Is there a role for capsule endoscopy in the staging work-up of patients with gastric marginal zone B-cell lymphoma of MALT?

INTRODUCTION: In earlier studies, involvement of the small intestine was reported in patients with gastrointestinal lymphoma. Prospective data on the involvement of the small intestine in patients suffering from gastric extranodal MZBCL of MALT do not exist so far. In this study, we investigated the frequency of the involvement of the small intestine and the role of capsule endoscopy in patients with gastrointestinal extranodal MZBCL of MALT and of follicular lymphoma. PATIENTS AND METHODS: 40 consecutive patients with gastrointestinal extranodal MZBCL of MALT (26 men, 14 women, aged 27 - 80 years), and 7 patients with known follicular lymphoma of the small intestine (5 men, 2 women, aged 34 - 63 years) underwent capsule endoscopy. RESULTS: Involvement of the small intestine was identified by capsule endoscopy in all 7 patients with known follicular lymphoma of the small intestine. In 6 of 40 patients with gastric extranodal MZBCL of MALT abnormal findings could be observed, three of these findings indicative for lymphoma involvement of the small intestine. However, in each of these 3 cases, intestinal involvement had been already diagnosed by conventional GI endoscopy before capsule endoscopy. CONCLUSIONS: Capsule endoscopy is able to detect involvement of the small intestine in patients with gastrointestinal lymphoma. However, involvement of the small intestine seems to be rare in patients with gastric extranodal MZBCL of MALT. In summary, routine diagnostic work-up of the small intestine, e. g. by capsule endoscopy seems unnecessary because of the rare involvement of the small intestine and an excellent long-term outcome irrespective of a possible intestinal manifestation.

[Rectal goblet cell carcinoid. Primary tumor or metastasis?]. / Becherzellkarzinoid des Rektums. Primarius oder Metastase?

Goblet cell carcinoids are biphasic neoplasms of the gastrointestinal tract composed of a glandular and neuroendocrine differentiation. Typically, goblet cell carcinoids are localized in the vermiform appendix. We report the case of a 60-year-old female patient with the diagnosis of a 1.2-cm rectal goblet cell carcinoid tumor discovered during prophylactic proctocolonoscopy. Because of the known aggressive behavior of this entity, a rectosigmoidectomy was performed. The preoperative staging revealed neither local nor systemic spread. After 8 months, the patient is in good health. As a primary tumor of the extraappendiceal gastrointestinal tract, goblet cell carcinoids are a rarity. It is generally recommended to exclude metastasis of a primary appendiceal neoplasm. However, since the patient underwent an appendectomy in 1974, primary origin in the rectum is favored.

A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction.

BACKGROUND: The combination of irinotecan with 5-fluorouracil demonstrates efficacy with tolerable safety in the first-line treatment of metastatic gastroesophageal cancer (mGC). This randomized phase II trial compared for the first time capecitabine with irinotecan or cisplatin in this setting. PATIENTS AND METHODS: Patients were randomly assigned to receive 3-week cycles of capecitabine 1000 mg/m(2), twice daily for 14 days, with on day 1 either irinotecan 250 mg/m(2) (XI) or cisplatin 80 mg/m(2) (XP). The primary end point was overall response rate (ORR) and secondary end points included progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Of 118 patients recruited, 112 were eligible for safety analysis and 103 for efficacy analysis. In the XI and XP treatment arms, there were no marked differences in ORR, 37.7% versus 42.0%, and median PFS, 4.2 versus 4.8 months, although median OS was longer, 10.2 versus 7.9 months, respectively. Grade 3/4 toxicity was higher in the XP regimen for thrombocytes (18.2% versus 1.8%), nausea (23.6% versus12.3%) and vomiting (16.4% versus 1.8%) and in the XI arm for diarrhea (22.8% versus 7.3%). CONCLUSION: The comparable activity and safety of the XI and XP regimens establish XI as a relevant platinum-free first-line treatment choice for patients with mGC.

[Littoral cell angioma of the spleen. Association with colon and hepatocellular carcinoma]. / Littoralzellangiom der Milz. Assoziation mit Kolon- und hepatozellulärem Karzinom.

Littoral cell angioma is a rare vascular tumor of the spleen. An increased association with concomitant malignancies has been described. We report the case of a 67-year-old man suffering from colon carcinoma and presenting with a tumor of the spleen which could be seen using radiography. Splenectomy was performed and histology revealed a 2.1 cm vascular tumor with a characteristic immunophenotype (CD31/68+). In addition a hepatocellular carcinoma was found. Due to the relationship with malignant tumors littoral cell angioma should be considered in every case of a splenic tumoral space-occupying mass, particularly in carcinoma patients.

Abnormal blood monocytes in chronic lymphocytic leukemia.

Blood monocytes were analyzed in 28 patients with chronic lymphocytic leukemia without previous cytotoxic therapy and without recent infection. Using monoclonal antibodies and flow cytometry, monocytes identified by LeuM3 or My4 were low in percentage (2.3%), but absolute numbers were increased in many patients with values exceeding the normal range (120 to 510/microliter) in seven of 28 patients. Monocytosis was more prominent in patients with high leukemic counts, but there was no correlation to clinical stages. Monocytopenia was evident with less than 50 LeuM3+ cells/microliter in three patients. Two-color fluorescence was used for the analysis of cell surface expression of major histocompatibility complex (MHC) Class II molecules, complement receptors, and Fc receptors on the LeuM3+ monocytes. Compared to cells from control donors, there was an increase for MHC class II antigens, complement receptors, and Fc receptors on the monocytes in chronic lymphocytic leukemia, in terms of both the percentage of positive cells among the LeuM3+ monocytes and of fluorescence intensity. This increase was not restricted to patients with monocytosis nor were the molecules always upregulated concomitantly. The increase of antigen expression on LeuM3+ monocytes was more than 50% (1.5-fold) in seven of 22 patients for MHC Class II antigens, in seven of 16 patients for complement receptor and in six of 12 patients for Fc receptor. A similar decrease of antigen expression was observed only in one patient for MHC Class II and in one patient for complement receptor expression. Monocytosis and increased expression of monocyte cell surface antigens described for a large portion of patients might be causally involved in the immunodeficiency in chronic lymphocytic leukemia.

Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial.

Therapeutic vaccination of tumor patients with cytokine gene-transfected tumor cells leads to tumor regression in animal models but has so far not resulted in significant clinical benefit. We and others demonstrated that tumor cells transfected to mediate overexpression of a cytokine gene activate immunologic effector cells for an improved proliferation rate and significantly higher antitumoral cytotoxic activity. Here, we performed a pilot study of therapeutic vaccination in patients with metastatic disease. Autologous tumor cells were simultaneously transfected with novel minimalistic, immunogenically defined, gene expression constructs (MIDGE) for overexpression of the two cytokines interleukin 7 (IL-7) and GM-CSF and newly designed double stem-loop immunomodulating oligodeoxyribonucleotides (d-SLIM) as a Th1-promoting and NK cell-stimulating adjuvant. Transfection was performed ex vivo by ballistomagnetic gene transfer. Patients received four subcutaneous injections of at least 1 x 10(6) of their expression-modulated and immunomodified autologous tumor cells. Ten patients have been enrolled in the study protocol. In all patients no adverse effects could be detected. IL-7 and interferon gamma levels were elevated in the serum of the patients after treatment. Interestingly, cytotoxicity of patient-derived PBLs increased significantly during treatment. All 10 patients had progressive disease when entering our protocol. One complete, one partial, and one mixed response with progression of abdominal metastases and regression of lung metastases were observed. Two patients showed a stable disease after treatment and five patients remained in progressive disease. Our observations confirm the capability of autologous expression-modified and immunomodulated tumor cell vaccines to stimulate a strong immune response in patients with metastatic cancer even in the presence of a large tumor burden.

Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the alpha-chain of the human interleukin-2 receptor.

The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the alpha-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2R alpha chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.

A novel non-radioactive cellular cytotoxicity test based on the differential assessment of living and killed target and effector cells.

Monocyte/macrophage-mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) are slow processes, requiring cocultivation of effector and target cells for up to several days. Because of the high spontaneous release and possible reutilization of isotopic labels, the conventional radioactive release assays are unsuited for measuring long term cytotoxicity. We developed a non-radioactive flow cytometric assay for the quantitative analysis of cell-mediated cytotoxicity. Because dead cells can dissolve and disappear during the incubation period (lysis, phagocytosis), we determined the absolute numbers of living cells in the well. Prior to incubation the effector cells are stained with the red lipophilic fluorescent dye PKH26 and the target cells with the green fluorescent dye PKH2. At the end of the incubation (1-6 days) a defined number of bright fluorescent cell standards and propidium iodide for staining of dead cells was added to each well. Using flow cytometric analysis, we determined the ratio of targets to standards and calculated the absolute target cell number by multiplication with the known number of standards added. The main advantages of the assay are the possibility of extended incubation periods, the avoidance of radioactivity and its potential applicability to autologous culture systems, where effector and tumor cells are derived from the same patient. The assay opens new avenues for preclinical testing of tumor therapeutics such as monoclonal antibodies and/or cytokines.

The Torre syndrome with gastrointestinal polyposis.

Multiple cutaneous sebaceous neoplasms with or without keratocanthomas are associated with internal low-grade malignant neoplasms, usually of the gastrointestinal (GI) tract (Torre syndrome). We describe a 75-year-old man with multiple sebaceous adenomas, sebaceous epithellomas, and keratoacanthomas in association with multiple colonic polyps. In one polypoid lesion, an adenocarcinoma was noted histologically. Although GI tract carcinoma is clearly established with the Torre syndrome, the occurrence of multiple GI polyps has not been recognized to our knowledge.

The monoclonal antimonocyte antibody My4 stains B lymphocytes and two distinct monocyte subsets in human peripheral blood.

The monoclonal antibody (MAB) My4 was produced against human myelo-monocytic leukemia cells and stains regular monocytes with high intensity. Employing logarithmic amplification in immunofluorescence flow cytometry an additional low intensity - My4+ - and a very low intensity population - My4(+) - can be identified. Light scatter analysis reveals monocyte features for the My4++ and for the My4+ cells, while the My4(+) cells exhibit characteristics of lymphocytes. The two low intensity (My4+ and My4(+)) populations are clearly discernable only after two color immunofluorescence analysis using MABs VEP13 (CD16) and B1 (CD20). The My4+ cells coexpress the CD16 antigen and comprise a unique monocyte subset. The My4(+) cells coexpress the B1 antigen, characteristic of B cells. In addition, the My4(+) cells are depleted after treatment of mononuclear cells with the anti-B cell MAB BA-1 plus complement. Finally, leukemic cells from patients with B cell type chronic lymphocytic leukemia are stained in 18/20 cases. Hence, the MAB My4 identifies regular monocytes and in addition, with lower intensity of staining a new monocyte subset and a subset of B cells in human peripheral blood.

Enhancement of antibody dependent cellular cytotoxicity (ADCC) by combination of cytokines.

Monoclonal antibodies (MAb) specific for tumor-associated antigens (TAA) can induce an immunological cellular attack of tumor cells by a process termed antibody dependent cellular cytotoxicity (ADCC). Cytokines may augment ADCC by direct activation of immune cells or by enhancement of TAA on tumor cells. Thus, we investigated whether ADCC by MAb 17-1A and BR55-2, which recognize TAA on colorectal tumor cells, can be augmented by 3-day incubation with different concentrations of IL-2, IL-4, IL-6, IL-12, IFN-alpha, IFN-gamma, GM-CSF, M-CSF, and TNF-alpha. ADCC was assessed by a new flowcytometric cytotoxicity assay (Flieger et al. Immunol Methods 1995; 180:1-13) using PKH-2 labeled HT29 cells as targets and PKH-26 labeled peripheral blood mononuclear cells from three healthy volunteers as effector cells. We found three reaction patterns with the cytokines tested: (a) cytokines, which increase ADCC (IL-2, IL-12, IFN-alpha, and IFN-gamma, which represent Thl cytokines); (b) cytokines with no effect (GM-CSF, M-CSF, and TNF-alpha); and (c) cytokines, which decrease ADCC (IL-4 and IL-6, which represent Th2 cytokines). Then, we tested cytokines that increase ADCC in combination with the other cytokines. We found that the combinations IL-2/IFN-alpha, IL-2/IFN-gamma, IL-2/IL-12, and IL-12/IFN-alpha potentiated ADCC. By contrast, IL-4 reduced the IL-2, IL-12, and IFN-alpha-induced ADCC. Since the Thl response, cooperation of monocytes and CD4 cells is involved, we plan to elucidate by magnetic cell sorting (MACS) separation techniques, which cells are involved in cytokine-induced ADCC. Our results may be useful for finding combinations of cytokines and MAb for the locoregional treatment of colorectal cancer.

[MALT-lymphoma]. / MALT-Lymphom.

Gastric lymphoma is most frequently an extranodal marginal zone-B-cell-lymphoma of mucosa-associated lymphoid tissue (MALT). The diagnosis is established by biopsy of the tumor. Computed-tomography, endosonography and recently capsule-endoscopy are used for staging. It is a relative new finding that MALT-lymphomas of the stomach are induced by Helicobacter pylori. A side-effect-poor breakthrough has been achieved by eradication of this bacterium with antibiotics. Refractory cases are amenable to radiotherapy, chemotherapy or surgical resection. The rarer aggressive lymphomas of the stomach are treated primarily by chemotherapy and radiotherapy. For both entities a further improvement may be achieved in ongoing prospective clinical trials by addition of the monoclonal antibody rituximab, which targets CD20 on lymphoma cells.

Capsule endoscopy in gastrointestinal lymphomas.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) is a new procedure for small-bowel imaging. The potential contribution of this method to the diagnosis and staging of gastrointestinal lymphomas has not yet been evaluated. The aim of this prospective study was to assess the frequency and morphology of different forms of intestinal pathology in patients with gastrointestinal lymphomas. PATIENTS AND METHODS: Commercially available capsule video endoscopes were administered to 27 patients (16 men and 11 women, aged 27-77) with known gastrointestinal lymphomas. CE was also carried out in 30 control individuals. RESULTS: All seven patients with primary intestinal lymphomas who were examined were found to have pathological findings on CE--four with ulcerations, four with nodes, three with villous atrophy, and one with plaques/white villi. One patient with severe diarrhea was examined three times before and after chemotherapy, and improvement of the lesions was evident, as well as resolution of diarrhea. Twenty patients with gastric lymphoma were examined (16 with low-grade and four with high-grade B cell lymphomas). The capsule did not leave the stomach in three patients, suggesting impaired motility. The small-bowel transit times were 261+/-41 min for intestinal lymphoma, 245+/-62 min for gastric lymphoma, and 224+/-82 min for controls (P>0.05). Five of the 20 patients with gastric lymphoma had pathological findings in the intestine--three with plaques/white villi, two with nodes, and two with villous atrophy. In two patients, subsequent biopsies revealed secondary follicular lymphoma and high-grade lymphoma, respectively. CONCLUSIONS: CE is a valuable diagnostic tool for defining the extent of bowel involvement and assessing the efficacy of treatment in patients with gastrointestinal lymphoma.

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer.

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

[Palliative treatment for colorectal cancer]. / Kolorektales Karzinom.

Over 50,000 new cases of colorectal cancer are diagnosed in Germany every year. About half of these patients will be cured by surgery. The other reoccur or present primarily with advanced disease. Recently, the survival of patients with metastasized disease has been prolonged from about 6 months with best supportive care alone to more than 20 months with combination chemotherapy. Therefore, adequate palliation is reasonable. Irresectable liver metastasis can be treated by locally ablative procedures such as radiofrequency ablation (RFA) or laserinduced thermotherapy (LITT). In the individual case resection of lung or brain metastasis should be discussed. Practitioners have to deal with plenty of supportive opportunities e.g. analgesics, bisphosphonates, central acting drugs, nutrition but also with drug side effects. In centers different endoscopic or interventional radiologic procedures are offered. Considering the variety of therapeutic options, it is prudent to discuss individual treatment plans in an interdisciplinary "tumor board" and involve the practitioners in the decision making.

Identification and characterization of a novel monocyte subpopulation in human peripheral blood.

With the aid of two-color immunofluorescence and flow cytometry, a new subset of cells coexpressing CD14 and CD16 antigens can be identified in human peripheral blood. Using the monoclonal antibody My4, these CD14+/CD16+ cells account for 2.2% of the mononuclear cells and form about 13% of all cells identified by the monocyte-specific CD14 monoclonal antibody. The CD14+/CD16+ cells can be assigned to the monocyte lineage based on typical morphology, on expression of additional monocyte-associated molecules, on the ability to form reactive oxygen intermediates and on the expression of monocyte-specific NaF-sensitive esterase. Light scatter analysis revealed lower forward angle and right angle light scatter for the CD14+/CD16+ cells compared with the regular monocytes, and the average cell size was determined to be 13.8 and 18.4 microns, respectively. Expression of class II antigens on these "small monocytes" was twofold higher compared with the regular monocytes. By contrast, the capacity to perform adherence to plastic surfaces, as well as the ability to phagocytize antibody-coated erythrocytes was clearly reduced in the CD14+/CD16+ monocyte subset as compared with the regular monocytes. Hence the CD14+/CD16+ cells appear to represent a new monocyte subset with a distinct functional repertoire. A survey of various tissues revealed that a large proportion of the alveolar macrophages, but not of the peritoneal macrophages, express the CD14+/CD16+ phenotype.

Zn++ inhibits both tumor necrosis factor-mediated DNA fragmentation and cytolysis.

The cellular events involved in direct tumor-cell destruction by tumor necrosis factor (TNF) are still incompletely understood, but a role of endonucleases has been suggested. In the present study we have analyzed in detail the effect of Zn++, an inhibitor of endonucleases, on TNF-mediated DNA-fragmentation and on cytolysis in Actinomycin-D-pre-treated WEHII 64-S cells. Beginning 2 hr after addition of TNF, a rapid degradation of cellular DNA is observed, as evidenced by release of 3H-Thymidine (TdR) label from nuclei into cytoplasm. TNF-mediated lysis of WEHII64-S cells begins at 3 hr and reaches plateau levels at 7 hr. Addition of Zn++ to TNF-treated WEHII64 cells completely abrogates DNA fragmentation at ImM. Of greater importance is the fact that Zn++ treatment also completely blocks TNF-mediated cytolysis of the target cells. Concentrations-between 0.1 and I mM ZnSO4 prevent cell death, as assessed by chromium-release and Trypan blue dye exclusion. In addition, ZnCl2, but not other divalent cations like CaCl2, MgSO4 and CuSO4 in the same concentration range, prevents cell death as well, demonstrating that the effect in fact is mediated by Zn++. Zn++ added 2 hr after TNF treatment, still effectively inhibits cell lysis, indicating that it acts at a late stage after binding of TNF to its receptor. Our data suggest that activation of endonucleases is not an accompanying effect but an essential step in TNF-mediated tumor-cell destruction.

Better acceptance of Fecal Occult Blood Test (FOBT) for colorectal cancer screening during hospitalization.

INTRODUCTION: Colorectal cancer (CRC) is a leading cause of illness and death in the Western world. Screening with fecal occult blood test (FOBT) significantly reduces the death rate and the incidence from CRC but these tests are not widely accepted. We investigated the possible contribution of hospitalization to a better acceptance of CRC screening. PATIENTS AND METHODS: From October 1998 through September 2000, 721 consecutive patients between 45 and 75 years of age admitted for various reasons were asked for participation in the study. They were asked to participate in FOBT-screening. In case of refusal of FOBT they were asked a second time after detailed information. In patients who accepted 3 consecutive FOBT's were performed. In case of positive FOBT results colonoscopy and gastroscopy were performed. RESULTS: 149 (82 male/67 female) patients were included. 94 (63.5%) of them agreed to undergo FOBT primarily and 10 (6.8%) secondarily after detailed information. The total acceptance rate of the FOBT was 69.8% (m/w : 69.1%/71.6%). In one of 5 cases with a positive FOBT result colorectal cancer (CRC) was diagnosed. Information on repetition of FOBT after one year could be obtained from 82 patients (55%). 37 patients (45%) had undergone repeated FOBT. None of the 37 patients was motivated by the FOBT screening during hospitalization. CONCLUSIONS: Staying in a hospital offers a good chance to achieve a higher acceptance of the FOBT. Therefore, hospitalization may contribute to a better colorectal cancer prevention. However, motivation to regularly repeat screening does not last in all patients. Therefore, public campaigns as well as medical counseling need to continuously stress the necessity of CRC screening procedures.

The combination of interleukin-2 and interferon alpha effectively augments the antibody-dependent cellular cytotoxicity of monoclonal antibodies 17-1A and BR55-2 against the colorectal carcinoma cell line HT29.

Monoclonal antibodies (mAb) are promising substances for the treatment of colorectal carcinoma, but the efficiency of this therapy still needs further improvement. We used a flow-cytometric cytotoxicity test to determine the efficacy of the cytokines interferon alpha (IFNalpha) and gamma (IFNgamma), interleukin-2 (IL-2), macrophage-colony-stimulating factor (M-CSF), granulocyte/macrophage-CSF (GM-CSF) and tumor necrosis factor alpha (TNFalpha) in enhancing the antibody-dependent cellular cytoxicity (ADCC) of the mAb 17-1A and the mAb BR55-2 against the colorectal carcinoma cell line HT29. In experiments performed at an effector to target ratio of 9:1, with peripheral blood mononuclear cells from five healthy volunteers as effector cells, we found that IFNalpha, IFNgamma and IL-2 significantly augmented the ADCC of both mAb at concentrations between 3 ng/ml and 30 ng/ml. The other three cytokines were not effective. In further experiments we examined combinations of the three effective cytokines in different concentrations. The combination of IFNalpha and IL-2 proved to be optimal in enhancing ADCC of both mAb. Thus, the examination of ADCC by flow cytometry may reveal potentially useful combinations of cytokines and mAb for the treatment of colorectal carcinoma.

[Interferon alfa-2B in chronic lymphatic leukemia of the B-cell type]. / Interferon alpha-2b bei chronischer lymphatischer Leukämie vom B-Zell-Typ.

In a clinical phase II study nine patients (five men and four women; mean age 48 [42-58] years) in an early stage of chronic lymphatic leukaemia (CLL) of the B-cell type were treated with recombinant alpha-2b interferon (IFN alpha-2b), initially at a dosage of 5 mega units subcutaneously three times weekly, but in some cases reduced to 2.5 or raised to 10 mega units. Duration of treatment has been 15-36 months. Through-flow cytometry in seven patients demonstrated a definite fall in circulating B1-positive lymphocytes. Lasting partial remission (duration of 106-134 weeks) was achieved in four patients, in a further four the condition remained stable. A recurrence was noted in the patient with the initially highest lymphocyte count (52,000/microliters) after 28 weeks, control being achieved only after 64 weeks of chemotherapy. Side effects were flu'-like symptoms and (in two instances) depression. In three patients there was a clear rise in serum immunoglobulin concentrations as sign of IFN alpha-2b-induced increased immune response, while in four HLA-DR expression on monocytes was doubled. It is concluded that early treatment of CLL with IFN alpha-2b may delay the onset of necessary chemotherapy, any antibody-deficiency may be improved and survival time may ultimately be lengthened.