Repurposing antifungals: population pharmacokinetics of itraconazole and hydroxy-itraconazole following administration of a nanocrystal formulation.

OBJECTIVES: To describe itraconazole and hydroxy-itraconazole pharmacokinetics following intravenous (IV) administration of a previously developed nanocrystal formulation (NCF) in haematopoietic cell transplant (HCT) recipients for prophylaxis of invasive fungal disease. METHODS: In a prospective Phase II study, 10 HCT recipients received itraconazole NCF administered in 2-hour infusions of 200 mg twice daily for 2 days, followed by 200 mg once daily until Day 14. Full pharmacokinetic curves were obtained on Days 7 and 14. Additional samples were collected pre- and post-infusion until Day 6, pre-infusion on Days 10 and 12, and during washout on Days 16, 17, 18, 19 and 28. Itraconazole and hydroxy-itraconazole pharmacokinetics were analysed by non-linear mixed-effects population pharmacokinetic modelling. RESULTS: Four-hundred and seventy-one itraconazole and 471 paired hydroxy-itraconazole concentrations from 10 patients were included for analysis. Data were best described by a semi-mechanistic model with central and peripheral itraconazole compartments and a hydroxy-itraconazole compartment with dissolution of itraconazole drug particles from nanocrystals and first-order distribution and elimination. The final model included interindividual variability on itraconazole clearance and hydroxy-itraconazole clearance. CONCLUSIONS: This study provides information on the pharmacokinetic properties of the itraconazole NCF useful for development of this formulation. Our results suggest that itraconazole NCF is a suitable formulation and may warrant renewal in the setting of repurposing. Our findings may be useful for the reformulation of other highly lipophilic compounds as well.

The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis.

BACKGROUND: The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. OBJECTIVES: To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA). METHODS: As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression. RESULTS: In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%-12%) compared with the non-prophylaxis group (18%-19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)]. CONCLUSIONS: Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.

Interlaboratory evaluation of Mucorales PCR assays for testing serum specimens: A study by the fungal PCR Initiative and the Modimucor study group.

Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility and performance of methods currently used. The participants comprised 12 laboratories from French university hospitals (nine of them participating in the Modimucor study) and 11 laboratories participating in the Fungal PCR Initiative. For panel 1, three sera were each spiked with DNA from three different species (Rhizomucor pusillus, Lichtheimia corymbifera, Rhizopus oryzae). For panel 2, six sera with three concentrations of R. pusillus and L. corymbifera (1, 10, and 100 genomes/ml) were prepared. Each panel included a blind negative-control serum. A form was distributed with each panel to collect results and required technical information, including DNA extraction method, sample volume used, DNA elution volume, qPCR method, qPCR template input volume, qPCR total reaction volume, qPCR platform, and qPCR reagents used. For panel 1, assessing 18 different protocols, qualitative results (positive or negative) were correct in 97% of cases (70/72). A very low interlaboratory variability in Cq values (SD = 1.89 cycles) were observed. For panel 2 assessing 26 different protocols, the detection rates were high (77-100%) for 5/6 of spiked serum. There was a significant association between the qPCR platform and performance. However, certain technical steps and optimal combinations of factors may also impact performance. The good reproducibility and performance demonstrated in this study support the use of Mucorales qPCR as part of the diagnostic strategy for mucormycosis.

Epidemiology of invasive aspergillosis and triazole-resistant Aspergillus fumigatus in patients with haematological malignancies: a single-centre retrospective cohort study.

Objectives: To investigate the epidemiology and clinical relevance of triazole resistance among patients undergoing treatment for haematological malignancies who are at risk of invasive aspergillosis (IA). Methods: This was a retrospective cohort study for which the records of consecutive patients given chemotherapy for AML or myelodysplastic syndrome (MDS) or who had received an allogeneic HSCT from 2006 to 2012 were reviewed for IA. Triazole resistance was detected by the VIPcheck™ screening method and confirmed by determining the MIC by EUCAST methodology. Results: A total of 432 patients were included, comprising 182 (42.1%) patients who had undergone chemotherapy for AML or MDS, and 250 (57.9%) patients who had undergone an allogeneic HSCT. Probable or proven IA was diagnosed in 36 cases (8.3%, 95% CI 6.0%-11.4%). Of these, 12 (33.3%) were based on recovery of Aspergillus fumigatus from sputum, bronchoalveolar lavage or biopsy, and triazole resistance was found in 2 instances. A. fumigatus was also recovered from one or more specimens from 13 patients without probable or proven IA. Triazole resistance was documented for three patients. The survival rate of patients with IA caused by voriconazole-resistant isolates could not be assessed. Conclusions: The overall frequency of voriconazole-resistant IA among patients at high risk was low. However, the rate of triazole resistance may have been underestimated by the low detection rate based on recovery of A. fumigatus. Alternative diagnostic tests, such as PCR-based assays, may prove better at detecting IA due to triazole-resistant A. fumigatus.

Hospital-onset Clostridium difficile infection among solid organ transplant recipients.

Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54-1.82, median 1.04, interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted.

A rationale for reduced-frequency dosing of anidulafungin for antifungal prophylaxis in immunocompromised patients.

OBJECTIVES: Reduced-frequency dosing strategies of anidulafungin may offer a more convenient way of providing adequate antifungal prophylaxis to patients at high risk of invasive fungal diseases. We aimed to provide the pharmacological rationale for the applicability of reduced-frequency dosing regimens. METHODS: We defined two groups of 10 patients that were to receive anidulafungin at 200 mg every 48 h or 300 mg every 72 h. Blood samples were drawn daily and two pharmacokinetic curves were constructed after 1 and 2 weeks of treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. ClinicalTrials.gov identifier: NCT01249820. RESULTS: The AUC over a 6 day period (IQR) for a typical patient on 200 mg every 48 h or 300 mg every 72 h resulted in 348 mg ·â€Šh/L (310.6-386.7) and 359 mg ·â€Šh/L (319.1-400.9), respectively, comparable to the licensed regimen [397.0 mg ·â€Šh/L (352.4-440.5)]. In the final model, the volume of distribution proved to be dependent on the lean body mass and CL of cyclosporine A. All three regimens resulted in comparable dose-normalized exposure over time. CONCLUSIONS: We now have sufficient evidence to start using less frequent dosing regimens and demonstrate their value in clinical practice. These less frequently applied infusions enable more personalized care in an outpatient setting with reduced costs.

Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients.

BACKGROUND: In the 1960s, it was reported that infectious complications were the main cause of fever during neutropenia that followed hematopoietic stem cell transplant (HSCT). More recently, mucositis has become recognized as an important determinant of the inflammatory response and infectious complications. METHODS: The objective of this prospective study was to determine the impact of intestinal mucositis, as measured by plasma citrulline, and neutropenia on the systemic inflammatory response (C-reactive protein) and the occurrence of bacteremia among 2 cohorts of HSCT recipients: 1 composed of 18 patients who had been treated with a myeloablative (MA) regimen (high-dose melphalan) and the other involving 19 patients who had received the non-myeloablative (NMA) regimen (fludarabine and cyclophosphamide). Blood cultures were obtained for surveillance from admission onwards as well as at the onset of fever. RESULTS: The MA regimen induced severe intestinal mucositis manifest by citrullinemia <10 µmol/L, which was accompanied by an inflammatory response, and bacteremia affected 8 (44%) of 18 patients and coincided with the nadir of citrullinemia. By contrast, those who had been treated with the NMA regimen did not develop severe intestinal mucositis, had a moderate inflammatory response, and only 2 (11%) of the 19 patients developed bacteremia. However, both groups experienced profound neutropenia and its duration was significantly longer for those receiving the NMA regimen. CONCLUSION: This study suggests that severe intestinal mucositis, i.e., citrullinemia <10 µmol/L, defines the period of risk of bacteremia better than does neutropenia, and that measuring plasma citrulline may prove useful in deciding who needs empirical antimicrobial therapy and when.

Integrated array of 2-µm antimonide-based single-photon counting devices.

A 32x32 Sb-based Geiger-mode (GM) avalanche photodiode array, operating at 2 µm with three-dimensional imaging capability, is presented. The array is interfaced with a ROIC (readout integrated circuit) in which each pixel can detect a photon and record the arrival time. The hybridized unit for the 1000-element focal plane array, when operated at 77K with 1 V overbias range, shows an average dark count rate of 1.5 kHz. Three-dimensional range images of objects were acquired.

How prompt is prompt in daily practice? Earlier initiation of empirical antibacterial therapy for the febrile neutropenic patient.

With fever being the most common manifestation of early sepsis, clinical practice guidelines emphasise the prompt institution of broad-spectrum antibacterial therapy at its onset. An audit was performed on the haematology ward to determine whether there was any delay in starting antibiotic treatment during neutropenia in clinical patients and to define the main reasons for this. Strategies were developed, implemented and evaluated on short- and long-term implications on the delay in the start of antibacterial therapy. The procedures specified in the protocol for starting empirical antibacterial therapy were audited to assess whether the target for starting therapy within 30 min of fever was achieved. Initial results indicated that two major changes to the protocol were necessary to achieve a reduction in the delay between detection of fever and starting antibacterial therapy. This modified protocol was evaluated 4 months after implementation by means of a consecutive audit. After 3 years, a third audit was performed to determine the long-term implications of the improved protocol. In the initial audit, the mean time interval between the onset of fever and the administration of antibacterial therapy was 75 min. With the modified protocol, the mean time to starting therapy was shortened to 32 min (P < 0.05). Changing the protocol for starting antibacterial therapy allowed nurses to administer the first dose of antibiotic significantly earlier.

Citrulline-based assessment score: first choice for measuring and monitoring intestinal failure after high-dose chemotherapy.

BACKGROUND: Currently, objective tests are lacking that enable the extent and duration of intestinal mucosal damage induced by myeloablative chemotherapy to be determined. To address this problem, we explored a citrulline-based assessment score as this amino acid is a simple quantitative marker of intestinal failure. PATIENTS AND METHODS: From March 2004 to June 2007, citrulline concentrations were determined at baseline and at least once weekly after the start of myeloablative chemotherapy until 30 days thereafter among 94 allogeneic or autologous haematopoietic stem-cell transplant recipients. The patients were divided into three groups according to the regimen they received: (i) carmustine, etoposide, cytarabine and melphalan/high-dose melphalan, (ii) cyclophosphamide and total body irradiation +/- antithymocyte globulin and (iii) idarubicin-containing regimens. Intestinal mucosal damage was described either by level of citrulline on each day, on the basis of different thresholds of citrulline indicating the severity of villous atrophy, or by area under the curve using reciprocal value of 10/citrulline. RESULTS: Regimens that incorporated idarubicin induced the most severe intestinal toxicity. Scores based on the level of citrulline, using severity thresholds, and on the area under the reciprocal curve are able to discriminate between the damage induced by different high-dose chemotherapy regimens. CONCLUSION: A citrulline-based assessment score appears objective, validated, reproducible, reliable, specific and sensitive making it a suitable first choice for measuring and monitoring intestinal mucositis.

Using routine blood parameters to anticipate clinical outcomes in invasive aspergillosis.

OBJECTIVE: In invasive aspergillosis (IA), monitoring response to antifungal treatment is challenging. We aimed to explore if routine blood parameters help to anticipate outcomes following IA. METHODS: Post hoc secondary analysis of two multicenter randomized trials was performed. The Global Comparative Aspergillosis Study (GCA, n = 123) and the Combination Antifungal Study (CAS, n = 251) constituted the discovery and validation cohorts respectively. The outcome measures were response to treatment and survival to 12 weeks. Interval platelet, galactomannan index (GMI) and C-reactive protein (CRP) levels prior and during antifungal treatment were analysed using logistic regression, Kaplan-Meier survival and receiver operating characteristic (ROC) analyses. RESULTS: The 12-week survival was 70.7% and 63.7% for the GCA and CAS cohorts respectively. In the GCA cohort, every 10 × 109/L platelet count increase at week 2 and 4 improved 12-week survival odds by 6-18% (odds ratio (OR) 1.06-1.18, 95% confidence interval (CI) 1.02-1.33). Survival odds also improved 13% with every 10 mg/dL CRP drop at week 1 and 2 (OR 0.87, 95% CI 0.78-0.97). In the CAS cohort, week 2 platelet count was also associated with 12-week survival with 10% improved odds for every 10 × 109/L platelet increase (OR, 1.10, 95% CI 1.04-1.15). A GMI drop of 0.1 unit was additionally found to increase the odds of treatment response by 3% at the baseline of week 0 (OR 0.97, 95% CI 0.95-0.99). Week 2 platelet and CRP levels performed better than GMI on ROC analyses for survival (area under ROC curve 0.76, 0.87 and 0.67 respectively). A baseline platelet count higher than 30 × 109/L clearly identified patients with >75% survival probability. CONCLUSIONS: Higher serial platelets were associated with overall survival while GMI trends were linked to IA treatment response. Routine and simple laboratory indices may aid follow-up of response in IA patients.

Loss of enterocyte mass is accompanied by diminished turnover of enterocytes after myeloablative therapy in haematopoietic stem-cell transplant recipients.

BACKGROUND: Intestinal mucosal barrier injury (MBI), resulting from myeloablative conditioning for haematopoietic stem-cell transplantation (HSCT), is an important cause of morbidity. Despite its frequency, recognition presents a challenge, while the aetiology needs still to be unravelled. The relationship between enterocyte mass and enterocyte loss was explored by examining citrulline serum levels and by assessing circulating intestinal fatty acid-binding protein (I-FABP) and ileal bile acid-binding protein (I-BABP), proteins released by dying mature enterocytes. PATIENTS AND METHODS: Thirty-four adult patients with haematological malignancy received allogeneic HSCT (HSCT day 0) 12 days after being given idarubicin, cyclophosphamide and total body irradiation as myeloablative conditioning, a regimen known to induce oral and intestinal MBI. Serum levels of citrulline, I-FABP and I-BABP were measured on HSCT days -12, -6, 0, +7, +14 and +21. RESULTS: Myeloablative conditioning resulted in a significant decrease in serum citrulline with the nadir on HSCT day +7; thereafter, levels rose gradually. Simultaneously, a significant decrease in I-FABP and I-BABP levels occurred from the day of transplant until day +14. CONCLUSIONS: Simultaneous reduction and subsequent increase of citrulline and I-FABP and I-BABP levels following cytotoxic treatment show that enterocyte mass corresponds to lower rate of dying enterocytes, indicating reduced turnover of enterocytes. Assessment of enterocyte turnover and mass offers opportunities for evaluation of new MBI therapies.

Bacteraemia coincides with low citrulline concentrations after high-dose melphalan in autologous HSCT recipients.

Mucosal damage to the intestines induced by myeloablative conditioning for allogeneic PBSC transplant (PBSCT) can be determined by the concentration of citrulline, which is a functional marker of small intestinal enterocytes. Low citrulline concentrations in blood coincide with and are a response to severe mucosal barrier injury. We treated 29 patients with high-dose melphalan 200 mg/m(2) (Mel-200) to prepare for an autologous PBSCT and collected plasma samples from each patient starting before the myeloablative regimen and three times per week thereafter until discharge. The baseline citrulline concentration was 27.6 mM+/-4.0 (mean+/-95% confidence interval; CI), and citrulline concentrations declined rapidly thereafter reaching a nadir averaging 6.7 mM+/-2.7, 12 days after starting Mel-200. Citrulline concentrations, only increased gradually and were still low (12 mM+/-4) at discharge. A total of 20 patients developed fever, which was associated with bacteraemia in 10 cases. Their mean citrulline concentrations were lower at 5.5 mM+/-1.5 than were those of patients without bacteraemia (10.2 mM+/-3.9). Importantly, neither the number of preceding neutropenic days nor the mean C-reactive protein (CRP) concentration at the onset of fever was different between these two groups. In conclusion, citrulline concentrations rapidly decline after Mel-200 reflecting intestinal mucosal barrier injury. Low citrulline, rather than the duration of neutropenia, is associated with bacteraemia indicating the importance of an intact mucosal barrier in neutropenic patients.

The potential role of lactoferrin and derivatives in the management of infectious and inflammatory complications of hematology patients receiving a hematopoietic stem cell transplantation.

Human lactoferrin is a natural defense protein belonging to the innate immune system present in several body fluids and secretions, as well as in the secondary granules of polymorphonuclear neutrophils. Lactoferrin and its derivatives have pleiotropic functions including broad-spectrum anti-microbial activity, anti-tumor activity, regulation of cell growth and differentiation, and modulation of inflammatory as well as humoral and cellular immune responses. This is the reason why much research has addressed the potential therapeutic activity of these molecules in different clinical settings, especially regarding infectious diseases and uncontrolled inflammatory conditions. In patients with hematological malignancies treated with a hematopoietic stem cell transplantation (HSCT), morbidity and mortality due to infections and uncontrolled inflammation remains high, despite many advances in supportive care. These life-threatening complications are a result of the damage caused by the conditioning regimens to the mucosal barrier, and the innate and adaptive, humoral, and cellular immune defenses. These complications necessitate the continued exploration of new treatment modalities. Systemic and probably local levels of lactoferrin are decreased following HSCT. Therefore, the use of lactoferrin, or short peptide derivatives that retain the cationic N-terminal moiety that is essential for the anti-microbial and anti-inflammatory activity, may prove to be a promising versatile class of agents for managing the complications that arise from HSCT.

[Invasive zygomycosis in patients treated for haematological malignancies]. / Invasieve zygomycose bij patiënten die worden behandeld voor een hematologische maligniteit.

A 52-year-old man underwent haematopoietic stem-cell transplant for myelodysplastic syndrome; after treatment with voriconazole for invasive aspergillosis, he was diagnosed with invasive zygomycosis caused by Rhizopus microsporus. He died despite treatment with intravenous liposomal amphotericin B and posaconazole. A 5-year-old boy with acute lymphatic leukaemia was diagnosed with invasive zygomycosis at autopsy. In a third case, a 16-year-old boy with acute myeloid leukaemia received repeated courses of empiric antifungal therapy, although the presence of an invasive fungal infection was not demonstrated. The patient died, and disseminated invasive zygomycosis caused by Rhizomucor pusillus was found at autopsy. Invasive infections by Zygomycetes are difficult to diagnose and are associated with a high mortality rate. The incidence of invasive zygomycosis appears to be increasing. Therefore, awareness of this type of invasive fungal infection is warranted. Lipid formulations ofamphotericin B remain the first choice for therapy.

Self-reported vs state-recorded motor vehicle collisions among older community dwelling individuals.

INTRODUCTION: Motor vehicle collisions (MVCs) continue to place an increased burden on both individuals and health care systems. Self-reported and state-recorded police reports are the most common methods for MVC evaluation in epidemiologic studies, with varying degrees of agreement of information when compared in previous studies. The objective of the current study is to address the differences in MVC reporting and provide a more robust measure of the agreement between self-reported and state-recorded MVCs in a community dwelling population of older adults. METHODS: A three-year prospective study was conducted in a population-based sample of 2000 licensed drivers aged 70 and older. At annual visits, participants were asked to self-report information on any MVC that occurred over the prior year where police were called to the scene. Information on police-reported MVCs was also ascertained from Alabama official state-recorded databases. The kappa coefficient was calculated to determine overall agreement between any self-reported and state-recorded crashes, as well as the raw number of crashes reported. In addition, agreement was stratified by demographics, health status, medication use, functional status (i.e. vision, cognition), and driving habits. RESULTS: 1747 participants who completed three years of follow up were involved in 225 state-recorded MVCs and 208 self-reported MVCs yielding overall substantial agreement between any self-report and state-recorded MVC (kappa=0.64). Cumulative number of self-reported and state-recorded MVCs was also compared, with agreement slightly reduced (kappa=0.55). The clinical characteristic resulting in the greatest variation in agreement with drivers was impaired contrast sensitivity showing better agreement between self-reported and state-recorded MVCs (kappa=0.9) than those with non-impaired contrast sensitivity (kappa=0.6). CONCLUSION: Study results showed substantial agreement between self-reported and state-recorded MVCs for any MVC involvement among the study population. When examining the reporting of the total number of MVCs over the three year period, agreement was reduced to a moderate level. There was consistency in agreement across MVC risk factors except among individuals with contrast sensitivity. These findings have implications for the design and analytic planning of epidemiologic and clinical research focused on MVCs.

Cyclosporine short infusion and C2 monitoring in haematopoietic stem cell transplant recipients.

Blood concentrations of cyclosporine A (CsA) >or=800 microg/l measured 2 h post-dosing, the C2 concentration, is necessary to obtain a maximal pharmacological effect and correlates well with transplant-related complications such as transplant rejection and toxicity. In an open crossover study CsA blood levels were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and 15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h infusion correlated better than C1 or C3 levels with the area under the concentration-time curve from 0 to 4 h (r2=0.62). C2 levels >or=800 microg/l were also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA without any increase of CsA-related toxicity but for only three of the 23 patients (13%) after continuous infusion. Therefore, we recommend CsA infusions in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2 levels >or=800 microg/l.

Prospective evaluation of gut mucosal barrier injury following various myeloablative regimens for haematopoietic stem cell transplant.

We determined gut mucosal barrier injury (MBI) among 129 recipients of an allogeneic or autologous haematopoietic stem cell transplant (HSCT) who had been given different myeloablative regimens by measuring integrity using the lactulose/rhamnose (RHA) ratio and absorption using the ratios of rhamnose/3-O-methylglucose and xylose/3-O-methylglucose. Regimens that did not contain idarubicin induced oral mucositis and disturbed gut integrity and absorption earlier than did those containing the anthracycline. By contrast, regimens containing idarubicin induced more severe and prolonged oral and gut MBI. Gut integrity and absorption of most patients were still abnormal at discharge from hospital. These results confirm that the integrity and absorptive capacity of the gut is affected adversely by myeloablative regimens in general, although only two patterns of mucosal injury emerged depending on whether or not idarubicin was used.