Evidence for a Second Type of Resistance against Cydia pomonella Granulovirus in Field Populations of Codling Moths.

Cydia pomonella granulovirus (CpGV) is an important biocontrol agent for the codling moth (CM) in organic and integrated apple production worldwide. Previously, Z chromosome-linked dominant resistance in at least 38 CM field populations in Europe was reported, threatening organic apple production. Growers responded by switching to a different resistance-breaking isolate of CpGV that could control these populations. Here, we report a nonuniform response of different CM field populations to CpGV isolates from CpGV genome groups A to E. Even more strikingly, one field population, NRW-WE, was resistant to all known CpGV genome groups except group B. Single-pair crossing experiments with a susceptible strain, followed by resistance testing of the F1 offspring, clearly indicated cross-resistance to CpGV isolates that had been considered to be resistance breaking. This finding provides clear evidence of a second, broader type of CpGV resistance with a novel mode of inheritance that cannot be fully explained by Z-linkage of resistance. IMPORTANCE: CpGV is registered and used in virtually all commercial apple growing areas worldwide and is therefore the most widely used baculovirus biocontrol agent. Recently, resistance to CpGV products was reported in different countries in Europe, threatening organic growers who rely almost exclusively on CpGV products. This resistance appeared to be targeted against a 24-bp repeat in the pe38 gene in isolate CpGV-M of genome group A, which had been used commercially for many years. On the other hand, resistance could be broken by CpGV isolates from CpGV genome groups B to E. Here, we report clear evidence of a second type of field resistance that is also directed against resistance-breaking isolates of CpGV genome groups C, D, and E and which appears not to be targeted against CpGV pe38 Therefore, we propose to differentiate between type I resistance, which is targeted against pe38 of CpGV genome group A, and a novel type II resistance with an unknown molecular target. This finding stresses the need for further adoption of resistance management strategies for CpGV, since growers cannot rely solely on the use of resistance-breaking CpGV isolates.

A Third Type of Resistance to Cydia pomonella Granulovirus in Codling Moths Shows a Mixed Z-Linked and Autosomal Inheritance Pattern.

Different isolates of Cydia pomonella granulovirus (CpGV) are used worldwide to control codling moth larvae (Cydia pomonella) in pome fruit production. Two types of dominantly inherited field resistance of C. pomonella to CpGV have been recently identified: Z-chromosomal type I resistance and autosomal type II resistance. In the present study, a CpGV-resistant C. pomonella field population (termed SA-GO) from northeastern Germany was investigated. SA-GO individuals showed cross-resistance to CpGV isolates of genome group A (CpGV-M) and genome group E (CpGV-S), whereas genome group B (CpGV-E2) was still infective. Crossing experiments between individuals of SA-GO and the susceptible C. pomonella strain CpS indicated the presence of a dominant autosomal inheritance factor. By single-pair inbreeding of SA-GO individuals for two generations, the genetically more homogenous strain CpRGO was generated. Resistance testing of CpRGO neonates with different CpGV isolates revealed that isolate CpGV-E2 and isolates CpGV-I07 and -I12 were resistance breaking. When progeny of hybrid crosses and backcrosses between individuals of resistant strain CpRGO and susceptible strain CpS were infected with CpGV-M and CpGV-S, resistance to CpGV-S appeared to be autosomal and dominant for larval survivorship but recessive when success of pupation of the hybrids was considered. Inheritance of resistance to CpGV-M, however, is proposed to be both autosomal and Z linked, since Z linkage of resistance was needed for pupation. Hence, we propose a further type III resistance to CpGV in C. pomonella, which differs from type I and type II resistance in its mode of inheritance and response to CpGV isolates from different genome groups.IMPORTANCE The baculovirus Cydia pomonella granulovirus (CpGV) is registered and applied as a biocontrol agent in nearly all pome fruit-growing countries worldwide to control codling moth caterpillars in an environmentally friendly manner. It is therefore the most widely used commercial baculovirus biocontrol agent. Since 2005, field resistance of codling moth to CpGV products has been observed in more than 40 field plantations in Europe, threatening organic and integrated apple production. Knowledge of the inheritance and mechanism(s) of resistance is indispensable for the understanding of host response to baculovirus infection on the population level and the coevolutionary arms race between virus and host, as well as for the development of appropriate resistance management strategies. Here, we report a codling moth field population with a new type of resistance, which appears to follow a highly complex inheritance in regard to different CpGV isolates.

The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43.

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function.

Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone.

PURPOSE: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). PATIENTS AND METHODS: During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. RESULTS: Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. CONCLUSION: EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.

Retrospective assessment of quality of life and treatment outcome in patients with Hodgkin's disease from 1969 to 1994.

We determined the current quality of life (QoL) of patients with Hodgkin's disease treated at the Innsbruck University Hospital between 1969 and 1994 at a mean time of 9.1 +/- 7.0 years after their initial treatment. Further aims of our study were to assess potential differences in objective treatment outcome and QoL between patients treated with chemo-, radio- or combined modality therapy and those enrolled in randomised clinical trials or treated according to standard procedures. The QLQ-C30, a health-related and validated self-report questionnaire developed by the Study Group on Quality of Life of the European Organization for Research and Treatment of Cancer (EORTC) was mailed to a cohort of 194 survivors out of a total of 225 patients with Hodgkin's disease; 126 of them (64.9%) returned the completed questionnaire. The 5- and 10-year overall survival rates for the total group of 225 patients were 94.3% and 84.9%, respectively. Irrespective of stage, higher relapse-free survival rates were observed in patients receiving combined modality treatment (P = 0.025). Five-year relapse-free survival rates were 96.6% for patients enrolled in clinical trials and 82.8% for patients treated outside of randomised studies (P = 0.037 in univariate and P = 0.064 in multivariate analysis). Patients treated with combined modality regimens had reduced QoL scores in comparison with those treated with either radiation or chemotherapy alone, but QoL parameters did not differ between patients enrolled in clinical trials and those treated according to standard procedures. Patients with Hodgkin's disease had an excellent long-term prognosis and very high QoL scores a mean of 9.1 years after treatment of their disease. The improved relapse-free survival rates achieved by combined modality regimens must be carefully weighed against the accompanying reduced QoL, since lower relapse rates did not translate into a survival advantage.

Influence of local radiotherapy of breast cancer patients on the frequency of cytotoxic T lymphocyte precursor cells.

Alloantigen-specific cytotoxic T lymphocyte precursor (CTL-p) frequencies were analyzed in ten patients with histologically proven breast cancer receiving prophylactic RT. The frequency of CTL-p was assessed by limiting dilution (LD) analyses before, immediately after discontinuation of treatment and at various times following RT. The number of pbmnc, adherent cells and T cells was determined in parallel. Local RT led to a minor and transient reduction of CTL-p frequencies lasting approximately three months: on average a 25% decrease of CTL-p numbers was seen immediately after RT. Three months following treatment, a 20% reduction was still evident. Values subsequently returned to pretreatment levels. Moreover, these changes in the frequency of antigen-specific CTL were accompanied by a 25% to 39% decrease in the blood T cell counts lasting for more than 12 months. The reductions following local RT were less pronounced than those induced by immunosuppressive drugs in allograft recipients.

Mycosis fungoides. Intraocular and central nervous system involvement.

A 58-year-old man with mycosis fungoides was treated with chemotherapeutic agents and radiation for the recurrent cutaneous form of this disease. Five years after the onset, he developed blurring of vision, neurologic signs, and then lapsed into coma. Chemotherapy and radiation treatment resulted in improvement of the ocular and systemic picture. Within three months, however, the patient's vision deteriorated and swelling of both optic discs, along with retinal and vitreous infiltrates, was noted. Local radiation of the eyes was followed by improvement of the ocular changes. Five months later the patient died. Results of a histologic examination of the eyes showed extensive involvement of the retina and vitreous by tumor cells. The CNS was remarkably free of tumor cells and it was assumed that the radiation and chemotherapy were responsible for this.

Optic nerve decompression. A clinical pathologic study.

Decompression of the perioptic meninges for intractable chronic papilledema was done in a patient with a right parietal temporal glioblastoma multiforme. The patient died 39 days postoperatively. Histologic study of the optic nerves indicated fistulas in the dura compatible with cerebrospinal fluid (CSF) egress and maintenance of a normal subarachnoid space around the nerve. Two additional patients with unilateral optic nerve decompression producing bilateral resolution of papilledema were studied. We contend that egress of CSF was the principle mode of action in these three cases. How long the dural fistula remains patent is unknown. Reports in the literature show considerable variation in the effects of optic nerve decompression. Anatomic variation of the intracanalicular subarachnoid space together with differences in underlying pathologic condition, surgical technique, and patient response may explain discrepancies among the results reported.

Permeability barrier function of skin exposed to ionizing radiation.

OBJECTIVE: To characterize the epidermal permeability barrier function of skin during exposure to ionizing radiation. DESIGN: A prospective cohort study. SETTING: University hospital medical center. PATIENTS: Fifteen women receiving local radiation therapy (5000-6000 rad [50-60 Gy]) following breast-conserving surgery for breast cancer. MAIN OUTCOME MEASURES: Clinical symptoms and transepidermal water loss (TEWL). RESULTS: Epidermal permeability barrier function is impaired in patients who exhibit clinical signs of radiation dermatitis. The functional damage to the stratum corneum induced by ionizing radiation occurs with a delayed course, starting within a mean period of 11 days and reaching maximal values after a mean period of 27 days (range, 13-75 days). The onset of TEWL increase precedes the onset of radiation dermatitis and the maximal TEWL measurements precede the peak of skin changes. Patients with an early onset of TEWL increase show a longer duration of skin symptoms. CONCLUSIONS: Skin changes caused by radiation dermatitis are associated with an increase in TEWL. The barrier impairment is comparable to the changes observed with UV radiation exposure but exhibits an even more delayed course. Our results suggest that preservation of the epidermal permeability barrier function by topical treatment may ameliorate radiation dermatitis.

Ultrasound of the Achilles tendon after surgical repair: morphology and function.

Ultrasound is a well established method for the examination of the Achilles tendon. The objective of the study was to provide answers to the following questions: What ultrasonographic structural changes are long lasting after surgical repair? How important is ultrasound with regards to the functional evaluation of late results? 60 patients were examined at an average 11 years (2-19) after surgical repair of Achilles tendon rupture. In only four patients sonographic morphology of the tendon was according to the non-injured side. A variety of distinct basic alterations in ultrasound morphology was found: a hypoechogenic ribbon ventrally to the dorsal paratenon (n = 40), spots of hypoechogenic areas in the tendon (n = 18), dishomogeneous hyperechogenicity with preservation (n = 12) or dissolving (n = 22) of its fibrillar components along the longitudinal axis. In most of the cases the paratenon was thickened or could not be differentiated. In the dynamic ultrasound examination gliding mechanism of the achilles tendon was limited in 41 patients. Extensive functional subjective and objective parameters of all patients were evaluated in an Achilles tendon score. The results were rated as excellent (n = 18), good (n = 29), satisfactory (n = 12) and poor (n = 1). There was no statistical correlation between ultrasound morphology and clinical outcome. Therefore, it was concluded that ultrasound examination is able to reveal long-lasting alterations in echogenicity of the tendon but is only of limited value with regards to evaluation of the functional results after surgical repair.

Transrectal ultrasonography as a follow-up method in prostatic carcinoma after external beam and interstitial radiotherapy.

Transrectal ultrasonography and ultrasonometrics were employed for follow-up in a total of 28 prostatic carcinoma patients subjected to external beam or interstitial radiotherapy. These two methods permit more accurate staging of prostatic carcinoma and have also proved to be valuable in the follow-up care of patients suffering from locoregional prostatic carcinoma. Of the 20 patients subjected to external beam radiotherapy four patients initially did not show capsular infiltration, 2B2, 2A2, whereas 16 patients presented with infiltration of the capsule and seminal vesicles. After external beam radiotherapy the ultrasonomorphologic findings of four patients revealed a sharply demarcated capsule and unremarkable seminal vesicles, which indicated tumour regression. Of five patients with infiltration of the pelvic floor and/or seminal vesicles, three showed definite tumour regression, whereas the ultrasonograms of the other two patients demonstrated tumour progression despite radiotherapy. In eight patients the greatest reduction in tumour volume was found one year after interstitial radiotherapy. Only one patient, initially presenting with slight infiltration of the capsule, was shown to have infiltration of the capsule and seminal vesicles after interstitial radiotherapy. At follow-up, evaluation of the echo patterns in these patients was inaccurate on account of the dense echoes reflected by the seeds implanted.

The failed back surgery syndrome: reasons, intraoperative findings, and long-term results: a report of 182 operative treatments.

STUDY DESIGN: A retrospective study was performed of 182 revisions on failed back surgery syndrome from the years 1965 to 1990. OBJECTIVE: To analyze the reasons for failure of primary discectomy, the outcome of the revisions, and factors that influenced those outcomes. SUMMARY OF BACKGROUND DATA: The reported reintervention rates after lumbar discectomy range from 5% to 33% depending on the type of surgical procedure. The authors' former investigations reported a revision rate of 10.8% in evaluating 1500 lumbar discectomies. METHODS: Because the documentation was standardized, detailed data of all patients were available. To gain further information concerning the long-term results a questionnaire was used. Computer processing and statistical tests were performed. RESULTS: One hundred eighty-two revisions were performed on 136 patients. Forty-four patients (34%) were revised multiple times. Generally, recurrent or uninfluenced sciatic pain and neurologic deficiency or lumbar instability led to reintervention. Recurrent lumbar disc herniation mainly was found at the first reintervention. In multiple revision patients the rate of epidural fibrosis and instability increased to greater than 60%. In 80% of the patients the results were satisfactory in short-term evaluation, decreasing to 22% in long-term follow up (2-27 years). CONCLUSIONS: Laminectomy performed in primary surgery could be detected as the only factor leading to a higher rate of revisions. A trend toward poor results after recurrent disc surgery seems to be fateful because of the development of epidural fibrosis and instability. In severe discotomy syndrome, a spinal fusion seems to be more successful than multiple fibrinolyses.

Primary lumbosacral stability after open posterior and endoscopic anterior fusion with interbody implants: a roentgen stereophotogrammetric analysis.

STUDY DESIGN: After posterior stabilization of the spondylolytic lumbosacral level, mobility of the fused vertebrae could be studied before and after an additional anterior endoscopic interbody fusion using roentgen stereophotogrammetric analysis. OBJECTIVE: To determine the in vivo primary lumbosacral stability of additional anterior interbody fusion after transpedicular screw fixation. SUMMARY OF BACKGROUND DATA: In vitro studies indicate a significant decrease in segmental motion after pedicle screw fixation and additional anterior fusion. Roentgen stereophotogrammetric studies demonstrate the adequacy of transpedicular lumbar instrumentation in posterolateral fusions. There are no studies examining the effect of additional anterior interbody fusion after posterior instrumentation in vivo. METHODS: In this study, 15 patients with low-grade spondylolisthesis at L5-S1 underwent a two-stage open posterior and endoscopic anterior lumbar fusion using carbon fiber (Brantigan I/F) cages. At surgery, tantalum markers were implanted into the fifth lumbar (L5) and the first sacral (S1) vertebra. All the patients were examined by roentgen stereophotogrammetric analysis after the first and second surgical procedures. RESULTS: After implantation of the posterior pedicle system only, the mean intervertebral mobility determined by roentgen stereophotogrammetric analysis was 0.23 mm in the transverse (x), 0.54 mm in the vertical (y), and 1.2 mm in the sagittal (z) axes. After additional anterior endoscopic fusion with carbon cages, the remaining translation between the fused segment L5/S1 decreased to 0.17 mm in the x, 0.16 mm in the y, and 0.44 mm in the z axes. CONCLUSION: Anterior endoscopic lumbosacral fusion significantly increases the primary stability of the posterior fusion with a pedicle system in two axes of motion.

[Combined radio-/chemotherapy of invasive bladder cancer]. / Kombinierte Radio-/Chemotherapie des invasiven Harnblasenkarzinoms.

In a prospective study, 19 patients with advanced transitional carcinoma of the bladder (stages T.3 and T.4) were treated by combined radiotherapy and chemotherapy. A total of 450 mg cis-platinum or 1.6 mg/kg body weight were given in four treatment periods with three-week intervals. At the same time, the total dose of 60 Gy was given to the tumour over two periods (telecobalt or high-energy photons). There were few systemic or toxic side effects. Recurrence-free survival during the next 36 months was 76%, which compares with a control group treated by irradiation only, who had a survival of 48%.

[Mammography and sonography in the diagnosis of recurrence after breast-preserving therapy of breast carcinoma]. / Mammographie und Sonographie in der Rezidivdiagnostik nach brusterhaltender Therapie des Mammakarzinoms.

89 patients, who underwent conservative surgery for breast cancer were followed up with mammography and real-time sonography. 78 patients underwent postoperative irradiation. Depending on the time interval between irradiation and examination various alterations in mammographic and sonographic patterns were evident. Of 14 biopsy-confirmed local recurrences, 11 were diagnosed by mammography and 12 by sonography. Sonography was superior in the diagnosis of small recurrences in breasts with radiation-induced increased density, whereas mammography showed better results in the detection of tumours with microcalcifications. As a result of the different sonographic aspect of recurrent tumours and scar tissue, the number of false positive diagnoses of sonography was markedly lower compared to that of mammography (2 versus 18). Combined use of mammography and sonography should therefore lead to better results in the diagnosis of local recurrences and to a reduction of unnecessary biopsies.

Radiotherapy in early glottic carcinoma.

Radiotherapy is widely accepted as primary treatment in the T1 stage of glottic cancer, but controversy surrounds the proper approach to T2 lesions of the glottis. A retrospective review of 90 patients addresses treatment results for T1 and T2 lesions of glottic carcinoma managed by primary radiotherapy with 60 to 64 Gy from 1977 to 1989. Seventy-nine patients met the criteria for local control analysis with a minimum follow-up of 5 years. Radiotherapy alone controlled disease in 93% (43 of 46) of patients with T1 lesion and 18% (6 of 33) of those with T2 tumors (including 10 patients in whom radiotherapy was terminated at 40 Gy because of persistent tumor). Ultimate control of disease for T1 and T2 lesions, including surgical salvage, was 100% and 82%, respectively. Larynx preservation was achieved in 100% of T1 and in 45% of T2 lesions. Extension of tumor and impaired vocal cord mobility showed statistical significance for adverse prognosis (p < .001). This paper discusses how these results affect treatment of glottic carcinoma, particularly in the T2 stage.

Expandable metal stents versus laser combined with radiotherapy for palliation of unresectable esophageal cancer: a prospective randomized trial.

BACKGROUND/AIMS: Because of the short life expectancy of patients with esophageal cancer, relief of dysphagia associated with low morbidity and mortality must be the aim of any therapeutic strategy. METHODOLOGY: A total of 39 patients with unresectable esophageal cancer were randomly allocated to either receive combined laser-percutaneous radiotherapy (group 1, n = 21) or to have a self-expanding metal stent placed (group 2, n = 18). Some patients in group 2 required initial laser therapy (group 2a, n = 8). Treatment efficacy was evaluated on the basis of improved dysphagia, restenosis, hospital stay, survival time and costs. RESULTS: Both treatments were able to significantly improve dysphagia. Restenosis occurred in 43% of group 1 and 22% of group 2 patients. In group 1, 2 patients had severe bleeding episodes and 2 patients developed esophago-tracheal fistulas. One group 1 patient died due to uncontrollable bleeding and 1 patient to recurrent aspiration. No treatment-related death was observed in group 2. Hospital stay was 30.0 (mean: 5.4) days in group 1, 18.9 (mean: 4.2) days in group 2a and 7.1 (mean: 3.1) days in group 2b. There was no statistical difference between the 3 groups with regard to survival. Costs were highest in group 1 and lowest in group 2b. CONCLUSIONS: The treatment of unresectable esophageal cancer with self-expanding metal stents appears to be simple, safe, as good as laser combined with radiotherapy and cost efficient.

Photodynamic treatment of malignant brain tumors.

30 patients with primary or recurrent malignant brain tumors (9 primary, 18 recurrent malignant gliomas, 1 malignant meningioma, 2 melanomas) were treated altogether 37 times by photodynamic therapy (PDT) whether after intravenous, intraarterial or direct intratumoral sensitisation by hematoporphyrin (HPD) after conventional surgical removal of the tumor mass. The light was produced by an Argon pumped dye laser at doses varying from 40-220 J/cm2. A single dose of radiation of 4 Gy was administered to 18 patients immediately after PDT. The 9 patients with primary glioblastomas received in addition a full course of radiation therapy. The histological specimens taken during PDT demonstrated tumor necrosis, with oedema of normal brain tissue adjacent to the tumorbed. The median survival of patients with multiple recurrences and various radio- and chemotherapeutic modalities was 6 months (range 4-13 months). 9 patients with primary manifestation of a glioblastoma had a median survival of 19 months (0.5-29 months). Increased phototoxicity of the skin was the only side effect of PDT and did not reduce the quality of life of the patients.

[Intraoperative radiotherapy of brain gliomas]. / Intraoperative Bestrahlung (IORT) von Hirngliomen.

11 patients with recurrent brain tumours underwent intraoperative radiotherapy (IORT) at a dosage of 15-25 Gy of fast electrons (17-20 MEV). IORT allows a higher dose of irradiation to be delivered to a well-defined target than is possible with external radiation, in anticipation of favourable results. However, tumour growth was not influenced in 7 out of the 11 patients and these patients died between 2 and 10 months following IORT. The remaining four patients are living still up to 15 months postoperatively. Due to the inhomogeneity of our patients no definitive conclusions can be drawn. However, well-defined tumours which can be radically excised are definitely more suitable for IORT than large, infiltrating tumours.

[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. / Innsbrucker Ergebnisse mit der Knochenmarktransplantation in der Behandlung hämatologischer Neoplasien und solider Tumoren.

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).