decreased platelet count, increased lactate dehydrogenase level, extramedullary disease, and CD56- (all P <0.05). The results of multivariate Cox regression analysis showed that advanced age, type IgG, elevated lactate dehydrogenase level, extramedullary disease, and CD56- were independent prognostic factors for poor PFS (all P <0.05); and decreased platelet count, elevated lactate dehydrogenase level, and extramedullary disease were independent adverse prognostic factors for OS (all P <0.05), while there was no significant independent correlation between CD56 and OS (P >0.05).@*CONCLUSION@#Most of the newly diagnosed MM patients have positive expression of CD56. Loss of CD56 expression was associated with unfavorable biological and clinical parameters and poor prognosis, suggesting that CD56 has important clinical value in the prognosis of newly diagnosed MM patients.

Analysis of the Prognostic Value and Risk Factors of Early Relapse for Newly Diagnosed Multiple Myeloma Patients in the Era of Novel Agents / 中国实验血液学杂志

OBJECTIVE@#To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma（NDMM） and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment.@*METHODS@#The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival（PFS） was more than 12 months, they were divided into early relapse group（≤12 months） and late relapse group（＞12 months）. The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase（LDH） level, Extramedullary disease (EMD), International Staging System（ISS） stage, Revised International Staging System （R-ISS） stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization（FISH）, and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse.@*RESULTS@#170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups（P<0.001）. Fifteen patients（56.0％）in early relapse group obtained ≥VGPR, and 113（77.9%） patients in late relapse group, the difference was statistically significant（P=0.011）. Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse.@*CONCLUSION@#The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.

Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience / 中华血液学杂志

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

Vasculitis crioglobulinémica por hiperviscosidad y formación de criogel como debut de mieloma múltiple. Caso clínico / Cryoglobulinemic vasculitis due to hyperviscosity and cryogel formation as the onset of multiple myeloma. Report of one case

Multiple Myeloma (MM) is characterized by a clonal expansion of plasma cells in the bone marrow. These cells typically produce a monoclonal immunoglobulin, and its symptoms arise either from plasma cell infiltration in several organs, or secondary to the presence of a monoclonal protein peak. Symptoms can be summarized by the acronym CRAB (hypercalcemia, renal failure, anemia and bone lesions). Sometimes, in the setting of a protein secreting monoclonal gammopathy, formation of cryoglobulins develops. Cryoglobulins are plasma proteins that precipitate at low temperatures, forming a cold - induced precipitate at small vessels, causing a wide range of clinical manifestations. We report a female consulting for ulcers lasting 2 months in the left foot associated with purpuric lesions in both lower limbs. Protein electrophoresis showed a monoclonal peak in the gamma region. Bone marrow aspirate showed 27% of plasma cells with kappa chain restriction by cytometry. The presence of cryoglobulins was confirmed. The patient was treated with dexamethasone and bortezomib, with a progressive healing of lower limb lesions and disappearance of cryoglobulins. She was discharged in good conditions.

Valor diagnóstico de la electroforesis de proteínas y cadenas ligeras libres en suero en el mieloma múltiple / Diagnostic value of serum protein electrophoresis and free light chains in the multiple myeloma's diagnosis

RESUMEN Fundamento: La electroforesis de proteínas y las cadenas ligeras libres en suero son técnicas utilizadas en el diagnóstico del mieloma múltiple. Sin embargo, la utilidad diagnóstica de ambas pruebas puede variar según el método empleado y condiciones reales del medio donde se realicen. Objetivo: Determinar el valor diagnóstico de la electroforesis de proteínas y de las cadenas ligeras libres en suero en el mieloma múltiple. Metodología: Se realizó un estudio retrospectivo de los parámetros electroforesis de proteínas en suero y cadenas ligeras libres en suero a 43 pacientes con diagnóstico de mieloma múltiple por evaluación de la médula ósea. La electroforesis de proteínas se realizó por el método convencional de separación de proteínas sobre papel de acetato de celulosa y para las cadenas ligeras libres se aplicó un ensayo inmunoturbidimétrico en el que se usó un analizador químico (Cobas 311). Se calcularon 7 parámetros que evaluaron la exactitud diagnóstica. Resultados: Todos los parámetros que evaluaron la exactitud diagnóstica estuvieron dentro de los intervalos de confianza en ambas pruebas. Conclusiones: La electroforesis de proteínas y las cadenas ligeras libres en suero son ensayos de gran utilidad en el diagnóstico del mieloma múltiple y se deben utilizar en conjunto para la mayor captación posible de casos.

ABSTRACT Background: Protein electrophoresis and serum free light chains are techniques used in the diagnosis of multiple myeloma. However, the diagnostic utility of both tests may vary according to the method used and the actual conditions of the environment where they are performed. Objective: To determine the diagnostic value of protein electrophoresis and serum free light chains in multiple myeloma. Methodology: A retrospective study of serum protein electrophoresis parameters and serum free light chains was conducted in 43 patients diagnosed with multiple myeloma by bone marrow evaluation. Protein electrophoresis was completed by the conventional method of protein separation on cellulose acetate paper and for free light chains an immunoturbidimetric assay was applied in which a chemical analyzer (Cobas 311) was used. Seven parameters were calculated to evaluate diagnostic accuracy. Results: All parameters assessing diagnostic accuracy were within confidence intervals in both tests. Conclusions: Protein electrophoresis and serum free light chains are very useful assays in the diagnosis of multiple myeloma and should be used in conjunction for the highest possible approval of cases.

Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma / 中华肿瘤杂志

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

Avaliação Radiográfica da Maxila e da Mandíbula de Pacientes Diagnosticados com Mieloma Múltiplo: Estudo Retrospectivo / Radiographic Evaluation of the Maxilla and Mandible of Patients Diagnosed with Multiple Myeloma: Retrospective Study Evaluación / Radiográfica del Maxilar y de la Mandíbula de Pacientes Diagnosticados de Mieloma Múltiple: Estudio Retrospectivo

Introdução: O mieloma múltiplo é caracterizado como uma neoplasia maligna plasmocitária com a proliferação anormal de plasmócitos clonais na medula óssea de etiologia desconhecida. Objetivo: Caracterizar os pacientes com mieloma múltiplo atendidos no Setor de Estômato-Odontologia e Prótese do INCA, por meio de dados sociodemográficos, clínicos, laboratoriais e radiográficos. Método: Estudo transversal retrospectivo de pacientes com diagnóstico de mieloma múltiplo, no período de 2000 a 2018, que realizaram radiografia panorâmica no período do diagnóstico da doença. Os dados sociodemográficos e clínico-radiográficos da população em estudo foram coletados nos prontuários dos pacientes, armazenados em banco de dados, analisados de forma descritiva e submetidos ao teste não paramétrico X2 (qui-quadrado). Resultados: Na amostra final, foram totalizados 163 casos. A maioria era de homens (56,4%), brancos (55,8%), com idade ≤55 anos (54%), ensino fundamental incompleto (30,7%), não fumantes (54,6%) e não bebedores (54,6%). Havia lesões líticas em 46 pacientes (28,2%) com predileção pela mandíbula (82,6%; p=0,000). Houve maior frequência de margens parcialmente definidas (50,0%), não escleróticas (78,2%) e de aspecto unilocular (43,5%). Dos 46 pacientes que apresentaram lesão lítica maxilomandibular, 27 pacientes tinham >55 anos (p=0,042). Conclusão: Há maior ocorrência de lesões ósseas na mandíbula quando comparada à maxila

Introduction: Multiple myeloma is defined as a plasma cells malignant neoplasm with abnormal proliferation of clonal plasma cells in the bone marrow of unknown etiology. Objective: To characterize patients with multiple myeloma treated at INCA's Department of Stomato-Dentistry and Prosthodontics, utilizing sociodemographic, clinical, laboratory and radiographic data. Method: Retrospective cross-sectional study of patients diagnosed with multiple myeloma from 2000 to 2018 who underwent panoramic radiography at the diagnosis of the disease. The sociodemographic and clinical-radiographic data of the study population were collected from the patients' medical records stored in a database, analyzed descriptively and submitted to the X2 non-parametric test (chisquare). Results: In the final sample, 163 cases were totaled, mostly men (56.4%), white (55.8%), aged ≤55 years (54%), with incomplete elementary education (30.7%), non-smokers (54.6%), and non-alcoholics (54.6%). There were lytic lesions in 46 patients (28.2%) concentrated in the mandible (82.6%; p=0.000). Higher frequency of partially defined margins (50.0%), non-sclerotic (78.2%) and unilocular aspect (43.5%) were found. Of the 46 patients who presented with a maxillomandibular lytic lesion, 27 were older than 55 years (p=0.042). Conclusion: There was higher occurrence of bone lesions in the mandible when compared to the maxila

Introducción: El mýeloma multiple se caracteriza por ser una neoplasia maligna de células plasmáticas con proliferación anormal de células plasmáticas clonales en la médula ósea de etiología desconocida. Objetivo: Caracterizar a los pacientes con mýeloma multiple atendidos en el Departamento de Estomato-Odontología y Prostodoncia del INCA, utilizando datos sociodemográficos, clínicos, de laboratorio y radiográficos. Método: Estudio transversal retrospectivo de pacientes diagnosticados de mýeloma multiple de 2000 a 2018 a los que se les realizó una radiografía panorámica durante el período de diagnóstico de la enfermedad. Los datos sociodemográficos y clinicorradiográficos de la población de estudio fueron recolectados de la historia clínica de los pacientes, almacenados en una base de datos, analizados descriptivamente y sometidos a la prueba no paramétrica X2 (chi-cuadrado). Resultados: En la muestra final, había un total de 163 casos, en su mayoría hombres (56,4%), blancos (55,8%), edad ≤55 años (54%), con educación primaria incompleta (30,7%), no fumadores (54,6%) y no bebedores (54,6) %). Hubo lesiones líticas en 46 pacientes (28,2%) con predilección por la mandíbula (82,6%; p=0,000). Hubo una mayor frecuencia de márgenes parcialmente definidos (50,0%), no escleróticos (78,2%) y de apariencia unilocular (43,5%). De los 46 pacientes que tenían lesión lítica maxilomandibular, 27 pacientes tenían >55 años (p=0,042). Conclusión: Existe una mayor ocurrencia de lesiones óseas en la mandíbula en comparación con el maxilar

The Relationship between Hematopoietic Scoring System Composed of HB，PLT and MCV and Prognosis and Curative Effect of Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the prognostic value of hemopoietic scoring system composed of hemoglobin (HB), platelet count (PLT) and mean corpuscular volume (MCV) in MM patients and its correlation with curative effect.@*METHODS@#The clinical data of 172 newly diagnosed MM patients treated by bortezomib as the first-line regimen in our hospital from May 2014 to December 2019 were collected, three variables (HB≤100 g/L, PLT≤150×109/L, MCV≥96 fl) were introduced, each variable was distributed 1 score, the patients were divided into four groups (0, 1, 2 and 3 points in group 1, 2, 3 and 4, respectively), and the clinical characteristics and prognosis of the patients in the four groups were analyzed. The initial efficacy evaluation after 3-4 courses of treatment was carried out, and the curative effect of the patients in the different hematopoiesis score groups were compared.@*RESULTS@#The median OS time of the patients in group 1, 2, 3 and 4 was 27.0, 22.5, 20.7 and 18.1 months, while the median PFS time were 23.0, 19.0, 18.0 and 14.0 months, respectively. The OS and PFS of the patients in low score group were significantly better than those in high score group (P=0.045, P=0.048). There was no significant difference in the curative effect of the patients treated by bortezomib after 3-4 courses (P>0.05).@*CONCLUSION@#Hematopoiesis score can preliminarily predict the overall survival of newly diagnosed MM patients, but there is no significant difference between different scoring groups in the initial curative effect.

Prospective identification of potential factors influencing stem cell mobilization and the necessity for plerixafor use in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation

ABSTRACT Introduction: To study the efficacy and safety of single large volume leukapheresis by using generic G-CSF or G-CSF plus Plerixafor in achieving adequate stem cell yield and various factors influencing thereof in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant . Method: This prospective study was undertaken among 55 newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant and aged between 18 and 75 years. Mobilization and harvesting of stem cells were performed by using GCSF or GCSF plus Plerixafor and large volume leukapheresis, respectively. A stem cell yield of ≥2 × 106 kg-1 and the number of apheresis procedures were primary efficacy endpoints, while the ideal stem cells yield >5 × 106 kg-1, the engraftment day and D100 response/graft sustainability were secondary endpoints. Result: The primary endpoint was achieved in all cases in both the groups by using a single LVL leukapheresis procedure. Fulfillment of all the secondary endpoints was satisfactory and comparable in both the groups. Age, pre-apheresis CD34+ count and number of interruptions during the LVL were significant factors influencing the stem cell yield (p < 0.05). Adverse drug reactions during the apheresis and post-ASCT period were manageable. Conclusion: The LVL is safe and cost-effective in attaining a minimum of CD34+ cells in a single procedure with manageable adverse reactions. Judicious intervention during the procedure may be helpful in ensuring the adequate yield.

Young age and autologous stem cell transplantation are associated with improved survival in newly diagnosed multiple myeloma

ABSTRACT Background: Multiple myeloma is a disease of the elderly. However, 40% of patients are diagnosed before 65 years old. Outcomes regarding age as a prognostic factor in MM are heterogeneous. Method: We retrospectively analyzed clinical characteristics, response to treatment and survival of 282 patients with active newly-diagnosed multiple myeloma, comparing results between patients younger and older than 65 years. Main results: The frequency of multiple myeloma in those younger than 66 years was 53.2%. Younger patients presented with a more aggressive disease, more advanced Durie-Salmon stage (85.3% vs 73.5%; p = 0.013), extramedullary disease (12.7% vs 0%; p < 0.001), osteolytic lesions (78.7% vs 57.6%; p < 0.001) and bone plasmacytoma (25.3% vs 11.4%; p = 0.003). In spite of this, the overall response rate was similar between groups (80.6% vs 81.4%; p = 0.866). The overall survival was significantly longer in young patients (median, 65 months vs 41 months; p = 0.001) and higher in those who received autologous hematopoietic stem cell transplantation. The main cause of death was disease progression in both groups. Multivariable analysis revealed that creatinine ≥2 mg/dl, extramedullary disease, ≤very good partial remission and non-autologous hematopoietic stem cell transplantation are independent risk factors for shorter survival. Conclusion: Although multiple myeloma patients younger than 66 years of age have an aggressive presentation, this did not translate into an inferior overall survival, particularly in those undergoing autologous hematopoietic stem cell transplantation.

Huge Sellar Plasmacytoma as Differential Diagnosis of Invasive Pituitary Adenoma: A Case Report

Sellar plasmacytomas are rare tumors arising from plasma cells. They are often misdiagnosed as adenomas.We report the case of a 63-year-old woman with headache, cranial nerve III palsy and decreased visual acuity. Imaging revealed an extensive lesion centered on the clivus, extending to the cavernous sinus bilaterally and into the sphenoid sinus. The hormonal tests were compatible with panhypopituitarism and mild hyperprolactinemia. The first hypothesis was invasive pituitary adenoma. Partial resection was achieved, and the immunohistochemical evaluation was compatible with plasmacytoma. After a few weeks, she developed lumbar and hip pain, and the imaging confirming osteolytic lesions. The final diagnosis was multiple myeloma.

Encefalite herpética associada a mieloma múltiplo: desafio diagnóstico / Herpetic encephalitis associated with multiple myeloma: a diagnostic challenge

O mieloma múltiplo é a segunda neoplasia onco-hematológica mais comum, correspondendo a 1% das neoplasias malignas. Trata-se de uma condição subdiagnosticada, assim como a encefalite herpética. Entretanto, é comum a relação do mieloma com infecções, em decorrência do acometimento da imunidade humoral. A encefalite viral herpética tem como principal agente o vírus do herpes simples 1. O caso foi descrito baseado em um raciocínio clínico, visando contribuir para uma melhor caracterização do quadro clínico e do diagnóstico de duas entidades clínicas que possuem baixa suspeição diagnóstica e elevada morbimortalidade. Durante o curso da investigação, foram propostas variadas etiologias como responsáveis pelo rebaixamento do nível de consciência, levando a uma pesquisa de um espectro mais amplo de hipóteses diagnósticas, as quais precederam a confirmação do diagnóstico final. O quadro clínico atípico descrito apresentou obstáculos à suspeição diagnóstica correta, pois a ausência dos sinais e sintomas característicos de ambas as doenças levaram à pesquisa de um arsenal mais amplo de diagnósticos diferenciais. Assim, o atraso no diagnóstico e o início tardio do tratamento foram fatores que contribuíram para o prognóstico reservado do paciente. A associação dessas doenças é pouco descrita na literatura, de modo que mais estudos acerca do assunto se fazem necessários. (AU)

Multiple myeloma is the second most common onco-hematologic neoplasm, accounting for 1% of malignant neoplasms. As herpetic encephalitis, it is an underdiagnosed condition. However, the relation of myeloma with infections is common, due to the involvement of humoral immunity. Herpetic encephalitis has as its main etiological agent the herpes simplex virus 1. The case was described based on a clinical reasoning, aiming to contribute to a better characterization of the clinical picture and diagnosis of two entities that have low rates of diagnostic suspicion and high rates of morbidity and mortality. During the course of investigation, several etiologies were proposed as responsible for the decreased level of consciousness, leading to a search for a broader range of diagnostic hypotheses, which preceded confirmation of the final diagnosis. The atypical clinical picture described presented obstacles to the correct diagnostic suspicion, as the absence of symptoms and signs characteristic of both diseases led to the search for a broader arsenal of differential diagnoses. Thus, delayed diagnosis and late treatment were factors that contributed to the patient's reserved prognosis. The association of these diseases is poorly described in the literature, so further studies on that subject are required. (AU)

Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) .@*METHODS@#Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression.@*RESULTS@#Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range.@*CONCLUSION@#Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.

Early Diagnosis of One Multiple Myeloma Patient with Cold Agglutinin Syndrome as the Initial Presentation / 中国实验血液学杂志

OBJECTIVE@#To analyze one case of multiple myeloma (MM) initially presenting cold agglutinin syndrome (CAS), so as to improve clinical understanding and screening of this disease.@*METHODS@#The clinical data, laboratory examination, bone marrow result, diagnosis and treatment of the patient were analyzed and summarized to provide ideas and clinical experience for the early diagnosis and treatment of CAS secondary to MM.@*RESULTS@#The clinical manifestations of asthenia, hemolysis, jaundice and scattered livedo reticularis were caused by CAS secondary to MM, which was different from the general Raynaud's phenomenon. IgMκ type MM was definitely diagnosed according to the morphological features of bone marrow cells and immunofixation electrophoresis. After 3 courses of chemotherapy with BAD regimen and enhanced thermal support, anemia was corrected, M protein was decreased and the cold agglutinin phenomenon was significantly reduced. The evaluation of efficacy reached very good partial response.@*CONCLUSION@#There are very few MM patients with CAS as the initial presentation, so it is easy to misdiagnose. Early diagnosis and individual therapy are particularly important, which requires clinicians to observe and gain experience further.

The Influence of CONUT Score on the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of controlling nutritional status (CONUT) score on the prognosis of newly diagnosed patients with multiple myeloma (MM).@*METHODS@#The clinical data 119 patients with MM who were diagnosed according to the international myeloma diagnostic criteria in Lanzhou University Second Hospital from April 2010 to October 2018 were collected and retrospectively analyzed. The relationship between clinical indexes, including age, sex, MM type, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), hemoglobin (Hb), platelet (PLT), β@*RESULTS@#Compared with high-scoring group, low-scoring group had a better OS ［median OS was 43.3 months and 127.67 months, respectively, 95% confidence interval (CI): 57.065-78.345, P=0.038］. At the same time, the low-scoring group also had higher level of ALC, ANC, AMC, Hb, PLT, ALB, and CHO but lower of GLO. Multivariate survival analysis showed that age (HR=1.027, 95%CI: 1.000-1.054, P=0.048), AMC (HR=11.284, 95%CI: 22.968-42.897, P<0.001), CONUT score (HR=1.198, 95%CI: 1.036-1.385, P=0.015), M protein (non-IgG/IgG type) type (HR=0.503, 95%CI: 0.259-0.977, P=0.043) were independent factors affecting the prognosis of MM patients.@*CONCLUSION@#The CONUT score as an immune-nutrition score is a convenient and easy-to-obtain index to effectively predict the prognosis of MM patients.

Diagnóstico de mieloma múltiplo pelo cirurgião-dentista: relato de caso / Diagnosis of multiple myeloma by the dental surgeon: case report

Objetivo: o mieloma múltiplo é uma neoplasia maligna progressiva de células B, caracterizada pela proliferaçãodesregulada e clonal de plasmócitos na medula óssea. O presente trabalho tem como objetivo descreverum caso clínico de mieloma múltiplo diagnosticado pelo cirurgião-dentista. Descrição do caso: paciente de60 anos, sexo feminino, compareceu à Clínica-escola de Odontologia da Universidade Estadual de Feira deSantana, Bahia, Brasil, cuja queixa principal era: "Tô sentindo uma dor dentro da boca parece que minhaboca soltou". Na história da doença atual, a paciente relatou que há cerca de dois meses, ao mastigar alimentosde consistência dura, observou um estalido e que, a partir de então, a sensação era de uma luxação dearticulação temporomandibular, porém, com uma sintomatologia dolorosa branda. Na história médica, foirelatado que há 3 anos vem apresentando sinais de dor nos ossos, letargia, disfagia, anemia, perda de peso emal-estar crônico. No exame físico extrabucal, foi observado aumento de volume em região de corpo mandibularesquerdo e na clavícula direita. No exame físico intrabucal, foi observado um pequeno aumento devolume na mandíbula do lado esquerdo. Foram solicitados exames de imagem e foi realizada biópsia incisional.Diante do quadro clínico, imaginológico e histológico, chegou-se ao diagnóstico de mieloma múltiplo.Conclusão: é de suma importância conhecer o comportamento clínico epidemiológico do mieloma múltiplo,para que seja realizado um diagnóstico oportuno, abrangente e precoce, com o objetivo de melhorar o prognósticoe a sobrevida do paciente.(AU)

Objective: multiple myeloma is a progressive malignancy of B cells, characterized by unregulated and clonal proliferation of plasma cells in the bone marrow. The present work aims to describe a clinical case of multiple myeloma diagnosed by the dentist. Case description: a 60-year-old female patient attended the Dentistry School of the State University of Feira de Santana, Bahia, Brazil, whose main complaint was: "I feel a pain inside my mouth, it seems that my mouth has loosened". In the history of the current disease, the patient reported that, approximately 2 months ago, when chewing hard food, she noticed a click and that since then the sensation was of a dislocation of the temporomandibular joint, but with mild painful symptoms. In medical history it has been reported that for 3 years it has been showing signs of bone pain, lethargy, dysphagia, anemia, weight loss and chronic malaise. On physical examination, an increase in volume was observed in the region of the left mandibular body and in the right collarbone. On intraoral physical examination, a small increase in volume was observed in the left side of the mandible. Imaging exams were requested and an incisional biopsy was performed. In view of the clinical, imaging and histological picture, the diagnosis of multiple myeloma was reached. Conclusion: it is extremely important to know the epidemiological clinical behavior of multiple myeloma in order to make a timely, comprehensive and early diagnosis, with the aim of improving the patient's prognosis and survival.(AU)