Induction of HLA-DC/DS (LEU 10) antigen expression by human precursor B cell lines.

The expression of HLA-DC/DS antigen detected by the monoclonal antibody Leu 10 was studied in three human precursor and pre-B cell lines (Josh 7, Reh, and Nalm 12). Flow cytometric analysis showed that none of these cell lines stained for the HLA-DC/DS antigen. In the presence of 1.6 X 10(-9) M of 12-O-tetradecanoylporbol-13-acetate (TPA), expression of this antigen was detected. The expression was completed after 168 h of incubation. Iodination of cell surface, immunoprecipitation by Leu 10 antibody, and two-dimensional gel analysis revealed that TPA-treated Josh 7 cells synthesized and expressed a 29,34 kD bimolecular complex with both alpha and beta chains different from those of HLA-DR antigen. Quantitative absorption experiments with cell lysates indicated a greater than 25-fold increase in HLA-DC/DS antigen in TPA-treated cells. With the induction of HLA-DC/DS antigen expression, there are concomitant decreases in the expression of the common acute lymphoblastic leukemia antigen (CALLA) and the enzymatic activity of terminal deoxynucleotidyl transferase. No appreciable changes in HLA-DR and Ig expression were observed. There was also no change in HLA-SB expression as detected by antibody ILR-1. However, DNA synthesis was markedly inhibited by TPA treatment. These results indicate that precursor and pre-B cell lines can be induced to mature in vitro. They also suggest that the expression of HLA-DC/DS antigen which precedes the expression of membrane Ig and follows the HLA-DR expression is relevant to human B cell development and cell interaction.

Distribution of latex-ingesting cells, T cells, and B cells in the peripheral blood of patients with malignant melanoma.

The distribution among peripheral blood mononuclear cells of latex-ingesting cells, T cells, and B cells was determined with samples from 38 normal donors and 25 patients with malignant melanoma. The mean percentage of latex-ingesting cells, as well as B and T cells, was significantly reduced in the 25 patients with malignant melanoma, stages I and II, compared to the controls. Several explanations for these unexpected findings were considered; possibly the presence of occult neoplasm was responsible for the observed changes in cell distribution.

Predictive model for prognosis in advanced diffuse histiocytic lymphoma.

The purpose of this study was to examine the validity of a predictive model for response to treatment and survival in advanced diffuse histiocytic lymphoma. One hundred twenty-seven consecutive patients with Ann Arbor stage II-IV diffuse histiocytic lymphoma, who completed treatment between 1974 and 1984 in one of four different Memorial Hospital combination chemotherapy protocols, were reviewed. The median follow-up time was 66.9 months for survivors (range, 21-153.1 months). Factors studied included: age; sex; Ann Arbor stage; prior therapy; B symptoms; serum lactic dehydrogenase (LDH); sites of initial disease; and tumor bulk. LDH was grouped accordingly (units/liter): low, less than 225; medium, 225-500; high, greater than 500. Each patient was assigned an overall level of site involvement (LSI) from the following mutually exclusive groups: group I, peripheral lymph node (PLN) (including +/- Waldeyer ring involvement, +/- spleen); group II, extranodal disease (EN) +/- PLN; group III, retroperitoneal lymph node (RLN) +/- PLN; group IV, bulky mediastinal disease (MED) +/- any other disease; group V, EN with RLN +/- PLN. The Ann Arbor staging system failed to dissect patient groups differing significantly in their prognosis. Serum LDH, LSI, and age were the only factors important for predicting response and survival after multivariate logistic regression and a parametric Weibull survival analysis. Using three levels of serum LDH and correlating them with the different LSI, four tentative "stages" differing significantly in their survival at 48 months were defined: stage I, low LDH, any LSI (80% alive); stage II, medium LDH, PLN, and/or EN (50% alive); stage III, high LDH, PLN, and/or EN or medium LDH, RLN +/- PLN +/- EN, and/or MED (35% alive); stage IV, high LDH, RLN +/- PLN +/- EN, and/or MED (15% alive). Identification of prognostic stages on the basis of LDH level and LSI will allow more accurate comparison of clinical trials for patients with advanced diffuse histiocytic lymphoma.

Distribution of a new B-cell-associated surface antigen (BL7) detected by a monoclonal antibody in human leukemic disorders.

A murine monoclonal antibody (anti-BL7) was raised by immunization of BALB/c mice with a precursor B-cell line (Josh-7) which detects a heat-stable, nonimmunoprecipitable antigen. The expression of BL7 was investigated in peripheral blood and/or bone marrow leukemic cell suspensions stained by indirect immunofluorescence and analyzed by flow cytometry. Lymphoblasts from 43 of 43 cases of "null" acute lymphoblastic leukemia were BL7-. Five cases of T-acute lymphoblastic leukemia and 5 cases of terminal deoxynucleotidyl transferase-positive blastic chronic myelogenous leukemia were also BL7-. All 63 cases of B-cell chronic lymphocytic leukemia were BL7+. Neoplastic cells in 22 of 28 cases of B-cell non-Hodgkin's lymphomas in leukemic phase were also BL7+. Expression of BL7 showed some correlation with Rappaport's histological classification. Four cases of multiple myeloma and plasma cell leukemia were BL7-. Twenty-three cases of acute nonlymphocytic leukemias were also analyzed. Of these, only the acute promyelocytic (M3,4 cases) and acute myelomonocytic (M4, one case) varieties expressed BL7 on a small proportion (approximately 15%) of the leukemic cells. All other subgroups were BL7-. The reactivity of anti-BL7 was compared to other B-cell antibodies on selected samples and was shown to be different from B1, B2, and the BA antibodies. Anti-BL7 is a unique monoclonal antibody useful in the study of B-cell cancers.

Cellular distribution of a B-cell specific surface antigen (gp54) detected by a monoclonal antibody (anti-BL4).

A monoclonal antibody (anti-BL4) recognizing a previously characterized Mr 54,000 glycoprotein (gp54) was developed by immunizing BALB/c mice with cells from a precursor B-cell line (Josh-7). In normal individuals, this antigenic molecule was present on tonsillar B-cells (60-80%) and on a fraction of peripheral blood B-cells (5-25%). BL4 (gp54) expression was investigated in 186 patients with a variety of hematological malignancies using indirect immunofluorescence and flow cytometric analysis. Twenty-six of 37 cases of B-cell chronic lymphocytic leukemia (CLL) and 18 of 33 cases of B-cell non-Hodgkin's lymphoma were BL4 positive. Surface expression of BL4 on reactive cases of CLL and non-Hodgkin's lymphoma was brighter than those of B1, B2, and B4, BL4 positive CLL cases expressed a higher proportion of mouse rosette forming cells and Leu-1 positive cells than the BL4 negative subgroup and were not associated with elevated serum immunoglobulin levels. Four of 7 BL4 negative CLL cases were associated with increased serum levels of immunoglobulin M. Lymphoblasts from 14 of 14 cases of non-T acute lymphoblastic leukemia and 3 of 3 pre-B lymphoid blast crisis of chronic myeloid leukemia were BL4 negative. Neoplastic cells from 2 of 3 cases of Waldenstrom's macroglobulinemia and 4 of 7 cases of hairy cell leukemia were BL4 reactive. None of 7 cases of multiple myeloma and plasma cell leukemia were BL4 positive. All 11 T acute lymphoblastic leukemia cases, 6 other T-cell malignancies, 5 cases of Hodgkin's disease, 51 cases of acute nonlymphocytic leukemia, and 9 cases of chronic myeloid leukemia in chronic phase thus far studied were BL4 negative. An in vitro induction experiment using phorbol ester on a case of B-CLL demonstrated disappearance of BL4 accompanied with further B-cell differentiation. Our study further substantiates the previous finding that gp54 is a differentiation antigen restricted to the B-cell lineage and expressed during the intermediate stage of B-cell ontogeny.

Spectrum of Kaposi's sarcoma in the epidemic of AIDS.

Kaposi's sarcoma (KS) is seen with increased frequency in the course of the epidemic of acquired immune deficiency syndrome. In this population, KS has manifested in an aggressive and more disseminated fashion as compared to the classical type. As the epidemic of acquired immune deficiency syndrome continues to spread and more cases of KS are evaluated, a distinct diversity in the clinical presentation and in the course of the disease as well as in variation in the prognosis and response to therapy is being observed. A preliminary description of the spectrum of KS in the epidemic of acquired immune deficiency syndrome is presented here.

Autologous bone marrow transplantation for patients with poor-prognosis lymphoma.

Review of prognostic factors at Memorial Hospital in New York City has shown that adult patients with large-cell lymphoma (diffuse histiocytic lymphoma by Rappaport classification) who have high lactic dehydrogenase (LDH) and/or bulky mediastinal or abdominal disease are destined to do poorly with conventional combination chemotherapy, with a 2-year disease-free survival of about 20%. Patients who relapse after conventional combination chemotherapy have a similar poor prognosis. Thirty-one such patients with lymphoma were studied to evaluate the efficacy of intensive radiotherapy (hyperfractionated total body irradiation [TBI] [1,320 rad]), and cyclophosphamide (60 mg/kg/d for two days) followed by autologous bone marrow transplantation (ABMT). Our results show a disease-free survival advantage (P = .002) for 14 patients who underwent ABMT immediately after induction of remission with 79% surviving at a median follow-up 49.2+ months, compared with a median survival of 5.2 months for 17 patients administered ABMT while in relapse and/or after failing conventional treatment. Our results support the use of aggressive therapy as early treatment for patients with poor prognostic features.

Lymphoblastic lymphoma in adults.

Fifty-one patients with lymphoblastic lymphoma (LBL) treated with one of five successive intensive chemotherapy protocols for acute lymphoblastic leukemia (ALL) since 1971 were reviewed. The patients were divided into leukemic and nonleukemic groups, and their clinical and laboratory parameters compared. The projected 5-year survival rate for all patients treated with the L10/17 protocols was 45% for both leukemic and nonleukemic LBL. The response to treatment was compared with that of 111 patients with ALL and was nearly identical. Poor prognostic factors were age beyond 30, WBC greater than 50,000/microL, failure to achieve a complete response (CR), and a late CR during induction. Leukemia at presentation, T cell surface markers, and the presence of a mediastinal mass did not adversely affect survival. The use of intensive chemotherapy protocols has proven to be a significant advance in the treatment of LBL.

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10M protocols.

Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.

Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.

Semen cryopreservation and artificial insemination for Hodgkin's disease.

Seventy-nine men with Hodgkin's disease were treated with chemotherapy protocols at Memorial Sloan-Kettering Cancer Center and had pretreatment semen analysis performed at the area semen bank. The patients were evaluated to determine: the quality of pretreatment semen, the effect of treatment on spermatogenesis, and the success rate of artificial insemination after semen cryopreservation. Pretreatment sperm concentration, fresh motility, fresh progression, postthaw motility and postthaw progression were all significantly decreased in men with Hodgkin's disease compared with normal controls. Posttreatment semen analysis in 44 men showed azoospermia in 80%, sperm concentration, less than or equal to 10 X 10(6)/mL in 11%, and sperm concentration greater than 10 X 10(6)/mL in 9%. Eleven couples attempted artificial insemination using cryopreserved semen, thus far resulting in three pregnancies. Semen cryopreservation and artificial insemination offer a partial solution to posttreatment azoospermia in this population, but further methods are needed to minimize gonadal toxicity without compromising therapy for Hodgkin's disease.

Unexplained persistent lymphadenopathy in homosexual men and the acquired immune deficiency syndrome.

Ninety-three homosexual men with persistent lymphadenopathy were followed at the Memorial Sloan-Kettering Cancer Center for a mean period of 20.8 months. Histories and serologic evidence of a number of previous infections were common, but the lymphadenopathy was not due to recognizable infections or neoplastic disease. Leukopenia, lymphopenia, granulocytopenia, monocytopenia, decreased ratios of T-helper to T-suppressor cells, decreased natural killer cell activity and increased serum immunoglobulin concentrations were common. Lymph node biopsies showed reactive hyperplasia without any unique histopathologic features. Antibody to the human T-lymphotropic virus-III (HTLV-III or LAV), a newly described retrovirus believed to be the etiologic agent of the acquired immune deficiency syndrome (AIDS), was detected in 91.4%. Over a 3-year period, 11 cases of AIDS were recognized in these patients: Kaposi's sarcoma developed in 7 and opportunistic infections in 4. The lymphadenopathy resolved in six patients and the others remained unchanged. Although most of these patients are asymptomatic and remain well, the risk of AIDS in this group of men was higher than in other groups of homosexual men in New York.

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Hairy cell leukemia: a model for studying the B cell family of diseases.

Nineteen patients with hairy cell leukemia (HCL) were treated with recombinant interferon alpha-2a/Roche (Roferon) given by daily intramuscular injection of 3 X 10(6) for 6 months followed by three injections per week. Pretreatment and follow-up marker studies were performed on 14 of 16 evaluable patients. Peripheral blood and bone marrow mononuclear cells were analyzed by flow cytometry for reactivity with monoclonal antibodies to B cell associated surface antigens (B1, B2, B4, BL1, BL3, and BL7) and two hairy cell (HC) antibodies, anti-HCL1 and HCL3. B cell monoclonality was determined by clonal excess calculation of immunoglobulin light chains. Right angle scatter analysis showed that HCs are scattered between lymphocytes and monocytes. Nine of the 14 patients achieved a partial remission, three patients achieved a minimal response, and two patients failed therapy. Phenotypically, ten patients had kappa clonal excess and four had lambda clonal excess. These cases expressed a mature B cell phenotype, ie, BL1-, BL7+, BL3+, B1+, B2-, B4+, HCL1+, HCL3+. All 12 responders became nonreactive with monoclonal antibodies 4 to 8 weeks after therapy; in five of these cases, reactivity with monoclonal antibodies was again detected at the time of maximum clinical response (2 to 8 months), without affecting clinical response status. In four of 12 responders, clonal excess disappeared 4 to 8 weeks after therapy; in three more patients, clonal excess disappeared at the time of maximum clinical response (2 to 4 months); in three patients, clonal excess disappeared from the peripheral blood, but not from the bone marrow at the time of maximum clinical response (3 to 5 months); two patients had persistent clonal excess. In the two failures, there was persistence of clonal excess and reactivity with monoclonal antibodies. This study shows that phenotypic analysis is a sensitive and objective method of assessing response of HCL to alpha interferon. This system could be used as a model for the study of other B cell neoplasms.

Steroid-related development of Kaposi's sarcoma in a homosexual man with Burkitt's lymphoma.

The development of Kaposi's sarcoma has been associated with either iatrogenic or disease-related immunodeficiency. This report describes a homosexual man who presented with Burkitt's lymphoma and later had pneumonitis, which was treated with a high dose of corticosteroids. Kaposi's sarcoma subsequently developed, and regressed completely when the chemotherapy and corticosteroid therapy were withdrawn. The evidence from the literature relating corticosteroid therapy to the development of Kaposi's sarcoma is discussed, as well as the possible multifactorial origin of the immunodeficiency in which setting this tumor occurs. The observations in this patient suggest that corticosteroids should be used with extreme caution in patients with acquired immunodeficiency and those at risk for its development.

Massive lymphadenopathy mimicking lymphoma in leukemic reticuloendotheliosis.

Leukemic reticuloendotheliosis is increasingly noted to have a spectrum of laboratory findings suggestive of both lymphocytes and monocytes. However, previous reports have not noted a clinical presentation which may be confused with lymphoma. This report documents a case of leukemic reticuloendotheliosis in a 29 year old man with clinical findings of diffuse lymphadenopathy, organomegaly and cutaneous involvement. As cytotoxic agents may be dysfunctional in leukemic reticuloendotheliosis, the ability to distinguish between the disorder and a lymphomatous process may be critical to the patient's management. Both morphologic examination of the "hairy-cell" and cytochemistry may not give an unequivocal differentiation between these two diseases. However, functional studies of the neoplastic cell, such as cell-marker analysis, phagocytic function and ultrastructural morphology, can define by noninvasive methods the correct diagnosis in the atypical presentation of leukemic reticuloendotheliosis.

Phenotypic analysis by flow cytometry of surface immunoglobulin light chains and B and T cell antigens in lymph nodes involved with non-Hodgkin's lymphoma.

The objective of this study was to demonstrate the diagnostic usefulness of flow cytometric analysis of surface membrane immunoglobulin light chain and monoclonal antibody reactivities in B cell non-Hodgkin's lymphoma. For this purpose, lymph node cell suspensions from 80 patients (20 normal lymph nodes, 11 lymph nodes with benign lymphoid hyperplasia, and 47 lymph nodes with B cell non-Hodgkin's lymphoma) were studied to detect the expression of surface B and T cell differentiation antigens recognized by a panel of monoclonal antibodies (anti-Leu-1, anti-Leu-5, anti-HLA-DR, J-5, anti-BL-1, anti-BL-2, and anti-BL-7). The clonal excess calculation, percent kappa-positive minus percent lambda-positive/percent kappa-positive plus percent lambda-positive cells per discrete level of fluorescence intensity, was used to study the clonality of surface membrane immunoglobulin light chain expression. Among the BL surface antigens, BL-7 proved to be most consistently expressed in B cell non-Hodgkin's lymphoma (79 percent). It was also present in 57 percent of lymph nodes with benign hyperplasia. No significant relationships were detected between the patterns of reactivity with the anti-BL monoclonal antibodies and histologic subtypes, although the small number of cases tested in each category precludes any definitive conclusions. Immunophenotypic heterogeneity within subgroups was also observed with expression of the other antigens examined. Monoclonal expression of surface membrane immunoglobulin light chain was seen in 43 of 47 (91 percent) of lymph nodes with non-Hodgkin's lymphoma, three of 11 (27 percent) hyperplastic lymph nodes, and one of 22 (4 percent) normal lymph nodes. When the presence of BL-7 and clonal excess was examined as a panel, 83 percent of B cell non-Hodgkin's lymphomas were positively identified, whereas one normal lymph node and no hyperplastic lymph nodes gave positive results. The simultaneous presence of clonal excess and BL-7 can be a useful diagnostic aid in the differentiation of lymphomatous from hyperplastic lymph nodes. Cytofluorimetry provides a rapid, objective, and reproducible technology to confirm the diagnosis of lymph node involvement in B cell non-Hodgkin's lymphoma.

Characterization of B-cell type chronic lymphocytic leukemia cells by surface markers and a monoclonal antibody.

This study was carried out to determine the reactivity of the Leu-1 mouse monoclonal antibody with B-chronic lymphocytic leukemia and other B-cell leukemias. This antibody has been previously reported to recognize a surface antigen expressed by almost all human thymocytes and peripheral T cells. It was also detected on surface immunoglobulin-bearing cells of most patients with chronic lymphocytic leukemia but was not detectable in normal B-cells and B-cell lines. In the present series, the neoplastic lymphocytes in 33 cases of B-chronic lymphocytic leukemia expressed surface immunoglobulin, Ia antigen, and receptors for Fc, C3, and mouse erythrocytes. All but one case expressed the Leu-1 antigen as detected by indirect immunofluorescence using flow cytometry. In three other cases, the leukemic cells in the peripheral blood reacted with anti-Leu-1, whereas the bone marrow lymphocytes did not. Moreover, quantitative differences in the surface density of Leu-1 were apparent by flow cytometry. The peripheral blood and bone marrow lymphocytes in other B-cell leukemias, including 15 cases of leukemic B-cell lymphomas and three cases of hairy-cell leukemia, failed to stain positively with the anti-Leu-1 antibody. The recognition of the Leu-1 antigen adds to the phenotypic characterization of b-chronic lymphocytic leukemia and may contribute to a better understanding of the pathogenesis of the disease and its expression in different tissues.

Analysis of T cell subsets in cancer patients treated with interferon.

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.