Summary. We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n 32). In multivariate analysis the only two signi®cant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graftversus-host disease (GvHD, P < 0á0001; OR 4á6) and having received steroid prophylaxis for GvHD (P 0á04; OR 2á1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0á0001; OR 5á6), nonearly disease phase (P 0á0001; OR 1á9), steroid prophylaxis (P 0á02; OR 1á4), moderate-to-severe GvHD (P 0á01; OR 1á6) and cytomegalovirus infection post transplant (P 0á001; OR 1á8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors.

Diagnosis of invasive pulmonary aspergillosis (IPA) is often difficult. Recently, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) has proposed new criteria for the classification of invasive fungal infections. We have studied the clinical applicability of this classification in 22 patients with hematological malignancies who had IPA at autopsy. While alive, according to the EORTC/MSG criteria, only 2 patients were classified as having proven IPA, 6 as probable, 13 as possible, and 1 was unclassifiable. Of the patients, 64% had no microbiological or major clinical criteria before death. Although the EORTC/MSG criteria are an important step forward in the standardization of definitions used for IPA in clinical research studies, most patients who die with extensive lung disease only reach a level of possible or probable IPA during life, further highlighting that these guidelines should not be used for clinical decision-making.

In this retrospective monocenter study, we analyzed the outcomes of 130 adult hematological patients who developed a proven (n 5 23), probable (n 5 71), and possible (n 5 36) invasive aspergillosis (IA) in a 13-year period. Forty-nine patients (38%) were recipients of an allogeneic hematopoietic stem cell transplantation (AlloHSCT). The main goal of the study was the identification of prognostic factors for 4-month aspergillosis free survival (AFS) and overall survival (OS). IA was identified as the main cause of death in 27/49 recipients of an AlloHSCT (55%) and 28/81 nontransplanted patients (35%). Diagnosis of IA at or before 2000 had a negative impact in both 4-month AFS and 4-month OS in the entire group. In multivariate analysis performed separately for nontransplanted and allo-HSCT patients, five variables (excluding the year of diagnosis) decreased 4-month AFS: (i) impairment of one organ function (OF), (ii) impairment of two or more OFs (two points), (iii) disseminated IA, (iv) neutropenia lasting more than 10 days (non-AlloHSCT group only) or monocytopenia (<0.1 3 10 9 /l) [AlloHSCT group only], and (v) high-dose steroids (nonAlloHSCT group only) or an alternative donor (AlloHSCT group only). According to the number of adverse risk factors, three prognostic subgroups were defined in non-transplanted and alloHSCT patients with good (97% and 78% AFS), intermediate (73% and 32% AFS) and poor prognosis (20% and 11% AFS) of IA [P < 0.01]. In addition, we validated the French and Seattle prognostic indexes for allo-HSCT recipients and the Strasbourg model for all hematological patients with IA. Am. J. Hematol. 84:571-578, 2009. V

This randomized trial suggests that ABLC at 1 mg/kg/d produces less nephrotoxicity than c-AmB, without differences in the incidence of IRAEs and with similar efficacy.

Summary:Acute graft-versus-host disease (AGVHD) severity is usually graded (grades 0-IV) by the pattern of organ involvement using the classic Glucksberg-Seattle criteria (GSC). Recently, the International Bone Marrow Transplant Registry (IBMTR) developed a new Severity Index by regrouping the patterns of organ involvement into five Indexes (0-D) that appeared more predictive of transplant-related mortality (TRM) and transplant failure (TF, relapse or TRM). We studied the predictive value of both grading systems of TRM, TF and GVHDrelated mortality (GTRM) in a series of 114 consecutive patients у12 years old allografted from a histocompatible sibling at our institution, 100 of whom were evaluable for AGVHD. The IBMTR Severity Index showed better incremental prediction of TRM (relative risks (RR) of 1, 1.5, 1.4, 2 and 2.5 for Indexes 0, A, B, C and D), TF (RRs of 1, 1.6, 1.6, 2 and 2.3, respectively) and GTRM (RRs of 1, 2.2 and 4.8 for Indexes B, C and D) than the GSC. With the GSC different outcomes for TRM and TF were found only from grade 0 to I-II and 0 to IV or I-III to IV, but not from I-II to III. The GSC also appeared less predictive of GTRM (RRs of 1, 0.4 and 2.9 for grades II, III and IV). In our relatively small patient sample, the new IBMTR Severity Index appeared more predictive of transplant outcome than the GSC, especially between no AGVHD, early Indexes (A-B) and advanced Indexes (C-D). Keywords: stem cell transplantation; graft-versus-host disease; grading Moderate-to-severe acute GVHD (AGVHD) develops in 20-50% of adult recipients of an HLA-identical sibling allogeneic stem cell transplant (SCT). Mortality directly attributable to AGVHD or its treatment occurs in 10-20% of patients. 1-3 For classification and prognostic information, AGVHD has been graded according to the classic Glucksberg-Seattle criteria (GSC) for more than 20 years. 4,5 Recently, the International Bone Marrow Transplant Registry (IBMTR) designed a new staging system from a large data set of adult patients receiving an HLAidentical sibling BMT. 6 This IBMTR Severity Index appeared more predictive of the risk of transplant-related mortality (TRM) and treatment failure (TF) than the GSC. We report the results of a comparative analysis of these two staging systems in patients allografted at our institution from an HLA-identical sibling over an 8-year period. Materials and methods PatientsFrom January 1990 to March 1998, 114 consecutive patients aged у12 years received an allogeneic SCT at our institution. Patient characteristics are shown in Table 1. The median age was 36 years (range 12-58), and 68% of patients were male. GVHD prophylaxis consisted of CYA plus short-course MTX in 79%, CYA plus prednisone in 11% and CYA alone in 10%. CYA was given at 3 mg/kg/day i.v. started on day Ϫ1, which was later switched to the oral route with the aim of maintaining a trough whole blood concentration of 200-300 ng/mL. Short-course MTX consisted of 15 mg/m 2 on day ϩ1 and 10 mg/m 2 on days ϩ3, ϩ6 and ϩ11. The source of the stem cells was BM ...

Summary:We investigated whether daily oral washings with recombinant human granulocyte-macrophage colonystimulating factor (rhGM-CSF) solution improved grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Forty-one consecutive patients (21 males and 20 females, median age (range) 44 (16-69) years) were prospectively randomized to perform daily mouth-washes with either a 400 g rhGM-CSF (Molgramostin, Schering-Plough) solution (group A, n ‫؍‬ 18) or with a saline solution (group B, n ‫؍‬ 23). Primary end-points were the intensity of OM, night rest quality and characteristics of food intake. Secondary end-points were need for and duration of parenteral nutrition, oral and intravenous analgesic requirements, incidence of viral or fungal oral infections and development of neutropenic fever. No differences were found between the placebo and rhGM-CSF-treated groups regarding overall duration of OM, maximum grade, reduction in at least one grade of OM (nine patients (56%) in group A vs 13 patients (68%) in group B), reduction of spontaneous or swallowing-induced pain, improvement in oral food intake, use of parenteral nutrition or use of systemic analgesics. In conclusion, mouth-washings with a 400 g of rhGM-CSF solution do not improve severe OM in hematological patients undergoing stem cell transplantation.

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Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia. Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation). All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant. Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation. All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS. These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.