RESUMEN
The prognosis of primary plasma cell leukemia (pPCL) is poor, and the relevant prognostic factors are incompletely understood. We aimed to explore the prognostic factors and develop a validated prognostic prediction model for pPCL patients in the new era. This multicenter retrospective study was conducted across 16 hospitals in China. Cox proportional hazards regression analysis was used to develop a prediction model. The predictive performance of the model was assessed using multiple metrics. Internal validation was conducted using bootstrap resampling. A total of 102 pPCL patients were included in this study, and 57 (55.9%) were male. The 12-month, 24-month, and 36-month OS rates for pPCL patients were 75.4%, 58.3%, and 47.6%, respectively. An overall survival prognostic nomogram for pPCL patients was established by integrating independent prognostic factors, including age, B2MG, and del17p. The nomogram exhibited good performance, with a C-index of 0.720 (95% CI 0.642-0.797) and an AUC of 0.653. Bootstrap validation yielded a C-index of 0.721 (95% CI 0.629-0.787) and an AUC of 0.653 (95% CI 0.546-0.759), indicating a relatively good fit of the calibration curve. A nomogram incorporating age, B2MG grade, and del17p were developed and validated to accurately and consistently predict the prognosis of pPCL patients.
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Leucemia de Células Plasmáticas , Nomogramas , Humanos , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Femenino , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/terapia , Leucemia de Células Plasmáticas/tratamiento farmacológico , Anciano , Pronóstico , Adulto , Tasa de Supervivencia , Anciano de 80 o más Años , China/epidemiologíaRESUMEN
Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated. The phenotypic profile of the PCs was also analysed to determine if there is an association with clinical outcomes and to evaluate the prognostic value of analysed markers. Our results revealed that FC is an excellent method for identifying circulating PCs as a significantly higher number was identified by FC than by morphology (26·7% vs. 13·5%, P = 0·02). None of secondary PCL cases expressed CD19 or CD20. A low level of expression with similar positivity of CD27, CD28, CD81 and CD117 was found in both PCL groups. A decrease of CD44 expression was detected only in secondary PCL. Expression of CD56 was present in more than half of PCL cases as well as cytoplasmic nestin. A decreased level of platelets, Eastern Cooperative Oncology Group score of 2-3 and lack of CD20+ PC were associated with a higher risk of death. FC could be incorporated in PCL diagnostics not only to determine the number of circulating PCs, but also to assess their phenotype profile and this information should be useful in patients' diagnosis and possible prognosis.
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Recuento de Células Sanguíneas , Citometría de Flujo/métodos , Leucemia de Células Plasmáticas/sangre , Células Neoplásicas Circulantes , Células Plasmáticas , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Antígenos de Neoplasias/análisis , Recuento de Células Sanguíneas/métodos , Médula Ósea/patología , Células de la Médula Ósea/química , Detección Precoz del Cáncer , Reacciones Falso Negativas , Femenino , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Células Plasmáticas/química , Células Plasmáticas/ultraestructura , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Secondary plasma cell leukaemia (sPCL) is an aggressive form of multiple myeloma (MM), but the mechanism underlying MM progresses into PCL remains unknown. METHODS: Gene expression profiling of MM patients and PCL patients was analysed to identify the molecular differences between the two diseases. Cox survival regression and Kaplan-Meier analysis were performed to illustrate the impact of integrin subunit alpha 6 (ITGA6) on prognosis of MM. Invasion assays were performed to assess whether ITGA6 regulated the progression of MM to PCL. RESULTS: Gene expression profiling analyses showed that cell metastasis pathways were enriched in PCL and ITGA6 was differentially expressed between PCL and MM. ITGA6 expression was an independent prognostic factor for event-free survival (EFS) and overall survival (OS) of MM patients. Moreover, the stratification ability of the International Staging System (ISS) of MM was improved when including ITGA6 expression. Functional studies uncovered that increased ITGA6 reduced the myeloma cell invasion. Additionally, low expression of ITGA6 resulted from epigenetic downregulating of its anti-sense non-coding RNA, ITGA6-AS1. CONCLUSION: Our data reveal that ITGA6 gradually decreases during plasma cell dyscrasias progression and low expression of ITGA6 contributes to myeloma metastasis. Moreover, ITGA6 abundance might help develop MM prognostic stratification.
Asunto(s)
Integrina alfa6/genética , Leucemia de Células Plasmáticas/genética , Mieloma Múltiple/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Regulación hacia Abajo/fisiología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Integrina alfa6/fisiología , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/patología , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , PronósticoRESUMEN
OBJECTIVE: To evaluate the clinical outcomes of patients with primary plasma cell leukemia (pPCL) defined by 5% or greater clonal circulating plasma cells on peripheral blood smear and treated with novel agent induction therapies. PATIENTS AND METHODS: A cohort of 68 patients with pPCL diagnosed at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, to December 31, 2019, and treated with novel agent induction therapies was evaluated. RESULTS: The median follow-up was 46 (95% CI, 41 to 90) months. The median bone marrow plasma cell content was 85% (range, 10% to 100%) and median clonal circulaitng plasma cell percentage on the peripheral blood smear was 26% (range, 5% to 93%). There was a preponderance of t(11;14) primary cytogenetic abnormality in this cohort. The median time to next therapy (TTNT) and overall survival (OS) for all patients with pPCL patients in this cohort was 13 (95% CI, 9 to 17) and 23 (95% CI, 19 to 38) months, respectively. However, when stratified by cytogenetic risk, the median TTNT and OS were 16 and 51 months for standard risk vs 9 and 19 months for high risk (P=.01 for OS). CONCLUSION: Primary plasma cell leukemia remains an aggressive disease with poor prognosis despite novel agent-based therapies. Some patients have better than expected survival and this phenomenon may be influenced by the absence of high-risk cytogenetics. Newer treatment regimens are needed to improve the prognosis of this devastating disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Adulto , Estudios de Cohortes , Femenino , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Minnesota , Pronóstico , Análisis de Supervivencia , Trasplante Autólogo , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia de Células Plasmáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Terapia Combinada , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/mortalidad , Pronóstico , Resultado del TratamientoRESUMEN
We analyzed variations in terms of chromosomal abnormalities (CA) by fluorescence in situ hybridization (FISH) analysis on purified bone marrow plasma cells throughout the progression from monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (MGUS/SMM) to newly diagnosed MM/plasma cell leukemia (NDMM/PCL) at diagnosis and from diagnostic samples to progressive disease. High risk was defined by the presence of at least del(17p), t(4;14), and/or t(14;16). 1p/1q detection (in the standard FISH panel from 2012 onward) was not available for all patients. We analyzed 139 MM/PCL diagnostic samples from 144 patients, with a median follow-up of 71 months: high-risk CA at diagnosis (MGUS/SMM or NDMM) was present in 28% of samples, whereas 37-39% showed high-risk CA at relapse. In 115 patients with NDMM who evolved to relapsed/refractory MM, we identified 3 different populations: (1) 31/115 patients (27%) with gain of new CA (del13, del17p, t(4;14), t(14;16) or 1q CA when available); (2) 10/115 (9%) patients with loss of a previously identified CA; and (3) 74 patients with no changes. The CA gain group showed a median overall survival of 66 months vs. 84 months in the third group (HR 0.56, 95% CI 0.34-0.92, p = 0.023). Clonal evolution occurs as disease progresses after different chemotherapy lines. Patients who acquired high-risk CA had the poorest prognosis. Our findings highlight the importance of performing FISH analysis both at diagnosis and at relapse.
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Aberraciones Cromosómicas , Cromosomas Humanos/genética , Evolución Clonal , Leucemia de Células Plasmáticas , Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple Quiescente , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia de Células Plasmáticas/genética , Leucemia de Células Plasmáticas/mortalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Mieloma Múltiple Quiescente/genética , Mieloma Múltiple Quiescente/mortalidad , Tasa de SupervivenciaRESUMEN
Plasma cell neoplasms (PCNs), comprising plasma cell myelomas (PCMs) and plasmacytomas, which occur after solid organ transplantation, represent rare subtypes of monomorphic post-transplant lymphoproliferative disorders (M-PTLDs). Data regarding the clinical and pathological features of post-transplant (PT)-PCMs are limited. To gain a better understanding of disease biology, we performed comprehensive immunophenotypic analysis, reviewed cytogenetic analysis results and evaluated clinical outcomes of PT-PCMs diagnosed and treated at our institution. Fifteen PT-PCM (M: F - 4:1) and two PT-MGUS (two males) cases were identified. The median age of PT-PCM patients was 68 years (29-79 years) and PCMs presented at a median of 9.7 years (0.5-24.7 years) after transplantation. The PT-PCMs accounted for 11.6% of all M-PTLDs and the period prevalence was 9/3108 (0.29%), 3/1071 (0.28%), 2/1345 (0.15%) and 1/878 (0.11%) post kidney, heart, liver and lung transplantation. Lytic bone disease was observed in 1/11 (9%) patients. Marrow plasma cell infiltration ranged from 10%-70% (median 20%), with 10/15 (67%) and 5/15 (33%) cases manifesting immature and plasmablastic morphology. The immunophenotype of all cases and cytogenetic abnormalities, identified in 60% of cases, were similar to multiple myeloma (MM) of immunocompetent individuals. All PT-PCMs were EBER negative. Ten of 11 (91%) patients with active MM were treated, all with proteasome inhibitor-based therapy. Treatment response and 5-year overall survival (54.5%) was comparable to MM of immunocompetent individuals. However, the survival of patients with plasmablastic PCMs was inferior to those with immature PCMs. 0ur findings indicate PT-PCMs to be predominantly late onset PTLDs that have similar clinicopathologic characteristics as conventional MM.
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Leucemia de Células Plasmáticas , Trasplante de Órganos , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia de Células Plasmáticas/etiología , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Primary plasma cell leukemia (PPCL) is a rare and aggressive plasma cell disorder. The use of novel agents, together with autologous stem cell transplantation, has improved survival outcome in PPCL. However, the prognosis is still very poor, and the optimal treatment remains an unmet clinical need. PATIENTS AND METHODS: We studied the efficacy and prognostic impact of novel agents in 46 patients with PPCL patients at the Blood Diseases Hospital in China. We examined the impact of clinical and laboratory features, as well as therapies (bortezomib- and/or immunomodulatory drug-based therapies, chemotherapy) on survival and extent of clinical response, including progression-free survival and overall survival (OS). Progression-free survival and OS were assessed by the Kaplan-Meier method, and survival distributions were compared by log-rank test. RESULTS: In our cohort of 46 PPCL patients, the median age at the time of diagnosis was 54 years. Overall response rate was 54% (25/46). The median (95% confidence interval) progression-free survival time was 6 (0-12.5) months, and OS time was 14 (4.6-23.4) months. The OS time was significantly longer in patients treated with bortezomib-based versus non-bortezomib-based therapies (median [95% confidence interval], 19 [9-28.9] vs. 5 [4-24] months; P = .019). CONCLUSION: This large single-center study of PPCL supports the use of bortezomib-based therapies as frontline treatment in PPCL patients.
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Leucemia de Células Plasmáticas/diagnóstico , Adulto , Anciano , China , Femenino , Humanos , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The diagnosis of primary plasma cell leukemia (pPCL) has been made by quantifying circulating plasma cells (cPCs) morphologically on a peripheral blood (PB) smear. However, this technique is not sufficiently sensitive. Multiparametric flow cytometry (MFC) provides a readily available and highly sensitive method to identify and quantify cPCs that could complement PB smear assessment. However, an optimal quantitative cutoff for cPCs by MFC to identify pPCL has not been established. Thus, a total of 591 patients newly diagnosed multiple myeloma (NDMM) patients who had their PB samples evaluated morphologically by PB smear, and immunophenotypically by MFC prior to beginning therapy were evaluated. The presence of ≥200 cPCs/µL by MFC (N = 25 or 5% of the total population) was chosen to identify patients with ≥5% cPCs by PB smear with a specificity of 99% and a sensitivity of 77%. For patients with ≥200 cPCs/µL by MFC compared to the remainder of the cohort, the median Time to next therapy (TTNT) was 18 vs 30 months and the median OS was 38 vs 70 months respectively. Thus, MFC assessment of PB can be utilized in conjunction with the morphological assessment of a PB smear to aid in improving the identification of pPCL among NDMM patients.
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Citometría de Flujo , Leucemia de Células Plasmáticas , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia de Células Plasmáticas/sangre , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia de Células Plasmáticas , Anciano , Autoinjertos , Bortezomib/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Multiple myeloma (MM) usually follows a clinical course leading to refractoriness and limited treatment options in advanced stages, which might need bridge therapies to either autologous stem cell transplantation or novel therapies. We report our experience with the high-dose chemotherapy mCBAD (modified cyclophosphamide, bortezomib, doxorubicin, and dexamethasone) regimen in newly diagnosed MM (NDMM), relapsed/refractory MM (RRMM), and plasma cell leukemia (PCL) patients. PATIENTS AND METHODS: We searched our electronic records database for MM patients who received mCBAD from 2010 to 2016 for 28-day cycles of cyclophosphamide 350 mg/m2 intravenously (I.V.) twice daily with mesna 400 mg/m2 I.V. daily (days 1-4), bortezomib 1.3 mg/m2 subcutaneously/I.V. (days 1, 4, 8, 11), doxorubicin 9 mg/m2 daily continuous infusion (days 1-4), dexamethasone 40 mg orally daily (on days 1-4, 9-12, 17-20). International Myeloma Working Group (IMWG) criteria were used for response assessment and diagnosis. Descriptive statistics, Fisher exact test, χ2, Wilcoxon rank sum, and Kaplan-Meier were used for statistical purposes. RESULTS: One hundred forty patients met the inclusion criteria. A median of 2 cycles of therapy was administered. The overall response rate was 85% in patients with RRMM (n = 116) and 100% in NDMM (n = 13) and PCL (n = 11) patients. Respective median progression-free survival (mPFS) for NDMM, PCL, and RRMM were 19.61 months (95% confidence interval [CI], 5.26 to not applicable [NA]), 7.56 months (95% CI, 4.7 to NA), and 4.64 months (95% CI, 3.75-6.73). Patients with RRMM who used mCBAD as a bridge to autologous transplant (36.2%) had mPFS (11.48 months; 95% CI, 7.52-15.9 months) compared with those who did not (mPFS: 3.19 months; 95% CI, 2.4-3.75 months). Cytopenias occurred in more than 90% of patients, and febrile neutropenia was noted in 26%. All cases of treatment-related mortality (8%) occurred in patients with RRMM, except for 1 patient with PCL. CONCLUSION: mCBAD results in high response rates in myeloma and PCL, however, with high treatment-related mortality. Its use in RRMM should be limited to patients who have immediate need for therapy without other treatment options and who have good performance status (score of 0-1) or NDMM if novel agents are not available depending on practice setting. mCBAD can be a treatment option for patients with PCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia de Células Plasmáticas/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Resistencia a Antineoplásicos , Femenino , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Pronóstico , Recurrencia , Proyectos de Investigación , Retratamiento , Resultado del Tratamiento , Adulto JovenRESUMEN
This multicenter retrospective study included 101 patients (median age 62 years) with secondary plasma cell leukemia (sPCL). The median time from initial multiple myeloma diagnosis to sPCL was 31 months. Fifty-five out of 72 patients (75%) who received any therapy were treated with immunomodulators (IMiDs) and/or proteasome inhibitors (PIs), and 14/72 (19%) underwent salvage autologous stem cell transplantation (ASCT). The overall response rate in patients who received ASCT or PI (either alone or in combination) was higher than in those who did not (93% vs. 36% and 60% vs. 30%, respectively). The median overall survival (OS) in patients who received therapy was 4.2 months (95% CI: 1.3; 8.0) with a 1-year OS of 19%. Platelet count ≤100 × 109/L at sPCL diagnosis was the only independent predictor of a poorer OS in treated patients (HR = 3.98, p = .0001). These findings suggest that patients with sPCL may benefit from salvage ASCT- and PI-based regimens.
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Leucemia de Células Plasmáticas/terapia , Mieloma Múltiple/complicaciones , Terapia Recuperativa/métodos , Trasplante de Células Madre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Factores Inmunológicos/uso terapéutico , Leucemia de Células Plasmáticas/etiología , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Inhibidores de Proteasoma/uso terapéutico , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Autólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Primary plasma cell leukemia (pPCL) is an aggressive plasma cell disorder characterized by circulating plasma cells and a poor prognosis. Although patients who have pPCL benefit from the use of stem cell transplantation (SCT) and novel agents, their prognosis remains inferior to that of patients who have myeloma. METHODS: This was a retrospective analysis of 38 consecutive patients with pPCL who were diagnosed between October 2005 and July 2016 and were registered in the Winship Cancer Institute of Emory University database. Baseline characteristics as well as data about treatment and survival outcomes were collected. RESULTS: The median patient age at diagnosis was 58 years. All patients received a bortezomib-based induction regimen, and 92% received both bortezomib and an immunomodulatory drug (thalidomide or lenalidomide); in addition, 74% of patients underwent autologous SCT (ASCT), and 61% received maintenance therapy. The best response to first-line therapy was a partial response or better in 87% of patients, and 45% had a complete response (CR). The achievement of ≥CR was a predictor for prolonged progression-free survival (PFS) and overall survival (OS). The median PFS was 20 months, and the median OS was 33 months. PFS was prolonged in patients who underwent ASCT compared with those who did not undergo ASCT (25 vs 6 months; P = .004), and patients who received maintenance therapy after ASCT had prolonged median PFS (27 vs 11 months; P = .03) and a trend toward prolonged OS (median, 38 vs 22 months; P = .06) compared with those who did not receive maintenance therapy. CONCLUSIONS: The current data support the use of regimens combining novel agents in the upfront treatment of patients with pPCL as well as the role of ASCT and maintenance therapy for long-term disease control.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Bortezomib/uso terapéutico , Quimioterapia Adyuvante , Drogas en Investigación/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Talidomida/uso terapéutico , Terapias en Investigación , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) with poor long-term survival after cytotoxic chemotherapy. Many novel drugs have revolutionized the treatment algorithms for MM. The impact of targeted therapy, both pre- and post-autologous stem cell transplant (auto-HCT) remains an area of ongoing interest. In this study, we report outcomes post auto-HCT for pPCL and the impact of maintenance therapy posttransplant with novel agents.
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Quimioterapia de Inducción , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Trasplante de Células Madre , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The current definition of plasma cell leukemia (PCL)- ≥ 20% circulating plasma cells (CPCs) on peripheral smear and plasma cell count ≥ 2 × 109/L-may be too stringent. We reviewed outcomes of 176 multiple myeloma (MM) patients diagnosed between 1971 and 2016, and who had CPCs detectable at diagnosis, to determine whether a lower threshold could be used to diagnose PCL. Median overall survival (mOS) was 1.1 years (95% CI 0.8-1.4) and was similar between patients with < 5% (n = 54, mOS = 1.4 years [0.7-2.0]), 5-19% (n = 63, mOS = 1.1 years [0.7-1.4]), and ≥ 20% CPCs (n = 59, mOS = 1.1 years [0.7-1.5], p = 0.349). As survival was similar between those with 5-19% and ≥ 20% CPCs, we stratified patients by < 5% (mOS = 1.4 years [0.7-2.0]) and ≥ 5% CPCs (mOS = 1.1 years [0.8-1.4], p = 0.154). Outcomes of those with ≥ 5% CPCs were much poorer when compared with a cohort of MM patients diagnosed between 1971 and 2016, who did not have CPCs at diagnosis (n = 9724, mOS = 4.4 yrs [4.3-4.5], p < 0.001); survival was also lower in patients diagnosed after 2001 with ≥ 5% CPCs (n = 62, mOS = 1.4 years [0.8-2.5]) compared with patients with standard risk (n = 1326, mOS = 7.5 years [7.0-8.7]) and high-risk MM (n = 381, mOS = 4.3 years [3.5-4.9], p < 0.001). We therefore propose that the definition of PCL be revised to patients with ≥ 5% CPCs on peripheral blood smear, who otherwise meet diagnostic criteria for MM.
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Leucemia de Células Plasmáticas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Biopsia , Médula Ósea/patología , Femenino , Humanos , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Análisis de SupervivenciaRESUMEN
We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 18 months respectively, both significantly longer in patients treated with bortezomib-based therapy + ASCT vs. others (PFS: 18 vs. 9 months; p = 0.004, OS: 48 vs. 14 months; p = 0.007). Bortezomib-based therapy + ASCT predicted for OS in univariate analysis. In multivariate analysis, achievement of ≥vgPR and LDH ≥ 300 U/L were significant predictors for OS. These real-world data, based on one of the largest reported national multicenter series of pPCL patients treated mostly with novel agents support that, among the currently approved induction therapies, bortezomib-based regimens are highly effective and reduce the rate of early mortality whereas in combination with ASCT consolidation they prolong OS.
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Bortezomib/administración & dosificación , Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Trasplante de Células Madre , Adulto , Anciano , Anciano de 80 o más Años , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Grecia/epidemiología , Humanos , Leucemia de Células Plasmáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 109 /l and peripheral blood plasma cell count ≥20 × 109 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2-3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.
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Leucemia de Células Plasmáticas/mortalidad , Leucemia de Células Plasmáticas/terapia , Trasplante de Células Madre , Adulto , Anciano , Anciano de 80 o más Años , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia de Células Plasmáticas/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Solitary plasmacytoma (SP) and plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study, we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP) (n=124) and extramedullary plasmacytoma (EMP) (n=67) have better overall survival (OS) than MM (n=3549). Progression to MM was higher in SBP than in EMP (35% and 7% at 2 years, respectively), but this did not translate into better survival in EMP. In spite of treatment developments, the OS of primary PCL is still dismal (median of 11 months, 0% at 5 years). Hence, there is a great need for diagnostic and treatment guidelines as well as prospective studies addressing the role for alternative treatment options, such as allogeneic stem cell transplantation and monoclonal antibodies in the treatment of PCL.
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Leucemia de Células Plasmáticas/epidemiología , Plasmacitoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Femenino , Humanos , Incidencia , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Plasmacitoma/diagnóstico , Plasmacitoma/mortalidad , Vigilancia de la Población , Sistema de Registros , Análisis de Supervivencia , Suecia/epidemiologíaRESUMEN
The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×109/L vs 214×109/L, P<0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia.
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Mieloma Múltiple/diagnóstico , Células Plasmáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/mortalidad , Persona de Mediana Edad , Mieloma Múltiple/patología , Recuento de Plaquetas , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. The introduction of novel agents and modern technologies has recently partially changed the clinical and biological scenario of this malignancy, allowing limited, but not negligible, progresses. Areas covered: We will discuss: the complex landscape of genetic alterations in PPCL, derived from conventional and high-throughput technologies; the best available treatments for PPCL; the possible future therapeutic perspectives. Expert commentary: PPCL requires an immediate and intensive multi-phase treatment with short therapy-free intervals, which should include novel agents and autologous stem cell transplantation in eligible patients. Allogeneic transplantation should be considered in selected cases. In older and/or frailer individuals, personalized approaches should be applied. Integrated treatments with next generation proteasome inhibitors/IMIDs and monoclonal antibodies are currently planned or under investigation. The identification of novel genomic biomarkers may be potentially helpful for risk stratification and future personalized therapies.