Non-Hodgkin's lymphomas in leukaemic phase: incidence, prognosis and therapeutic implications

248 patients with non-Hodgkin lymphomas (NHL) were retrospectively analysed in an attempt to elucidate the risk factors, the prognostic importance and the therapeutic implications of blood involvement. Bone marrow involvement and large spleen were significantly correlated to leukaemic manifestations (P less than 0.0001 and P less than 0.0005, respectively); conversely no correlations were seen with bulky disease and symptoms. Among low-grade malignant lymphomas (LGML) centroblastic-centrocytic follicular and diffuse or diffuse and "CLL" subtypes were mostly associated with blood involvement (31% and 55%, respectively). Among high-grade malignant lymphomas (HGML) lymphoblastic type is more frequently associated with blood involvement (42%) than the other subtypes. Blood involvement was not clearly correlated with the prognosis either in LGML (median survival 39 and 36 months for leukaemic and non-leukaemic patients, respectively) or HGML (median survival 12 and 18 months, respectively), although a shorter survival of leukaemic than non-leukaemic lymphoblastic lymphoma was observed (median survival 8 months versus 14 months, respectively). The poorer response rate to therapy of leukaemic patients (median duration of CR22 and 5 months in LGML and HGML, respectively) as opposed to non-leukaemic patients (median duration of CR 29 and 23 months, respectively) led us to consider an alternative treatment in such patients.     

T-cell subsets in malignant lymphomas and monoclonal gammopathies

159 patients with malignant lymphomas or monoclonal gammopathies were investigated for lymphocytes and their subsets using conventional surface markers and a panel of monoclonal antibodies. In untreated patients with Hodgkin's disease, non-Hodgkin lymphomas and multiple myeloma, (MM) a reduction of T-cells and especially of the "helper/inducer" subset (OKT4+) was found to be a common phenomenon. The major abnormalities occurred in advanced stages of disease. Patients previously treated by chemo- and/or radiotherapy had a further decrease of T-cells, whereas the loss of OKT4+ cells was more pronounced than that of the "suppressor/cytotoxic" lymphocytes (OKT8+). The alterations of lymphocyte subsets persisted even in long-term remitters. Comparing the lymphocyte subsets in MM and benign monoclonal gammopathies (BMG), patients with BMG showed a significant reduction in OKT8+ cells, whereas the OKT4+ population was within normal range, resulting in a significant elevation of the OKT4/OKT8-ratio compared to the controls and untreated multiple myeloma.     

Peripheral blood T lymphocyte subpopulations defined by monoclonal antibodies in rheumatoid arthritis: distribution in patients untreated and treated by oral gold therapy

The distribution of T lymphocyte subsets was determined in peripheral blood (PB) of two groups of patients with rheumatoid arthritis by using monoclonal antibodies (OKT). In untreated patients the percentage of OKT4+ cells (helper/inducer) was found to be significantly increased as compared to healthy controls. In patients receiving oral gold therapy a similar increase in OKT4+ cells was confirmed; furthermore, these patients showed a significant decrease in OKT8+ cell population (cytotoxic/suppressor) compared to untreated patients and to normal controls. A small numerical superimposition of values of OKT4+ and OKT8+ lymphocytes was observed in untreated but not in treated patients.     

Determination of T lymphocyte subpopulations in patients with lung cancer. A comparison between lung lavage and peripheral blood by monoclonal antibodies and flow cytometry

In order to determine whether the alterations of immunoregulatory T cells described both in smokers and in patients with lung cancer occur in the deep lung as well as in peripheral blood, we analyzed T lymphocyte subpopulations in bronchoalveolar lavage (BAL) and in the blood of 12 patients with untreated lung cancer and of 8 controls. The immunocompetent cellular population of BAL fluid analyzed by differential cell count of alveolar macrophages, lymphocytes and neutrophils did not show considerable differences in the two groups studied. By contrast, the analysis of BAL T lymphocytes and their subsets showed significant alterations in patients compared with controls: a percentage increase of OKT3+ and OKT8+ lymphocytes and a decrease of the OKT4+/OKT8+ ratio was found in both the involved and uninvolved lung of patients. The immunologic pattern of T lymphocytes in blood did not show significant differences between patients and controls. Our data indicate that alterations in immunoregulatory T cells in lung cancer are more pronounced in BAL fluid obtained from both lungs than in peripheral blood.     

T-Cell chronic lymphocytic leukemia: Report of a case studied with monoclonal antibody

A previously healthy 74 year old woman presented with T-cell chronic lymphocytic leukemia, lymphadenopathy, hepatosplenomegaly and a mediastinal mass. The circulating lymphocytes were small to medium in size (some with convoluted nuclei) and E rosette-positive; they could be assigned to the inducer-helper subset of T cells with the aid of monoclonal antisera. These cells reacted with OKT3, which detects peripheral t cells; OKT4, which detects the inducer-helper subset of T cells; and OKT11, which detects the sheep cell receptor. It is noteworthy that they were also positive for the la-like antigen found on T cells only after activation. Microscopic examination of a lymph node biopsy specimen revealed a diffuse pattern of pleomorphic large cells characteristic of the T-cell lymphomas and lymphocytic leukemias reported from Japan. However, the lymph node cells lacked the T-cell differentiation antigens present on the circulating lymphocytes. The findings in this case provide insight into the pathogenesis of this unusual disorder and are relevant to our understanding of the spectrum of surface antigens in the more common malignant lymphomas.     

Monoclonal antibody studies in non-Hodgkin's lymphoma

The cell lineage of suspensions prepared from 85 non-Hodgkin's lymphomas was investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin, assessed with specific heteroantisera, proved to be the most useful characteristic and defined the clonal character and B-cell lineage of 63 specimens: almost all nodular lymphocytic (21 of 22) and diffuse lymphocytic (11 of 13) lymphomas, most diffuse histiocytic (29 of 33) and diffuse mixed (2 of 2) lymphomas, and a few nodular mixed (2 of 12) and nodular histiocytic (0 of 3) lymphomas. Monoclonal antibodies provided useful ancillary surface marker criteria. Thus, positivity with OKT1 (which detects both thymic and peripheral T cells) in the absence of reactivity with monoclonal antisera, which detect only peripheral T cells (OKT3, OKT4, OKT8, and OKT11), was seen only in diffuse lymphocytic lymphoma of B lineage. Ia-like antigen could be demonstrated in all B-cell lymphocytic lymphomas and most B-cell diffuse histiocytic lymphomas. Approximately one-half of diffuse histiocytic lymphomas also reacted with OKT9, which detects the transferrin receptor, while few lymph nodes involved by other conditions displayed this reactivity. Most diffuse histiocytic lymphomas and many non-Hodgkin's lymphomas of other subtypes reacted with OKT10, an antiserum that detects an antigen on replicating lymphoid cells. The lineage of approximately one-fourth of the lymphoma suspensions was not resolved conclusively: In most of these, T lymphocytes predominated with a normal proportion of inducer-helper (OKT4) and cytotoxic-suppressor (OKT8) cells. The inability to establish the clonal character of T-cell proliferation in cell suspensions remains an obstacle to completely defining the lineage of non-Hodgkin's lymphomas.     

Bone marrow and blood involvement by non-Hodgkin's lymphoma: a study of clinicopathologic correlations and prognostic significance in relationship to the Working Formulation

In a series of 172 patients with non-Hodgkin's lymphoma (NHL) classified according to the Working Formulation (WF) the overall incidence of bone marrow infiltration (BM+) at diagnosis was 39%: 59% for low-grade (LGML), 30% for intermediate-grade (IGML), and 25% for high-grade malignant lymphomas (HGML). The features most significantly correlated with the presence of BM+ were a low grade of histological malignancy, the degree of splenomegaly and high values of LDH, while those correlated with the extent of BM+ were a non-focal pattern of BM disease, the presence of blood involvement at diagnosis, and the degree of BM fibrosis. Blood involvement was detected at diagnosis in 13% of patients, and a further 16% developed a leukemic phase during the course of the disease. Blood involvement correlated significantly with splenomegaly, bulky disease, advanced clinical stage, and extent of BM+. The presence of BM infiltration 'per se' at diagnosis did not significantly affect prognosis. However, the extent of BM disease was correlated with a poorer outcome in IGML and HGML patients. Regarding peripheral blood involvement, in LGML patients only late leukemic conversions were significantly associated with a worse prognosis. In patients with IGML and HGML, either initial or subsequent blood involvement was correlated with significantly poorer outcome.     

The production of granulocyte-monocyte colony-stimulating activity by isolated human T lymphocyte subpopulations

Isolated human T lymphocyte subpopulations were obtained by fluorescence-activated cell sorting using the murine monoclonal antibodies, OKT4 and OKT8. The capabilities of the isolated lymphocytes to produce granulocyte-monocyte colony-stimulating activity (CSA) in response to mitogen challenge were assessed by in vitro assays employing light density nonadherent bone marrow cells. Essentially, no CSA production was noted by any isolated T lymphocyte population [OKT4 positive (+) or OKT8 positive (+)] cultured alone or following the addition of 10(4) autologous monocytes/ml. When phytohemagglutinin (PHA) alone was added, OKT4+ lymphocytes elaborated small amounts of CSA. With the addition of concanavalin A (Con-A) alone, both OKT4+ and OKT8+ cells were able to produce modest amounts of CSA. Significantly enhanced CSA production was observed when either OKT4+ or OKT8+ lymphocytes were coincubated with autologous monocytes in the presence of mitogen. We conclude that highly purified T lymphocyte subpopulations, free of monocytes as assessed by nonspecific esterase staining, can elaborate small amounts of CSA in response to PHA or Con- A challenge. A synergistic augmentation of CSA production was noted with coincubation of sorted lymphocytes and autologous monocytes in the presence of mitogen. Finally, our results suggest that the ability of T lymphocytes to make CSA is not exclusively limited to either the OKT4+ or OKT8+ defined subsets.     

Regulation of human peripheral blood erythroid burst-forming unit growth by T lymphocytes and T lymphocyte subpopulations defined by OKT4 and OKT8 monoclonal antibodies

To reexamine the influence that T lymphocytes have on the regulation of human peripheral blood burst-forming unit (BFU-E) proliferation in the absence of a statistically significant number of monocytes, very low numbers (3 to 10 X 10(3)/mL) of a null cell fraction highly enriched for BFU-E were cultured alone and in the presence of 5 X 10(5) sheep erythrocyte-purified, autologous T lymphocytes in a methylcellulose culture system containing erythropoietin. T lymphocytes consistently enhanced the growth of BFU-E from the null cell fraction, as reflected in both their number and size. Irradiation of T lymphocytes prior to coculture with null cells markedly reduced this enhancement, strongly suggesting that T lymphocytes synthesize erythroid burst-promoting factors (BPA). To determine whether there were functional differences between the two major T lymphocyte populations as defined by OKT4 (T helper/inducer) and OKT8 (T suppressor/cytotoxic) murine monoclonal antibodies to stimulate the growth of BFU-E, both T cell subpopulations were isolated by negative (panning) or positive (fluorescence-activated cell sorting) selection and cocultured with null cells. No statistically significant differences emerged between unseparated, OKT4+ and OKT8+ T lymphocytes in their ability to stimulate the growth of BFU-E. Thus, these studies provide further evidence that T lymphocytes are a major population of BPA-producing cells and further that OKT4+ and OKT8+ T lymphocytes equally elaborate these factors.     

T lymphocyte subsets of the infiltrating cells in the salivary gland and kidney of a patient with Sj?gren's syndrome associated with interstitial nephritis

Lymphocyte subsets in the salivary gland and kidney were examined in a 38 years-old female patient with Sj?gren's syndrome associated with interstitial nephritis by PAP immunoperoxidase method using monoclonal antibodies. Predominant cells of the infiltrating cells in both tissues were T lymphocytes and most of them were Ia+, OKT4+ cells (activated helper/inducer T lymphocytes). A small number of T lymphocytes were OKT8+ (suppressor/cytotoxic T lymphocytes). Moreover, we found the OKT8+ cells invading the salivary duct epithelial cells. There was no difference in the proportion of lymphocyte subsets of the infiltrating cells between the salivary gland and kidney. A similar pathologic mechanism of tissue damage, therefore, was suggested in both tissues.     

Suppressor cell function and T lymphocyte subpopulations in peripheral blood of patients with progressive systemic sclerosis

Three different in vitro assays--immunofluorescence with monoclonal anti-T cell reagents, enumeration of T gamma cells, and nonspecific suppressor cell function--were used for the analysis of suppressor lymphocytes in the circulation of 28 patients with progressive systemic sclerosis (PSS, scleroderma) and 20 normal individuals. Both OKT8+ and T gamma lymphocytes were significantly reduced (P less than 0.001 and P less than 0.02, respectively) in patients with PSS compared with controls. The OKT4/OKT8 ratio was increased (P less than 0.02). However, the mean suppressor cell index (SCI) of 1.9 (range 0.4-6.6) for patients with PSS was not significantly different (P greater than 0.05) from the SCI of 2.9 (range 1.2-14) for controls. Eleven of the patients had depressed suppressor cell function as indicated by the index value of less than 1.2. In only 5 of these patients, simultaneously measured T gamma and OKT8+ cells were reduced and OKT4+ lymphocytes were concomitantly increased. There were no significant correlations between the numbers of T gamma or OKT8+ cells and the SCI in patients and controls. Neither depressed suppressor cell function nor the OKT4+/OKT8+ ratio greater than 4.2 (greater than 2 SD of normal) in the patients could be related to other immunologic findings, to disease duration and severity, or to involvement of internal organs. These results suggest that depressed suppressor cell activity and immunoregulatory T cell imbalance in PSS may not be directly related to the pathogenesis of the disease.     

T lymphocyte subsets in inflammatory bowel disease: peripheral blood

Peripheral blood T lymphocytes and T lymphocyte subsets have been quantified in 28 patients with ulcerative colitis and 26 with Crohn's disease by an indirect immunofluorescence technique using monoclonal antibodies: OKT3, which detects all peripheral blood T lymphocytes; OKT4 (T cells of helper phenotype); and OKT8 (T cells of supressor-cytotoxic phenotype). Eighteen normal subjects and 16 patients with a variety of non-inflammatory gastrointestinal disorders were studied as controls. No significant differences were found between patient and control groups in the proportions of circulating T lymphocytes or their subsets. When compared with normal subjects, absolute numbers of T lymphocytes were reduced in patients with active ulcerative colitis or Crohn's disease (p less than 0.05). OKT4+ T cell numbers were reduced in ulcerative colitis, whether active (p less than 0.02) or inactive (p less than 0.05) and in active Crohn's disease (p less than 0.05) Numbers of OKT8+ T cells were reduced in active Crohn's disease (p less than 0.01). There were no differences in T lymphocyte numbers between the patient groups and the disease control subjects. The OKT4+:OKT8+ ratio in patients with inflammatory bowel disease did not differ from that in controls. No relation was found between any of the parameters studied and disease activity, site, or extent of disease, or treatment with sulphasalazine or corticosteroids. The presence of Ia-like, HLA-DR antigens on T cells was detected using a double marker immunofluorescence technique. In control subjects up to 7% of OKT3+ cells were HLA-DR+. In only three patients was the proportion of HLA-DR+ cells greater than in controls. These results indicate that the pathogenesis of ulcerative colitis or Crohn's disease does not depend upon an alteration in the proportion of circulating T lymphocytes nor upon an imbalance of T lymphocyte subsets as defined by monoclonal antibodies. The reduction in T lymphocyte numbers may result from mucosal infiltration. The findings also suggest that circulating T lymphocytes are not activated.     

T lymphocyte subpopulations in myelodysplastic syndromes

T cell subpopulations, defined by monoclonal antibodies (OKT3, OKT4 and OKT8), were assessed on 13 patients with myelodysplasia (MDS). The percentage and numbers of OKT3- and OKT4-positive lymphocytes were significantly lower (p less than 0.025) than in normal controls, whereas those of OKT8 were not. In the group of patients with refractory anemia with excess of blasts (RAEB) and in those with chronic myelomonocytic leukemia, the percentage and absolute numbers of OKT8 lymphocytes were significantly lower (p less than 0.025) than in patients with refractory anemia or with primary acquired sideroblastic anemia, while those of OKT3 and OKT4 did not differ significantly. Quantitative impairment of T cell subpopulations may be part of the myelodysplastic situation as a result of the dyslymphopoiesis, according to the hypothesis that MDS originate from pluripotent stem cells. The decrease of OKT8 in RAEB and chronic myelomonocytic leukemia could be related to the previously shown insufficient erythropoietic activity in these patients.     

Immunoregulation of B lymphocyte colony formation by T cell subsets in patients with chronic lymphocytic leukemia

Normal B lymphocytes are activated, proliferate, and then differentiate into plasma cells and secrete immunoglobulin (Ig). We have reported that chronic lymphocytic leukemia (CLL) T4 cells help and CLL T8 cells lack suppressor effects on Ig synthesis by normal B cells (Blood 62:767, 1983). We have now explored the earlier phase, proliferation, using B cell colony formation; in semisolid media. B lymphocyte colonies from normal individuals and from patients with CLL were grown in 0.3% agarose overlayed with T cells or T cell subsets and the B cell mitogen staphylococcal protein A. Enriched T cells, OKT4 or OKT8, were obtained either by sheep erythrocyte rosettes or depletion of OKT8 or OKT4 cells by monoclonal antibody or complement, respectively. Twenty thousand B cells from normal subjects yielded 65 +/- 9, 64 +/- 7, and 19 +/- 6 colonies with autologous unfractionated T-, OKT4-, or OKT8- positive cells, respectively. This compared to 29 +/- 11, 81 +/- 11, and 15 +/- 4 colonies from patients with CLL with added autologous unfractionated T-, OKT4-, or OKT8-positive cells. To determine whether the fewer number of colonies in both normal subjects and patients with CLL with OKT8-positive cells was due to suppression or lack of help, the number of OKT4-positive cells was held constant, and OKT8-positive cells were added in increasing numbers. No suppression of colony formation could be demonstrated. Furthermore, the addition of increasing numbers of concanavalin A (Con A)-activated OKT8-positive cells did not suppress colony formation. These results suggest that the CLL T cell subsets behave in a functionally similar manner to normal T cell subsets, namely, (1) that normal and CLL B cell colony growth is helped by OKT4 cells; and (2) in contrast to immunoglobulin secretion by B cells, neither normal nor CLL OKT8 cells, unstimulated or activated by Con A, suppress B cell colony growth.     

T-lymphocyte subpopulations in the peripheral blood and bone marrow of patients with aplastic anemia

Summary A decrease in the absolute number of total lymphocytes, OKT3⁺ and OKT4⁺ lymphocytes, and a normal number of OKT8⁺ lymphocytes were found in the peripheral blood of patients with aplastic anemia. The OKT4: OKT8 ratio was decreased in patients due to a reduction in the percentage of OKT4⁺ cells and 3 out of 18 patients had a ratio less than 1. The values of the OKT4:OKT8 ratio were not associated either with the severity of the disease or with treatment with androgens. There was no correlation between the OKT4:OKT8 ratio and the number of transfusions received by patients. On the other hand, studies performed with bone marrow lymphocytes showed that the OKT4:OKT8 ratio for both patients and controls was lower than that of the peripheral blood. Since the ratio of OKT4:OKT8 cells in aplastic and control bone marrow was similar no direct pathogenic role can be assigned to the marrow for the imbalance detected in the peripheral blood.     

Abnormalities of peripheral blood T lymphocyte subsets in polymyalgia rheumatica

The T lymphocyte subsets were studied by monoclonal antibodies in the blood of eight patients with polymyalgia rheumatica. The percentages of circulating T cells (OKT3+) were lower when compared with normal controls (p less than 0.02), as were the proportions of suppressor/cytotoxic (OKT8+) T cells (p less than 0.001), whereas the proportions of helper/inducer (OKT4+) T lymphocytes were not changed. Consequently, the OKT4:OKT8 ratio was higher in patients with polymyalgia rheumatica than in controls (p less than 0.001). On the contrary, circulating B cells were not altered. The decrease in peripheral blood OKT3+ and OKT8+ lymphocyte subsets suggests that there is an impairment of cell-mediated immunity in polymyalgia rheumatica.     

Effect of activated lymphocytes on the regulation of hematopoiesis: suppression of in vitro granulopoiesis and erythropoiesis by OKT8+ Ia- T cells induced by concanavalin-A stimulation

The effects of activated lymphocytes were studied in the regulation of in vitro hematopoiesis. Peripheral blood lymphocytes stimulated by concanavalin A (Con A) were cocultured with normal bone marrow cells in the assay system of hematopoietic stem cells. Con-A-stimulated lymphocytes and their supernatants showed significant suppression of in vitro growth of myeloid and erythroid progenitor cells (CFU-C, CFU-E, and BFU-E). Suppressive activity detected in the T-cell fraction was completely abolished by treatment with OKT3 or OKT8 monoclonal antibody and complement and 20 Gy radiation but not OKT4 or OKIa1 antibody and complement. These observations indicate that peripheral blood lymphocytes can be induced by Con-A stimulation to become suppressor T cells for myeloid and erythroid progenitor cells that are OKT8 positive, Ia negative, and radiosensitive. Together with our previous observation that CFU-C suppressor cells induced by alloantigen stimulation are radioresistant and OKT8- and Ia-positive T cells, it is suggested that in vitro hematopoiesis may be regulated by heterogeneous subpopulations of activated T-lymphocytes.     

Lymphocytotoxic antibodies in systemic lupus erythematosus: studies of their temperature dependence, binding characteristics, and specificity in vitro.

The lymphocytotoxicity of 33 lupus sera was tested against purified helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of T lymphocytes at 15 degrees C and 37 degrees C in vitro. There was significantly less killing of both OKT4 and OKT8 cells at 37 degrees C (p less than 0.001 and p less than 0.01) and the ratio of OKT4/OKT8 cell killing at 15 degrees C (1.39 (0.73); mean (SD] was different from that observed at 37 degrees C (0.79 (0.42)) (p less than 0.001). OKT4 killing was greater than OKT8 killing in 21 out of 33 sera at 15 degrees C, while 22 of these sera showed predominantly OKT8 cytotoxicity at 37 degrees C. The relation between the OKT4/OKT8 cell ratio and OKT4/OKT8 serum killing was examined in 22 patients at both temperatures: a significant inverse correlation was observed at 37 degrees C (r = -0.53; p = 0.015) but not at 15 degrees C (p greater than 0.05). The addition of metabolic and cytoskeletal inhibitors increased cytotoxicity at 37 degrees C, but not IgM surface binding. A Scatchard binding analysis of the reaction at 15 degrees C showed that large numbers of antibody molecules were bound to both subsets, with a low average dissociation constant of less than or equal to 6 x 10(-8) mol/l, and electrophoretic blotting indicated that the target surface antigens varied in type and number among individual lymphocytotoxic sera. The demonstration of temperature dependent, tight binding between lymphocytotoxic antibody and variable antigens on the T cell surface emphasises the potential for this phenomenon to affect lymphocyte function in vivo in patients with systemic lupus erythematosus.     

T lymphocyte subpopulations in chronic lymphocytic leukemia of B cell type in relation to immunoglobulin isotype(s) on the leukemic clone and to clinical features

Total blood T lymphocytes and subpopulations (OKT4+ and OKT8+ cells) were studied in 59 patients with B cell chronic lymphocytic leukemia (B-CLL). In 48 previously untreated patients, total T lymphocytes were higher as compared to healthy controls (p less than 0.001). T-cells and OKT8+ cells were significantly increased in patients in advanced clinical stage and with progressive disease in comparison to patients with low stage and indolent disease. High numbers of OKT8+ lymphocytes were also seen in patients with a dominance of mu heavy chains on the leukemic clone. Moreover, in this patient group the OKT8+ subpopulation correlated with total B cells (r = 0.68, p less than 0.001) while in patients with a mu delta phenotype no such correlation was seen. After successful cytostatic therapy there was a reduction in total numbers of both OKT4+ and OKT8+ cells, in particular, with a concomitant increase in OKT4/OKT8 ratios.     

T-lymphocyte subsets and serum carcinoembryonic antigen in patients with lung cancer and its dynamic changes after therapy]

Using the indirect immunofluorescent assay, we observed the variation of T-lymphocyte subsets of peripheral blood in 100 patients of primary bronchogenic carcinoma and 31 cases with active pulmonary tuberculosis. Serum CEA were measured simultaneously. The decrease of OKT3+, OKT4+, OKT8+ lymphocytes were significant in patients with lung cancer than that in healthy controls (P less than 0.01). The ratio of OKT4+/OKT8+ increased. It suggested that both cellular immunoincompetence and immunoregulatory abnormality were present in patients with lung cancer. After the resection of tumors 65 cases, the percentage of OKT4+ cells increased at the first week. Fourty seven cases were observed continuously for six months, it was found that OKT8+ cells increased (P less than 0.01). After anticancer chemotherapy, the patients with small cell carcinoma revealed a similar changes too. After operation and chemotherapy, serum CEA level decreased significantly too.