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To retrospectively analyze whether the second revision of the international staging system (R2-ISS) influenced prognosis at treatment initiation in patients with multiple myeloma (MM) receiving anti-CD38 antibody-based triplet treatments. High-risk chromosomal abnormalities were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at the initiation of treatment and defined as "dynamic R2-ISS." Data from 150 patients who underwent the defined treatments were analyzed. The median progression-free survival (PFS) was 19.5 months, and the median overall survival (OS) was 36.5 months. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS. The median PFS for patients with dynamic R2-ISS IV was 3.3 months, and the median OS was 11.7 months, indicating extremely poor outcomes. Although the Revised International Staging System (R-ISS) calculated at the initiation of treatment significantly stratified treatment outcomes, the patients classified as R-ISS could be further stratified by R2-ISS to provide better prognostic information. Dynamic R2-ISS showed potential as a prognostic tool in patients with MM who are treated with anti-CD38 antibody-based triplet therapies.
Asunto(s)
ADP-Ribosil Ciclasa 1 , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Mieloma Múltiple/patología , Masculino , Femenino , ADP-Ribosil Ciclasa 1/antagonistas & inhibidores , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Tasa de Supervivencia , Glicoproteínas de MembranaRESUMEN
INTRODUCTION: Some treatments are associated with cytomegalovirus (CMV) reactivation (CMVRA) in patients with multiple myeloma (MM). However, no reports exist on the association between elotuzumab and CMVRA. Therefore, we assessed the incidence of CMVRA in patients with MM who received elotuzumab therapy. METHODS: The medical records of 85 patients who underwent elotuzumab therapy were included in the retrospective analysis for CMV positivity. RESULTS: Thirty patients were tested for CMV antigenemia during elotuzumab therapy, and 16 were positive for CMV antigenemia; the cumulative incidence rate of CMVRA 6 months after elotuzumab initiation was 18.4%. The history of allogeneic stem cell transplantation (allo-HSCT) was significantly more common in the CMVRA group (31.2%) than that of the group without CMVRA (8.7%). However, even among patients who did not undergo allo-HSCT, the cumulative incidence rate of CMVRA at 6 months was 15.1%. During CMVRA, the symptoms included fever in 8 cases, while retinitis was observed in 1 case. Five patients required antiviral therapy and CMV antigenemia resolved in all but 1 case. CONCLUSION: Although the patient population was heterogeneous, CMVRA cannot be underestimated during elotuzumab therapy, and evaluation of CMVRA, especially in symptomatic cases, is clinically important.
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Background: The ARROW study demonstrated that once-weekly carfilzomib and dexamethasone (wKd) therapy significantly prolonged progression-free survival compared with twice-weekly carfilzomib and dexamethasone therapy in relapsed or refractory multiple myeloma patients. Aim: To describe the treatment patterns, effectiveness and safety of wKd therapy in real-world settings in Japan. Methods: We investigated data from the medical records of 126 Japanese patients with relapsed or refractory multiple myeloma. Results: The overall response rate was 66.3%. The median progression-free survival was 9.5 months. The incidence of treatment-emergent adverse events of any grade and grade ≥3 were 45.8 and 20.8%, respectively. Conclusion: There were no new or unexpected safety signals in this study. This study demonstrated the effectiveness and safety profiles of wKd therapy in Japan.
Carfilzomib became available for daily clinical practice as a drug for cancer of bone marrow (multiple myeloma) that comes back or does not respond to previous drug (relapsed or refractory). This drug was approved in the USA in 2012, and in Japan in 2016. In this study, we looked at how once-weekly carfilzomib works and how safe it is in real-life situations in Japan. We screened 126 patients with relapsed or refractory multiple myeloma in Japan. The median age of the patients was 70 years, with 25% being over 75 years. This study also included some patients who were not in the best overall health, had a history of many treatments or had heart complications. In 66.3% of patients, the cancer had disappeared or the extent of the cancer had reduced after treatment. Side effects and serious side effects occurred in 45.8 and 14.2% of patients, respectively. The most common side effects were low levels of blood platelets (9.2%), high blood pressure (5.8%), loose or watery stools (5.0%), fever (5.0%), and low levels of red blood cells (4.2%). Heart disorders occurred in five patients. But all patients recovered or improved with treatment such as blood pressure lowering drugs and diuretics. These results showed that once-weekly carfilzomib works well and is safe in real-world settings in Japan. This information can help us think about how to pick the right patients and handle heart disease risks when using carfilzomib treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiple , Oligopéptidos , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Oligopéptidos/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Japón/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Anciano de 80 o más Años , Esquema de Medicación , Adulto , Supervivencia sin Progresión , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/epidemiologíaRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment option for multiple myeloma (MM), but few patients are eligible due to its high risk of treatment-related toxicity and relapse. Here, we report the feasibility and efficacy of allo-SCT after myeloablative conditioning with 8 Gy of total body irradiation (TBI) for reducing relapse of MM. We retrospectively analyzed data from 30 consecutive patients who received allo-SCT for MM after 8 Gy of TBI at Japanese Red Cross Medical Center between 2012 and 2021. Median age at allo-SCT was 47 (range 31-61) years. Stem-cell sources were peripheral blood from an HLA-matched related donor (MRD, n=5), bone marrow from an HLA-matched unrelated donor (MUD, n=5), bone marrow from an HLA-mismatched unrelated donor (MMUD, n=13), and cord blood (n=7). All patients received conditioning with 8 Gy of TBI combined with Flu/Mel (n=28) or others (n=2). Five-year PFS and 5-year OS were 36.7% and 46.2%, respectively. Sixteen patients died during the observation period (12 of primary disease and 4 of treatment-related toxicity). Patients with VGPR or better before allo-SCT had significantly better PFS (p=0.009) and OS (p=0.01) than others. Patients who received MMUD cells tended to have better PFS than those with other cell sources. Our report showed that allo-SCT for MM after 8 Gy of TBI is feasible, and the better PFS of MMUD suggests graft-versus-myeloma effects.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Acondicionamiento Pretrasplante , Trasplante Homólogo , Irradiación Corporal Total , Humanos , Mieloma Múltiple/terapia , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Masculino , FemeninoRESUMEN
ANO3 encodes Anoctamin-3, also known as TMEM16C, a calcium-activated chloride channel. Heterozygous variants of ANO3 can cause dystonia 24, an adult-onset focal dystonia. Some pediatric cases have been reported, but most patients were intellectually normal with some exceptions. Here, we report a two-year-old girl who showed mild to moderate developmental delay, tremor, and ataxic gait, but no obvious dystonia. Trio exome sequencing identified a heterozygous de novo missense variant NM_031418.4:c.1809T>G, p.(Asn603Lys) in the ANO3 gene. Three cases with ANO3 variants and intellectual disability have been reported, including the present case. These variants were predicted to face in the same direction on the same alpha-helix (the transmembrane 4 domain), suggesting an association between these variants and childhood-onset movement disorder with intellectual disability. In pediatric cases with developmental delay and movement disorders such as tremor and ataxia, specific variants in the transmembrane 4 domain of ANO3 may be a cause, even in the absence of dystonia.
Asunto(s)
Distonía , Discapacidad Intelectual , Preescolar , Femenino , Humanos , Anoctaminas/genética , Canales de Cloruro/genética , Discapacidades del Desarrollo/genética , Distonía/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , TemblorRESUMEN
Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1 months, during which they received a median of two cycles of VTD-PACE. The overall response rate (ORR) was 66.7%; ORRs of 53.1 and 82.1% were noted in patients with ≥ 4 and ≤ 3 prior lines (P = 0.027), respectively. The median overall survival (OS) was 17 months, with a median progression-free survival (PFS) of 9.8 months. Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and OS of patients who received or did not receive HSCT or CART after VTD-PACE treatment. Patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE showed a trend of longer PFS and OS than those who did not undergo subsequent HSCT or CART. The median OS in patients with and without renal dysfunction was 10.7 months and 21.5 months, respectively (P = 0.0091). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response can be expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Estudios Retrospectivos , Dexametasona , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib , Doxorrubicina , Resultado del TratamientoRESUMEN
This nationwide, multicenter, open-label, single-arm study evaluated the efficacy and safety of the oral proteasome inhibitor (PI), ixazomib plus lenalidomide (LEN) and dexamethasone (DEX) (IRd) following injectable PI-based therapy for relapsed/refractory multiple myeloma (RRMM). Of 45 patients enrolled, 36 patients received IRd after achieving at least a minor response to 3 cycles of bortezomib or carfilzomib plus LEN + DEX (VRd, n=6; KRd, n=30). At median follow-up of 20.8 months, the 12-month event-free survival rate (primary endpoint) was 49% (90% CI: 35.9-62.0), counting 11 events of progressive disease/death, 8 dropouts and 4 missing response data. The 12-month progression-free survival (PFS) rate by Kaplan-Meier analysis (dropouts as censoring) was 74% (95% CI: 56-86). Median PFS and time to next treatment (95% CI) were 29.0 (21.3-NE) and 32.3 (14.9-35.4) months, respectively; median OS was not evaluable. The overall response rate was 73%, and 42% of patients had a very good partial response or better. Frequent (≥10% incidence) grade ≥3 treatment emergent adverse events were decreased neutrophil and platelet counts (n=7 [16%] each). Two deaths occurred (one during KRd treatment and one during IRd treatment), both due to pneumonia. IRd following injectable PI-based therapy was tolerable and efficacious in RRMM patients. TRIAL REGISTRATION NUMBER: NCT03416374; Date of registration: January 31, 2018.
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Mieloma Múltiple , Humanos , Lenalidomida/efectos adversos , Dexametasona , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Isatuximab and daratumumab are anti-CD38 monoclonal antibodies used to treat refractory multiple myeloma. Isatuximab is often used after unsuccessful daratumumab treatment; however, the clinical benefits of receiving isatuximab after daratumumab treatment have not been fully evaluated. Therefore, this retrospective cohort study assessed the clinical outcomes of 39 patients with multiple myeloma who were administered isatuximab after daratumumab. The median follow-up period was 8.7 months (range 0.1-25.0 months). The overall response rate was 46.2% (18 patients). The 1-year overall survival was 53.9%, with a median progression-free survival of 5.6 months. The median progression-free survival in patients with high and normal lactate dehydrogenase levels was 4.5 and 9.6 months, respectively (P = 0.004). The median progression-free survival in patients with and without triple-class refractory disease was 5.1 months and not reached, respectively (P = 0.001). The median overall survival in patients with high and normal lactate dehydrogenase levels was not reached and 9.3 months, respectively (P = 0.001). The median overall survival in patients with and without triple-class refractory disease was 9.9 months and not reached, respectively (P = 0.038). Our findings provide insight into the optimal use and timing of anti-CD38 antibody therapy.
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Mieloma Múltiple , Humanos , Estudios Retrospectivos , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Lactato Deshidrogenasas , DexametasonaRESUMEN
A 28-year-old female was diagnosed with acute myeloid leukemia (AML) due to t (8;21) (q22;q22.1); RUNX1-RUNX1T1 at 21 weeks of gestation. Because no adverse prognostic genetic mutations were discovered, we decided to continue the pregnancy without chemotherapy for as long as possible. After careful monitoring with blood tests every two weeks, the disease did not progress until full-term, and a cesarean section was performed at 39 weeks of gestation. About two months after delivery, blasts in the peripheral blood increased to 46.5%, and myeloblasts in the bone marrow increased to 21.2%. The patient received idarubicin and cytarabine induction therapy, followed by three cycles of high-dose cytarabine consolidation therapy, and complete remission was maintained. Here we report a rare case who could avoid chemotherapy until full-term labor without progression of AML.
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Cesárea , Leucemia Mieloide Aguda , Embarazo , Humanos , Femenino , Adulto , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Translocación Genética , Idarrubicina/uso terapéutico , Citarabina/uso terapéuticoRESUMEN
The IFM/DFCI group reported that VRD induction followed by up-front autologous peripheral blood stem cell transplantation (ASCT) and maintenance therapy led to median PFS of 50 months, which established up-front ASCT as the standard of care even in the era of novel agents. We conducted a retrospective analysis on outcomes of patients who received triplet induction therapy followed by up-front ASCT at our institution. A total of 124 patients received ASCT between November 2016 and December 2021 at Japanese Red Cross Medical Center. Patient characteristics, treatment response before and after ASCT, and PFS and OS were retrospectively analyzed. VRD-based induction therapy was used for 94%. Among 118 evaluable patients, 116 (98%) received either consolidation and/or maintenance therapy. Best responses were ≥CR 77% and ≥VGPR 94%, respectively. Sixty-eight out of 104 patients achieved MRD-negativity by multiparameter FCM (<10-5). Five-year estimated PFS and OS were 54.7% and 80.2%, respectively. Age ≥65, high-risk cytogenetic abnormalities, and Asunto(s)
Trasplante de Células Madre Hematopoyéticas
, Mieloma Múltiple
, Humanos
, Protocolos de Quimioterapia Combinada Antineoplásica
, Bortezomib/uso terapéutico
, Quimioterapia de Inducción
, Mieloma Múltiple/tratamiento farmacológico
, Estudios Prospectivos
, Estudios Retrospectivos
, Trasplante Autólogo
, Resultado del Tratamiento
, Anciano
RESUMEN
Congenital myasthenic syndromes (CMS) is a group of diseases that causes abnormalities at the neuromuscular junction owing to genetic anomalies. The pathogenic variant in ALG14 results in a severe pathological form of CMS causing end-plate acetylcholine receptor deficiency. Here, we report the cases of two siblings with CMS associated with a novel variant in ALG14. Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. Ptosis, low-set ears, and high-arched palate were noted. Deep tendon reflexes were symmetrical. They showed worsening swallowing and respiratory problems; hence, nasal feeding and tracheotomy were performed. Cranial magnetic resonance imaging scans revealed delayed myelination and cerebral atrophy. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14. Repetitive nerve stimulation test showed an abnormal decrease in compound muscle action potential. After treatment with pyridostigmine, the time off the respirator increased. Their epileptic seizures were well controlled by anti-epileptic drugs. Their clinical course is stable even now at the ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant thus far.
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Síndromes Miasténicos Congénitos , Exones , Humanos , Mutación , Síndromes Miasténicos Congénitos/complicaciones , Síndromes Miasténicos Congénitos/diagnóstico , Síndromes Miasténicos Congénitos/genética , Hermanos , Sobrevivientes , Secuenciación del ExomaRESUMEN
Almost 40% of medical radiation exposure is related to cardiac imaging or intervention. However, the biological effects of low-dose radiation from medical imaging remain largely unknown. This study aimed to evaluate the effects of ionized radiation from cardiac catheterization on genomic DNA integrity and inflammatory cytokines in patients and operators.Peripheral mononuclear cells (MNCs) were isolated from patients (n = 51) and operators (n = 35) before and after coronary angiography and/or percutaneous coronary intervention. The expression of γH2AX, a marker for DNA double-strand breaks, was measured by immunofluorescence. Dicentric chromosomes (DICs), a form of chromosome aberrations, were assayed using a fluorescent in situ hybridization technique.In the patient MNCs, the numbers of γH2AX foci and DICs increased after cardiac catheterization by 4.5 ± 9.4-fold and 71 ± 122%, respectively (P < 0.05 for both). The mRNA expressions of interleukin (IL)-1α, IL-1ß, leukemia inhibitory factor, and caspase-1 were significantly increased by radiation exposure from cardiac catheterization. The increase in IL-1ß was significantly correlated with that of γH2AX, but not with the dose area product. In the operators, neither γH2AX foci nor the DIC level was changed, but IL-1ß mRNA was significantly increased. The protein expression of IκBα was significantly decreased in both groups.DNA damage was increased in the MNCs of patients, but not of operators, who underwent cardiac catheterization. Inflammatory cytokines were increased in both the patients and operators, presumably through NF-κB activation. Further efforts to reduce radiation exposure from cardiac catheterization are necessary for both patients and operators.
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Exposición a la Radiación , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/métodos , Citocinas , Daño del ADN , Humanos , Hibridación Fluorescente in Situ , ARN Mensajero , Exposición a la Radiación/efectos adversosRESUMEN
Chromosome rearrangements, which are structural chromosomal abnormalities commonly found in human cancer, result from the misrejoining between two or more DNA double-strand breaks arising at different genomic regions. Consequently, chromosome rearrangements can generate fusion genes that promote tumorigenesis. The mechanisms of chromosome rearrangement have been studied using exogenous double-strand break inducers, such as radiation and nucleases. However, the mechanism underlying the occurrence of chromosome rearrangements in the absence of exogenous double-strand break-inducing stimuli is unclear. This study aimed to identify the major source of chromosome rearrangements and the DNA repair pathway that suppresses them. DNA repair factors that potentially suppress gene fusion were screened using The Cancer Genome Atlas dataset. In total, 22 repair factors whose expression levels were negatively correlated with the frequency of gene fusion were identified. More than 60% of these repair factors are involved in homologous recombination, a major double-strand break repair pathway. We hypothesized that DNA single-strand breaks are the source of double-strand breaks that lead to chromosome rearrangements. This study demonstrated that hydrogen peroxide (H2O2)-induced single-strand breaks gave rise to double-strand breaks in a replication-dependent manner. Additionally, H2O2 induced the formation of RPA and RAD51 foci, which indicated that double-strand breaks derived from single-strand breaks were repaired through homologous recombination. Moreover, treatment with H2O2 promoted the formation of radial chromosomes, a type of chromosome rearrangements, only upon the downregulation of homologous recombination factors, such as BRCA1 and CtIP. Thus, single-strand breaks are the major source of chromosome rearrangements when the expression of homologous recombination factors is downregulated.
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Cromosomas/genética , Reordenamiento Génico/genética , Recombinación Homóloga/genética , Células Cultivadas , Cromosomas/efectos de los fármacos , Cromosomas/metabolismo , Roturas del ADN de Doble Cadena/efectos de los fármacos , Reparación del ADN , Reordenamiento Génico/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/farmacologíaRESUMEN
Minimal residual disease (MRD)-negative status in multiple myeloma (MM) is associated with favorable outcomes. Although EuroFlow next-generation flow (NGF) is a global standard for MRD detection, its operating cost is high. Therefore, it is desirable to develop a less expensive method with equivalent sensitivity to that of EuroFlow-NGF. In this study, we compared the analytical ability of our BML 10-color multiparameter flow cytometry (MFC) to that of EuroFlow-NGF. Bone marrow samples collected from 51 patients with MM were subjected to MRD detection using BML 10-color-MFC and EuroFlow-NGF. Our antibody panel consisted of CD38 multiepitope, CD138, CD45, CD56, CD19, CD27, CD81, CD117, cytoplasmic immunoglobulin (cIg) κ, and cIgλ in a single tube. The median percentages of total plasma cells, as per 10-color-MFC and EuroFlow-NGF, were 0.2148% and 0.2200%, respectively, with a good correlation between the methods (r = 0.950). The median percentages of myeloma cells determined via 10-color-MFC and EuroFlow-NGF were 0.0012% and 0.0007%, respectively, with a strong correlation (r = 0.954). Our 10-color-MFC demonstrated high sensitivity to detect MRD; the results showed a good correlation with those obtained using EuroFlow-NGF. Therefore, our cost-effective single-tube MFC (approximately 100 USD/sample) is a promising alternative method for the detection of MRD in patients with MM.
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Citometría de Flujo/métodos , Mieloma Múltiple/diagnóstico , Neoplasia Residual/diagnóstico , Adulto , Anciano , Antígenos CD/análisis , Médula Ósea/patología , Femenino , Humanos , Inmunoglobulinas/análisis , Masculino , Persona de Mediana EdadRESUMEN
These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rates (ORRs), and safety. Eighty-three eligible patients were enrolled between October 2012 and August 2014. The median PFS was 28.0 months (95% CI 19.6-36.7) and the median OS was 55.3 months (95% CI 51.6-NA). Among the patients who received lenalidomide maintenance therapy, median PFS was significantly improved in patients who had achieved a very good partial response (VGPR) or better (41.8 vs 20.7 months, p = 0.0070). As the best response, the rates of partial response or better were 85.5% comprising stringent complete response (sCR, 21.7%), complete response (CR, 10.8%), VGPR (18.1%), and partial response (PR, 34.9%). The most frequently observed grade 3 or higher adverse events during the VMP therapy were anemia (28.9%), neutropenia (15.6%), thrombocytopenia (6.0%), and peripheral neuropathy (2.4%). The most frequently observed grade 3 or higher adverse events during the Rd therapy were anemia (3.5%), neutropenia (1.8%), and skin rush (5.3%). The most frequently observed grade 3 or higher adverse events during lenalidomide maintenance therapy were anemia (7.4%) and neutropenia (24.1%). Thus, VMP induction therapy followed by Rd consolidation and lenalidomide maintenance is considered a well-tolerated and effective regimen in transplant-ineligible NDMM. This trial is registered with UMIN-CTR with the identification number UMIN000009042.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Tasa de SupervivenciaRESUMEN
OBJECTIVES: Bortezomib with lenalidomide and dexamethasone (VRd) is a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). However, some patients discontinue VRd because of severe adverse events, despite its high efficacy. We aimed to study the efficacy of modified dose of VRd (VRd lite) in transplant-eligible patients with NDMM. METHODS: Forty-eight transplant-eligible patients with NDMM were included. VRd lite was administered every 4 weeks. Bortezomib 1.3 mg/m2 was administered subcutaneously on days 1, 8, 15 and 22, and dexamethasone 20 mg was administered orally on the day of and the day after bortezomib administration. Lenalidomide was omitted on days 1, 8 and 15, which are the days of bortezomib administration. RESULTS: The overall response rate (ORR) after four cycles of VRd lite was 83%, including a complete response of 25%. Thirty-eight among the 45 patients who completed at least four cycles of VRd lite received autologous stem cell transplantation (ASCT). The ORR and very good partial response or better were upgraded to 100% and 74%, respectively, following ASCT. CONCLUSION: Our strategy consisting of VRd lite followed by ASCT is, thus, a highly effective and well-tolerated regimen resulting in durable responses in patients with NDMM.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Autoinjertos , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Humanos , Lenalidomida/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Estudios RetrospectivosRESUMEN
Plerixafor is increasingly used in combination with granulocyte-colony-stimulating factor (G-CSF) for peripheral blood stem cell collection. Although it is an expensive drug, its cost-benefit performance is not well investigated. Thus, we analyzed its cost-effectiveness in our hospital. A retrospective observational analysis was performed in patients who underwent stem cell collection between December 2013 and November 2018. A total of 203 patients were investigated and classified into three groups according to their pre-mobilization regimen: G-CSF alone, G-CSF and cyclophosphamide (G+CY), and G-CSF and plerixafor (G+plerixafor). The cost-effectiveness of apheresis of the collected cluster of differentiation (CD) 34+ cells was assessed based on two viewpoints: cost of drugs and cost of equipment. Due to the high cost of plerixafor, the cost of apheresis was higher in patients who received G+plerixafor. However, the difference narrowed when we calculated the cost to collect 2.0×106 CD34+ cells/kg body weight required for a single transplant. The number of stem cells collected from patients who received G+plerixafor was higher than those who received other regimens (median CD34+ cells harvested/day were 2.90 for G-CSF, 2.13 for G+CY, and 4.63 for G+plerixafor, ×106/kg body weight, P<0.01). Our results show that plerixafor enables efficient apheresis.
Asunto(s)
Compuestos Heterocíclicos/uso terapéutico , Células Madre de Sangre Periférica , Antígenos CD34 , Bencilaminas , Análisis Costo-Beneficio , Ciclamas , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Humanos , Mieloma Múltiple/terapia , Estudios RetrospectivosRESUMEN
Unbalanced translocations of Y-chromosomal fragments harboring the sex-determining region Y gene (SRY) to the X chromosome or an autosome result in 46,XX and 45,X testicular disorders of sex development (DSD), respectively. Of these, Y;autosome translocation is an extremely rare condition. Here, we identified a 20-year-old man with a 45,X,t(Y;7)(q11.21;q35) karyotype, who exhibited unilateral cryptorchidism, small testis, intellectual disability, and various congenital anomalies. The fusion junction of the translocation was blunt, and the breakpoint-flanking regions shared only 50% similarity. These results indicate that Y;autosome translocations can occur between 2 low-similarity sequences, probably via nonhomologous end joining. Furthermore, translocations of a Ypterq11.21 fragment to 7q35 likely result in normal or only mildly impaired male-type sexual development, along with various clinical features of 7q deletion syndrome, although their effects on adult testicular function remain to be studied.