Assessment of the Role of 1,3-ß-d-Glucan Testing for the Diagnosis of Invasive Fungal Infections in Adults.

Detection of 1,3-ß-d-glucan (BDG) in serum has been evaluated for its inclusion as a mycological criterion of invasive fungal infections (IFI) according to EORTC and Mycoses Study Group (MSG) definitions. BDG testing may be useful for the diagnosis of both invasive aspergillosis and invasive candidiasis, when interpreted in conjunction with other clinical/radiological signs and microbiological markers of IFI. However, its performance and utility vary according to patient population (hematologic cancer patients, solid-organ transplant recipients, intensive care unit patients) and pretest likelihood of IFI. The objectives of this article are to provide a systematic review of the performance of BDG testing and to assess recommendations for its use and interpretation in different clinical settings.

Is the middle cerebral artery bifurcation aneurysm affected by morphological parameters of bifurcation?

BACKGROUND: Aneurysm formation is a multifactorial process involving genetic, anatomical and environmental risk factors. A research focusing on the relationship between the presence of aneurysm and the morphology of the arteries will help in the pathogenesis and prediction of intracranial aneurysms. In this study, the relationship between the presence of aneurysm and various morphological parameters of aneurysm-related arteries was evaluated in patients with saccular middle cerebral artery (MCA) bifurcation aneurysm. MATERIALS AND METHODS: The archival images of 74 patients (62.2% women) were evaluated retrospectively. In this study, the angle between the ipsilateral MCA M1 segment and the dominant truncus (Φ1), the angle between the M1 segment and the recessive truncus (Φ2), and the bifurcation angle (Φ1 + Φ2) were compared. Bilateral internal carotid artery (ICA), MCA M1 segment, dominant and recessive truncus diameters and these diameters ratios were compared with the aneurysmal side and the contralateral side without aneurysm. RESULTS: When the dominant truncus, recessive truncus angles and bifurcation angle were compared, a significant difference was found on the aneurysmal side (p < 0.0001). In the receiver operating characteristic analysis, when the bifurcation angle of 147.5° was accepted as the limit value, 78.4% sensitivity, 79.7% specificity, 79.5% positive predictive value and 78.7% negative predictive value were determined (area under the curve: 0.85). CONCLUSIONS: Our study of the morphological features of arteries associated with MCA bifurcation aneurysms showed that the presence of MCA aneurysms was significantly associated with large bifurcation angles.

Effects of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: The impact of ABO mismatch on outcomes following allo-HSCT remains controversial. In this study, our aim is to define the effect of ABO mismatch on post-transplant outcomes, engraftment kinetics and complications in a large cohort. PATIENTS AND METHODS: We retrospectively identified 1000 patients who underwent allo-HSCT from either bone marrow or peripheral blood stem cells at our center between 1988 and 2016. P<0.05 was considered statistically significant. RESULTS: Five hundred and ninety (59%) patient-donor pairs were ABO matched, 164 (16.4%) were ABO major mismatched (MM), 191 (19.1%) were ABO minor MM, and 55 (5.5%) were ABO bi-directionally MM. ABO matched pairs were more common in transplants from related donors (P<0.001) and using bone marrow as a stem cell source (P<0.001). In minor ABO MM transplantations, mild delayed hemolytic reaction occurred more frequently compared to major and bidirectional ABO MM transplantations (47% vs 35% and 18%, P<0.001). Neutrophil engraftment was slightly delayed in ABO MM patient-donor pairs when compared ABO matched donor pairs according to median engraftment time in all group (167/410, 41% vs 204/590, 35%, P=0.046). Pure red cell aplasia was diagnosed in 6 patients (1%). Higher risk of death was shown in ABO MM transplants compared to ABO matched transplants in overall survival (OS) analysis (HR:1.201, 95% CI:1.004-1.437, P=0.045). The non-relapse mortality (P=0.546) and cumulative incidences of acute graft versus host disease (aGVHD) and chronic (c) GVHD were comparable between ABO MM and ABO matched patient-donor pairs (for aGVHD, P=0.235; for cGVHD, P=0.137). CONCLUSION: ABO MM transplants were associated with decreased OS and slightly delayed neutrophil engraftment. NRM and the risk of GVHD were not related to ABO incompatibility.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction).

BACKGROUND: The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized clinicians. AIMS: The present consensus document is an initiative of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) aimed at analysing, from an infectious diseases perspective, the safety of targeted and biological therapies. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: The document is structured in sections according to the targeted site of action of each drug class: proinflammatory cytokines; interleukins, immunoglobulins and other soluble immune mediators; cell surface receptors and associated signaling pathways; intracellular signaling pathways; lymphoma and leukaemia cells surface antigens; and other targeted therapies. A common outline is followed for each agent: summary of mechanism of action, approved indications and common off-label uses; expected impact on the host's susceptibility to infection; available clinical evidence (i.e. pivotal clinical trials, postmarketing studies, case series and case reports); and suggested prevention and risk minimization strategies. The methodologic and practical difficulties of assessing the specific risk posed by a given agent are also discussed. IMPLICATIONS: This ESGICH consensus document constitutes not only a comprehensive overview of the molecular rationale and clinical experience on the risk of infection associated with approved targeted therapies but also an attempt to propose a series of recommendations with the purpose of guiding physicians from different disciplines into this emerging framework.

Extracorporeal photochemotherapy in mycosis fungoides.

OBJECTIVES: Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF. METHODS: We retrospectively evaluated 50 MF patients who received ECP for clinical activity, toxicity, and response and outcome rates, and we compared these with combination therapies. RESULTS: The overall response rate (ORR) was 42% (21/50), while the median time to response was 11months (range, 3-48months). Ten of the responders (48%) had 3 or more treatment lines prior to ECP. Eight patients (16%) had adverse events related to ECP. The overall survival (OS) of 50 patients was 72months (range, 3-211). There was no statistically significant difference in the OS in early-stage vs late-stage patients (77 vs 69months, P=0.077). The stage 3 and 4 patients received an average of 31 cycles compared to 55 cycles in stage 1 and 2 patients (P=0.006). The increased extent of ECP was not correlated with the response. Combined treatment with ECP significantly improved the OS (84months vs 62months, P=0.005). DISCUSSION: A low frequency of side effects and improved OS observed in combination therapy makes ECP a favorable option for treating MF.

Factors affecting uptake of influenza vaccination among family physicians.

AIM: The aim of this study was to determine the factors that influenced the decisions of family physicians working in primary care health services to receive influenza vaccines. METHODS: This cross-sectional study was performed between June 2014 and September 2014. Physicians were reached electronically via e-mail. A self-reported questionnaire consisting of 50 items covering potential factors that may have influenced their decision to receive vaccination, including perceived risk, severity of the perceived risk, perceived benefit, perceived barriers, cues to action, attitudes, social influences and personal efficacy, was administered to the study participants. Cronbach's alpha for the questionnaire was determined to be 0.92 in the pilot study. RESULTS: The response rate was 27.5% (n=596). Regularly vaccinated physicians accounted for 27.3% of the responses. The median age was 41.84±7.80, and the median working duration of the group was 17.0±7.8years. The factors that led to increased vaccination compliance (p<0.05) included working duration, age, chronic disease history and living with a person over 65years. Nearly all major domains, i.e., perceived risk, severity of the perceived risk, perceived benefit, perceived barriers, attitudes, social influences and personal efficacy, there were differences between the compliant and noncompliant groups. Multi-regression analyses revealed that risk perception, organizational factors such as time and convenient vaccination increased vaccine compliance. However, the perceived necessity to be vaccinated annually had a negative effect on vaccination behaviour (p<0.05). CONCLUSION: Strategies aimed to increase the flu vaccination ratio among physicians that do not take different factors into account are more likely to be unsuccessful. In the planning and implementation of strategies aiming to increase the vaccination ratio among physicians, it is both necessary and important to take into account behavioural and organizational factors.

Karyotype analyses of ten sections of Trigonella (Fabaceae).

Karyotypes of ten sections of genus Trigonella Linnaeus, 1753 (Fabaceae) from Turkey were investigated. Somatic chromosome numbers of examined species were determined as 2n=14 and 16. The karyotype analyses of the species were carried out and somatic chromosome numbers of Trigonella plicata Boiss., 1872, Trigonella brachycarpa (Fisch.) Moris, 1833, Trigonella rostrata Boiss., 1872, Trigonella lunata Boiss., 1843, Trigonella isthmocarpa Boiss. et Balansa 1856, Trigonella rhytidocarpa Boiss. et Balansa, 1859, Trigonella spicata Sibth. et Sm., 1813, Trigonella cephalotes Boiss. et Balansa 1856, Trigonella capitata Boiss., 1843 and Trigonella gladiata Steven, 1808 were reported for the first time. Two pairs of satellite metaphase chromosomes were observed in Trigonella cariensis Boiss., 1843 and one pair in Trigonella lunata.Moreover, 2 B-chromosomes were found only in Trigonella procumbens Rchb., 1830 among all studied species. The aims of this study are to provide karyological data for a significant pool of the taxa, to show differences among them in the number, size and morphology of somatic chromosomes, to verify previous reports or represent numbers which are different from those cited previously.

Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study.

Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neutropenic (<500/microl) at baseline, 10 received steroids and 16 calcineurin inhibitors or sirolimus. Median duration of caspofungin treatment was 24 days. At the end of caspofungin therapy, 10 (42%) patients had complete or partial response (95% confidence interval: 22-63%); 1 (4%) and 12 (50%) had stable and progressing disease, respectively; one was not evaluable. At week 12, eight patients (33%) had complete or partial response. Survival rates at week 6 and 12 were 79 and 50%, respectively. No patient had a drug-related serious adverse event or discontinued because of toxicity. Caspofungin first-line therapy was effective and well tolerated in allogeneic hematopoietic SCT patients with mycologically documented IA.

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients.

OBJECTIVES: Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants. METHODS: Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified intention to treat (MITT) group; secondary endpoints were response and survival at day 84 and safety. RESULTS: In the MITT group (n = 61), 75% of patients had cancer not in remission (relapsing or refractory), 85% were neutropenic at enrolment and 49% had a Karnofsky score of < or =50. At end of treatment, 1 and 19 patients had complete and partial response, respectively [success rate 33% (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression. One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61) and 53% (32/60), respectively. Baseline characteristics associated with survival at day 84 were an underlying disease in remission (not relapsing or refractory) and Karnofsky score. Recovery from neutropenia at the end of treatment was also significantly associated with survival. No serious drug-related adverse events or discontinuations due to drug-related adverse events were observed. CONCLUSIONS: Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of < or =35%. Underlying disease-related factors had a major impact on results.

Treatment of Multiple Oral and Oropharyngeal Venous Malformations in Maffucci's Syndrome with a Combination of Percutaneous Sclerotherapy and Ligation. A Case Report.

Maffucci's Syndrome is an osteochondromatous syndrome with congenital vascular malformations. Major ailments involved are habitual fractures, length discrepancy of the extremities, impediment of the affected parts, extremity overgrowth and pain. The vascular lesions, aside from their mass effects, tend to ulcerate and bleed. Endotracheal intubation is also troublesome in these patients. Malignant tranformation of mesodermal tissue is the major lethal factor in this syndrome. This report describes severe respiratory impairment caused by venous malformations in a young girl. Multiple bunched venous malformations within the tongue, oral cavity and oropharynx were treated with percutaneous sclerotherapy and a simple ligation technique. Airway obstruction was cleared following repetitive treatment sessions.

The value of three-dimensional computed tomography in diagnosis and management of Jacob's disease.

This study reports a case of Jacob's disease characterized with limited mouth opening due to bilateral coronoid hyperplasia forming pseudojoints with zygomatic arches. Magnetic resonance (MR) examination of temporomandibular joint (TMJ) is usually the imaging method chosen in patients with such symptoms. However, the coronoid processes can not be displayed because they are not included in field of view in MR imaging of TMJ. For that reason, these patients may be treated for a misdiagnosis of TMJ disorders. In this study, the aetiology and diagnostic methods of Jacob's disease, the pre-operative/post-operative role of three-dimensional computed tomography and some measurements used in diagnosis were evaluated.

Tuberculosis in stem cell transplant patients.

Tuberculosis (TB) is an increasing health problem, and patients undergoing stem cell transplantation (SCT) are at high risk of acquiring TB. Following a review of the medical literature, this article reports the current situation of TB in SCT patients. A PubMed search was undertaken using the keywords 'tuberculosis', 'stem cell transplantation' and 'bone marrow transplantation', and cases with meaningful data for analysis were included. The medical literature contains relatively few data on TB and SCT. Although there is a risk of TB in allogeneic SCT patients, this is less than in solid organ transplant patients, and the risk in autologous SCT patients is similar to the risk in the general population. The incidence of TB in SCT patients is proportional to the incidence of TB in the general population. Evidence favouring TB prophylaxis is not well established. While allogeneic transplantation carries a risk of TB, this is not true for autologous transplantation. Prophylaxis can only be an option for selected patients or countries with high rates of TB.

Evaluation of the effect of transplant-related factors and tissue injury on donor-derived hepatocyte and gastrointestinal epithelial cell repopulation following hematopoietic cell transplantation.

The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.

Sphenoid sinus mucocele causing third nerve paralysis: CT and MR findings.

A 64-year-old woman presented with a 2 week history of ptosis and medial-gaze paralysis of her left eye. Computed tomography scanning of the paranasal sinuses revealed an expansile, homogeneous lesion with no contrast enhancement in the sphenoid sinus. The mass was hyperintense on all MR sequences and there was extension of the mass to the left cavernous sinus and optic canal. Operation revealed a large mucocele. Third nerve palsy disappeared 4 weeks after operation. Because the spread of mucoceles is variable, they may cause different symptoms. Radiological evaluation, especially computed tomography and magnetic resonance imaging, are useful in diagnosis of mucoceles and help to explain the clinical symptoms by showing the spread of the lesion.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation in patients with lymphoma -- a retrospective evaluation.

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.

Mycobacterial infection: a difficult and late diagnosis in stem cell transplant recipients.

The Infectious Diseases Working Party of the European Blood and Marrow Transplant Group conducted a survey to obtain information about the frequency, presentation, and treatment of mycobacterial infection (MBI) in stem cell transplant (SCT) recipients. Among 29 centers, MBI was diagnosed in 0.79% of 1513 allogeneic and 0.23% of 3012 autologous SCT recipients during 1994-1998 a median of 160 days after transplantation. The mean interval between first symptoms and diagnosis was 29 days and was still longer for patients with atypical MBI or recipients of corticosteroid therapy. The prevalence of MBI was highest among those who received matched unrelated or mismatched STCs from related donors. Of 31 patients, 20 had tuberculosis, 8 had atypical MBI, and 3 had diagnoses based on histological findings only. Five patients (16%) died, all of whom had received an allogeneic SCT. Because of the increased numbers of unmatched donors and transplantation programs in countries with a high prevalence of tuberculosis, constant vigilance is required to early detect MBI in SCT recipients.

Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies.

Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV-related mortality was observed in either group. In the lamivudine-treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine-related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy-induced HBV reactivation.

Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy.

This prospective, double-blind trial assessed whether the addition of a glycopeptide would be able to reduce the time to defervescence in neutropenic patients with cancer who had persistent fever 48-60 h after the initiation of empirical piperacillin-tazobactam monotherapy. Of 763 eligible patients, 165 with persistent fever were randomized to receive piperacillin-tazobactam therapy plus either vancomycin therapy or placebo. Defervescence was observed in 82 (95%) of 86 patients in the vancomycin group and in 73 (92%) of 79 patients in the placebo group (P=.52). The distributions of the time to defervescence were not statistically significant between the 2 groups (estimated hazard ratio, 1.03; 95% confidence interval, 0.75-1.43; P=.75). The number of additional episodes of gram-positive bacteremia and the percentage of patients for whom amphotericin B was empirically added to their therapy regimen were also similar in both groups. This study failed to demonstrate that the empirical addition of vancomycin therapy to the treatment regimen is of benefit to persistently febrile neutropenic patients with cancer.

Role of pretransplant interferon-alpha(IFN) treatment in the outcome of stem cell transplantation (SCT) from related donors in chronic myelogenous leukemia (CML): results from three Turkish transplant centers.

Since transplantation cannot be performed immediately after the diagnosis of chronic myelogenous leukemia (CML), interferon treatment is usually required. This study aims to analyze the effects of interferon-alpha (IFN) treatment on allogeneic stem cell transplantation (SCT) outcome. A total of 106 patients aged 16-47 years and transplanted from HLA-identical sibling donors for CML in chronic phase (CP) were evaluated. In all, 48 had received IFN-alpha for a median duration of 5 months (1-18 months) until a median of 1 month prior to transplantation. Of the patients, 50 have received bone marrow transplant (BMT) whereas 56 have received peripheral blood stem cells (PBSCT) between 1991 and 1999 in three major transplant centers in Turkey. Patient characteristics in both groups were similar. More hematological responders were present in the IFN(+) patients (P=0.0001). No difference was found in engraftment kinetics. The incidences of acute or chronic graft-versus-host disease (GVHD), relapse and graft failure were similar in all patients regardless of stem cell source. Overall survival (OS) and disease-free survival (DFS) at 2 years were similar for both IFN(+) or (-) patients following SCT. With multivariate analysis, pretransplant IFN-alpha use, stem cell source, transplant year and CD34+ cell content were not found to be risk factors for OS. In conclusion, prior IFN exposure did not impair BMT or PBSCT outcome.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation.

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.