Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease.

Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients, leading to end stage liver disease in about 20-30% of these patients. Apart from the virus itself, host factors that modulate the immune response are likely to be involved in determining the outcome of HCV infection. Studies on the association of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent results. Selection of patient subgroups may be crucial. However, any association relevant to HCV disease progression will become evident, especially in those patients with end stage liver disease. Therefore, we analysed the phenotype frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced liver cirrhosis who had received a transplant or were awaiting liver transplantation. The first group was typed serologically and compared with 331 blood and liver donors. The second group, prospectively HLA typed by a polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB and DQB alleles, was compared with another 170 PCR-SSO typed and randomly selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found in one group of patients with HCV induced liver cirrhosis compared with the control groups. In the second analysis comparing 39 patients with end stage liver cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11 and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens, respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease.

Endogenous serum levels of thrombopoietic cytokines in healthy whole-blood and platelet donors: implications for plateletpheresis.

Serum concentrations of the thrombopoiesis-enhancing cytokines thrombopoietin (TPO), erythropoietin (EPO), interleukin (IL)-6 and IL-11 were determined in 119 healthy whole-blood (WBD) and 101 platelet donors (PD) prior to donation. The 90% TPO reference interval in WBD of 64-867 pg/ml (median 163, 100% range 45-7572) was significantly higher than in PD of 56-524 (median 122, range 44-801, P = 0.004), whereas their platelet counts were lower (P < 0.001). EPO levels were not different (WBD 7.7 +/- 3.8, PD 8.0 +/- 4.9 IU/l), IL-6 and IL-11 were below the detection limit in >/=90% of cases (IL-6 < 3.2 pg/ml, IL-11 < 31.2 pg/ml). None of the cytokines correlated with platelet counts, other blood parameters, or in the PD group with the frequency of platelet donations within the last 6 months. We conclude that plateletpheresis does not lead to a lasting increase of thrombopoietic cytokines and provide reference data for potential platelet mobilization strategies with recombinant growth factors.

Improvement of HLA class I and class II PCR-SSP typing by using timed-release activity of DNA polymerase.

Variable amounts of non-specific amplification may occur in HLA PCR-SSP typing, and this can be significantly reduced by the use of AmpliTaq Gold. In an effort to achieve an optimal balance between specificity and efficiency of the PCR amplification for both HLA alleles and the internal control, we designed a system of timed-release activity by combining two different Taq DNA polymerases. The reaction was started at a relatively low level of enzyme activity and as thermal cycling progressed more and more Ampli-Taq Gold was slowly activated for the reaction to continue. We applied this system to all routine HLA PCR-SSP typing. The number of repeat typings due to non-specific amplification and/or amplification failure of the internal control was remarkably reduced.

Sustained decrease of peripheral lymphocytes after allogeneic blood stem cell aphereses.

48 healthy donors underwent peripheral blood stem cell (PBSC) apheresis for allogeneic transplantation beginning on day 4 of G-CSF (2 x 5 microg/kg) mobilization. In one to four (median two) large-volume mononuclear cell aphereses, a median of 55.9 x 10(9) of lymphocytes (range 21.0-109.2 x 10[9]) were collected, an amount comparable to lymphocyte numbers removed by therapeutic lymphaphereses in autoimmune diseases. Mean peripheral lymphocyte counts decreased from premobilization values of 2.31 x 10(9)/l to 1.31 x 10(9)/l at a median of 34 d (1 month) and 1.53 x 10(9)/l at a median of 327 d (11 months). The decrease in peripheral lymphocyte counts was significantly correlated with the number of lymphocytes removed and the number of aphereses. Neutrophil and platelet counts returned to normal values after 1 month whereas monocyte counts and haemoglobin concentrations were significantly decreased at 1 month but not at 11 months.

Simultaneous genotyping of human platelet antigens by hot start sequence-specific polymerase chain reaction with DNA polymerase AmpliTaq Gold.

OBJECTIVES: Human platelet alloantigen (HPA) typing has potential clinical relevance in a variety of contexts. We can improve methods for HPA genotyping by complementing our knowledge of the DNA sequence polymorphisms of HPA genes and experience with various DNA-based HPA typing techniques. METHODS: A newly available DNA polymerase, AmpliTaq Gold (Perkin Elmer), provided in an inactive state and activated by heat, makes it possible to perform a hot start polymerase chain reaction (PCR) in order to prevent nonspecific amplification during the setup of PCR. To establish a practical procedure for HPA-1, 2, 3 and 5 genotyping, we applied the AmpliTaq Gold for a hot start PCR and employed 8 pairs of published sequence-specific primers (SSP). A simple simultaneous genotyping of these 4 HPA systems could be rapidly achieved with high specificity. RESULTS: The HPA gene frequencies observed in 126 randomly selected German blood donors were 0.82 and 0.18 for HPA-1a and 1b, 0.92 and 0.08 for HPA-2a and 2b, 0.63 and 0.37 for HPA-3a and 3b and 0.90 and 0.10 for HPA-5a and Sb, respectively. CONCLUSION: Using our hot start PCR-SSP procedure with AmpliTaq Gold a simple, rapid and reproducible genotyping for HPA-1, 2, 3 and S systems could be achieved.

A novel DRB1*0801 haplotype carrying DRB3*0202 found in a German pedigree.

DRB1*08 haplotypes have not been known to carry a DRB3 gene. We have found a patient suffering from liver disease who has a novel HLA haplotype of DRB1*0801 with DRB3*0202 as established by family segregation. These two genes were confirmed by sequencing. DR8 and DR52 antigen specificities were serologically detected, indicating expression of these genes.

No significant influence of HLA determinants on susceptibility to hepatitis C virus infection in Caucasian patients with end-stage renal disease.

In hepatitis C, both susceptibility to infection and the course of disease may depend on differences in the immune response. As the major histocompatibility complex (MHC) plays a crucial role in antigen presentation, we investigated a possible relationship between susceptibility to hepatitis C virus (HCV) infection and human leucocyte antigen (HLA) alleles. Therefore, phenotype frequencies of HLA were compared in 186 anti-HCV positive patients with end-stage renal disease (ESRD) to 328 anti-HCV negative patients with ESRD. HLA class I alleles were determined serologically and HLA class II alleles (DRB1, DQA1, DQB1) by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) technique. Additionally, in anti-HCV positive patients we looked for a relationship between the activity of hepatitis C (indicated by elevation of transaminases or the presence of viremia) and HLA determinants. For the three criteria (antibody status, elevation of transaminases and viremia) a significant association to HLA alleles was not found in patients with ESRD. This suggests that neither susceptibility to HCV infection nor the biochemical activity of hepatitis and HCV-RNA positivity seem to be strongly related to HLA status in Caucasian patients with end-stage renal disease.

Relationship between human leukocyte antigen determinants and courses of hepatitis B virus infection in Caucasian patients with end-stage renal disease.

BACKGROUND: Divergent results have been reported with regard to the relationship between the course of hepatitis B virus (HBV) infection and the human leukocyte antigen (HLA) determinants. The aim of the present study was to investigate the phenotype frequencies of HLA class-I and -II alleles in Caucasians with and without HBV infection. METHODS: Fifty-eight patients with persistent HBV infection (group 1), 119 patients with resolved HBV infection (group 2), and 106 patients neither infected by HBV nor vaccinated against HBV (group 3) were analyzed. All patients had end-stage renal disease. HLA class-I antigens were serologically determined. For HLA class-II typing we performed DRB1, DQA1, and DQB1 genotyping using a polymerase chain reaction-sequence-specific oligonucleotide procedure. RESULTS: Compared with group 2, group 1 showed increased frequencies of HLA-B8, DR3 (P < 0.05), A30, DQA1*0501 (P < 0.01), and a decreased frequency of HLA-B12 (P < 0.05). Decreased frequencies of HLA-B27, B40, DR13, and DQ1*0604 (P < 0.05) and an increased frequency of HLA-B35 (P < 0.05) were found in groups 1 and 2 compared with controls (group 3). None of the differences detected in the phenotype frequencies of HLA alleles were statistically significant after correction. CONCLUSIONS: We conclude that the susceptibility to HBV infection and the different courses of HBV infection are not strongly related to HLA status in Caucasians.

Technical and safety aspects of blood and marrow transplantation using G-CSF mobilized family donors.

An allogeneic transplantation programme using immunoselected blood progenitor and bone marrow CD34+ cells has been established. Thirteen healthy HLA-matched, MLC negative sibling donors received two doses of 5 micrograms kg-1 G-CSF (s.c. daily) for 5 days. On days 4 and 5, large-volume mononuclear cell aphereses were performed (COBE Spectra) and on day 5 one unit of autologous blood was obtained. Mononuclear cells were pooled and cryopreserved after CD34+ cell-immunoselection on day 5. Bone marrow (BM) of the same donors was procured under routine conditions 10-45 days later (median: 27 days). The final graft consisted of blood CD34+ cells with either complete BM (n = 5) or immunoselected BM CD34+ cells (n = 8). The present paper describes the progenitor cell mobilization and apheresis protocol and analyzes the cell loss by BM and peripheral blood progenitor cell (PBPC) donation. Considerably larger amounts of mononuclear cells (CD45+), T-lymphocytes (CD3+) and platelets were lost by the apheresis as compared to bone marrow without apparent immediate clinical consequences for the donors. Owing to cross-cellular contamination of the apheresis concentrate, blood platelet count (PC) significantly decreased (mean PC after the second apheresis 116 x 10 microL-1); furthermore on average 3.04 x 10(10) CD3+ cells were removed by two apheresis sessions. This loss did not lead to long-term total lymphocyte count changes (2370 microL-1 versus 1889 microL-1) as observed during the long-term follow-up of 7/13 donors (mean 290 days). Subjectively, the PBPC collections were better accepted than BM donations in all but one family donor.

Simplified PCR-SSO procedure for DQA and DQB typing. Simultaneous hybridization of two probes to one membrane.

To simplify DQA and DQB oligotyping, we applied our improved PCR-SSO procedure for DR typing. We used 12 oligonucleotide probes for DQA typing and 18 for DQB typing. Oligonucleotide probes that require the same hybridization and stringent washing conditions were selected as pairs for simultaneous hybridization to a dot-blot membrane containing various DNA samples. One probe of each pair was labeled with digoxigenin and the other with biotin. After hybridization, the dot-blot membranes were incubated with a mixture of conjugates. Specific binding of the corresponding DNA probes was visualized on an X-ray film using a chemiluminescent substrate (CSPD) and by staining using a chromogenic substrate (TMB). This approach, previously employed for DR typing, is also suitable for DQA and DQB oligotyping and significantly reduces the labor inherent in PCR-SSO typing.

[10 years transplantation of bone marrow and hematopoietic stem cells in adults at the Hannover Medical School]. / Zehn Jahre Transplantation von Knochenmark und hämatopoetischen Stammzellen bei Erwachsenen an der Medizinischen Hochschule Hannover.

PATIENTS AND METHODS: From January 1986 until August 1995 230 adult patients received an allogeneic or autologous transplantation of bone marrow or hematopoietic blood stem cells. The conditioning and myeloablative treatment regimens were chosen according to the underlying disease and type of transplant. RESULTS: The observation period comprises 1 to 115 months after transplantation. After allogeneic transplantation from HLA-identical family donors, the probabilities of disease-free survival were for acute myeloid leukemia in first complete remission (CR) (n = 35) 77%, for acute lymphoid leukemia in 1st CR (n = 7) 72% and in 2nd CR (n = 10) 40%, in first chronic phase of chronic myeloid leukemia (n = 34) 50% and in severe aplastic anemia (n = 7) 100%. Following myeloablative therapy and autologous transplantation the probabilities of disease-free survival were 47% in relapsed Hodgkin's disease (n = 22) and 42% for relapsed high-grade non-Hodgkin's lymphoma (n = 12). Eight of 10 patients with acute myeloid and 7 of 8 with acute lymphoid leukemia suffered a leukemic relapse after autologous bone marrow transplantation. Three of 8 patients with relapsed testicular cancer survived relapse-free. Treatment failures were due to more advanced acute graft versus host disease after allogeneic transplantation and caused by relapse after autologous transplantation. Current protocols evaluate the allogeneic transplantation of enriched CD34+ blood stem cells. In chronic myeloid leukemia the autologous transplantation of blood stem cells after myeloablative therapy is being studied.

Flow cytometry quantification of CD34+ cells and other leukocyte subpopulations in frozen-thawed blood cell suspensions: investigation of a new teflon container for cryopreservation of hematopoietic progenitor cells.

BACKGROUND: Cryopreservation is the only available method for the long-time maintenance of blood cells. The present study was designed to prove: (i) the reliability of multiparameter flow cytometry (MFC) for estimation of CD34+ cells in frozen-thawed cell suspensions and (ii) the acceptability of a new teflon container for the cryopreservation of hematopoietic progenitor cells. MATERIALS AND METHODS: Each of 15 ABO-compatible buffy coats (BC) were pooled, and mononuclear cells (MNC) were then separated with the Fresenius AS 104 device (n = 10). MNC harvested by apheresis were then divided into 2 portions and transferred pairwise into either the new Fresenius or into Gambro cryopreservation containers. Paired samples were frozen at controlled rates (9% DMSO final concentration) and stored at -196 degrees C in liquid nitrogen for 2 weeks. Leukocyte, MNC and differential blood counts and proportions of CD3+, CD4+, CD8+, CD14+ and CD34+ cells were assessed from the pooled BC, the apheresis products, and the frozen-thawed samples. Methyl cellulose culture assays as well as trypan blue viability staining were also carried out. RESULTS: The mean content of the divided apheresis products was 4.9 x 10(9) leukocytes with 86% MNC, 6.89 x 10(6) CD34+ cells, 2.1 x 10(5) granulocyte-macrophage colony-forming units (CFU-GM) and 7.1 x 10(5) erythroid burst-forming units (BFU-E). As expected, there were virtually no granulocytes after freezing in both types of container. The corresponding mean cell content was as follows: 6.3 x 10(6) CD34+ cells, 2.5 x 10(5) CFU-GM, and 8.1 x 10(5) BFU-E in Fresenius containers, and 6.1 x 10(6) CD34+ cells, 1.3 x 10(5) CFU-GM, and 7.7 x 10(5) BFU-E in Gambro containers. The mean MNC viability of the samples frozen in Fresenius was 81.5% and 82.7% in the Gambro containers. MFC was found to compare with stained smear differentials. CD34+ cell counts correlated with CFU-GM (0.69, p = 0.03) and BFU-E (0.63, p = 0.02) colony formation. CONCLUSIONS: The study reported here revealed no significant differences between the 2 types of storage containers. The new Fresenius teflon container could thus be recommended for cryopreservation of hematopoietic progenitor cells. MFC provided reliable data on CD34+ cell content and leukocyte subset composition of the frozen-thawed cell suspension.

Transfusion results of cytapheresis platelet concentrates stored in two different polyolefin containers for five days.

OBJECTIVE: Two different types of polyolefin storage containers were compared in order to estimate their ability to preserve apheresis platelet concentrates for 5 days. MATERIAL AND METHODS: Ten pairs each consisting of one patient with thrombocytopenia following chemotherapy and one healthy platelet apheresis donor were examined. The platelet concentrates stored in the LE-2 bag were collected with a Fresenius AS 104 cell separator and those stored in the PL 732 with a Fenwal CS 3000. RESULTS: The separation efficiency of both cell separators was similar; the mean yields were 3.37 +/- 0.83 x 10(11) platelets in 274 +/- 26 ml for the AS 104 and 3.87 +/- 1.31 x 10(11) platelets in 318 +/- 22 ml for the CS 3000 (mean +/- SD). Storage for 5 days did not influence the platelet count significantly. The platelet loss due to filtration was 16 and 13%, respectively. The mean platelet volume obtained with both systems was reduced from a mean of 8.4 fl immediately after harvesting to 7.6 fl after storage (p < 0.0001) and to 7.3 fl after filtration (p = 0.001). The established corrected count increments (CCI) and the pre- and posttransfusion platelet counts were satisfactory and comparable for the 2 systems tested. The mean CCI of the AS 104-LE-2 system was 14.5 1 h and 7.4 x 10(9) platelets 24 h after transfusion, the mean CCI of the CS 3000-PL 732 system was 12.5 and 5.2 x 10(9) platelets, respectively. CONCLUSIONS: Single-donor apheresis concentrates with a large platelet content may be stored in the new LE-2 polyolefin container for up to 5 days and used in clinical transfusion.

[Familial investigations of carriers of Rh 33]. / Familienuntersuchung einer Trägerin von Rh 33.

The erythrocytes of a blood donor (P) showed an unusual pattern with anti-D sera: no agglutination with incomplete sera, and a strong agglutination with 2 out of 5 complete, monoclonal sera. These findings suggested the presence of an Rh 33, which was then confirmed in two external laboratories as the genotyp R0Har. Using anti-e sera, the titer scores of the cells of P were comparable with those of Ee cells but were only half as high as the scores of ee cells. This is consistent with a weak e in R0Har. The red cells of the donor's daughter (T) gave a positive reaction with all anti-D sera, but we observed no or only weak agglutination with several anti-e sera. It is very probable that T is also carrier of R0Har.

[HLA-DR typing using PCR-SSO with simultaneous hybridization of each dot blot membrane with a digoxigenin- and a biotin-marked probe]. / HLA-DR-Typisierung mittels PCR-SSO bei gleichzeitiger Hybridisierung jeder Dot-blot-Membran mit einer Digoxigenin- und einer Biotin-markierten Sonde.

Here we present a PCR-SSO procedure designed to simplify HLA-DR typing. We labelled 8 of a total of 16 oligonucleotide probes with digoxigenin, the others with biotin, and formed 8 pairs, each containing a digoxigenin- as well as a biotin-labelled probe. Each pair was hybridized simultaneously to one of eight dot blot membranes containing the DNA to be typed. Specific binding was detected by incubation with a mixture of the appropriate conjugates followed by sequential addition first of a chemiluminescent substrate to detect the digoxigenin-labelled probe and then a chromogenic substrate for detection of the biotin-labelled probe. With this procedure, the specific binding of two different probes to the same dot blot membrane could be evaluated, considerably reducing the labor inherent in PCR-SSO typing.

A polymerase chain reaction-sequence-specific oligonucleotide procedure for HLA class II typing using biotin- and digoxigenin-labeled probes simultaneously in hybridization.

To simplify PCR-SSO HLA-DRB generic typing, we labeled eight of 15 oligonucleotide probes with DIG and the others with biotin, and hybridized each dot blot with both a biotin-labeled probe and a DIG-labeled probe simultaneously. We chose oligonucleotide pairs which require the same hybridization and stringent washing conditions and do not compete with each other during hybridization. After incubation with a mixture of anti-DIG Fab fragment-alkaline phosphatase and streptavidin-peroxidase conjugates, specific binding of the DIG-labeled probe was revealed by a chemiluminescent substrate (CSPD) and specific binding of the biotin-labeled probe was subsequently visualized by a chromogenic substrate (TMB). The sensitivity of both probes was similar and gave comparable hybridization signals. Using this simplified procedure, the number of hybridizations or dot blots can be reduced to half the usual amount and the labor involved in PCR-SSO typing significantly reduced.

Influence of the freezing-thawing-washing procedure on the cytomegalovirus DNA content of cellular blood products.

There is a proven relation between cytomegalovirus (CMV) infection in seronegative immunocompromised patients and transfusion of random CMV unscreened cellular blood products (BP), where the leukocytes are thought to be the vector of transmission. We examined whether freezing, thawing, and washing, in attempt to reduce the quantity of leukocytes, also reduces the CMV-DNA-carrying cells of BP of CMV-seropositive donors and their infectivity for fibroblasts, using the polymerase chain reaction (PCR). The leukocyte contamination of the thawed-washed erythrocyte concentrates was < 1 x 10(8)/l and of the thawed-washed platelet concentrates, approximately 2.5 x 10(8)/l. All plasma samples and most samples of BPs of the CMV-seronegative controls were PCR-CMV-DNA-negative. The differences of the PCR results with the samples of CMV-seropositive donors before and after freezing were not significant. Thus we concluded that freezing-thawing-washing of cellular BP could not eliminate all CMV-DNA-bearing leukocytes. Plasma carries low risk for CMV infection, if at all.

Simultaneous detection of whole blood chemiluminescence in microtitre plates.

The measurement of reactive oxygen species provides a simple method for monitoring the degree of activation of leukocytes in various disorders, and for determining the effects of drugs on this activation. The present report describes the determination of luminol- or lucigenin-amplified chemiluminescence of whole blood in a microtitre plate assay with a 96-well luminometer (HAMAMATSU MTP reader). Using heparinized venous human blood from healthy donors, optimal chemiluminescence intensities were determined at a blood dilution of 1/100 in a total volume of 0.25 ml of Hank's balanced salt solution, containing 0.4 mmol/l luminol as enhancer and either opsonized zymosan (1 milligram) or the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (10(-6) mol/l), as stimuli. The in vitro effects of nordihydroguaiaretic acid, diphenylene iodonium, and diclofenac were tested. After preincubation of the diluted whole blood with these drugs for 15 min, the zymosan-stimulated chemiluminescence was diminished in all cases. The specific NADPH oxidase inhibitor, diphenylene iodonium, was most effective (half maximal inhibition at 1.5 x 10(-8) mol/l), whereas higher concentrations of the antioxidant, nordihydroguaiaretic acid (1.6 x 10(-6) mol/l), or the nonsteroidal antiinflammatory drug, diclofenac (about 10(-5) mol/l), were needed to achieve half maximal inhibition. In addition to its usefulness in the rapid screening of drug effects this assay system seems to be very beneficial for the clinical diagnosis of congenital disorders. Furthermore, it is suited as an effective and simple method for the continuous determination of the phagocyte functional state in patients in pathophysiological situations and during therapy.

Hetero- and homozygosity of MHC class II gene products in systemic lupus erythematosus. The Members of the Deutsche Multizentrische SLE-Studie.

An analysis of HLA class II antigens in 356 white patients with systemic lupus erythematosus (SLE) showed that all HLA-DR and -DQ homozygous and heterozygous combinations appear with frequencies expected from the observed gene frequencies. HLA-DR2 and HLA-DR3 gene frequencies were both increased in SLE, as were the odds ratios of all DR2 and DR3 hetero- and homozygous combinations. HLA-DR2/C4AQ0 heterozygotes were also not increased over expected values. Therefore, gene complementation at MHC loci does not contribute to susceptibility to SLE, but rather one or two MHC allele(s) in linkage with HLA-DR2 and HLA-DR3.

Stress, cancer and immunity. New developments in biopsychosocial and psychoneuroimmunologic research.

Research in biobehavioral oncology has been focused on stress as one dispositional factor in the multifactorial origin and in the clinical progression of malignant disease. New insights into the transduction of environmental influences to the immune system and to other body systems by the brain and neurotransmitters have increased the salience of this approach. Behavioral medicine in the area of cardiovascular disease has been successful due to the introduction of a "Type A" or coronary prone behavior pattern in large epidemiologic studies. This pattern is marked by both psychologic and physiologic hyperresponsiveness. Type A persons appear to be hostile, easily angered, competitive and hard-driving. More recently, behavioral oncologists have similarly attempted at conceptualizing a "Type C" or biopsychosocial cancer risk pattern, as they have noted the denial and suppression of emotions, in particular anger. Other features of this pattern are "pathological niceness", avoidance of conflicts, exaggerated social desirability, harmonizing behavior, over-compliance, over-patience, as well as high rationality and a rigid control of emotional expression ("anti-emotionality"). This pattern, usually concealed behind a facade of pleasantness, appears to be effective as long as environmental and psychological homeostasis is maintained, but collapses in the course of time under the impact of accumulated strains and stressors, especially those evoking feelings of depression and reactions of helplessness and hopelessness. As a prominent feature of this particular coping style, excessive denial, avoidance, suppression and repression of emotions and own basic needs appears to weaken the organism's natural resistance to carcinogenic influences. This may mean that the excessive use of denial and suppression/repression has important psychophysiologic effects linked to tumor biology and host-defense. Recent studies reveal that psychosocial stressors which are met by inadequate and repressive coping styles are associated with changes in immunocompetence, including both humoral and cell-mediated immunity. Relationships between different immune parameters (natural killer cell activity, lymphocytes, serotonin uptake, mean platelet volume) and mood states, psychological coping styles and personality variables are outlined. Recent findings indicate also that in certain malignancies (eg. breast cancer) the clinical course of the disease is influenced by psychosocial factors and coping style, as well as that the risk of cancer recurrence and metastasis is influenced by the type and duration of a given stressor. Individuals with a more favorable outcome have higher fighting spirit, a greater potential for aggression and lesser suppressive tendencies. Psychological intervention in cancer patients in its different forms and within the frame of the over-all treatment has now become a matter of scientific discussion and research.(ABSTRACT TRUNCATED AT 400 WORDS)