RESUMEN
Background and Objectives: Procalcitonin (PCT) is a useful biomarker for the diagnosis of sepsis. Inflammatory markers are elevated in patients with Hodgkin lymphoma (HL), and yet ongoing infection rarely coexists at diagnosis. PCT levels might be helpful in differentiating bacterial from disease-related inflammation. Materials and Methods: We evaluated serum PCT levels and other inflammation markers in newly diagnosed HL patients. Values < 0.50 ng/mL were considered normal (0.10−0.50 ng/mL: detectable, <0.10 ng/mL: undetectable), while values ≥ 0.50 ng/L were considered elevated. Results: Among 137 patients, 55 had B symptoms (40%), 77/130 (59%) had elevated Erythrocyte Sedimentation Rate (ESR) and 116 (85%) had elevated C-Reactive Protein (CRP) (median 38.1 mg/L (range; 2.97−328)). PCT levels were normal in most patients (undetectable 94/137 (68.5%) and detectable 41/137(30%)) with median value < 0.10 ng/mL (range; <0.10−15.90). Elevated PCT was recorded in only two patients (1.5%). Patients with PCT < 0.10 ng/mL had significantly lower median CRP (25.75; range (2.97−203.0)) compared to patients with PCT ≥ 0.1 ng/mL (median CRP 92.50 mg/L; range (3.34−328.0)). Almost all patients (40/41, 97.6%) with detectable PCT had elevated CRP. Conclusions: This is the first study showing that the inflammation characterizing HL is not associated with PCT elevations, although CRP levels are elevated in 85% of the patients. Normal PCT levels may rule out the possibility of occult infection, thus preventing extensive evaluation, which may delay treatment initiation.
Asunto(s)
Enfermedad de Hodgkin , Polipéptido alfa Relacionado con Calcitonina , Humanos , Calcitonina , Proteína C-Reactiva/análisis , Enfermedad de Hodgkin/diagnóstico , Biomarcadores , InflamaciónRESUMEN
Marginal zone lymphomas represent approximately 10-12% of all B-cell lymphomas. Extranodal marginal zone lymphomas (EMZL) or mucosa-associated lymphoid tissue (MALT) lymphomas are the most common subtype. Almost half of all MALT lymphomas arise in the gastrointestinal (GI) tract and, while the stomach is the most common site of GI involvement, the small and large intestines can also be involved. Rare cases of MALT lymphoma involving the rectum have been reported; however, to our knowledge, involvement of the anal canal has never been reported in the literature. Here, we describe a unique case of MALT lymphoma of the anal canal. Infectious agents have been implicated in the pathogenesis of MALT lymphomas, possibly through persistent antigenic stimulation of the area; however, in our case no such infection was documented.
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Neoplasias del Ano , Linfoma de Células B de la Zona Marginal , Neoplasias del Ano/inmunología , Neoplasias del Ano/metabolismo , Neoplasias del Ano/microbiología , Neoplasias del Ano/patología , Humanos , Linfoma de Células B de la Zona Marginal/inmunología , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/microbiología , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana EdadRESUMEN
Low absolute lymphocyte count (ALC) to absolute monocyte count (AMC) ratio (ALC/AMC) is an independent prognostic factor in Hodgkin lymphoma (HL), but different cutoffs (1.1, 1.5, and 2.9) have been applied. We aimed to validate the prognostic significance of ALC/AMC in 537 homogenously treated (doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalents ± radiotherapy) classical HL patients at various cutoffs. The median ALC/AMC was 2.24 (0.44-20.50). The median AMC was 0.653 × 10(9)/L (0.050-2.070). Lower ALC/AMC was associated with established markers of adverse prognosis. In total, 477 (89%), 418 (78%), and 189 (35%) patients had an ALC/AMC ratio of ≥1.1, ≥1.5, and ≥2.9; respectively; 20% had monocytosis (≥0.9 × 10(9)/L). Ten-year time to progression (TTP) was 77% versus 55% for patients with ALC/AMC ≥1.1 and <1.1 (p = .0002), 76% versus 68% for ALC/AMC ≥1.5 and <1.5 (p = .049), 77% versus 73% for ALC/AMC ≥2.9 and <2.9 (p = .35), and 79% versus 70% for ALC/AMC ≥2.24 and <2.24 (p = .08), respectively. In stages ΙΑ/ΙΙΑ and in patients ≥60 years old, ALC/AMC had no significant effect on TTP. In advanced stages, ALC/AMC was significant only at the cutoff of 1.1 (10-year TTP 67% vs. 48%; p = .016). In younger, advanced-stage patients, the differences were more pronounced. In multivariate analysis of TTP, ALC/AMC < 1.1 (p = .007) and stage IV (p < .001) were independent prognostic factors; ALC/AMC was independent of International Prognostic Score in another model. ALC/AMC was more predictive of overall survival than TTP. At the cutoff of 1.1, ALC/AMC had independent prognostic value in multivariate analysis. However, the prognostically inferior group comprised only 11% of patients. Further research is needed prior to the widespread use of this promising marker.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Linfocitos/patología , Linfopenia/patología , Monocitos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bleomicina/uso terapéutico , Terapia Combinada , Dacarbazina/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Enfermedad de Hodgkin/radioterapia , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Vinblastina/uso terapéutico , Adulto JovenAsunto(s)
Enfermedades de la Médula Ósea/patología , Inmunoterapia/métodos , Linfoma de Células B de la Zona Marginal/patología , Meninges/patología , Neoplasias del Bazo/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Errores Diagnósticos , Femenino , Humanos , Inyecciones Espinales , Leucemia de Células Pilosas/diagnóstico , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Masculino , Metotrexato/administración & dosificación , Inducción de Remisión , Rituximab/administración & dosificaciónRESUMEN
The significance of serum beta-2 microglobulin (sß2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sß2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8-3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sß2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sß2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff ("normal versus high"). In multivariate analysis, sß2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sß2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sß2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sß2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a "normal versus high" cutoff set at 2.4 mg/L.
RESUMEN
Serum ferritin (SF) is frequently elevated in classical Hodgkin lymphoma (cHL). We report on its prognostic significance in an unselected series of 529 cHL patients treated with state-of-the-art therapy. Higher baseline levels correlated with markers of advanced/aggressive disease. SF levels were significantly higher in male and older patients, those with high body mass index and mixed cellularity histology. The strongest correlation was recorded between SF and complement reactive protein (CRP) levels. Gender-specific SF cutoffs which provided the best discrimination in terms of freedom from progression (FFP) were identified. In multivariate analysis elevated SF levels, advanced stage and high lactate dehydrogenase (LDH) were independent prognostic factors of inferior FFP. SF also appears to retain independent prognostic significance for progression-free survival (PFS) but not for overall survival (OS). In conclusion, SF levels in cHL reflect disease activity and are associated with adverse patient outcomes.
Asunto(s)
Enfermedad de Hodgkin , Biomarcadores , Ferritinas , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/terapia , Humanos , Masculino , Pronóstico , Supervivencia sin Progresión , Estudios RetrospectivosRESUMEN
Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19+ B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19+ chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.
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Antígenos CD1d/genética , Tratamiento Basado en Trasplante de Células y Tejidos , Linfoma/tratamiento farmacológico , Células T Asesinas Naturales/citología , Animales , Antígenos CD19/genética , Antígenos CD19/inmunología , Antígenos CD1d/inmunología , Humanos , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Linfoma/inmunología , Ratones , Células T Asesinas Naturales/inmunologíaAsunto(s)
Enfermedad de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad Crónica , Terapia Combinada , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Recurrencia Local de Neoplasia , PronósticoRESUMEN
Pure red cell aplasia (PRCA) is a rare cause of severe hypoplastic anemia characterized by profound depletion of erythroid precursors. Although PRCA may be associated with lymphoproliferative diseases, it has never been described in mantle cell lymphoma (MCL). We report what to our knowledge is the first case of a patient with indolent, non-nodal MCL complicated by PRCA. The patient presented with severe hypoproliferative anemia in the setting of a long-standing diagnosis of B-cell chronic lymphocytic leukemia. Bone marrow studies revealed the complete absence of erythroid progenitors. Cyclin D1 positivity on immunohistochemistry, confirmed by a positive FISH for t(11;14) (q13;q32), established the final diagnosis of MCL in conjunction with PRCA. Rituximab monotherapy led to rapid remission of splenomegaly and the leukemic picture, but the patient achieved transfusion independency only with subsequent administration of cyclosporine-A, and remained so during the subsequent 15 months despite the gradual disease recurrence.
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Linfoma de Células del Manto/complicaciones , Aplasia Pura de Células Rojas/complicaciones , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Transfusión Sanguínea , Médula Ósea/patología , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/tratamiento farmacológico , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/terapia , Rituximab , Esplenomegalia , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Antineoplásicos/efectos adversos , Arsenicales/efectos adversos , Leucemia Promielocítica Aguda/complicaciones , Óxidos/efectos adversos , Pericarditis/diagnóstico , Pericarditis/etiología , Tretinoina/efectos adversos , Enfermedad Aguda , Adolescente , Antineoplásicos/uso terapéutico , Trióxido de Arsénico , Arsenicales/uso terapéutico , Electrocardiografía , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Quimioterapia de Mantención , Masculino , Óxidos/uso terapéutico , Inducción de Remisión , Tretinoina/uso terapéuticoRESUMEN
Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.