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.

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.

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.

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.

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.

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.

The clinical correlations of serum tumor necrosis factor-alpha in acute leukemias: a predictor of response and relapse?

The clinical correlations of serum tumor necrosis factor alpha (TNF-alpha), a cytokine which can be released from leukemic blasts, has not been extensively studied. We have analyzed serum TNF-alpha in 20 ANLL, one CML-myeloblastic crisis, and 14 ALL adult patients by using a commercial ELISA kit. Sterile serum samples were taken on day 0, day 7, during remission and relapse with a mean follow-up period of 4.2 (1-19) months. After a median of 7 days following chemotherapy, serum TNF-alpha decreased both in responding ANLL (p = 0.004) and ALL (p > 0.05) but remained high in refractory leukemias. Values on day 7 were significantly different between responding and refractory patients in both ANLL (p = 0.0027) and ALL (p = 0.0099). At relapse, serum TNF-alpha increased starting at a median of 3 months preceding clinical symptoms in ANLL (p = 0.002). However, the relapse of ALL coincided with a slight increase which was not significant (p > 0.05). Together these findings indicate that serum TNF-alpha can be used as an early predictor of clinical response and relapse in ANLL.

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.

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.

Febrile neutropenia in allogeneic and autologous peripheral blood stem cell transplantation and conventional chemotherapy for malignancies.

The risk and outcome of infection in febrile neutropenic patients is mainly determined by the duration of neutropenia, the underlying disease or the treatment. This study was undertaken to compare infections and the outcome after conventional chemotherapy (CCT), allogeneic PBSC transplantation (alloPBSCT) or autologous PBSC transplantation (autoPBSCT), during the period of neutropenia, in a single center. A total of 145 patients (50 in CCT group, 50 in alloPBSCT and 45 in autoPBSCT) were evaluated. In the alloPBSCT group, 86% of the patients (43/50), in the autoPBSCT group 93% of the patients (42/45) and in the CCT group 92% (46/50) of the patients had at least one febrile episode during their neutropenic period (P > 0.05). Microbiologically and/or clinically documented infection rates were 50% (25/50), 42% (19/45) and 48% (24/50) respectively. Gram-positive pathogens, mostly coagulase-negative staphylococci were the most frequent cause of bacteremias in all groups. The frequency of CNS infections was significantly higher in the alloPBSCT and autoPBSCT groups compared to the CCT group (P < 0. 008 and P < 0.04, respectively). Catheter infections were frequent in the PBSCT groups and pulmonary infections were more frequent in the CCT group (P < 0.05). The CCT group needed longer antibiotic usage compared to the alloPBSCT group (P < 0.006). The duration of neutropenia and the type of treatment given, does not affect the rate of febrile episodes, but affects the type of infections in febrile neutropenic patients.

Aerobic bacterial and fungal infections in peripheral blood stem cell transplants.

Allogeneic and autologous peripheral blood stem cell transplants are frequently complicated by infections. This study was performed to evaluate early and late infections in 74 patients who underwent peripheral blood stem cell transplantation (PBSCT). Fifty-eight patients received allogeneic and 16 autologous PBSCT. All patients received fluconazole, ciprofloxacin and acyclovir prophylaxis. 93.1% of alloPBSCT patients and 87.5% of autoPBSCT patients developed fever. Febrile episodes were commonly seen in the week of transplantation (66%). There was a median of 3 days with fever in alloPBSCT, and 2 days in autoPBSCT. Period of neutropenia was 15 days for AlloPBSCT and 12 days for AutoPBSCT. The microbiological identification rate was 47% (32/68). Gram-positive infections dominated the early period (50%) and Gram-negative bacterial infections dominated the late period (50%). All our patients had Hickman-type catheters and 26 infections involving catheters were seen. Sixteen occurred in the early, and 10 in the late period. Ten of 14 (71.4%) late bacterial infections were catheter-related. The dominance of Gram-positive infections and high rates of methicillin resistance warranted the use of vancomycin extensively. Surveillance cultures were found to be useful in selected patients. Although slime factor is an important virulence factor, there was no difference between slime factor positive and negative coagulase-negative staphylococci isolated during infections. In conclusion, febrile episodes are the most frequent complication of PBSCT and Gram-positive microorganisms remain the main pathogen in these patients because of catheter use, mucositis and ciprofloxacin prophylaxis. Methicillin resistance is increasing and glycopeptides remain the only choice for treating such infections. Although the infection rate is high, measures taken to prevent and treat infections result in very low rates of mortality from infection in PBSCT patients.

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.

Hepatitis B virus infection in allogeneic bone marrow transplantation.

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.

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.

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies.

The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m2 thiotepa and 100 mg/m2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m2, melphalan (100 mg/m2) and escalating doses of carboplatin 900-1500 mg/m2) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m2 thiotepa, 100 mg/m2 melphalan and 1350 mg/m2 carboplatin. Two consecutive patients receiving 1500 mg/m2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5x10(9)/l was 9 days (range 7-12 days) and platelet count of 20x10(9)/l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted.

Acquired ichthyosis associated with chronic graft-versus-host disease following allogeneic peripheral blood stem cell transplantation in a patient with chronic myelogenous leukemia.

Acquired ichthyosis (AI) has rarely been described following bone marrow transplantation (BMT). We report a 29-year-old male, who underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) for chronic myelogenous leukemia, and who developed AI associated with chronic graft-versus-host disease (cGVHD). Both of these disorders were treated successfully with cyclosporin A. We conclude that AI may be related to an autoimmune process on the basis of cGVHD, and dermathopathologic evaluation must be performed in patients with skin changes suggesting AI following allogeneic bone marrow transplantation.

Autoimmune thrombocytopenia in a patient with small cell lung cancer developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation.

A 46-year-old white male with small cell lung cancer (SCLC) limited to the thorax developed autoimmune thrombocytopenic purpura (AITP), following a cyclophosphamide, paclitaxel and G-CSF-containing regimen for peripheral blood stem cell (PBSC) mobilization. AITP associated with small or non-small cell lung cancer has been reported. We considered that the AITP in this case may be a part of paraneoplastic syndrome, which is frequently seen in patients with SCLC. The patient received HDC and autologous PBSC transplantation (APBSCT) for SCLC and the AITP resolved following transplantation, thus supporting the concept of HDC + APBSCT for the treatment of autoimmune diseases.