Recuperación temprana de linfocitos como factor pronóstico en el trasplante hematopoyético / Early lymphocyte recovery as a prognostic factor after hematopoietic stem cell transplantation

Introducción: la recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes sometidos a trasplante hematopoyético. Objetivo: determinar el valor pronóstico del recuento absoluto de linfocitos (RAL). Métodos: se realizó un estudio observacional analítico, transversal, ambispectivo, en pacientes pediátricos con hemopatías malignas trasplantados en el Instituto de Hematología e Inmunología de La Habana, Cuba, entre 1986 y 2008. Se estudiaron 36 pacientes: 15 con leucemia linfoide aguda, 13 con leucemia mieloide aguda, 6 con leucemia mieloide crónica y 2 con linfoma no hodgkiniano. Veintitrés trasplantes fueron autólogos y 13 alogénicos; 22 de médula ósea y 14 de sangre periférica. Resultados : de los trasplantes antólogos, el 60,9 por ciento alcanzó un RAL el día + 15 (RAL-15) = 500 x mm3, mientras en los alogénicos este se alcanzó en el 53,8 por ciento. La sangre periférica tuvo un RAL-15 mayor que la médula ósea y se obtuvo en el 78,6 por ciento y el 45,4 por ciento de los enfermos, respectivamente (p = 0.049). Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis (p <0.001), el RAL-15 < 500 x mm3 ( p= 0.001) y la recaída (p = 0.03). Las curvas de Kapplan-Meier mostraron una mejor supervivencia global y libre de eventos a los cinco años, en los pacientes con RAL-15 = 500 x mm3 (85 por ciento vs 15 por ciento; p <0.001). Conclusiones: el RAL-15 = 500 x mm3 es una herramienta simple y útil para predecir un mejor resultado en pacientes pediátricos sometidos a trasplante hematopoyético

Introduction: early lymphocyte recovery is a prognostic factor related to a higher event-free survival and overall survival in patients who have received hematopoietic transplantation. Objective: eo determine the prognostic value of absolute lymphocyte count (ALC). Method: a study in pediatric patients with hematological malignancies transplanted at the Institute of Hematology and Immunology from 1986 to 2011 was performed. The study group included 36 patients: 15 with acute lymphoid leukemia, 13 with acute myeloid leukemia, 6 with chronic myeloid leukemia and 2 with non Hodgkin lymphoma. Twenty transplants were autologous and 13 allogeneic. As stem cell source, bone marrow was used in 22 patients and peripheral blood in 14. Results : 60,9 percent of the autologous transplants reached an absolute lymphocyte count = 500 x mm3 on day 15 (ALC-15), whereas in the allogeneic this was achieved in 53,8 percent. Peripheral blood had a higher ALC-15 than bone marrow, 78,6 percent and 45,4 percent, respectively (p = 0.049). Prognostic factors associated to worse overall survival were sepsis (p <0.001), ALC-15 <500 x mm3 (p = 0.001) and relapse (p = 0.03). Kapplan-Meier curves showed better overall survival and event-free survival after five years in patients with ALC-15 = 500 x mm3 (85 percent vs. 15 percent, p <0.001). Conclusions: the ALC-15 = 500 x mm3 is a simple and useful tool to predict a better outcome in pediatric patients undergoing hematopoietic transplantation

Perfil de las isoenzimas de LDH en linfoma no Hodgkin: correlación con marcadores tumorales / Profiles of LDH isoenzymes in non-Hodking`s lymphoma: correlation with tumor markers

Lactate dehydrogenase (LDH) consists of five isoenzymes and is an important prognostic factor in non-Hodgkin’s lymphoma (NHL) patients. Our objective was to study the pattern of LDH isoenzymes in patients with NHL and its correlation with clinical pathological and biological tumor markers. We evaluated 67 newly diagnosed NHL patients clinically and histologically confirmed, previously untreated, HIV-negative and free from other diseases, during the period 1999-2004, the average follow-up time of 30 months (range 3-48), median age of 55 years (range 18-79), the International Prognostic Index (IPI ) 60 (90%) of low risk and 7 (10%) of high risk. Serum and whole blood samples were collected for the determination of LDH, LDH isoenzymes, enzymes (AST, ALT, phosphatase alkaline), Beta 2 Microglobulin, CA125, and IL-6, sRáIL-2, C Reactive protein, serum albumin and ESR. Serum samples were processed from healthy controls in order to set reference values of LDH isoenzymes. Serum levels of LDH and absolute values of LDH isoenzymes were significantly higher in patients compared to controls (p<0.001). Frequencies of high absolute values of LDH1, LDH2, LDH3, LDH4 and LDH5 isoenzymes were significantly elevated in 25 (37%), 29 (43%), 32 (48%), 20 (39%) and 11 (16%) of cases, respectively. LDH1 activity associated and correlated with adverse clinical pathological, biological factors and high risk IPI, suggets that it is an indicator of cell turnover and disease activity. LDH2 changes reflected its association and correlation with clinical pathological and biological factors which are indicators of disease progression, tumor proliferative activity, adverse IPI and the patient’s response to the illness. LDH3 was elevated with greater frecuency and its activity was associated with clinical pathological and biological prognostic factors reflecting the patient’s response against the tumor, as well as inflammatory activity and disease extension...

La enzima lactato deshidrogenasa (LDH) está conformada por cinco isoenzimas y es un importante factor pronóstico en pacientes con Linfoma No Hodgkin (LNH). Nuestro objetivo fue estudiar el patrón de las isoenzimas de LDH en pacientes con LNH y su correlación con marcadores tumorales clínico-patológicos y biológicos. Se evaluaron 67 pacientes de primera consulta con diagnóstico de LNH confirmados clínica e histopatológicamente, sin tratamientos previo, VHI negativo y sin presentar otras enfermedades, durante el período 1999-2004, siendo el tiempo promedio de seguimiento de 30 meses (rango 3-48 meses), edad promedio 55 años (rango 18-79), Índice Pronóstico Internacional (IPI) 60 (90 por ciento) bajo riesgo y 7 (10 por ciento) alto riesgo. Se recolectaron muestras de sangre, para la obtención de suero y sangre total para la determinación de LDH, Isoenzimas de LDH, enzimas (AST, ALT, fosfatasa alcalina), Beta 2 Microglobulina, CA125,IL-6,sRIL-2, Proteína C Reactiva, Albúmina sérica y VSG. Se procesaron muestras de suero de controles sanos para establecer los valores de referencia de las isoenzimas de LDH. Los nieveles séricos de la LDH y los valores absolutos de las isoenzimas de LDH fueron significativamente superiores en los pacientes respecto al grupo control (p<0,001). Las frecuencias de las isoenzimas LDH1, LDH2, LDH3, LDH4 y LDH5 resultaron con niveles absolutos significativamente elevados en 25 (37 por ciento), 29 (43 por ciento), 32 (48 por ciento), 20 (39 por ciento) y 11 (16 por ciento) de los casos respectivamente. La asociación y correlación de la actividad de LDH1 con los factores clínico-patológicos adversos, IPI alto riesgo y marcadores biológicos alterados , sugieren su expresión como un indicador de recambio celular y actividad de la enfermedad. Los cambios en el patrón de la LDH2 reflejaron su asociación y correlación con factores clínico-patológico y biológicos indicadores de la pregresión de la enfermedad...

Serum lactate dehydrogenase 2 isoenzyme as marker of bone marrow infiltration in non hodgkin lymphoma

To assess the level of serum lactate dehydrogenase 2 [LD2] in the patients of NHL with and without bone marrow infiltration. Lactate Dehydrogenase [LDH] is commonly increased in patients with haemopoietic malignancies and has been shown to be of prognostic value in patients with Non- Hodgkin lymphoma [NHL] especially. Serum LD2 isoenzyme level was determined in already diagnosed 60 patients of NHL. Patients were divided into two groups, 30 patients with bone marrow infiltration [group B] and remaining without infiltration [group C]. The values were compared with 20 healthy age and sex matched contrtols [groupA]. The estimations were made prior to the institution of chemotherapy. LD2 level was significantly raised in NHL patients compared with controls. There was also significant difference when the values were compared between the patients of NHL with and without bone marrow infiltration. The levels showed positive correlation with the extent of the disease. We conclude that the above mentioned non invasive parameter is useful indicator of the extent of the disease

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.

Paraproteins: a regional South Australian experience.

We have performed a systematic review of all new serum and urinary paraproteins detected over a six year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses and associated laboratory features were ascertained from a computerized laboratory database or from clinical notes. Over the period of study, serum or urine paraproteins were detected in 613 new patients. These consisted of 568 patients with serum paraproteins and 45 patients with urinary monoclonal free light chain (in the absence of a serum paraprotein). These paraproteins occurred more commonly in males and the frequency increased with age. Approximately 30% of the serum paraproteins and 60% of urinary monoclonal free light chain were associated with B cell lymphoproliferative disorders (multiple myeloma, plasmacytoma, Waldenstrom's macroglobulinemia, non-Hodgkins lymphoma, chronic lymphocytic leukemia, etc) with the remainder being labeled as monoclonal gammopathies of uncertain significance (MGUS). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of paraprotein, B2 microglobulin, the presence of free urinary light chain and demonstrated molecular size heterogeneity of the paraprotein but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients. In conclusion paraproteins were most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of serum paraprotein (> 15 g/l), elevated levels of B2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen with patients with MGUS, regular monitoring of paraprotein level is considered mandatory in the management of these patients.

Método de reação em cadeia por polimerase para a pesquisa de retrovírus em casos de linfomas não-Hodgkin de células T periféricas e paraparesias crurais espásticas / PCR methods for retrovirus search in cases of non-Hodgkin lynphoma of peripheral T-cells and crural spastic paraparesis

Partindo de dois oligonucleotídeos degenerados derivados de uma fração conservada da região pol de retrovírus conhecidos, foi pesquisada a presença de agente viral exógeno ou de uma seqüência endógena similar as retrovirais (ERV). A partir da amplificação do DNA pela técnica de PCR, foram testadas células mononucleares periféricas de 33 portadores de paraparesia crural espática de evolução crônica sem agente etiológico conhecido, produzindo um fragmento de aproximadamente 500 bp em 8 destas amostras...

Linfoma näo-Hodgkin em adultos: perfil proteico do LCR e do soro de 25 doentes / Non-Hodgkin lymphoma in adult: protein profile of CSF and serum in 25 patients

Vinte e cinco pacientes com linfoma nao-Hodgkin estudados para detecçao de sinais e sintomas de comprometimento neurológico foram investigados quanto ao perfil proteico do líquido cefalorraqueano (LCR). Amostras de LCR e de soro sanguíneo colhidas no mesmo período foram estudadas comparativamente para analisar a barreira hemato-encefálica e a produçao intratecal de IgG. Em 48 por cento dos doentes foram registradas queixas e/ou sinais ao exame neurológico. A análise demonstrou: aumento das proteínas totais no LCR em 52 por cento; imunoliberaçao local em um paciente HIV soropositivo; aumento de globulinas gama no LCR de dois pacientes na ausência de células neoplásicas no LCR e melhora clínica pós-quimioterapia; e registro de banda oligoclonal apenas no LCR em um doente HTLV-I soropositivo. Esses dados mostram que o estudo do perfil proteico no LCR contribui para a caracterizaçao das manifestaçoes do linfoma nao-Hodgkin no sistema nervoso.

Serum levels of soluble Fas [S-FAS] and soluble intercellular adhesion molecule-1 [S-ICAM-1] in childhood solid tumors: correlation with clinical features and outcome

The levels of s-Fas and s-ICAM-1 conjointly in sera of patients with malignant diseases were evaluated in sera of sixty-two children with solid tumor on admission. They included thirty-four children with non- Hodgkin's lymphoma [NHL], three with Hodgkin's lymphoma [HL], eight with neuroblastoma, four with retinoblastoma, five with osteosarcoma, three with Ewing's sarcoma and five with Wilm's tumor. For comparative purposes, serum samples were obtained from ten healthy children who were comparable in age and sex with the patients. The study revealed significant increase of s-Fas as well as sICAM-1 in children with solid malignant tumors as a whole and irrespective of the pathological type compared with controls. The sensitivities were 100% and 93.5%, respectively. The levels of either s-Fas or sICAM-1 reflected organomegaly and outcome in children with solid tumor as a whole. Moreover, they reflected tumor spread, grade and burden in cases with NHL. Significant positive correlation existed between s-Fas and sICAM-1

Soluble interleukin-2 receptor [sIL-2R] as a tumor marker in hematologic malignancies

This work aimed to evaluate serum levels of sIL-2R in some of the hematologic malignancies and to find out if it could be a predictive marker of tumor burden and response to therapy. The mean value of sIL-2R in patients with acute lymphoblastic leukemia [ALL] was significantly higher than the controls. It was also significantly high in the patients with activity as compared with those at remission. Patients with chronic lymphocytic leukemia [CLL] had significantly elevated sIL-2R compared with the controls. The mean value of sIL-2R in the newly diagnosed cases of CLL was significantly higher than that of the group under treatment. There was no significant difference in the mean value of sIL-2R on comparing patients with stage I CLL to those with stage II. There was a significant difference between patients with stage I CLL and those with stage IV and between patients with stage II and stage IV. Newly diagnosed cases had a significantly high mean serum value of sIL-2R compared with those under treatment. Also, patients under treatment showed a significantly high mean serum value of sIL-2R compared with those at remission. Thus, it is clear that measurements of serum sIL-2R in patients with ALL, CLL, non-Hodgkin's lymphoma [NHL] and Hodgkin's lymphoma [HL] could offer a useful marker for tumor burden, prognosis and monitoring of treatment

Soluble interleukin-2 receptor [sIL-2R] in some hematologic malignancies

The aim of this study was to evaluate serum levels of sIL-2R in some of the hematologic malignancies and to find out if it could be a predictive marker of tumor burden and response to therapy. The mean value of sIL-2R in ALL was significantly elevated than in the controls. It was also significantly high in the patients with activity as compared with those at remission. Also, the mean value of sIL-2R in NHL was significantly elevated compared with the controls. Newly diagnosed cases had a high mean serum value of sIL-2R compared with those under treatment and a more significant elevation in comparison with the cases at remission. Also, patients under treatment showed a significantly higher mean serum value of sIL-2R than patients at remission. In patients with HL the mean value of sIL-2R was significantly elevated as compared with the controls. Newly diagnosed cases with HL had a significantly high mean serum value of sIL-2R as compared with patients under treatment and at remission. Also, patients under treatment showed a significantly high mean serum value of sIL-2R compared with those at remission

Utilidad de la relación cobre/zinc en pacientes con linfoma o leucemias aguda o crónica / Serum copper and zinc levels and Cu/Zn ration in lymphoma and acute and chronic leukemia

Objetivo. Conocer si la relación cobre/zinc (cobre elevado, zinc bajo) se encuentra aumentada en pacientes con neoplasias malignas hematológicas comparada con sujetos controles sanos de edad y sexo similares. Metodología. Se estudiaron 44 pacientes con neoplasias hemato-concológicas de reciente diagnóstico, sin tratamiento previo: 17 linfomas (11 no-Hodgkin), 15 con leucemia aguda (10 mieloblásticas) y 12 con leucemia crónica (8 granulocíticas). También se incluyeron 95 sujetos controles sanos. Se utizó un espectrofotómetro de absorción atómica (Perkin Elmer modelo 2380) para la cuantificación de los niveles séricos de cobre y zinc. Resultados. Los niveles séricos de cobre (µg/dL) fueron significativamente menores en los sujetos controles(54.4 ñ 8.9, p< 0.05), en comparación con los pacientes con linfoma (93.7 ñ 37.5), con leucemia aguda (80.6 ñ 44.6) y con leucemia crónica (95.7 ñ 28.9) mientras que los niveles séricos de zinc (µg/dL) resultaron significativamente mayores en sujetos controles (100.4 ñ 14, p< 0.05) en comparación con los pacientes con linfoma (77.2 ñ 22.6), leucemia aguda (66 ñ 15.6) o leucemia crónica (74.8 ñ 14.7). La relación cobre/zinc resultó ser significativamente más baja en sujetos controles (0.54 ñ 0.13, p< 0.05) que en pacientes con linfoma (1.21 ñ 0.5), leucemia aguda (1.22 ñ 0.7) o leucemia crónica (1.28 ñ 0.4). Veintitrés pacientes falleciron durante el seguimiento (media de 13 meses) observándose que sus niveles séricos de zinc fueron significativamente más bajos (68 ñ 28) que en los pacientes que sobrevivieron (76 ñ 15, p< 0.05). Conclusión. La relación sobre/zinc se encuentra significativamente elevada en pacientes con neoplasias malignas hematológicas

Comparative analysis of the phagocytic power and immunoglobulin status in hemopoietic malignancies and solid tumors

This study was carried out to evaluate the phagocytic activity of neutrophils and immunoglobulins among patients with ALL, lymphomas and some solid tumors. This study involved 107 patients who presented to National Cancer Institute [ALL, NHL, solid tumors and normal controls]. All patient groups showed a statistically significant decrease of phagocytic power of neutrophils in comparison to control group, pre and post-treatment. Also, solid tumors showed significantly lower post-treatment than pre-treatment levels. The NBT test showed lower levels in remission as compared to pre- treatment ones in all groups except in ALL, where it showed higher levels in remission. In ALL, there was a significant decrease in IgA level [pre and post treatment] than controls. There was a significant increase of IgM levels in patients with HD in remission than pre- treatment levels. In solid tumors, pre-treatment Ig status showed significant increase in IgM level. Lymphoma group [HD and NHL] showed non- significant change in all Ig levels in pre and post-treatment states, except for IgM in HD. In ALL group, the pre-treatment and remission Ig levels were significantly lower than those of lymphomas and solid Tumors