The role of surgery in primary central nervous system lymphomas / El rol de la cirugía en los linfomas primarios del sistema nervioso central

ABSTRACT Background Primary central nervous system lymphomas (PCNSL) are infrequent. The traditional treatment of choice is chemotherapy. Complete resections have generally not been recommended, because of the risk of permanent central nervous system deficits with no proven improvement in survival. The aim of the current study was to compare survival among patients with PCNSL who underwent biopsy versus surgical resection. Methods A retrospective study was conducted on 50 patients with a confirmed diagnosis of PCNSL treated at our center from January 1994 to July 2015. Results Patients in the resection group exhibited significantly longer median survival time, relative to the biopsy group, surviving a median 31 months versus 14.5 months; p = 0.016. Conclusions In our series, patients who had surgical resection of their tumor survived a median 16.5 months longer than patients who underwent biopsy alone.

RESUMO Introducción Los linfomas primarios del sistema nervioso central (LPSNC) son infrecuentes. Tradicionalmente el tratamiento de elección es la quimioterapia. Existe un paradigma de no indicar resección, por el riesgo de déficit neurológico sin aumento de la sobrevida. El objetivo del presente estudio es comparar la sobrevida de pacientes con LPSNC sometidos a biopsia versus resección. Métodos Estudio retrospectivo que incluye 50 pacientes con diagnóstico confirmado de LPSNC tratados en nuestra Institución desde enero de 1994 hasta julio de 2015. Resultados Los pacientes del "grupo resección" mostraron una sobrevida media significativamente mayor respecto a los del "grupo biopsia"; 31 meses versus 14,5 meses respectivamente, p = 0,016. Conclusiones En nuestra serie, los pacientes que con resección quirúrgica de su tumor tuvieron una sobrevida media de 16,5 meses superior que los pacientes biopsiados.

Estudio restrospectivo de 48 casos de linfoma primario del sistema nervioso central / Retrospective study of 48 cases of primary central nervous system lymphoma

Los linfomas primarios del sistema nervioso central (LPSNC) son neoplasias infrecuentes confinadas al SNC. Más del 90% son de tipo B y afectan principalmente a pacientes entre 50-70 años. La inmunodeficiencia es el factor de riesgo más importante. El objetivo de nuestro trabajo fue evaluar las características demográficas, estado inmunológico y los hallazgos en los estudios complementarios de pacientes con LPSNC. Se realizó el análisis retrospectivo de 48 casos estudiados en nuestro centro desde enero 1992 a mayo 2015. La edad mediana de presentación fue 61 años (25-84); la relación hombre:mujer 2.1:1. El 85% (41 casos) fueron inmunocompetentes al momento del diagnóstico. El 94% (45 casos) tuvo compromiso parenquimatoso, 4% (2 casos) meníngeo y 2% (1 caso) ocular. El lóbulo más afectado fue el frontal (43%) y 35% tuvieron compromiso ganglio basal. En RM, el 89% mostró realce con contraste y 55% restricción en difusión. El síndrome piramidal fue la manifestación inicial más frecuente (56%). El LCR fue inflamatorio en el 72%, aunque solo 11.1% presentó examen citológico positivo. El tipo más frecuente de LPSNC fue no-Hodgkin B (96%) y el subtipo difuso de células grandes el más habitual (83%). En nuestra serie la ausencia de inmunocompromiso fue una característica frecuente y la presentación clínico-radiológica fue muy pleomórfica. La sospecha inicial permitiría arribar a un diagnóstico temprano, evitando tratamientos empíricos que puedan confundir o retrasar el diagnóstico.

Primary central nervous system lymphoma (PCNSL) is an infrequent form of non-Hodgkin lymphoma restricted to the CNS. More than 90% are type B and mainly affect patients aged 50-70 years. Immunodeficiency is the most important risk factor. The aim of our study was to evaluate the immune status, clinical presentation and findings in complementary studies of PCNSL patients. A retrospective analysis of 48 cases treated in our center between January 1992 and May 2015 was performed. Median age at diagnosis was 61 years (range 25-84); with male predominance (2.1:1). Forty one cases (85%) were immunocompetent patients. Brain MRI findings showed parenchymal involvement in 45 cases (94%), 43% with frontal lobe and 35% basal ganglia, 4% had meningeal involvement and 2% had ophthalmic involvement at diagnosis. Fifty-five percent had restricted signal on diffusion weighted imaging and contrast enhancement was found in 89%. Pyramidal syndrome was the main initial clinical manifestation (56%). There were abnormal findings in 62% of CSF samples, but in only 11.1% positive cytology results were detected. The most frequent type was diffuse large B-cell lymphoma (83%), being B-cell type the most common form between them (96%). In our series PCNSL was more frequent in immunocompetent elderly male subjects. At initial evaluation, clinical manifestations and MRI findings were variable. The initial suspicion of this entity would allow an early diagnosis, avoiding empirical treatments that may confuse or delay diagnosis.

The need for endodontic treatment and systemic characteristics of hematopoietic stem cell transplantation patients

Abstract The aim of this study is to investigate the relationship between the epidemiological and clinical profiles of patients before and after hematopoietic stem cell transplantation (HSCT) and the need for endodontic treatment. The subjects included 188 individuals enrolled in the dental care program for transplanted patients of the School of Dentistry, Federal University of Minas Gerais (Faculdade de Odontologia da Universidade Federal de Minas Gerais, FO-UFMG) from March 2011 through March 2016. The patients were subjected to an HSCT conditioning dental regimen based on a thorough clinical and radiographic evaluation. Intraoral periapical and bite-wing X-rays were obtained, and after evaluation, specific dental treatment was planned and performed. The following demographic and clinical data were collected from the patients' medical records: age, gender, transplantation stage, primary disease, transplant type, medication used, complete blood count at the time of visit, and need for endodontic treatment. The Kolmogorov-Smirnov and the chi-square tests were used. Leukemia (31.3%) and multiple myeloma (17.9%) were the most prevalent primary diseases. Most patients were subjected to allogeneic-related transplantation (83.6%). Most patients exhibited platelet counts and hemoglobin concentrations below the reference values in the pre-transplantation stage, while the neutrophil and platelet counts and the hemoglobin levels were within the reference ranges in the post-transplantation stage. The proportions of individuals requiring endodontic treatment were similar between the pre- and post-transplantation groups: 24.3% and 24.7%, respectively. The systemic conditions of the patients referred for dental treatment were compromised.

Morphological Typing of Lymphomas with Immunohistochemistry.

Lymphoid malignancies (LM) are a heterogeneous group of disorders that are broadly divided into Hodgkin disease (HD) and Non-Hodgkin Lymphoma (NHL). Diagnosing lymphoid malignancies based on morphology in conjunction with immunohistochemistry (IHC) forms the basis of WHO classification and this has prognostic implications.With this background this study was designed thus including all the lymphoid malignancies both NHL and HD. Materials and Methods: This study was conducted at a tertiary centre in Uttarakhand and included a total of 116 cases of lymphoid malignancies. Of these 41 cases were of Hodgkin disease and 75 cases were of NHL. These cases were initially diagnosed on morphology employing Hematoxylin and Eosin (H&E) and special stains like Reticulin. Subsequently, a preliminary panel of monoclonal antibodies using CD3, CD15, CD20, CD30, and CD45 were employed. All the cases were then classified using WHO classification. Results: HD- Of the 41 cases of Hodgkin’s disease the commonest subtype was Nodular Sclerosis seen in 26 cases (48.78%). Reed Sternberg in reactive milieu is diagnostic of Hodgkin disease. In all cases except one Reed Sternberg cells exhibited positivity for both CD15 and CD30. NHL – Of the 75 cases of NHL an initial classification based on morphology was done. All the cases were classified according to International Working Formulation initially. Subsequently, IHC was employed using CD3, CD15, CD20 and CD45. The disease was then classified according to WHO classification and broadly divided into B or T cell types. B cell expression was seen in 60 cases (80%) and T cell expression in 15 cases (20%). The commonest B cell subtype was Diffuse Large B cell Lymphoma (26.4%).

Neoplasia hematodérmica CD4+ CD56+ en la infancia / Hematodermic CD4+ CD56+ neoplasm in childhood

La neoplasia hematodérmica CD4+ CD56+ con fenotipo de célula dendrítica plasmocitoide es una rara y agresiva neoplasia recientemente reconocida por la WHO-EORTC classification. Afecta adultos de edad media y ancianos, siendo muy pocos los casos descriptos en niños. Presentamos el caso de una niña de 12 años con grave retraso mental, estigmas genéticos y múltiples lesiones cutáneas localizadas en miembros inferiores y superiores. Histológicamente se observó un infiltrado dérmico difuso de células pequeñas y medianas con expresión de CD4, CD56, CD43 y S100 así como de marcadores dendríticos plasmocitoides: CD 123 y BDCA-2 confirmados por citometría de flujo, sin compromiso de sangre periférica ni médula ósea. Cumpliendo dos semanas de tratamiento para leucemia linfoblástica aguda evolucionó con remisión clínica de las lesiones cutaneas.

Hematodermic CD4+ CD56+ neoplasm with plasmacytoid dendritic cell phenotype is a rare and aggressive neoplasm recently recognized by the WHO-EORTC classification. It generally appears in elderly adults, exceptionally in childhood. We present a 12-year-old girl with severe mental retardation, genetic clinical features and multiple nodular cutaneous lesions on legs and arms. Histologically the nodules showed diffuse dermal infiltrate of medium and small cells and expression of CD4, CD56, CD43, S100 and plasmacytoid dendritic markers: CD123, BDCA-2 under flow cytometry study. Peripheral blood and bone marrow were not involved. Clinical remission of cutaneous lesions was observed after two weeks of acute lymphoblastic leukemia therapy.

Imunofenotipagem e rearranjo gênico em doenças pulmonares linfocíticas e linfoproliferativas / Immunophenotyping and gene rearrangement analysis in lymphoid/lymphoproliferative disorders of the lungs

OBJETIVO: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. MÉTODOS: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL) e 7 casos de doenças linfoproliferativas pulmonares. RESULTADOS: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vgama11/Jgama12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dbeta1/Jbeta2 e Vgama101/Jgama12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. CONCLUSÕES: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnóstica.

OBJECTIVE: To determine the usefulness, in routine practice, of using polymerase chain reaction to analyze B and T lymphocyte clonality in pulmonary tissue as a tool for the diagnosis of pulmonary lymphoproliferative disorders. METHODS: Immunohistochemistry and molecular gene rearrangement analysis were performed in order to assess 8 cases of lymphoid interstitial pneumonia (LIP) and 7 cases of pulmonary lymphoproliferative disorders. RESULTS: All 8 cases of LIP presented moderate to strong immunostaining for CD3, compared with only 2 cases of lymphoma and 1 case of pseudolymphoma (p = 0.02). Gene rearrangement was detected in 4 of the 8 cases, which changed the diagnosis from LIP to lymphoma, showing the importance of gene rearrangement detection in cases of LIP. In this situation, gene rearrangement using the VH/JH and Vgamma11/Jgamma12 primer pairs was detected in 3 cases and 1 case, respectively, and no gene abnormalities were found using the Dbeta1/Jbeta2 and Vgamma101/Jgamma12 primer pairs in any of the cases. A significant positive association was found between the intensity of CD20 and CD68 expression and gene rearrangement using the VH/JH primer pair. Prior to the gene rearrangement, 4 patients with LIP died quickly, whereas only one patient with LIP died after the gene rearrangement. CONCLUSIONS: Detection of monoclonal B and T cells by immunophenotyping and polymerase chain reaction had an impact on the diagnosis of pulmonary lymphomas in patients previously diagnosed with LIP. Therefore, immunophenotyping and polymerase chain reaction should be used as 'gold standard' techniques in routine practice.

BAFF: Una citoquina reguladora de linfocitos B implicada en autoinmunidad y cáncer linfoide / BAFF: A regulatory cytokine of B lymphocytes involved in autoimmunity and lymphoid cancer

BAFF (B cell activating factor belonging to the TNF family) is a cytokine implicated in the survival and maturation of peripheral B lymphocytes and T and B cell activation. BAFF binds to three different receptors: TACI, BCMA and BAFF-R, whose expression is restricted to B and T lymphocytes. BAFF and BAFF-R-deficient mice show a dramatic loss of peripheral B lymphocytes and a severely reduced immune response. In contrast, an enhanced BAFF expression leads to B cell hyperplasia and autoimmunity in mice. In vivo, administration of soluble decoy receptors for BAFF effectively decreases disease progression in various autoimmune mouse models. These evidences render BAFF as a potentially new therapeutic target. Elevated BAFF levels have been detected in the serum of patients with autoimmune diseases, such as Systemic Lupus Erythematosus, rheumatoid arthitis, Sjõgren's syndrome, lymphoid cancers and HIV infection. In addition to BAFF receptors, malignant B cells abnormally express BAFF, which attenuates apoptosis through both autocrine and paracrine pathways. The data suggest that an increase in the expression of BAFF induces an enhanced B and T cell activation and the survival of pathologically active B cells. In this article, we review and discuss the participation of BAFF and its receptors in the immune response and its involvement in immunodeficiency, autoimmunity, infections and lymphoid cancers as well as the currently investigated therapies using BAFF antagonists in the treatment of these diseases.

Active Immunization Using Dendritic Cells Mixed With Tumor Cells Inhibits The Growth Of Lymphomas

Dendritic cells (DCs) are potent antigen-presenting cells for the induction and activation of cytotoxic T lymphocytes. We tested whether bone marrow derived DCs are capable of inducing protective immunity against a murine lymphoma (A20). DCs were grown from tumor-bearing BALB/c mice by culturing bone marrow cells. BALB/c mice were injected (sc) with A20 cells on day 0. Intraperitoneal immunization with DCs mixed with lethally irradiated A20 cells were started when the tumor reached ca. 4-5 mm in diameter (Group A) or on day -7 (Group B). Booster immunizations were given every 3-4 days for four weeks. By 31 days in group A, there was a significant reduction in tumor growth in the mice immunized with DCs mixed with irradiated A20 cells as compared with the control groups (p=0.016). In group B, tumor growth was completely inhibited and there was no tumor growth following extended observations after completion of immunization. Thus, DCs mixed with irradiated tumor cells can induce an antitumor effect. This provides a rationale for the use of DCs mixed with irradiated tumor cells in immunotherapy for minimal residual disease of lymphomas.

Targetted localisation and imaging of a murine lymphoma using 131I-labelled monoclonal antibody.

In vivo tumor targetting with radiolabelled monoclonal antibodies is a promising approach for the diagnosis and therapy of tumors. A specific monoclonal antibody (mAb), DLAB was generated to the Dalton's lymphoma associated antigen (DLAA) from Haemophilus paragallinarum-induced spontaneous fusion. In order to study the tumor localisation and biodistribution properties of the monoclonal antibody, scintigraphic studies were performed using the radiolabelled DLAB. 131-labelled DLAB was administered intravenously into Swiss mice bearing Dalton's lymphoma and external scintiscanning was performed at different time intervals. Clear tumor images were obtained which revealed selective and specific uptake of radiolabel and the results were compared with biodistribution data. The radioiodinated monoclonal antibody showed fast tumor uptake which increased significantly to 14.6% injected dose (ID)/g at 12 hr post-injection. Enhanced blood clearance of radioactivity resulted in higher tumor/blood ratio of 5.96 at 48 hr. 131I-labelled DLAB resulted in selective and enhanced uptake of the radioactivity by the tumor compared to the non-specific antibody and the results suggest the potential use of spontaneous fusion for producing specific monoclonal antibodies for tumor detection and therapy.

Production of monoclonal antibodies to a tumor--associated antigen by spontaneous cell fusion.

Spontaneous cell fusion induced by the bacterium Haemophilus paragallinarum has been recently reported as an alternative technique to generate hybridomas producing monoclonal antibody (mAb). In order to investigate the advantages of this technique to produce anti-tumor monoclonal antibodies we performed comparative experiments between H. paragallinarum induced spontaneous cell fusion and polyethylene glycol (PEG) mediated fusion. Hybridomas producing monoclonal antibodies to an experimental murine lymphoma antigen, the Dalton's lymphoma associated antigen (DLAA) were generated and their sensitivity and specificity were ascertained. The spontaneous fusion yielded more number of stable and specific hybridomas than PEG mediated fusion. The results suggest the advantage of H. paragalinarum induced cell fusion for the simplified production of specific antitumor monoclonal antibodies.

Detection of a factor released by L5178Y lymphoblasts that inhibits mouse Macrophage-Activation induced by lipopolysaccharides

Background. Several factors inhibit cellular immune response by deactivating macrophages, but very few, such as those described here, prevent macrophage activation. Methods. Ascites liquid from 12-day-old BALB/c mice bearing 5178Y lymphoma tumors was collected, and cell-free ascites liquid (CFAL) was separated from lymphoblasts. The supernatant (SI) was obtained from the homogenized and centrifuged lymphoblasts Then, macrophage cultures contaning 0.2 X 10 a the sixth cells from lymphoma-bearing or hearthly mice were added to 10 µL of CFAL or S1, plus 5 µg of lipopolysaccharides (LPS)/mL, 40 U interferon-ç or a blend of both. Macrophages were incubated with CFAL or S1 prior to or after adding the activators to investigate whether any of the previously mentioned lymphoma fraction inhibited macrophage activation or whether they deactivated them. The effect of CFAL or S1 was estimated as the diminution of the amount of nitric ixide released by the experimental macrophage cultures with respect to controls (activated macrophages treated with none of the lymphoma fractions). Results. LPS, IFN-ç, and the LPS/ç blend activated macrophages from both lymphomabearing and healthy mice. None of the lymphoma fractions deactivated macrophages. CFAL, but not S1, inhibited the macrophage activation, i.e., the percentage of inhibition of nitric oxide releasing 76.7 percent in macrophages from healthy and lymphomabearing mice, respectively. In addition, CFAL was unable to inhibit macrophage-activation effect of IFN-ç or the LPS/IFN-ç blend. Conclusions. Mouse L5178Y Lymphoma releases a factor that in vitro inhibits the macrophage activation induced by LPS, but not by IFN-ç controls

Analysis of immunoglobulin deficiency cases: a five year study.

A total of 734 serum specimens from various clinical disorders along with 100 control samples from healthy subjects were processed for estimation of serum IgG, IgA and IgM employing single radial immunodiffusion procedure. Immunoglobulin deficiency, either selective or combined was noted in 31 males and 24 females in all age groups. Of the 55 cases encountered it was secondary immunoglobulin deficiency which was seen on a larger scale and encountered in patients with Multiple myeloma (16 out of 32) followed by Leprosy (14 out of 250), Lymphoma (5 out of 43), Malaria (4 out of 137), Burns (4 out of 52), Rheumatoid arthritis (2 out of 69) and non lymphoreticular malignancies (1 out of 41) in decreasing order of frequency. Primary immunoglobulin deficiency was observed in nine cases comprising of six belonging to Idiopathic late onset immunoglobulin deficiency, two of dysgammaglobulineamia and a solitary case of Ataxia telangiectasia. Panimmunoglobulin deficiency was observed in six cases, 11 had a dual deficiency while 38 showed deficiency of an isolated class with selective IgA deficiency in 20 cases. Furthermore, one patient each had total absence of IgG or IgA while IgM was not detectable in seven patients. A high suspicion index along with a regular rapport between the clinician and the laboratory personnel is necessary in the diagnostic set up of immunoglobulin deficiency states.

Prevalencia de seropositividad a citomegalovirus en pacientes con neoplasias hematológicas / Seroprevalence infection with sytomegalovirus in hematological malignancies patients

La infección por citomegalovirus es ubicua y generalmente asintomática. La reactivación o infección primaria en pacientes con cáncer, particularmente leucemia y linfoma, en individuos con inmunosupresión celular y receptores de transplante, establecen a este virus como importante patógeno en humanos. Con el propósito de determinar la prevalencia de seropositividad a cintomegalovirus en pacientes con neoplasias hematológicas en el Instituto Nacional de Cancerología, se realizó la detección de anticuerpos séricos totales contra citomegalovirus en un grupo de pacientes con este padecimiento. La prevalencia de seropositividad a citomegalovirus fue eleva uniformemente mayor de 85 por ciento en los cuatro grupos de estudio, independiente de sexo y diagnóstico. De los factores estudiados, la edad fue el único que se asoció a la presencia de anticuerpos contra citomegalovirus. Es necesario extender estos resultados, a través de un análisis comparativo en muestras de individuos de otras instituciones con diferentes niveles de ingreso. De esta manera, se podrá obtener mejor conocimiento de la distribución de infección de este virus en la población mexicana.

Effect of Vibrio cholerae-L-asparaginase on surface structure of splenic lymphocytes.

The surface ultrastructure of splenic lymphocytes and rosetting properties of lymphocytes of Swiss mice were studied under scanning electron microscope following transplantation of Dalton's lymphoma and ascites fibrosarcoma tumour cells and administration of Vibrio cholerae-L-asparaginase. The results were compared to those obtained with the standard Escherichia coli-L-asparaginase. The surface structure of the lymphocytes (T cells) following L-asparaginase administration was not so different from that of normal lymphocytes. V. cholerae-L-asparaginase did not cause higher number of rosette formation in T cells as compared to the normal group. The study thus revealed that V. cholerae-L-asparaginase did not have a significant stimulatory or non-immunosuppressive effect on the lymphocyte functions.

Multiple lymphomatous polyposis of the gastrointestinal tract: a report of two cases with immunohistochemical studies

We describe two cases of multiple lymphomatous polyposis in the gastrointestinal tract from the esophagus to the rectum. Clinical findings, histopathologic and immunohistochemical findings in paraffin embedded tissue are discussed. It is important to recognize this rare form of gastrointestinal lymphoma because of the prognostic and therapeutic implications.

Linfocitoma cutis: su ubicación en la clasificación actual. Utilidad de las técnicas de inmunomarcación / Lymphocytoma cutis: clasification utility of inmunolabeling techniques

Se presenta un caso de linfocitoma cutis localizado en dorso, en el que se efectuaron técnicas de inmunomarcación, para establecer el diagnóstico diferencial con el linfoma maligno. Se considera su ubicación en la clasificación actual de los pseudolinfomas cutáneos

Rearranjo gênico e diagnóstico de leucemias e linfomas: o DNA ao pé do leito / Gene rearrangement and the diagnosis of leukemias and limphomas: the DNA at bedside

Um dos maiores problemas no diagnóstico e terapêutica dos processos hematológicos malignos é a dificuldade em se estabelecer com precisäo a clonalidade de uma determinada lesäo. Com a descoberta dos mecanismos que governam a síntese das imunoglobulinas, foi possível o estabelecimento de um método simples que determina de maneira exata a presença ou ausência de uma expansäo clonal, dentro de uma populaçäo celular. Dessa maneira, ficou possível um melhor acompanhamento clínico do doente hematológico, uma vez que a metodologia permite a análise quantitativa das células clonais, a detecçäo precoce de recidiva e o diagnóstico preciso de remissäo. Esta revisäo sumaria os princípios que norteiam a utilizaçäo do método, a técnica propriamente dita e alguns resultados que vêm sendo obtidos com a utilizaçäo crescente desta metodologia, e aponta para a participaçäo cada vez maior de conceitos e técnicas moleculares na prática médica

Assessment of immunological parameters during tumour development in a murine model.

Natural Killer activity assessed by 51Cr release assay from K-562 cells showed detectable activity from 5th day after tumour transplantation, reaching a peak on 12th day and thereafter showing a gradual decline in the activity. Antibody dependent cell mediated cytotoxicity estimated by 51Cr labelled sheep red blood cells anti SRBC system demonstrated a peak activity on 5th day. Cytotoxic T lymphocyte activity detected by 51Cr release of Dalton's lymphoma ascites target cells showed a peak on 10th day. Antibody complement mediated cytotoxicity revealed a similar pattern as natural killer cell activity.