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Residual normal plasma cells (NPCs), which compete with tumor plasma cells, play an important role in multiple myeloma. However, large-scale cohort studies investigating residual NPCs, especially at the minimal residual disease (MRD) phase, are currently lacking. In this study, we conducted a comprehensive investigation into the clinical significance of residual NPCs throughout the entire disease course in 1363 myeloma patients from the NICHE cohort (NCT04645199). Our results revealed that myeloma patients with high baseline NPCs ratio (≥5%) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPCs ratio at diagnosis or relapse was independently associated with favorable survival. High absolute percentages of NPCs at undetectable MRD were related with superior clinical benefit and immune reconstitution. At MRD-positive phases, grouping based on NPCs ratio (<50%, 50-90%, ≥90%) demonstrated better risk stratification compared to residual tumor log levels. Based on the time-dependent NPCs ratio trend, we developed a dynamic MRD model that classifies patients into three groups with diverse longitudinal trends, leading to distinct prognoses. Collectively, residual NPCs serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.
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Rabbit hemorrhagic disease virus (RHDV) can cause fatal fulminant hepatitis, which is very similar to human acute liver failure. The aim of this study was to investigate whether adipose-derived stem cells (ADSCs) could alleviate RHDV2-induced liver injury in rabbits. Twenty 50-day-old rabbits were divided randomly into two groups (RHDV2 group, ADSCs + RHDV2 group). Starting from the 1st day, two groups of rabbits were given 0.5 ml of viral suspensions by subcutaneous injection in the neck. Meanwhile, the ADSCs + RHDV2 group was injected with ADSCs cell suspension (1.5 × 107 cells/ml) via a marginal ear vein, and the RHDV2 group was injected with an equal amount of saline via a marginal ear vein. At the end of the 48 h experiment, the animals were euthanized and gross hepatic changes were observed before liver specimens were collected. Histopathological analysis was performed using hematoxylin-eosin (HE), periodic acid schiff (PAS) and Masson's trichrome staining. For RHDV2 affected rabbits, HE staining demonstrated disorganized hepatic cords, loss of cellular detail, and severe cytoplasmic vacuolation within hepatocytes. Glycogen was not observed with PAS staining, and Masson's Trichrome staining showed increased hepatic collagen deposition. For rabbits treated with ADSCs at the time of inoculation, hepatic pathological changes were significantly less severe, liver glycogen synthesis was increased, and collagen fiber deposition was decreased. For RHDV2 affected rabbits, Tunel and immunofluorescence staining showed that the number of apoptotic cells, TGF-ß, and MMP-9 protein expression increased. And that in the ADSC treated group there was less hepatocyte apoptosis. In addition, RHDV2 induces liver inflammation and promotes the expression of IL-1ß, IL-6, and TNF-α. In rabbits administered ADSCs at time of inoculation, the expression of inflammatory factors in liver tissue decreased significantly. Our experiments show that ADSCs can protect rabbits from liver injury by RHDV2 and reduce the pathological and inflammatory response of liver. However, the specific protective mechanism needs further study.
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Tecido Adiposo , Vírus da Doença Hemorrágica de Coelhos , Animais , Coelhos , Vírus da Doença Hemorrágica de Coelhos/fisiologia , Tecido Adiposo/citologia , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/terapia , Fígado/patologia , Transplante de Células-Tronco/métodos , Células-Tronco , Apoptose , Masculino , Distribuição AleatóriaRESUMO
PURPOSE: We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma. EXPERIMENTAL DESIGN: A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10-5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated. RESULTS: Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26-7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12-0.52) and overall survival (HR, 0.16; 0.06-0.40). CONCLUSIONS: EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.
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Mieloma Múltiplo , Humanos , Neoplasia Residual/diagnóstico , Prognóstico , Sensibilidade e Especificidade , Citometria de Fluxo/métodosRESUMO
Prognostic significance of multiple immune antigens in multiple myeloma has been well established. However, a level of uncertainty remains regarding the intrinsic relationship between immunophenotypes and cytogenetic stability and precise risk stratification. To address these unresolved issues, we conducted a study involving 1389 patients enrolled in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Our results revealed that the correlation between antigen expression and cytogenetics is more prominent than cytopenia or organ dysfunction. Most immune antigens, apart from CD38, CD138, and CD81, exhibit significant associations with the incidence of at least one cytogenetic abnormality. In turn, we identified CD138-low/CD27-neg as specific adverse immunophenotypic profile, which remaining independent impact on progression-free survival (HR, 1.49; P = 0.007) and overall survival (HR, 1.77; P < 0.001) even in the context of cytogenetics. Importantly, CD138-low/CD27-neg profile was also associated with inferior survival after first relapse (P < 0.001). Moreover, the antigen expression profiles were not strictly similar when comparing diagnosis and relapse; in particular, the CD138-low/CD27-neg pattern was notably increased after disease progression (19.1 to 29.1%; P = 0.005). Overall, our study demonstrates that diverse immune profiles are strongly associated with cytogenetic stability, and a specific immunophenotype (CD138-low/CD27-neg) could effectively predict prognoses across different disease stages.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico , Aberrações Cromossômicas , Análise Citogenética , RecidivaRESUMO
Objective: To explore clinical effects of neoadjuvant chemotherapy (NAC) in treating breast cancer. Materials and Methods: Retrospective analysis was performed among 26 breast cancer patients receiving NAC. Chemotherapeutic effects were evaluated using Response Evaluation Criteria In Solid Tumors (RECIST), Japanese Breast Cancer Society (JBCS) grading, and Miller and Payne (MP) grading. Results: After chemotherapy, the percentage of tumor cells was significantly reduced, but chemotherapeutic period possessed no dramatic influence on curative effects. Among 20 patients with complete data, 2 achieved clinically complete response (CR), 10 showed partial response (PR), 4 had stable disease (SD), and 4 exhibited progress disease (PD). The total effective rate (CR + PR) of NAC was 60% (12/20). Besides, evaluation results from RECIST were generally in line with those from JBCS grading and MP grading. Conclusion: NAC is effective among the majority of patients with breast cancer. In addition, tumor size determined through clinical palpation is generally in accordance with responses to chemotherapy, and consistent performance is observed for three systems in grading responses to chemotherapy.
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Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Feminino , Humanos , Estudos RetrospectivosRESUMO
INTRODUCTION: The translocation t(8;21) is one of the most frequent chromosome translocations in AML. Molecular (cyto)genetics is regarded as the gold standard for diagnosis. However, due to the complicated variety of AML-related genetic abnormalities, comprehensive screening for all of these abnormalities may not be cost-effective. Therefore, a flow cytometric (FC) scoring system was generated in this study for rapid screening and diagnosis of t(8;21)AML. METHODS: The immunophenotypic characteristics of leukemic cells and neutrophils in cases with t(8;21) AML or other subtypes of AML were analyzed to find a method for the flow diagnosis of t(8;21) AML. RESULTS: In this study, we picked six FC features pointing to the diagnosis of t(8;21) AML: The blasts show high-intensity expression of CD34; aberrant expression of CD19, cCD79a, and CD56 in myeloblasts; co-expression of CD56 in neutrophils, especially in immature neutrophils; and a maturity disturbance in granulocytes. A six-point score was devised using these features. By ROC analysis, the AUC was 0.952, and the sensitivity, specificity, PPV, and NPV were 0.86, 0.90. 0.91, and 0.84 when the score was ≥3 points. The score was then prospectively validated on an independent cohort, and the AUC of the ROC curve for the validation cohort was 0.975. When the cutoff value was set at 3, the obtained sensitivity and specificity values were 0.91 and 0.94, respectively. CONCLUSIONS: The FC score described can be used for the identification and rapid screening of t(8;21) AML.
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Citometria de Fluxo/métodos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Translocação Genética , Área Sob a Curva , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/patologia , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Elevated inflammatory markers are associated with poor outcomes in various types of cancers; however, their clinical significance in multiple myeloma (MM) have seldom been explored. This study investigated the prognostic relevance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in MM. Totally 559 MM patients were included in this study. NLR, PLR and MLR were calculated from whole blood counts prior to therapy. Kaplan-Meier curves and multivariate Cox proportional models were used for the evaluation of the survival. It has shown that newly diagnosed MM patients were characterized by high NLR and MLR. Elevated NLR and MLR and decreased PLR were associated with unfavorable clinicobiological features. Applying cut-offs of 4 (NLR), 100 (PLR) and 0.3 (MLR), elevated NLR, MLR and decreased PLR showed a negative impact on outcome. Importantly, elevated NLR and decreased PLR were independent prognostic factors for progression-free survival. Thus, elevated NLR and MLR, and decreased PLR predict poor clinical outcome in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.
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Biomarcadores Tumorais/imunologia , Contagem de Leucócitos , Mieloma Múltiplo/imunologia , Adulto , Idoso , Área Sob a Curva , Plaquetas , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Neutrófilos , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To evaluate the mutation frequency of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 and the value of the combined tests in the diagnosis of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). METHODS: In the current study, mutations of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 were analyzed in 929 Chinese patients with BCR-ABL1-negative MPN, including 234 cases of polycythemia vera (PV), 428 ETs, 187 PMFs, and 80 unclassifiable MPNs (MPN-Us). RESULTS: Our result showed that the positive rate of any of four mutations in patients with PV, ET, PMF, and MPN-U was 89.3%, 83.4%, 87.2%, and 77.5%, respectively, which significantly improved the diagnostic rate, especially in ET and PMF. Meanwhile, we also found that the patients without any of four mutations were younger than those with one or more mutations. Unexpectedly, the coexistence of JAK2 V617F and CALR exon 9 was identified in six (0.6%) patients, and JAK2 V617F and MPL exon 10 were present simultaneously in two (0.2%) patients. In addition, we also identified several novel mutation types in CALR exon 9. CONCLUSIONS: The combined genetic tests of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 help improve the diagnostic rate for BCR-ABL1-negative MPN.
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Calreticulina/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Receptores de Trombopoetina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Proteínas de Fusão bcr-abl , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
PURPOSE: Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value. EXPERIMENTAL DESIGN: We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma. RESULTS: We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%-10%, 10.5%-20%, 20.5%-50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes. CONCLUSIONS: Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality.
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Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Aberrações Cromossômicas , Ciclofosfamida/administração & dosagem , Análise Citogenética , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Prognóstico , Talidomida/administração & dosagemRESUMO
Multiple myeloma (MM) is a heterogeneous disease, and the benefit from bortezomib treatment is not uniform among all patients subgroups. Currently, little information is available to predict patients response to bortezomib treatment. In this study, we aimed to identify patients benefiting minimally from bortezomib as part of first-line therapy and to define high-risk MM in the context of bortezomib treatment. We compared the effect of a bortezomib-based treatment (arm B) with that of a treatment without bortezomib (arm A) on different genetic patient subgroups in a series of 273 cases of newly diagnosed MM. These patients were enrolled in a prospective, non-randomized clinical trial (BDH 2008/02). A subgroup of patients exhibiting little benefit from bortezomib treatment was identified. These patients had at least one of the following characteristics: del(17p13), 1q21 gain, or high lactate dehydrogenase levels. In this subgroup, survival of patients treated with bortezomib was comparable (progression-free survival: 14.0 vs. 15.0 months, p = 0.992; overall survival: 21.0 vs. 14.0 months, p = 0.472) to that of patients undergoing thalidomide-based treatment. We propose that all patients with newly diagnosed MM should be evaluated for these three markers before bortezomib treatment. Other novel drugs and alternative therapeutic strategies are needed for patients with such markers.
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Ácidos Borônicos/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mutação/genética , Pirazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Bortezomib , Aberrações Cromossômicas , Humanos , L-Lactato Desidrogenase/sangue , Pessoa de Meia-Idade , Mieloma Múltiplo/enzimologia , Mieloma Múltiplo/genética , Análise Multivariada , Valor Preditivo dos Testes , Fatores de Risco , Análise de Sobrevida , Talidomida/uso terapêuticoRESUMO
The common features shared by primary plasma cell leukemia (pPCL) and multiple myeloma (MM) with circulating plasma cells (CPCs) are peripheral blood invasion and expansion of plasma cells independent of the protective bone marrow (BM) microenvironment niche. However, few studies have addressed the relationship between pPCL and MM with CPCs. Here, we quantitated the number CPCs by conventional morphology in 767 patients with newly diagnosed MM; their clinic features were compared with those of 33 pPCL cases. When the presence of CPCs was defined as more than 2 % plasma cells per 100 nucleated cells on Wright-Giemsa stained peripheral blood smears, the incidence of MM with CPCs was 14.1 % in newly diagnosed MM. Patients with CPCs shared many clinical features with pPCL, especially clinical parameters related to tumor burden. However, no commonalities were found in immunophenotyping and cytogenetics. The prognosis of pPCL was poor, with a median progression free survival (PFS) of 12 months and an overall survival (OS) of 15 months. MM patients with CPCs had a clearly inferior PFS and OS as compared with the control cohort. Most interestingly, although the CPCs were not high enough to meet the diagnostic criteria for pPCL, the survival of MM patients with CPCs was comparable with that of pPCL, with a median PFS of 17 months and an OS of 25 months.
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Leucemia Plasmocitária/patologia , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Terapia Combinada , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Plasmócitos/metabolismo , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
Normal plasma cells (PCs) are either undetectable or outnumbered by the myelomatous PC compartment in bone marrow of multiple myeloma (MM). However, residual normal PCs have been detected in a minority of symptomatic MM patients with superior survival. The number of normal PCs is also an important factor to identify monoclonal gammopathy of undetermined significance (MGUS)-like MM. We speculate that the polyclonal serum IgM level in non-IgM myelomas may reflect the number of residual normal PCs. Here we investigated the prognostic relevance of polyclonal serum IgM level in a series of 485 newly diagnosed symptomatic MM (NDMM) patients. Our results showed that symptomatic MM patients with polyclonal IgM more than 0.5g/L displayed a favorable baseline clinical feature, together with a significantly lower frequency of high-risk cytogenetic abnormalities. This group of patients had a significantly prolonged progression-free survival (PFS) and overall survival (OS) regardless of thalidomide or bortezomib therapy. Furthermore, the superior outcome was independent of the depth of response. Our findings suggest that polyclonal IgM level is capable of identifying a group of symptomatic MM patients with distinct clinicobiological characteristics and favorable survival, similar with MGUS-like MM.
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Imunoglobulina M/sangue , Mieloma Múltiplo/imunologia , Antígenos CD19/sangue , Ácidos Borônicos/uso terapêutico , Bortezomib , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-kit/sangue , Pirazinas/uso terapêuticoRESUMO
Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon that occurs during the treatment of multiple myeloma (MM). The incidence, biological characteristics, and prognostic value of secondary MGUS in patients with MM remain undefined. We proceed with a retrospective systematic review of serum immunofixation electrophoresis studies performed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia. Secondary MGUS was more common in patients with myeloma who had undergone stem cell transplantation than in those who had not (17 [29.8%] of 57 versus 5 [1.4%] of 352, P < .001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The complete response rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (P < .01). For the cohort as a whole, secondary MGUS was associated with significantly prolonged progression-free survival (median, 52.0 months versus 22.5 months; P = .002) and overall survival (median, not reached versus 35.0 months; P < .001). The presence of secondary MGUS retained independent prognostic value with a moderate impact on overall survival (hazard ratio .128 [95% confidence interval .018 to .922]; P = .041) in the multivariate Cox regression model. However, when analysis was restricted to patients undergoing stem cell transplantation, no statistical differences in progression-free survival and overall survival were found. In conclusion, we observe that secondary MGUS was frequently observed in MM patients after transplantation and conferred a survival prolongation. The favorable survival in patients with secondary MGUS may be explained by beneficial effect from myeloablative therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Transplante de Células-Tronco Hematopoéticas , Leucemia Plasmocitária/terapia , Gamopatia Monoclonal de Significância Indeterminada/terapia , Mieloma Múltiplo/terapia , Adulto , Idoso , Ácidos Borônicos/administração & dosagem , Bortezomib , Progressão da Doença , Feminino , Humanos , Leucemia Plasmocitária/complicações , Leucemia Plasmocitária/imunologia , Leucemia Plasmocitária/mortalidade , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/etiologia , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Gamopatia Monoclonal de Significância Indeterminada/mortalidade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Prognóstico , Pirazinas/administração & dosagem , Estudos Retrospectivos , Análise de Sobrevida , Talidomida/administração & dosagem , Transplante AutólogoRESUMO
Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.
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Antineoplásicos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Cromossomos Humanos Par 1/genética , Dosagem de Genes , Mieloma Múltiplo , Plasmócitos , Pirazinas/administração & dosagem , Adulto , Idoso , Bortezomib , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Taxa de SobrevidaRESUMO
UNLABELLED: t(11;14)(q13;q32) is the most common chromosome translocation in multiple myeloma (MM), but a consensus of clinicopathological features and impact on survival is yet to be reached. We analyzed a cohort of 350 patients with various plasma cell malignancies, including newly diagnosed MM (NDMM, n=253), relapsed/refractory MM (RRMM, n=77), as well as primary and secondary plasma cell leukemia (PCL, n=10 and n=10, respectively). RESULTS: A remarkably higher frequency of t(11;14) was observed in the PCL than in the NDMM. A high incidence of t(11;14) was detected in the IgD, IgM, and nonsecretory MM. The t(11;14) MM group was associated with a significantly higher positive rate of B-lineage associated antigens CD20 and CD79a as well as the lack of CD56 expression. t(11;14) was less likely to be accompanied by 13q14 deletion than 13q14 deletion frequency in non-t(11;14) population (p=0.026), and fewer patients displaying t(11;14) were identified as belonging to the high-risk cytogenetic group due to the extremely low incidence of t(4;14) and t(14;16). As a whole, patients exhibiting t(11;14) had a comparable outcome with the control cohort in NDMM, but CD20 was able to identify two subsets of the disease with dissimilar outcomes. Among patients receiving bortezomib-based treatment, patients harboring t(11;14) without CD20 expression had a significantly shortened PFS (11.0 versus 43.0 months, p=0.005) and OS (16.5 versus 54.0 months, p=0.016) compared with patients displaying t(11;14) with CD20. Our findings suggest that although the t(11;14) plasma cell disorder displayed distinct biological, clinical and laboratory features, it was a heterogeneous disease with divergent outcome.
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Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Mieloma Múltiplo/genética , Translocação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Plasmócitos/metabolismo , Plasmócitos/patologia , PrognósticoRESUMO
OBJECTIVE: To study the cytogenetic characteristics of B cell non-Hodgkin's lymphoma (B-NHL) with bone marrow involvement, and to explore the clinical significance and prognosis. METHODS: Clinical data of 126 B-NHL patients with bone marrow involvement diagnosed in our hospital were retrospectively analyzed. Chromosome banding analysis was performed after 24 h culture. RESULTS: (1) The B-NHLs included were diffuse large B-cell lymphoma (DLBCL) 38.9% (49 cases), lymphoplasmacytic lymphoma (LPL) 19% (24 cases), mantle cell lymphoma (MCL) 16.7% (21 cases), follicular lymphoma (FL) 9.5% (12 cases), marginal zone lymphoma (MZL) 8.7% (11 cases) and small lymphocytic lymphoma (SLL) 7.1%(9 cases). (2) Chromosome aberrations (CA) were detected in 52 of 126 patients (41.3%) by conventional cytogenetics (CC), including clonal CA 38 cases, and non-clonal CA 14 cases. Ploidy levels in 38 clonal CA cases were pseudodiploid (57.9%), hypodiploid (15.8%) and hyperdiploid (26.3%). The incidence of chromosomal abnormalities among DLBCL, MCL, MZL, LPL, FL and SLL was 73.4%, 38.1%, 36.4%, 8.3%, 8.3% and 11.1%, respectively. (3) Clonal CA, CA more than two kinds, and CA of chromosomes 2, 3, 9, 11, 17, 18 and 20 were associated with shorter overall survival (OS) in DLBCL. More than two kinds of CA and CA of chromosome 3, 13 were associated with shorter OS in MCL. CONCLUSIONS: The incidence of CA was higher in aggressive lymphoma than in indolent lymphoma. Complex CA were quite common, and some specific CA might have prognostic significance.