SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

A unique schedule of palonosetron, ondansetron, and dexamethasone for the prevention of delayed nausea and vomiting in patients receiving myeloablative chemotherapy.

Myeloablative chemotherapy administered prior to autologous stem cell transplantation (auto-SCT) is associated with a significant amount of chemotherapy-induced nausea and vomiting (CINV). We conducted a phase II trial to assess the safety, efficacy, and impact on quality of life when palonosetron (PAL) 0.25 mg combined with dexamethasone were given on the final or only day of myeloablative chemotherapy for auto-SCT. The primary end point of this study was the incidence of achieving a delayed CINV complete response defined as no emetic episode and no use of rescue medications during the 24-120 h period post chemotherapy. Eighty-five patients were enrolled in the study and received PAL. A delayed CINV complete response was achieved in 15% of patients. A multivariate analysis demonstrated no associated differences between age, gender, diagnosis, or regimen. By day 5 after PAL, the mean nausea severity was 0.91 ± 2.45 vs. 0.09 ± 1.58 at baseline (p = 0.012). Quality of life measurements demonstrated similar quality of life between baseline and day 3. By day 6 however, nausea alone had a statistically significant impact on quality of life. In our study, PAL controlled nausea severity and sustained quality of life, but further strategies are needed to control delayed CINV associated with the auto-SCT process.

[Free flaps use in chronic wounds: Retrospective study about 91 cases]. / Utilisation des lambeaux libres dans la prise en charge des plaies chroniques.

INTRODUCTION: Chronic wounds represent a major health challenge with no current standardized surgical treatment. The use of free flaps is little discussed in the literature, with a supposed propensity to failure given unfavorable local conditions and land often debility. We present here the analysis of our monocentric experience of the use of free flaps in the curative treatment of chronic wounds. PATIENTS ET METHODS: We performed a retrospective monocentric study over 18 years of all free flaps used for the treatment of a chronic wound between January 2001 and September 2016. Several criteria were evaluated on patients, wounds, free flaps used and immediate to late outcomes. RESULTS: Ninety-one patients were included (sex ratio M/F: 3.55) with an average age of 41.6±16 years. Wounds were localized to the leg in 92.3% of cases and 58% of patients had initial osteomyelitis. The flaps used were predominantly muscle flaps (61.6%). The flaps survival rate was 92.3%. With a mean follow-up of 50 months, the reconstructive failure rate was 20.9%. The presence of a chronic osteomyelitis is the only statistically significant factor of reconstruction failure (P=0.0169) with a risk of failure multiplied by 5. CONCLUSION: Our study demonstrates that the reliability of free flaps in the treatment of chronic wounds is comparable, regardless of the time since the initial cutaneous lesion, to that existing in the treatment of acute wounds or in the reconstruction after oncological excision. The presence of a chronic osteomyelitis, however, represents a major risk of reconstruction failure by increasing 5 times the risk of failure. Recent changes in the integumentary reconstruction paradigm of the lower limb will undoubtedly allow in the next few years to establish more rationally the place of muscle free flaps in the therapeutic armamentarium of chronic wounds.

Surgical treatment of trans-sphincteric anal fistulas with the Fat GRAFT technique: a minimally invasive procedure.

AIM: Anal fistulas are common pathologies with a significant social impact; however, their treatment is often complex and the recurrence rate can be significant. Some surgical treatments for fistula are also associated with the risk of sphincter injury. In this technical note, we aim to evaluate the feasibility and efficacy of the Fat GRAFT technique (Fat Grafting in Anal Fistula Treatment) in the treatment of recurrent anal fistulas. METHOD: All patients presenting with recurrent trans-sphincteric anal fistulas over an 18-month period were included. After abdominal fat harvesting and fat preparation, fat grafting was performed in the track and peripheral area of the fistula. The internal and external openings of the fistula were closed to maximally preserve the retention of the adipocyte graft in the fistula. RESULTS: Eleven patients underwent the Fat GRAFT procedure (seven men, four women). The average re-injected volume for each fistula was 21 ml (range 10-30 ml). The postoperative course was uneventful. At 6 months three patients developed recurrence (73% healed). There were no postoperative complications. CONCLUSION: The Fat GRAFT technique appears to be a promising technique with a low risk of anal incontinence, in contrast to other techniques. This method was effective in > 70% of patients in a single session.

Clinical massively parallel sequencing for the diagnosis of myopathies.

Massively parallel sequencing, otherwise known as high-throughput or next-generation sequencing, is rapidly gaining wide use in clinical practice due to possibility of simultaneous exploration of multiple genomic regions. More than 300 genes have been implicated in neuromuscular disorders, meaning that many genes need to be considered in a differential diagnosis for a patient affected with myopathy. By providing sequencing information for numerous genes at the same time, massively parallel sequencing greatly accelerates the diagnostic processes of myopathies compared to the classical "gene-after-gene" approach by Sanger sequencing. In this review, we describe multiple advantages of this powerful sequencing method for applications in myopathy diagnosis. We also outline recent studies that used this approach to discover new myopathy-causing genes and to diagnose cohorts of patients with muscular disorders. Finally, we highlight the key aspects and limitations of massively parallel sequencing that a neurologist considering this test needs to know in order to interpret the results of the test and to deal with other issues concerning the test.

A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast.

X-linked recessive myotubular myopathy (MTM1) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. We have restricted the candidate region to 280 kb and characterized two candidate genes using positional cloning strategies. The presence of frameshift or missense mutations (of which two are new mutations) in seven patients proved that one of these genes is indeed implicated in MTM1. The protein encoded by the MTM1 gene is highly conserved in yeast, which is surprising for a muscle specific disease. The protein contains the consensus sequence for the active site of tyrosine phosphatases, a wide class of proteins involved in signal transduction. At least three other genes, one located within 100 kb distal from the MTM1 gene, encode proteins with very high sequence similarities and define, together with the MTM1 gene, a new family of putative tyrosine phosphatases in man.

Adult centronuclear myopathies: A hospital-based study.

INTRODUCTION: Centronuclear myopathies (CNM) are rare inherited disorders characterized by nuclei placed in rows in the central part of the muscle fibres. Three CNM-causing genes have been identified, with MTM1 mutations provoking X-linked myotubular myopathy, DNM2 mutations provoking autosomal dominant (AD) CNM, and BIN1 mutations provoking autosomal recessive (AR) CNM. METHODS: In this retrospective monocentric study, we describe 14 adult patients (age>18 years) diagnosed with CNM in our hospital in the 2000-2012 interval. Twelve patients originated from four families, and two patients presented with sporadic CNM. All patients underwent standardized clinical examinations, biological tests, electrophysiological studies, muscle biopsy, and molecular testing. RESULTS: Seven patients developed CNM before age 15, and seven after age 25. All patients presented with distal upper and lower limbs weakness, and normal CK levels. Disease severity remained mild, with all patients being able to walk without assistance even after decades-long disease duration. Cognitive impairment was found in seven cases, axonal polyneuropathy in six cases and ophthalmoparesis and ptosis in five cases. DNM2 gene mutations were found in eight patients, whereas BIN1 and MTM1 mutations were not observed. Overall, no molecular diagnosis was available for six patients. CONCLUSION: Adult CNM is a slowly progressive distal myopathy with normal CK levels sometimes associated with cognitive impairment, axonal polyneuropathy, and ophthalmoparesis and ptosis. DNM2 mutations were found in eight patients, including AD and sporadic cases, and represent the major cause of CNM in this adult cohort. In contrast, no MTM1 and BIN1 mutations were observed in our series, leaving six patients with no molecular diagnosis. As these six patients presented with AD (3 cases), AR (2 cases), and sporadic (1 case) CNM, it is likely that several CNM-causing genes remain to be discovered.

Exposure to medicines among patients admitted for hip fracture and the case-fatality rate at 1 year: a longitudinal study.

PURPOSE: To describe the demographic and clinical characteristics and the pre-fracture exposure to medicines of patients admitted for a hip fracture, and to explore their association with fatal outcome 1 year after the fracture. METHODS: All patients ≥ 65 years old admitted for a hip fracture in a tertiary hospital in Barcelona between January 1 and December 31 2007 were included. Data on the patients' clinical characteristics before and during hospital admission and on pre-fracture exposures to medicines were collected from the clinical records. One-year mortality was checked by approaching the patients and their families and was cross-checked with the national mortality statistics database. A Cox proportional hazards analysis was carried out. RESULTS: Four hundred and fifty-six patients [mean age (SD) 82.9 (7.2) years, 73.5 % female], were admitted with hip fracture during the study period. Almost 80 % of the patients (363, 79.6 %) had three or more associated conditions, and 41.7 % received pre-fracture treatment with five or more drugs. The case-fatality rate during hospital admission was 4.6 % (21 patients). One hundred and seven patients died within 1 year (23.5 %). Advanced age, male gender, two or more associated chronic conditions, cancer, severe cognitive impairment, and treatment with opiates before fracture were significantly associated with the risk of dying. An inverse association was recorded between mortality and pre-hospital exposure to medicines for osteoporosis. CONCLUSIONS: One-quarter of patients admitted for hip fracture died within 1 year after the fracture. Exposure to opiates before hip fracture was associated with an increased 1-year death rate, whereas treatment with drugs for osteoporosis was associated with a decrease in death rate. These results should be confirmed in studies with detailed prospective collection of information on exposure to medicines.

Production performance, stress tolerance and intestinal integrity of sunshine bass fed increasing levels of soybean meal.

Soybean meal (SBM) is perhaps the most common fish meal (FM) alternative used in aquafeeds; however, SBM cannot fully replace FM in sunshine bass Morone chrysops × M. saxatilis feeds without impacting growth. Reduced production performance may be the result of subtle changes in morphology and/or physiological status. Accordingly, our objective was to assess growth, gastrointestinal integrity and stress tolerance of sunshine bass fed increasing amounts of SBM. Fish (approximately 14.5 g) were fed diets (14% lipid and 40% protein) containing increasing amounts of SBM at the expense of FM (30% FM, 20% FM, 15% FM, 10% FM, 5% FM and 0% FM) for 8 weeks. As expected, complete replacement of FM reduced growth. Although some signs of enteritis were noted, no significant differences in gut integrity were observed. Following 15-min low-water stress challenge, plasma glucose levels were elevated, particularly among fish fed increasing amounts of SBM. Cortisol response was similar, but statistical differences were not resolved for this parameter. Completely replacing FM in feeds for sunshine bass elicits overt reductions in growth. More subtle physiological changes may also result from FM replacement, including alterations in stress tolerance, and these may be important to consider in terms of the suitability of aquafeed formulations and optimal nutrition of sunshine bass.

Nuclear localization of aspartate transcabamoylase in Saccharomyces cerevisiae.

The cytochemical technique using the in situ precipitation of orthophosphate ions liberated specifically by the aspartate carbamoyltransferase (ATCase) (EC 2.1.3.2) reaction indicated that in Saccharomyces cerevisiae this enzyme is confined to the nucleus. This observation is in accordance with the result reported by Bernhardt and Davis (1972), Proc. Natl. Acad. Sci. U. S. A. 69:1868-1872) on Neurospora crassa. The nuclear compartmentation was also observed in a mutant strain lacking proteinase B activity. This finding indicates that this proteinase is not involved in the nuclear accumulation of ATCase, and that the activity observed in the nucleus corresponds to the multifunctional form associated with the uracil path-specific carbamoylphosphate synthetase and sensitive to feedback inhibition by UTP. In a ura2 strain transformed by nonintegrated pFL1 plasmids bearing the URA2-ATCase activity encoding gene, the lead phosphate precipitate was observed predominantly in the cytoplasm. This finding enhances the reliability of the technique used by eliminating the possibility of an artifactual displacement of an originally cytoplasmic reaction product during the preparation of the material for electron microscopy. On the other hand, nuclei isolated under hypoosmotic conditions do not exhibit the ATCase activity that is recovered in the cytosolic fractions after differential centrifugation of the lysate in Percoll gradient. A release of the protein from the nuclei during the lysis step, consistent with its nucleoplasmic localization, is postulated.

Update on the management of febrile neutropenia in hematologic patients.

Febrile neutropenia is a common complication in patients with hematologic malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrug-resistant bacteria represent a therapeutic challenge in this high-risk patient population, since inadequate initial empirical antibiotic treatment can seriously compromise prognosis. Besides, reducing antimicrobial exposure is a cornerstone in the fight against resistance.

Use of granulocyte colony-stimulating factor (G-CSF) and outcome in patients with non-chemotherapy agranulocytosis.

PURPOSE: The use of granulocyte colony-stimulating factor (G-CSF) in the treatment of non-chemotherapy drug- induced agranulocytosis is controversial. We aimed at assessing the effect of G-CSF on the duration of agranulocytosis. METHODS: To assess the effect of G-CSF on the duration of agranulocytosis, a Cox proportional hazard model with an estimated propensity score covariate adjusting for several prognostic factors was used. RESULTS: One hundred and forty-five episodes of agranulocytosis were prospectively collected from January 1994 to December 2000 in Barcelona (Spain). No differences were found in the case-fatality rate between treated (9 of 101, 8.9%) and not treated (5 of 44, 11.4%) patients. The median time to reach a neutrophil count > or =1.0 x 10(9)/L was 5 days (95%CI 5-6) in patients treated with G-CSF compared to 7 days (95%CI 6-8) in those not treated, with a hazard ratio of 1.58 (95% CI 1.1-2.3). CONCLUSIONS: G-CSF shortens time to recovery in patients with agranulocytosis. However, as an effect on case-fatality has not been recorded, and data on cost-effectiveness are lacking, it would be wise to restrict its use to high-risk patients.

[Impact on renal function of an early switch from conventional to liposomal amphotericin B formulation in the empirical treatment of fungal infections]. / Impact sur la fonction rénale d'un relais précoce de la formulation conventionnelle de l'amphotéricine B par sa formulation liposomale dans le cadre d'un traitement empirique antifongique (Etude Nephemat).

OBJECTIVE: The authors had for aim to define the threshold of nephrotoxicity before switching to other antifungal treatment in hematological patients treated by conventional amphotericin B (AmB) as an empiric antifungal treatment. DESIGN: A prospective randomised multicenter study was made on 32 neutropenic hematological patients receiving conventional AmB for empirical antifungal treatment. The patients were randomised after a greater than or equal to 30% increase of serum creatinine (sCr). Patients in the early-switch group received liposomal AmB just after randomisation and patients in the late-switch group received liposomal AmB only when serum creatinine increase was greater or equal to 100% or sCr reached 170mumol/L. RESULTS: Thirty-one patients were analysed: 16 patients in the early-switch group and 15 patients in the late-switch group (seven switched to liposomal AmB and eight continued conventional AmB treatment). The mean age of patients was 48 years and 68% were men. The most frequent underlying haematological malignancy was acute leukemia (94%). In the late-switch group, the degradation of renal function continued after randomisation contrary to the early-switch group: median variations of calculated sCr clearance in early- and late-switch groups were -16.8 and -1.5%, respectively (P=0.03). Moreover, an early switch was cost-effective with a sCr lower duration of hospitalisation in comparison with a late switch. CONCLUSIONS: This randomised trial suggests that an early switch to Liposomal AmB improves and preserves renal function in comparison with a late switch.

The myotubularin family: from genetic disease to phosphoinositide metabolism.

The myotubularin-related genes define a large family of eukaryotic proteins, most of them initially characterized by the presence of a ten-amino acid consensus sequence related to the active sites of tyrosine phosphatases, dual-specificity protein phosphatases and the lipid phosphatase PTEN. Myotubularin (hMTM1), the founder member, is mutated in myotubular myopathy, and a close homolog (hMTMR2) was recently found mutated in a recessive form of Charcot-Marie-Tooth neuropathy. Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking.

Risk of acute liver injury associated with the use of drugs: a multicentre population survey.

BACKGROUND: Acute liver injury of uncertain aetiology is often drug related and quantitative information about the associated risk is scarce. AIM: To estimate the risk of acute liver injury associated with the use of drugs. METHODS: In a population survey study, 126 cases of acute liver injury were prospectively assembled from January 1993 to December 1999, in patients over 15 years of age, in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each drug as the ratio between the incidence of acute liver injury among the exposed population to the drug and the incidence of acute liver injury among those not exposed to it. Drug consumption data were used to estimate the exposed population. RESULTS: Isoniazid, pyrazinamide, rifampicin, amoxicillin with clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine presented the highest risk (point relative risk > 25). Amoxicillin, metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide, fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk < 5). CONCLUSIONS: This study provides a risk estimation of serious liver disease for various drugs that will be useful in its diagnosis and management, and when comparing with the drug therapeutic benefit in each indication. Some observed associations would be worth specific studies.

Characteristics, aetiology, antimicrobial resistance and outcomes of bacteraemic cholangitis in patients with solid tumours: A prospective cohort study.

OBJECTIVES: To asses the clinical features, aetiology, antimicrobial resistance and outcomes of bacteraemic cholangitis in patients with solid tumours (ST). METHODS: All consecutive episodes of bacteraemia in hospitalized patients were prospectively analysed (2006-2015). RESULTS: Of 1852 episodes of bacteraemia, 750 involved patients with ST. Among them, 173 episodes (23%) were due to cholangitis. The most frequent neoplasms were hepato-biliary-pancreatic tumours (68.2%) and gastrointestinal cancer (18.5%); 57.2% of patients had a biliary stent in place. The most frequent causative agents were Escherichia coli (39.3%) followed by Klebsiella pneumoniae (15.1%) and Enterococcus faecium (7.8%). Forty-one episodes (18.7%) were caused by multidrug-resistant (MDR) microorganisms. Patients with a second episode of cholangitis were more likely to have an MDR isolate and to had received inadequate empirical antibiotic therapy. 7-day and 30-day case-fatality rates were 7.6% and 26%, respectively. The only risk factors independently associated with 30-day case-fatality rate were corticosteroids and malignancy-related complications. CONCLUSIONS: Bacteraemic cholangitis is frequent in patients with ST, and is mainly caused by Enterobacteriaceae and E. faecium. The emergence of MDR is of special concern, particularly in patients with a second episode of bacteraemia. Case-fatality rates are high, especially among patients receiving corticosteroids and presenting malignancy-related complications.

Upper gastrointestinal bleeding associated with antiplatelet drugs.

BACKGROUND: The risk of major upper gastrointestinal bleeding associated with various antiplatelet drugs and the protection conferred by gastroprotective agents are not well defined. AIM: To estimate the risk of upper gastrointestinal bleeding associated with the use of antiplatelet drugs and its prevention by gastroprotective agents. METHODS: In a case-control study, we compared all cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients over 18 years of age (2813 cases), with 7193 matched controls. Odds ratios of upper gastrointestinal bleeding for individual antiplatelet drugs with adjustment for potential confounders were estimated. RESULTS: The individual risks of upper gastrointestinal bleeding were cardiovascular acetylsalicylic acid 4.0 (3.2-4.9), clopidogrel 2.3 (0.9-6.0), dipyridamole 0.9 (0.4-2.0), indobufen 3.8 (1.2-12.2), ticlopidine 3.1 (1.8-5.1) and triflusal 1.6 (0.9-2.7). Concomitant proton pump inhibitors decreased all risk estimates. For acetylsalicylic acid plus a proton pump inhibitor, the odds ratio was 1.1 (0.5-2.6). As a group, antiplatelet drugs accounted for 14.5% of all cases of upper gastrointestinal bleeding, i.e. 58 per million per year (334 per million per year among those older than 70 years). CONCLUSIONS: The risk of upper gastrointestinal bleeding is substantially decreased by the concomitant use of proton pump inhibitors. The risk of acetylsalicylic acid plus a proton pump inhibitor seems lower than that of ticlopidine or clopidogrel.

Evidence for absence of toxicity of T101 immunotoxin on human hematopoietic progenitor cells prior to bone marrow transplantation.

T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show that conditions previously defined to produce high tumor cell killing, i.e., a 20-hr incubation at 37 degrees in the presence of T101-ricin A-chain immunotoxin up to 10(-7) M in a 10 mM ammonium chloride solution, do not affect the in vitro proliferative capacity of human hematopoietic stem cells studied by means of semisolid medium cultures (granulocyte-macrophage progenitors, burst-forming units-erythrocyte) and continuous liquid cultures (pre-granulocyte-macrophage progenitors). Therefore, autologous bone marrow transplantation with T101-ricin A-chain immunotoxin-treated graft should be feasible.

The role of autologous bone marrow transplantation in 46 adult patients with non-Hodgkin's lymphomas.

Forty-six patients with non-Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation (ABMT) in two different institutions. All patients were pretreated with conventional chemotherapy. Three different conditioning regimens were used, and 20 patients underwent bone marrow purging. Twelve patients were treated in first complete remission (CR); eight are in unmaintained CR 8 to 104 months after ABMT. Five patients were grafted in first partial remission (PR) after conventional therapy; all achieved CR, and all remain in prolonged CR (first CR for four patients, second CR for one patient). Of 21 patients with chemosensitive relapses, 13 patients are in prolonged unmaintained CR 8 to 94 months after ABMT. Eight patients with resistant disease remained uncured by ABMT; all eight died, six from progressive illness and two from toxicity. The current 3-year disease-free probability is 60% for all patients, 0% for refractory disease; 82% for first PR or CR, and 60% for sensitive relapses (SRs). These results confirm the efficacy of ABMT in the treatment of chemosensitive NHL with bad prognosis.

Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma.

PURPOSE: To evaluate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo on the durations of intravenous (IV) antibiotic use, hospitalization, neutropenia, and fever, as well as remission rates, after high-dose melphalan (HDM) without stem-cell transplantation (SCT) in patients with multiple myeloma (MM). PATIENTS AND METHODS: One hundred two patients with high-risk MM were randomized 2:1 in a prospective multicenter trial to receive 5 microg/kg/d GM-CSF (69 patients) or placebo (33 patients) starting the day after 140 mg/m2 IV melphalan for up to 21 days. RESULTS: GM-CSF significantly reduced neutropenia after HDM (median, 23.5 v 29 days; P = .0468), with a trend to reduce the duration of hospitalization (median, 32 v 38 days; P = .0841). Nevertheless, GM-CSF did not significantly reduce infectious toxicity as regards the number of days with fever (median, 5 v 3; P = .359), the number of days with IV antibiotics (median, 22 v 27; P = .14), or early deaths, with an 11.5% treatment-related mortality rate in the GM-CSF group (eight of 69 v two of 32 patients in the placebo group; P = .686). There was no difference in response rates between the two groups of patients. CONCLUSION: GM-CSF after HDM without SCT is feasible and significantly shortens neutropenia with a trend toward reduction of hospitalization duration, but does not significantly reduce the morbidity and mortality of such therapy. Thus, when intensive therapy is indicated, given that the mortality of HDM followed by SCT reported in the literature is less than 5% and patients are discharged at approximately day 15, despite the risk of contamination by clonogenic malignant cells, SCT appears to be preferable to GM-CSF after HDM.