Simultaneous quantification of pirarubicin, doxorubicin, cyclophosphamide, and vincristine in human plasma of patients with non-Hodgkin's lymphoma by LC-MS/MS method.

Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography-tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1-500 ng/mL for THP, 2-1000 ng/mL for DOX, 2.5-1250 ng/mL for CTX, and 3-1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from -0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.

Serum organochlorines and non-Hodgkin lymphoma: A case-control study in Israeli Jews and Palestinians.

Associations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) with non-Hodgkin lymphoma are controversial. We compared serum levels of 6 OC pesticides and 38 PCBs in Israeli Jews (IJ) and Palestinian Arabs (PA) and assessed possible associations with B-cell non-Hodgkin lymphoma (B-NHL). Ninety B-NHL cases (50 IJ and 40 PA) and 120 controls (65 IJ and 55 PA) were included. Median concentrations of analytes in controls were compared across ethnic groups using quantile regression, adjusting for age and sex. We used logistic regression to derive odds ratios (OR) and 95% confidence intervals (CI) for detectable analytes and B-NHL, adjusting for age, ethnic group, faming and body mass index. Median values of PCBs and dichlorodiphenyldichloroethylene (DDE) were higher in IJ vs PA controls (P = 0.0007), as were several PCBs (74, 99, 118, 138, 146, 153, 156, 163, 170, and 180). Overall, OC pesticide and PCB exposures were comparable with reports from high-income countries. B-NHL was associated with PCB 146 (OR 1.70, 95% CI: 1.02, 2.83), PCB 156 (OR 1.75, 95% CI: 1.06, 2.89), and high-chlorinated PCBs (OR 1.55, 95% CI: 1.00, 2.40) in all study subjects. These associations were robust in quantile as well as sensitivity analyses. An association of DDE with B-NHL was noted in PA (OR 1.72, 95% CI: 1.07, 2.77), but not in IJ (OR 0.87, 95% CI: 0.59, 1.27). Although high-chlorinated PCB concentrations did not indicate high exposure levels, our findings indicate that B-NHL may be associated with this exposure.

Cytologic mimics of non-Hodgkin lymphoma in the head and neck.

Non-lymphoid small round blue cell tumors of the head and neck are particularly difficult to diagnose when metastatic to a lymph node. The cytopathologist or surgical pathologist evaluating these lesions has to be aware of the various non-hematopoetic neoplasms that present in the head and neck area that can mimic non-Hodgkin lymphoma. Presented here are the various lesions commonly seen which needs to be entertained depending on where in the head and neck the lesion is located. More recently, a plethora of HPV related head and neck tumors has been described and these lesions add to the mix in this challenging milieu of cases.

Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma.

31P magnetic resonance spectroscopy (31P MRS) can measure intracellular pH (pHi) using the chemical shift difference between pH-dependent inorganic phosphate (Pi) and a pH-independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using 1H MRS)] in a cohort of 10 volunteers and eight patients with non-Hodgkin's lymphoma (NHL). Well-resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct Pi­PCr method was best for those spectra with a very well-defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the Pi­αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water-based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the Pi­αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment-related changes of the order of 0.1 pH units should be detectable.

Complete response to induction therapy in patients with Myc-positive and double-hit non-Hodgkin lymphoma is associated with prolonged progression-free survival.

BACKGROUND: Myc-positive B-cell non-Hodgkin lymphoma (NHL) with or without a B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) rearrangement is associated with inferior progression-free survival (PFS) and overall survival (OS). In this study, the authors reviewed the outcomes of patients with myc-positive and double-hit NHL at The Ohio State University. METHODS: All patients who had non-Burkitt, aggressive B-cell NHL from 2008 to 2011 were assessed for the t(14;18) translocation and for v-myc avian myelocytomatosis viral oncogene homolog (CMYC) rearrangements at diagnosis, and all myc-positive patients were included in the current analysis. Associations with clinical characteristics were described, and univariable and multivariable models were used to assess correlations between clinical variables and outcomes. RESULTS: Of 49 myc-positive patients, 29 patients also had BCL2 rearrangements (double-hit NHL). No patients underwent autologous stem cell transplantation in first remission. For all myc-positive patients, the median PFS was 16.6 months, and the median OS was 37.7 months. For patients who had double-hit NHL, the median PFS was 8 months, and the median OS was 12.5 months; whereas the median PFS and OS were not reached for myc-positive patients. A complete response (CR) after front-line therapy, the presence of t(14;18), International Prognostic Index (IPI) group, and age were associated with PFS; whereas only the achievement of a CR and age >60 years were associated with OS in the multivariable setting. The median PFS was 3.3 months, and the median and OS was 7.0 months for patients who did not attain a CR; and the medians were not reached for patients who achieved a CR (P < .00001). CONCLUSIONS: The achievement of a CR with front-line therapy is associated with a prolonged PFS and OS in patients with myc-positive NHL, even after adjusting for type of initial therapy, histology, age, IPI, or the presence of a concurrent BCL2 translocation.

Linfoma primario de bazo. Presentación de un caso / Primary lymphoma of the spleen. Case presentation

Fundamento: en el bazo se pueden observar diferentes tipos de tumores, dentro de los cuales están los linfomas primarios del mismo, enfermedad infrecuente, de ahí la importancia de su presentación. Presentación de caso: paciente femenina de 66 años, raza blanca, con antecedentes de hipertensión arterial, lobectomía derecha del tiroides, que refiere venía presentando desde hacía más de un año dolor abdominal alto izquierdo que se hacía más intenso tras el esfuerzo físico, tos, presentando toma del estado general por lo que se ingresa en el servicio de cirugía. Se toman muestras para biopsia, después de ser intervenido quirúrgicamente de una esplenectomía, dando como resultado un Linfoma no Hodgkin de células grandes CD20 positivo, sin infiltración hepática, ganglionar ni epiplóica. Se realizó esplenectomía y quimioterapia. La paciente ha evolucionado favorablemente. Conclusiones: el linfoma primario de bazo es una entidad infrecuente y su diagnóstico es aún más raro en pacientes por encima de los 60 años, como ocurrió en el caso presentado. A medida que casos como este se divulguen entre los profesionales de la salud permitirán una aproximación diagnóstica más precisa a esta enfermedad poco común.

Background: in the spleen you can see different types of tumors; primary lymphomas are an example of them. This is an infrequent disease, hence the importance of its presentation. Case presentation: 66 year old white female patient with history of hypertension, thyroid right lobectomy that refers to have been suffering from high left abdominal pain for a year that became more intense after physical exertion, cough, presenting general malaise by what is admitted to the surgical service. Some samples for biopsy are taken, after being surgically operated of a splenectomy, showing as a result a non-Hodkin lymphoma of big cells resulting cell non-Hodgkin lymphoma CD20 Positive, without hepatic, ganglionic or epiploic infiltration. Splenectomy and chemotherapy were made. The patient has improved favorably. Conclusions: primary lymphoma of the spleen is a rare entity and its diagnosis is still rarer in patients over 60 years, as it happened in the case presented. As cases like these are disseminated among health professionals will allow a more accurate diagnostic approach to this rare disease.

Automated quantification of DNA aneuploidy by image cytometry as an adjunct for the cytologic diagnosis of malignant effusion.

DNA aneuploidy is a cancer biomarker, which may have a potential diagnostic value in body effusion specimen. DNA aneuploidy is determined by measuring the DNA content of tested cells and comparing them with diploid cells (2c). In order to assess the value of automated DNA image cytometry (DNA-ICM) in the cytologic diagnosis of effusion, we measured DNA ploidy using an automated DNA-ICM analysis system in 126 consecutive effusion specimens and followed the cases for histologic diagnosis. Half of each effusion specimen was used to prepare cytologic smears for conventional cytologic diagnosis, while the other half was used to prepare a monolayer slide stained by Feulgen stain for automated ICM. By using Youden index, we found that 4 cells exceeding 2.5c is the optimal cut off value for aneuploidy, which has a sensitivity of 88.3% and specificity of 100% for diagnosis of malignant effusion. We also found that the DNA aneuploidy thresholds used for other types of cytologic specimens cannot be used in the diagnosis of effusion specimens. Our study demonstrated that automated DNA image cytometry is a simple, practical and cost-effective method for adjunct diagnosis of malignant effusion.

Expression of FoxO3a in clinical cases of malignant lymphoma.

Cancer-initiating cells (CICs) are a limited number of cells with tumorigenic activity. Few studies have been performed on CICs in malignant lymphoma. We recently demonstrated that a small number of FoxO3a-expressing cells possessed CIC-like potential in Hodgkin's lymphoma (HL) cell lines. In the present study, FoxO3a expression was examined immunohistochemically in 137 patients with malignant lymphoma. Among patients with HL, FoxO3a-positive tumor cells were detected in 11 of 11 with nodular sclerosis classical HL, 8 of 15 with mixed cellularity classical HL, 0 of 1 with lymphocyte-rich classical HL, and 2 of 3 with nodular lymphocyte-predominant HL. Only limited numbers of patients with non-HL expressed FoxO3a: 4 of 66 with diffuse large B-cell lymphoma, 1 of 20 with follicular lymphoma, and 1 of 5 with peripheral T-cell lymphoma, not otherwise specified. No FoxO3a expression was detected in patients with mantle cell lymphoma (n=3), extranodal marginal zone B-cell lymphoma (n=3), mediastinal large B-cell lymphoma (n=1), NK/T cell lymphoma (n=5), anaplastic large cell lymphoma (n=2), or T-lymphoblastic lymphoma/leukemia (n=2). These results suggest that FoxO3a is expressed mostly in patients with HL, but not in patients with non-HL. FoxO3a expression was limited to a small number of Hodgkin cells in a quiescent state. FoxO3a may be a CIC marker of HL, but not of non-HL.

Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points.

BACKGROUND: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). METHODS: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (r(s)). RESULTS: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73-0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35-0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS. CONCLUSIONS: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data.

Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas.

OBJECTIVE: Diagnosis of low grade non-Hodgkin B-cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service. METHODS: Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow-up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains. RESULTS: Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B-cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series. CONCLUSIONS: FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B-cell non-Hodgkin lymphomas.

Differentiation of small round blue cell tumors using Raman spectroscopy.

PURPOSE: Small round blue cell tumors (SRBCTs) are aggressive undifferentiated embryonal tumors, including neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and non-Hodgkin lymphoma. They share similar histologic features. Additional studies such as immunohistochemistry and molecular techniques are required to differentiate them. There is no widely available tool for real-time diagnosis. Raman spectroscopy is an analytical technique with potential for quick and accurate diagnosis of tumors in near real-time. METHODS: Fresh or banked frozen tissue samples from SRBCTs were processed for routine pathology and Raman spectroscopy. Raman results were correlated with the final pathology diagnosis. RESULTS: The data set was composed of 480 spectra from 32 samples, including 179 neuroblastoma, 37 Ewing sarcoma, 164 rhabdomyosarcoma, and 100 non-Hodgkin lymphoma spectra. Discriminant function analysis showed that a combination of 18 peaks could accurately identify 94% of spectra. At the tissue level, all tumors were correctly identified. Only 10 peaks were needed to classify all tissues with 100% accuracy. Spectral-level classification with this model was 87.9%. CONCLUSION: Raman spectroscopy is an accurate technique for quickly and accurately differentiating SRBCTs. It could diagnose these specimens and provide a single, easy to use test for near real-time diagnosis.

Primary central nervous system lymphoma: immunohistochemical profile and prognostic significance.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL) with extranodal location affecting only the CNS, meninges and eye, without visceral or lymph node involvement. Its incidence has increased sharply over the past three decades, especially in immunocompetent subjects. Most PCNSL cases are diffuse large B-cell lymphomas (DLBCLs). However, it differs from nodal DLBCL in that it has a worse prognosis. DLBCLs are a heterogeneous entity and according to new genomic discoveries, classifications into prognostic subgroups have been embarked upon. Two prognostic algorithms were then prepared using a panel of immunohistochemical markers (CD10, Bcl6, MUM1/IRF-4, and Bcl2), thus categorizing DLBCL into two subgroups, GCB (germinal centre B-cell-like) or non-GCB, and into Group 1 or Group 2. Our goal is to apply both of these two sub-classifications to 39 PCNSLs, in order to assess their usefulness and prognostic relevance. 74.3% of our PCNSLs were of a non-GCB phenotype, corresponding to an activated postgerminal origin. They were evenly distributed across G1 and G2. Two- and 5-year overall survival rates were 34.8% and 19.6%, respectively. Younger age (<65) and a therapeutic combination of chemotherapy and radiotherapy significantly improved our patients' survival rates. The other clinical or biological markers tested had no prognostic impact. The two classifications did not reveal any significant survival difference. The recent discovery of a specific "transcriptional signature" of PCNSL, marking them out of DLBCL could account for the irrelevance of such prognostic classifications to PCNSL.

Immunohistochemical analysis for CD21, CD35, Caldesmon and S100 protein on dendritic cells types in oral lymphomas

OBJECTIVE: Follicular dendritic cells (FDCs) and interdigitating dendritic cells (IDCs) are dendritic cells found in lymphoid follicles, reactive follicles and in lymphomas. The goal of this study was to evaluate the presence and distribution of FDCs and IDCs in oral lymphomas. MATERIAL AND METHODS: Immunohistochemistry reactions were applied to 50 oral lymphomas using the antibodies anti-CD21, anti-CD35 and anti-caldesmon to FDCs, and anti-S100 protein to IDCs. Caldesmon+/FDCs and S100+/IDCs were quantified in Imagelab® software. RESULTS: FDCs revealed by CD21 and CD35 were positively stained in two cases of diffuse large B-cell lymphoma, one MALT lymphoma, and in one case of mantle cell lymphoma. FDCs were immunopositive to caldesmon in all cases, as well as IDCs to S100 protein. Burkitt lymphoma presented a lower amount of caldesmon+/FDCs and S100+/IDCs than diffuse large B-cell lymphoma and plasmablastic lymphoma of the oral mucosa type. CONCLUSIONS: The microenvironment determined by neoplastic lymphoid cells in oral lymphomas is responsible by the development and expression of dendritic cells types.

Immunohistochemical analysis for CD21, CD35, Caldesmon and S100 protein on dendritic cells types in oral lymphomas.

OBJECTIVE: Follicular dendritic cells (FDCs) and interdigitating dendritic cells (IDCs) are dendritic cells found in lymphoid follicles, reactive follicles and in lymphomas. The goal of this study was to evaluate the presence and distribution of FDCs and IDCs in oral lymphomas. MATERIAL AND METHODS: Immunohistochemistry reactions were applied to 50 oral lymphomas using the antibodies anti-CD21, anti-CD35 and anti-caldesmon to FDCs, and anti-S100 protein to IDCs. Caldesmon+/FDCs and S100+/IDCs were quantified in Imagelab software. RESULTS: FDCs revealed by CD21 and CD35 were positively stained in two cases of diffuse large B-cell lymphoma, one MALT lymphoma, and in one case of mantle cell lymphoma. FDCs were immunopositive to caldesmon in all cases, as well as IDCs to S100 protein. Burkitt lymphoma presented a lower amount of caldesmon+/FDCs and S100+/IDCs than diffuse large B-cell lymphoma and plasmablastic lymphoma of the oral mucosa type. CONCLUSIONS: The microenvironment determined by neoplastic lymphoid cells in oral lymphomas is responsible by the development and expression of dendritic cells types.

Absence of tumor-specific over-expression of Polo-like kinase 1 (Plk1) in major non-Hodgkin lymphoma and relatively low expression of Plk1 in nasal NK/T cell lymphoma.

Based on the presence of the tumor-specific over-expression of Plk1 (polo-like kinases) in various malignancies, we examined Plk1 expression in nine cases of reactive follicular hyperplasia (RFH), 42 of diffuse large B cell lymphoma (DLBCL), 16 of follicular lymphoma (FL), and 10 of nasal NK/T lymphoma. There was no significant difference in the Plk1-positive cell percentage between RFH and DLBCL. The Plk1-positive cell percentage ranged from 6 to 20% with a median of 12.9% in DLBCL. In FL, Plk1-positivity was at most 7%. Plk1-positivity in nasal NK/T cell lymphoma (4.7-14.1% with a median of 9.2%) was significantly higher than that of FL and tended to be lower than DLBCL (p < 0.001, p = 0.05, respectively). Although a strong correlation between positive cell percentages for Plk1 and Ki-67 in these three lymphomas specified Plk1 as a proliferation marker (r = 0.83-0.91), the Plk1-positive cell percentage relative to the other proliferation markers tended to be particularly low in nasal NK/T cell lymphoma. In 41 cases of DLBCL, the positive cell percentages of Plk1 and Ki-67 were both correlated with overall survival. The 4-year overall survival rates by Kaplan-Meier analysis for Plk1-negative and positive patients were 80 and 38%, respectively (p = 0.02).

A case of malignant primary non-Hodgkin's lymphoma in skeletal muscle treated by exclusive chemotherapy.

Malignant non-Hodgkin's lymphoma (MNHL) is a frequent tumour but a primary intra-muscular location is exceptional. Standard treatment combines wide surgical removal with chemotherapy and radiotherapy. The functional consequences of this large excision are sometimes very unsatisfactory. We report the case of an intra-muscular MNHL of the posterior and internal part of the thigh. The diagnostic was established thanks to selective biopsies. The treatment was purely medical and conservative with chemotherapy after a multidisciplinary oncological discussion. Three years after the treatment, the general state of health is excellent with no signs of local or remote recurrence.

TCL1A expression delineates biological and clinical variability in B-cell lymphoma.

The assembly of a collection of gene-expression signatures of the major types of B-cell non-Hodgkin's lymphoma has identified increased T-cell leukemia/lymphoma 1A (TCL1) expression in multiple lymphoma types and cases, and has enabled the investigation of the functional and clinical importance of TCL1 expression. Specifically, Burkitt's lymphoma cases show a homogeneously strong expression of TCL1, whereas diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, nodal marginal zone lymphoma, and splenic marginal zone lymphoma display a striking variability in the intensity of TCL1 staining. This was validated in two independent series. A Gene-Set Enrichment Analysis of the genes correlated with TCL1A expression found that variation in the level of expression of TCL1A was significantly associated with some of the most important gene signatures recognizing B-cell lymphoma pathogenesis and heterogeneity, such as germinal center, B-cell receptor, NF-kappaB (and its target genes), death, MAP kinases, TNFR1, TOLL, and IL1R. Additionally, TCL1 expression was correlated with shorter time to treatment in chronic lymphocytic leukemia cases and shorter lymphoma-specific survival in mantle cell lymphoma series, thus indicating the clinical and biological significance of TCL1 expression, and suggesting TCL1A as a potential therapeutic target.

Valor pronóstico de los niveles séricos del CA-125 en pacientes con linfoma no hodgkin / Prognostic value of serum CA 125 levels in non-hodgkin's lymphoma patients

El CA 125 ha sido considerado un nuevo marcador pronóstico en linfoma No Hodgkin (LNH). El objetivo del trabajo consistió en evaluar la significancia pronostica de los niveles del CA 125 en pacientes con LNH, asociación y correlación con factores clínicos patológicos, biológicos y sobrevida. Se procesaron muestras de suero de 67 pacientes con diagnóstico de LNH, de primera consulta, pretratamiento, VIH negativo y sin presentar otras enfermedades, edad promedio 55 años (rango 18-79 años), LNH agresivos 49 (73%) y LNH indolentes 18 (27%), IPI 60 (90%) de bajo riesgo y 7 (10%) de alto riesgo, tiempo promedio de seguimiento 30 meses (rango 3-48 meses). CA 125, B2M e IL-6 se determinaron por inmunoensayos enzimáticos y Proteína C Reactiva, Albúmina sérica, LDH, AST, ALT y fosfatasa alcalina por métodos de aglutinación directa, colorimétrico y cinético, respectivamente. 16 (24%) de los pacientes expresaron niveles elevados de CA 125 (>35u/ml) (p<0,001). Asociación significativa (p≤0,05) de CA 125 (35u/ml) con estadío clínico (EC) III-IV, enfermedad voluminosa (EV)>10cm, síntomas B (SB), enfermedad abdominal (EAb) y níveles elevados de LDH y B2M. Correlación significativa y directa con EC, EV, SB, LDH, B2M y AST (p≤0,05) y correlación inversa con albúmina sérica (p=0,02). El análisis univariado mostró una significativa disminución de la sobrevida global en los pacientes con LNH agresivos y niveles elevados de CA 125(>35u/ml) (p=0,03), LDH (p=0,048) y B2M(p=0,02). Según el análisis multivariado, Ca 125 perdió su significancia, LDH (p=0,04) y B2M (p=0,003) mantuvieron su valor pronóstico independiente. Los resultados del presente trabajo sugieren la utilidad pronóstica de los niveles séricos del CA 125, siendo recomendable su inclusión en la evaluación clínica inicial e los pacienten con LNH.

CA 125 has been considered a new prognostic marker in Non-Hodgkin lymphoma (NHL). The objetive of this study was to determine the prognostic significance of CA 125 levels in NHL patients, the association and correlation with clinical pathological and biological factos and survival. We processed 67 serum samples from newly diagnosed NHL patients previously untreated, HIV-negative and free from other diseases, mean age 55 years (range 18-79 Years), agressive NHL 49 (73%) and indolent NHL 18 (27%), IPI: 60 (90%) of low risk and 7 (10%) high risk, the average time of follow up was 30 months (range 3-48 months). CA 125, B2M and IL-6 were determined by enzyme immunoassay methods. C-reactive protein, serum albumin, LDH, AST, ALT and alkaline phosphatase were determined by direct agglutination, colorimetric and kinetic methods, respectively. Elevted levels of CA 125 (>35u/ml) were expressed in 16 (24%) of the patients (p<0.001). CA 125 levels (>35u/ml) were significantly (p≥0.05) associated with the follwing factors: clinicals stage (CS) III-IV, bulky disease (BD)>10 cm, B symptoms (BS), abdominal disease (ABD) and elevated levels of LDH and B2M. There was a significant and direct correlation (p≤0.05) with CS, BD, BS, LDH, B2M and AST and inversely with serum albumin (p=0,02). Univariate analysis showed a significant decreased of overall survival in patients with aggressive NHL with elevated levels of CA 125 (p<0.048), LDH (p=0.048) and B2M (p=0,02). In multivariate analysis Ca 125 lost its prognostic significance, LDH (p=0.04) and B2M (p=0.003) remained their independent prognostic value. The results of this study suggest the prognostic value of serum levels of CA 125, being recommended for inclusion in the initial clinical evaluation of patients with NHI.