CD15 - a new marker of pathological villous immaturity of the term placenta.

INTRODUCTION: Idiopathic immaturity is one of the main reasons for latent placental insufficiency and antenatal hypoxia. Postnatal identification of the immature placental phenotype may help early stratification of a heterogeneous population of newborns and individually identify risk of disease in the immediate postnatal life. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental immaturity. METHODS: 111 tissue samples from normal and pathological term placentas with persisting villous immaturity comprised the comparative immunohistochemical study (CD15, CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type. RESULTS: We have shown that pathological villous immaturity is attended by significantly increased CD15-expression in the macro- and microvascular endothelium compared with the normal placenta. CD34-expression was not different from that in normal placentas. DISCUSSION: This paper documents the correlation of CD15+ endothelium in the macrovascular fetoplacental vessels with a severe form of villous immaturity associated with fetal hypoxia/asphyxia and erythroblastosis. Increased CD15-expression only in the microvascular segment of the fetoplacental vessels correlated with moderate villous immaturity and was associated with GDM, idiopathic fetal macrosomia and nonspecific chronic villitis. CONCLUSION: We propose that "immature" CD15+ endothelium is an important diagnostic marker of persisting villous immaturity and chronic placental dysfunction. The level of CD15 expression in the macro- and microvasculature reflects the degree of pathological placental villous immaturity.

Transient CD15-positive endothelial phenotype in the human placenta correlates with physiological and pathological fetoplacental immaturity.

OBJECTIVE: Placental growth and villous maturation are critical parameters of placental function at the end of pregnancy. A failure in these processes leads to the development of placental dysfunction, as well as fetal and neonatal mortality and morbidity. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental development. STUDY DESIGN: Forty tissue samples from normal placentas of different gestational age and 68 pathological term placentas with defective villous maturation (GDM, idiopathic IUFD, preeclamsia, HELLP syndrome) comprised the comparative immunohistochemical study (CD15, CD45 and CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type. RESULTS: Physiologically immature placentas of the first and second trimester and pathologically immature term placentas were characterized by marked endothelial CD15-immunostaining. A significant loss of CD15-positive endothelium of the placentas was associated with a physiological and accelerated villous maturity. A spatio-temporal correlation was shown for CD15+ endothelial cells (ECs) and the number of CD45+ stromal cells (SCs). A negative temporal correlation was shown for CD15+ ECs and CD15+ myelomonocytes in the fetal blood. CD34 expression in the ECs was stable during the pregnancy. CONCLUSION: A correlation between a transient CD15-positive endothelial phenotype and a physiological and pathological fetoplacental immaturity was demonstrated. Physiological and accelerated placental maturation was accompanied by a significant disappearance of CD15-positive endothelium. We propose that "immature" CD15+ endothelium is an important diagnostic marker of the physiological and pathological fetoplacental immaturity.

Imbalance of expression of bFGF and PK1 is associated with defective maturation and antenatal placental insufficiency.

OBJECTIVE: Defective placental maturation is associated with restricted functional capacity and adverse perinatal fetal outcomes. The aim of the study was a comparative analysis of the role of mRNA expression of various angiogenic factors in placental maturation defects. STUDY DESIGN: We examined the mRNA expression patterns of prokineticin 1 (PK1), its receptors (PKRs), basic-fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in tissue from third-trimester placentae that exhibited delayed or accelerated villous maturation. RESULTS: The expression of PK1 and PKR2 was elevated in placental tissue exhibiting accelerated maturation and a predominant differentiation of terminal villi. The opposite was found in tissue exhibiting delayed maturation and deficiency of the terminal villi. In addition, low expression of bFGF correlated with the predominant differentiation of terminal villi, whereas the opposite was observed when terminal villi were deficient. The expression of VEGF, PIGF, and PKR1 showed no significant differences between the groups. CONCLUSION: Defective placental maturation is associated with an imbalance of expression of bFGF and PK1. Our results demonstrate an involvement of the PK1/PKR2-signalling pathway in the regulation of the functional adequate capillarization in late pregnancy. We propose the bFGF/PK1-ratio as a monitor of placental function and a possible indicator of latent clinical problems, such as placental dysfunction leading to fetal hypoxia.

2',5'-Oligoadenylate synthetase activity analysis and human papilloma virus typing as prognostic factors in patients with recurrent respiratory papillomatosis.

OBJECTIVE: Determination of early prognostic factors in patients with recurrent respiratory papillomatosis is extremely important, so the major goal of our prospective, multicentre study was to evaluate (1) the feasibility of various factors to determine prognosis of the clinical course, as well as (2) the response to interferon-alpha therapy in recurrent respiratory papillomatosis. METHODS: Forty-two patients with recurrent respiratory papillomatosis were treated with interferon-alpha (3 MU/m(2) three times per week; mean therapy duration was 2.7 +/- 1.8 years) in 1983-1994 and followed-up until 2003. Human papilloma virus (HPV) type, recurrent respiratory papillomatosis severity and 2',5'-oligoadenylate synthetase activity were determined by standard methods and analysed for correlation with the results of long-term clinical outcome. RESULTS AND CONCLUSION: Patients with HPV type 11, a severity score >4, a high number of surgical procedures prior to interferon-alpha therapy and a high basal 2',5'-oligoadenylate synthetase activity should be considered at high risk of an aggressive clinical course, often with spread to lower airway passages, malignant transformation and death. Human papilloma virus type, score for recurrent respiratory papillomatosis severity, number of surgical procedures and 2',5'-oligoadenylate synthetase activity showed significant association with response to interferon-alpha therapy and the long-term clinical course, so these factors have value in predicting prognosis in recurrent respiratory papillomatosis.

[Congenital disorders of the colonic innervation. A diagnostic guide]. / Kongenitale Innervationsstörungen des Kolon. Ein diagnostischer Leitfaden.

Hirschsprung's disease (HD, aganglionosis) is the most important form of congenital disturbance of intestinal innervation, requiring surgical intervention. Furthermore, hypoganglionosis of the transitional zone forms the most significant factor in morbidity. Pre-operative definition of the length of neuronally disturbed segment is still a diagnostic challenge for both clinical physician and pathologist. Enzyme histochemical studies form the method of choice, but certain limitations in their use must be observed. Other dysganglionoses, particularly the so-called "Intestinal Neuronal Dysplasia" (IND) cannot-because of an excessive overlapping with age-correlated normal values-unequivocally be defined as an entity on its own. The only exception to this, is the ganglionic neuromatosis, which arises as part of a genetic illness.

Large supraumbilical pseudocystic tumour due to ectopic pancreatic tissue located in a rest of the omphaloenteric duct.

Ectopic umbilical pancreatic tissue is extremely rare. We report on a case of a two-year-old boy who suffered from a large recurrent supraumbilical tumour with central cystic degeneration. Ectopic pancreatic tissue was located within the submucosal layer of an umbilical rest of the omphaloenteric duct. Peptic erosion and inflammatory alteration of tissue surrounding the umbilical vein caused recurrent bleeding and formation of a pseudocyst as well as chronical inflammatory granulations within the abdominal wall.

[Placenta in gestational hypertension]. / Plazenta bei Schwangerschaftshochdruck.

At an incidence of 3.2-4% world-wide, pregnancy-induced hypertension (PIH) is the most common disease of pregnancy. Since this holds a risk, not only for the mother, but also for the child, the placenta should undergo pathological-anatomical examination in every case. Pathomorphological findings can be described in the feto-maternal border zone as well as in the fetal placenta. These are not, however, specific, nor do they offer diagnostic proof. Pathomorphological findings in the feto-maternal border zone: defective invasion of the extravillous cytotrophoblast, hyperplastic arterio-/arteriolopathy, acute atherosclerosis, and fibrinoid necrosis of endothelium. Disorders of the fetal part of placenta: infarctions/fibrin deposits, obliterative angiopathy, stromal fibrosis/fibrinoid degeneration, syncytiotrophoblastic nodes (Tenney-Parker-phenomenon), and disturbances of maturation of the villi. There is a general lack of correlation between the seriousness of the disease and the morphology. The only exception in this respect are the findings in the vessels both of the placental bed and of the chronic villi. These show a high correlation with doppler sonographic findings.

[Interdisciplinary therapy management in malignancy of the paranasal sinus tumors in children]. / Interdisziplinäres Therapiemanagement maligner Nasennebenhöhlentumoren im Kindesalter.

BACKGROUND: Malignant tumors of the paranasal sinuses, such as rhabdomyosarcoma or Ewing's tumors, often have a mesenchymal origin. In the recent years, several prospective, randomized, multicenter studies have demonstrated a better outcome after new oncology therapy protocols. PATIENTS AND RESULTS: In the period from January 2000 to June 2001, we operated 610 patients with sinus disease. Only 23/610 were children or teenagers (3.8%). Half of the juvenile group suffered from chronic sinusitis, but 5/23 (22%) had a malignoma of the paranasal sinuses. In the adult population, malignoma was diagnosed in less than 1% of cases. We diagnosed and treated, in cooperation with our radiology, pathology and children's hematooncology department, one rhabdomyosarcoma, two malignant peripheral neuroectodermal tumors (PNET), one myelosarcoma and one malignant lymphoma in the paranasal sinuses. Two patients died. SUMMARY AND CONCLUSION: These five cases of paranasal sinus malignomas are discussed in relation to their history and clinical course. We suggest that interdisciplinary treatment involving otorhinolaryngology, pathology, children's hematooncology, radiology and radiation therapy is obligatory for the therapy and for the best possible outcome of such cases.

[Mesenchymal chondrosarcomas of the facial skull]. / Mesenchymale Chondrosarkome des Gesichtschädels.

A 13-year-old girl suffered from a mesenchymal chondrosarcoma of the left maxilla. The therapeutic options and the prognosis for this disease are described with respect to the currently known 72 cases in the literature. Mesenchymal chondrosarcomas are rare tumors of the bone and soft tissue. The first clinical symptom is a painless swelling of the facial skull. They occur largely in the 2nd and 3rd decades of life, preferentially in males. Radiological criteria for the identification of this type of tumor include focal ossification areas which are accompanied by non-calcified regions. Complete surgical removal of the tumor is the therapy of choice. Pre- and postoperative chemotherapy can have a beneficial effect. The final outcome of the disease is difficult to evaluate since late complications (e.g., reoccurrence and/or metastases) appear even after 20 years and only a small number of cases have been reported. At present, the 5-year survival rate is reported to be 54-82% and the 10-year rate 28-56%.

CD154 inhibits tumor-induced apoptosis in dendritic cells and tumor growth.

We have recently demonstrated that murine and human tumors induce apoptosis of dendritic cells (DC). Here, we evaluated the effect of CD40 ligation on the survival of tumor-associated DC and tumor growth. Retroviral transduction of MC38 colon carcinoma cells with the CD154 gene resulted in inhibition of tumor growth. This effect was abrogated in IL-12 knockout mice. Immunohistochemical analysis revealed an increase in CD11c+ (N418) and CD8+ but not NLDC-145+ cells in CD154-transfected tumors in wild-type mice. This increase was less pronounced in IL-12-deficient mice. In vitro, overexpression of CD154 on tumor cells significantly decreased the level of tumor-induced DC apoptosis. Surprisingly, the CD154-induced protection of DC from tumor-induced apoptosis was IL-12 independent in vitro, suggesting an IL-12-dependent and an IL-12-independent mechanism of CD154-induced anti-tumor immunity. Thus, our data suggest a new strategy to improve immunotherapy of cancer by protecting DC from tumor-induced apoptosis.

Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand.

The CD95/CD95L (Fas/Fas ligand) receptor/ligand system plays an important role in regulation of cell survival and induction of a programmed cell death. It is also involved in regulation of effector phase of T and NK cell cytotoxicity, establishment of immune privilege sites, and tumor escape from immune recognition. In this study, we assessed expression of CD95L in tumors obtained from patients with neuroblastoma (NB) and in established NB cell lines. We measured the presence of intratumoral T cell infiltrates and T cell survival in tumor tissue samples. High levels of apoptosis were observed in tumor-associated lymphocytes as well as in Jurkat T cells cocultured with NB cells in vitro. T cell death was reduced after treatment of NB cells (in vitro) with antibody to FAS ligand (FasL). Overall, our data suggest that NB-induced apoptosis of Fas-sensitive Jurkat T cells is mediated by functional FasL expressed on NB and Fas/FasL interaction may be responsible for the elimination of T cells in the NB microenvironment.

Differential diagnosis based on immunological-phenotyping in suspected malignant bone marrow involvement in childhood.

The diagnostic value of immunophenotyping (IP) as a first-line diagnostic method in diseases that infiltrate the childhood bone marrow (BM) or mimic infiltrated BM was examined. Two hundred and fifty unselected BM samples from 250 children suspected to have a malignancy infiltrating their BM were evaluated by means of IP and conventional morophological-cytochemical (MC) studies. We applied the alkaline phosphatase anti-alkaline phosphatase method for IP using a panel of monoclonal antibodies (Mabs) against leukocyte-associated antigens, neuroectodermal antigens, and intermediate filament antigens. Four cases of neuroblastoma, two cases of Ewing sarcoma, and one case of rhabdomyosarcoma were diagnosed by IP but not by MC studies. In nine cases of acute leukemia bone marrow blasts could not be ascribed to a specific lineage on the basis of blast morphology or histochemistry. Eight samples without morphological evidence of malignant infiltration revealed an increased percentage of immature B cell precursors (CD10+, TdT+) suggesting acute lymphoblastic leukemia. None of these children has developed malignant lymphoproliferative disease. Our data suggest that the immunological evaluation of BM in childhood is highly capable of discriminating between different malignant populations but it does not recognize malignancy and therefore supplements but cannot replace conventional methods for diagnosis.

[Hyper-IgE syndrome--two case reports of unusual complications]. / Hyper-IgE-Syndrom--Kasuistiken zweier seltener Komplikationen.

The hyper-IgE syndrome (HIS) is a complex immunologic disease, caused by an unknown basic defect. We report on two cases showing complications, which have not been described so far. Case 1: A 15-year-old boy suffering from HIS developed a liver tumour with severe eosinophilic infiltration and degranulation. The transformation process of the liver histologically resembled focal nodular hyperplasia. Therapy with cyclosporine A did not lead to clinical benefit. Now, a therapeutic attempt with interferon gamma is made. Case 2: In a 17-year-old female HIS patient, multiple papillomas and ulcers of the mucous membrane, caused by infection with human papilloma virus, emerged in the ENT region. Under treatment with interferon alpha, papillomatosis could be restrained. As therapy of the hyper-IgE syndrome only symptomatic treatment has been recommended so far. Future therapies should strive for systemic immunomodulation by application of cytokines or soluble cytokine receptors like interferons or sIL-4R.

Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia.

Three hundred twenty-six children with bone marrow (BM) relapse of non-B acute lymphoblastic leukemia (ALL) were stratified according to the time of relapse in three consecutive multicenter trials--ALL-REZ BFM 83, 85, and 87. Employing an intensive polychemotherapy regimen, extramedullary involvement appeared to be predictive of superior outcome in both strata as well as in the whole group (probability of 7-year event-free survival (EFS) 42% in combined vs. 15% in isolated BM relapse, P = 0.015). Children with combined BM relapse occurring later than 6 months after completion of front-line therapy reached EFS estimates of 60%. We conclude that results of conventional polychemotherapy with BFM relapse protocols are equivalent to those achieved by bone marrow transplantation in children with late combined BM relapse.

[High dosage methotrexate in combination with "8 in 1" in therapy of pediatric grade III/IV brain tumors]. / Hochdosiertes Methotrexat in Kombination mit "8 in 1" in der Therapie kindlicher Grad III/IV Hirntumoren.

20 patients with malignant brain tumors in childhood were treated according to a regimen which included initial surgery, preradiation chemotherapy and subsequent irradiation. The chemotherapy consisted of alternating cycles of high-dose methotrexate (12 g/m2) and "8 drugs in 1 day" (Bleyer, 1983). Each cycle was to be given up to six times, as tolerated. The diagnoses were medulloblastoma in 10 cases, astrocytoma in 5 cases, ependymoma and PNET in 2 patients each, and malignant mesenchymoma in 1 case. 15 patients were previously untreated, 5 patients experienced relapse after a different first line therapy and a longer time interval. 8 patients are in continuous complete remission for 13 to 54 months. The toxicity upon the bone marrow, the kidney and the inner ear was tolerable. Long lasting emesis contributed a marked problem to the patients but did not cause abbreviation of the therapy. The neurotoxicity was notably mild. Three episodes of generalized seizures were seen without subsequent sequelae, four cases of peripheral neuropathy were attributable to vincristine. A leukoencephalopathy was neither detected on clinical grounds nor on neuroradiological imaging. Therapy related deaths were not seen. We conclude that the combination of HD-MTX and "8 in 1" markedly contributes to the intensification of the chemotherapy for malignant brain tumors in childhood. In the setting as preradiation chemotherapy the toxicity is tolerable.

Fatal haemoptysis associated with invasive pulmonary aspergillosis treated with high-dose amphotericin B and granulocyte-macrophage colony-stimulating factor (GM-CSF).

Opportunistic pulmonary infections are a leading cause of morbidity and mortality in patients with chemotherapeutically treated neoplasias. With increasingly aggressive cytotoxic regimens causing prolonged neutropenia, the risk of systemic mycoses and in particular of invasive pulmonary aspergillosis has increased. We review the case of a 10-year-old child suffering from relapsed lymphoblastic leukaemia and from high-dose amphotericin B-treated invasive pulmonary aspergillosis acquired during long-standing neutropenia in the initial phase of remission induction chemotherapy. The patient died in remission after GM-CSF-induced bone marrow recovery and clinical and radiological improvement with stable plasmatic coagulation and normal thrombocyte count. Peracute massive pulmonary bleeding caused by the simultaneous arrosion of a greater pulmonary artery and a lobar bronchus by a liquefactive fungal focus was responsible. In patients with chemotherapeutically induced neutropenia and invasive aspergillosis, bone marrow recovery may lead to the liquefaction of pulmonary foci, and, in view of the well-known vasotropic nature of the infection, to a potentially lethal arrosion bleeding. With the emerging use of colony-stimulating factors for shortening and overcoming neutropenia, this so far rare complication may become of increasing importance.

Outcome of [131I]metaiodobenzylguanidine therapy of neuroblastoma: seven years after.

Beginning in 1984 and based on a total of 40 treatments with [131I]metaiodobenzylguanidine (131I-MIBG) in most cases with a follow-up of 5 years or more, it seems to be worthwhile reevaluating our clinical data and draw some final conclusions: We treated 12 children with a neuroblastoma (NB) IV and 3 with a NB III. In no case 131I-MIBG was the primary therapy. The great majority suffered from recurrence. The mean treatment interval after chemotherapy was 6 months (range 0-54). We calculated a median cumulative tumor dose of 77 Gy (range 0-259) in patients with stage III and 30 Gy (range 4-267) in stage IV NB. The tumor half-life time of 131I-MIBG does not significantly differ between stage III (3 days) and IV (2-5 days). Although the median tumor dose of stage III NB exceeded that of stage IV, we found in NB IV a significant tumor remission in 7 out of 12 cases. On the other hand, a slight reduction of tumor size was seen in only 1 case of stage III NB. This indicates a lower radiation sensitivity of stage III NB. Despite this fact, the two patients with stage III NB who presented a sufficient 131I-MIBG-tumor uptake turned to become operable after 131I-MIBG. Stage IV patients improved, too, even if most of them suffered from recurrence with a very poor prognosis: 3 patients of stage IV lived longer than 48-60 month or are still alive. However, no one of this group remitted completely.(ABSTRACT TRUNCATED AT 250 WORDS)

Low grade malignant non-Hodgkin's lymphomas and peripheral pleomorphic T-cell lymphomas in childhood--a BFM study group report.

Non-Hodgkin's lymphomas (NHL) are classified as low or high grade malignant lymphomas of either B or T cell origin. Cells of low grade malignant NHL (LG-NHL) of B cell type represent either follicular or postfollicular, cells of LG-NHL of T cell type postthymic maturation stages in the lymphoid differentiation pathway. LG-NHL often fail to undergo long-term complete remission or cure in adults, no matter what type of conventional therapy is applied. In three pediatric therapy studies frequency and probability of continuous complete remission (pCCR) were studied for LG-NHL and peripheral pleomorphic T-cell lymphomas (PTCL). Of 432 evaluated patients only six children (1.4%) were qualified as LG-NHL. LG-NHL of T cell type were diagnosed in three children (one T-zone lymphoma, two PTCL of small cell type), LG-NHL of B cell type in another three cases. Two children presented with nodular type of centroblastic/centrocytic lymphoma (CB/CC), one with lymphoplasmocytoid type of immunocytoma (IC). In addition to the two patients with low grade malignant PTCL, there have been also four children with high grade malignant PTCL. The analysis showed that there was not significant difference for event free survival of children with LG-NHL and HG-NHL, respectively (pCCR: 0.63 and 0.82, p = 0.29). In contrast, when comparing high and low grade PTCL versus all other types of childhood NHL (non-PTCL), a significant difference seems to exist (pCCR for PTCL: 0.44, for non-PTCL: 0.83; p = 0.02). However, for further concisive conclusions more patients are needed for evaluation.

[Neoadjuvant chemotherapy of osteosarcoma. Results of the cooperative studies COSS-80 and COSS-82 after 7 and 5 years]. / Neoadjuvante Chemotherapie des Osteosarkoms. Ergebnisse der kooperativen Studien COSS-80 und COSS-82 nach 7 bzw. 5 Jahren.

The analysis of the results of two German Pediatric Oncology (GPO) cooperative, neoadjuvant chemotherapy trials after a followup of 7 (COSS-80) and 5 years (COSS-82) allows several conclusions concerning both systemic and local treatment of patients suffering from osteosarcoma. A metastasis free survival rate (MFS) of 59% was reached in the reduced study group of the first study, COSS-80. In addition to size of the primary tumor, the extent of chemotherapy induced devitalisation was very closely related to the probability of survival without systemic recurrence. Following this observation, it was the aim of the next study, COSS-82, to improve the MFS of patients with poorly responding tumors by altering their postoperative chemotherapy regimen. However, this "salvage" approach failed. Moreover, an effort to reduce treatment related toxicity by sparing some patients from the side effects of two particularly toxic drugs, adriamycin (ADR) and cisplatinum (CDDP), by only giving these postoperatively and only after insufficient tumor response to preoperative therapy, failed (MFS of the study arm of COSS-82 45% at 5 years vs. 68% for the control arm with primary use of ADR and CDDP, p less than 0.05). The value of an effective primary chemotherapy is further enhanced by the observation, that en bloc resection of tumors which were poor responders to preoperative therapy was associated with an increased risk of distant metastases when compared with amputation and rotation plasty, while this was not the case for good responders. In conclusion, both systemic tumor control and optimal local therapy require that all effects drugs are to be used as early as possible in the primary treatment of osteosarcoma, in order to enforce maximum tumor cell destruction and hence an optimistic outlook for the individual patient.

[Prevention of cytomegalic inclusion disease in leukemia patients with a cytomegalovirus hyperimmune globulin preparation]. / Zytomegalie-Prophylaxe bei Leukämiepatienten mit einem Zytomegalie-Hyperimmunglobulinpräparat.

In a randomised study the efficacy of a cytomegalic hyperimmune globulin preparation (CMV-HIGP) which had been treated with beta-propiolactone was analysed. The study included 85 patients with acute lymphoblastic leukemia (ALL) and Non-B-Non-Hodgkin-lymphoma (NHL) who were treated initially or underwent a relapse therapy. During the intense chemotherapeutical period within leukemia treatment the patients were passively immunised by the intravenous route with CMV-HIGP (1 ml per kilogram of body weight) every two to three weeks at the latest. In the initial stages the basic immunisation protection was achieved by the application of double dose CMV-HIGP. The Frankfurt patients were recruited from the BFM-ALL- and the NHL-study since october 1982. When they were admitted their CMV serostatus was determined by means of the ELA-ELISA or IFA-method. Seronegative patients were given the passive immunisation immediately or 48 hours after the first blood transfusions at the latest. The patients who had become CMV-IgG-positive by passive immunisation were randomised when reaching long-term therapy according to the protocol. Because of a 30% cytomegaly disease incidence rate in our patient population a randomisation was unwarrantable at the beginning of leukemia treatment. During randomisation one group of patients were immunised by the intravenous route with CMV-HIGP (2 ml per kg body weight one time in four weeks), the second group was a control group.(ABSTRACT TRUNCATED AT 250 WORDS)