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Biomedical subjects

Jean-Pierre Marie

Publications and source records attributed to Jean-Pierre Marie.

At least 19 recordsLinked to original sources
PubMed2006

Flt3 internal tandem duplication and P-glycoprotein functionality in 171 patients with acute myeloid leukemia.

PURPOSE: Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification. EXPERIMENTAL DESIGN: We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they might lead to targeted therapy. We did a multivariate analysis on 171 patients with adult AML treated in the European Organization for Research and Treatment of Cancer protocols. RESULTS: ITD+ and high Pgp activity (Pgp+) were found in 26 of 171 (15%) and 55 of 171 (32%) of all patients, respectively. ITD and Pgp activities were negative in 94 of 171 (55%, Pgp-ITD- group), mutually exclusive in 73 of 171 (43%, Pgp-ITD+ and Pgp+ITD- groups), and only 4 of 171 (2%, Pgp+ITD+ group) patients were positive for both. In multivariate analyses, Pgp+ITD+ (P < 0.0001) and age (P = 0.0022) were independent prognostic factors for the achievement of complete remission (CR). Overall survival (OS), CR achievement (P < 0.0001), WHO performance status (P = 0.0007), and Pgp+ITD+ status (P = 0.0014) were also independent prognostic factors. In 95 patients with intermediate cytogenetics, the CR rates of ITD+ patients were 40% versus 62% for ITD- (P = 0.099) and 41% versus 67% (P = 0.014) for Pgp+ versus Pgp- patients. In the Pgp-ITD- group (41 of 95), CR rates were 70% versus 44% for others (P = 0.012), OS achieved 48% versus 16% (P < 0.0001) and disease-free survival was 56% versus 27% (P = 0.024), respectively. Furthermore, the OS curves of the intermediate cytogenetics-Pgp-ITD- group were not significantly different from the favorable cytogenetic group. CONCLUSION: Flt3/ITD and Pgp activity are independent and additive prognostic factors which provide a powerful risk classification that can be routinely used to stratify the treatment of patients with intermediate cytogenetic AML. ITD+ and Pgp+ patients should be considered for targeted therapy.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Prospective evaluation of a polymerase chain reaction-ELISA targeted to Aspergillus fumigatus and Aspergillus flavus for the early diagnosis of invasive aspergillosis in patients with hematological malignancies.

BACKGROUND: Current laboratory and radiological methods for diagnosis of invasive aspergillosis (IA) lack sensitivity and specificity. METHODS: We prospectively evaluated the diagnostic value of twice-weekly screening for circulating Aspergillus fumigatus and A. flavus DNA with a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA). RESULTS: Among the 201 adult patients with hematological malignancies who were included in the study, 55 IA cases were diagnosed. On the basis of the analysis of 1205 serum samples from 167 patients, the sensitivity, specificity, and positive and negative predictive values of the PCR-ELISA for proven and probable IA cases were 63.6%, 89.7%, 63.6%, and 89.7%, respectively, when samples with 2 consecutive positive results were used. The use of a combination of the PCR-ELISA and a galactomannan (GM) assay increased the sensitivity to 83.3%, increased the negative predictive value to 97.6%, and decreased the specificity to 69.8%. In most patients with IA, PCR-ELISA positivity anticipated or was simultaneous with the initiation of antifungal therapy, the abnormalities found by computed tomography, the mycological/histological diagnosis, and the GM positivity. Overall, 56.3% of the patients had at least 1 positive sample, and the false single-positive rate was 44.8%. CONCLUSIONS: In addition to serial screening for GM antigenemia and radiological surveillance, PCR-ELISA may improve the rates of early diagnosis of IA and the management of patients with hematological malignancies.

Aspergillosis↗
PubMed2006

JC-1, a sensitive probe for a simultaneous detection of P-glycoprotein activity and apoptosis in leukemic cells.

BACKGROUND: JC-1 probe has been successfully used for the analysis of either apoptosis or P-glycoprotein (P-gp) activity. Therefore, we wanted to see if JC-1 could also simultaneously assess both, P-gp activity and apoptosis, in acute myeloid leukemia (AML) cells. METHODS: P-gp activity was measured using JC-1 and compared to the results of the Rhodamine 123 (Rh 123) assay in P-gp negative and P-gp positive cell lines, and 12 AML samples. For apoptosis, spontaneous apoptosis, as well as, apoptosis induced by Cytosine Arabinosine and Homoharringtonine were analyzed. Both mitochondrial red fluorescence and cytoplasmic green fluorescence of JC-1 with and without a P-gp inhibitor (Cyclosporine A : CsA) were used for the identification of apoptotic cells, and this was compared to Annexin V/PI staining. RESULTS: (1) We found a good correlation between JC-1 and Rh 123 in viable cells. Even in a small population of viable cells, P-gp positive cells emitting low red fluorescence, gained on red fluorescence after P-gp inhibition with CsA permitting an evaluation of P-gp activity. (2) We found a good correlation between the Annexin V/PI staining and JC-1 (P < 0.0001) in the assessment of apoptotic cells. Most importantly, the apoptotic cells could be distinguished by the loss of red fluorescence and the increase of green fluorescence without any change after P-gp inhibition with CsA. CONCLUSIONS: JC-1 can simultaneously evaluate two important parameters involved in drug resistance in AML cells, P-gp activity and apoptosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Semisynthetic homoharringtonine induces apoptosis via inhibition of protein synthesis and triggers rapid myeloid cell leukemia-1 down-regulation in myeloid leukemia cells.

Semisynthetic homoharringtonine (ssHHT) is now being evaluated in phase II clinical trials for the treatment of chronic myelogenous leukemia and acute myelogenous leukemia patients. Here, we examined the mechanism of the apoptosis induced by ssHHT in myeloid leukemia cells. First, we have shown that ssHHT induces apoptosis in HL60 and HL60/MRP cell lines in a time- and dose-dependent manner, and independently of the expression of Bax. The decrease of mitochondrial membrane potential and the release of cytochrome c were observed in the apoptotic cells induced by ssHHT. To unveil the relationship between ssHHT and the mitochondrial disruption, we have shown that ssHHT decreased myeloid cell leukemia-1 (Mcl-1) expression and induced Bcl-2 cleavage in HL60 and HL60/MRP cell lines. The Bcl-2 cleavage could be inhibited by the Z-VAD.fmk caspase inhibitor. However, Mcl-1 turnover was very rapid and occurred before caspase activation. The Mcl-1 turnover was only induced by ssHHT and cycloheximide, but not by daunorubicin and cytosine arabinoside, and could be restored by proteasome inhibitors. Second, we confirmed that ssHHT rapidly induced massive apoptosis in acute myelogenous leukemia patient cells. We have also confirmed the release of cytochrome c and a rapid turnover of Mcl-1 in these patient cells, taking place only in apoptotic cells induced by ssHHT but not in cells undergoing spontaneous apoptosis. Finally, we have shown that ssHHT inhibits protein synthesis in both cell line and patient cells. We suggest that the inhibition of protein synthesis and resulting Mcl-1 turnover play a key role in the apoptosis induced by ssHHT. Our results encourage further clinical trials for the use of ssHHT in acute myelogenous leukemia.

Antineoplastic Agents, Phytogenic↗
PubMed2005

MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia.

PURPOSE: P-Glycoprotein (Pgp) is associated with poor outcome in acute myeloid leukemia (AML). We have investigated other ATP-binding cassette proteins such as BCRP, MRP1, MRP2, MRP3, and MRP5 for their potential implication in chemoresistance. EXPERIMENTAL DESIGN AND RESULTS: Eighty five AML patient samples were analyzed in this study. First, MRP3 function was higher in patients which had a high level of leukocytes (P = 0.01), a M5 FAB subtype (P = 0.04), and an intermediate or poor cytogenesis (P = 0.05). BCRP activity was not correlated with clinical or biological variables, but high Pgp activity was correlated with the following variables: CD34 expression (P = 0.002), FAB subtype (P = 0.002), intermediate or poor cytogenesis (P = 0.02), and elderly patients (P = 0.03). Second, Pgp, MRP3, and BCRP activities were correlated with complete remission (P = 0.02, P = 0.04, and P = 0.04, respectively), disease-free survival (P = 0.02, P = 0.03, and P = 0.25, respectively), and overall survival (P = 0.04, P = 0.04, and P = 0.05, respectively) in multivariate analysis. The patient samples expressing one or none of these Pgp, MRP3, or BCRP functional proteins have a better prognosis than the patients expressing two or three of these functional proteins (complete remission, P = 0.02; disease-free survival, P = 0.01; overall survival, P < 0.001). CONCLUSIONS: BCRP and MRP3 may also be involved in chemoresistance in AML, especially MRP3 in patients with M5 FAB. Additional modulation of BCRP or MRP3 to Pgp modulation may be necessary in some patients in order to improve the treatment outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Usefulness of PKH fluorescent labelling to study leukemic cell proliferation with various cytostatic drugs or acetyl tetrapeptide--AcSDKP.

BACKGROUND: PKH67 labelling was compared for classical proliferation assessment (using S phase evaluation) to analyse the cell proliferation of 29 AML patients treated or not with various drugs. Among these drugs, the effect of tetrapeptide AcSDKP or AcSDKP-NH2 on AML cells, stimulated or not by cytokines, was also evaluated in order to determine (i) if AcSDKP was able to inhibit blast cell proliferation as it inhibits haematopoietic progenitors (ii) if AcSDKP-NH2 was more stable than AcSDKP with FBS. METHODS: For PKH labeling, cells were suspended in Diluent C, and rapidly admixed with PKH67 solution at 20 microM PKH67. Staining was stopped by addition of FBS. RESULTS: A good correlation between PKH67 labelling and bromodeoxyuridine incorporation was obtained first with 6/9 patients for control cells, then for 11/17 AML patients treated with classical antileukemic drugs (among whom 4 were also treated with AcSDKP). The effect of AcSDKP was also studied on 7 patients. The discrepancy between both methods was essentially due to an accumulation of cells into different cycle phases measured by BrdUrd incorporation secondary to drug action and PKH67 labelling which measured the dynamic proliferation. This last method allows identifying resistant cells which still proliferate. AcSDKP or AcSDKP-NH2 induced a decrease of leukemic cell proliferation in 5/7 patients when cytokines were added (in order to stimulate proliferation) one day after tetrapeptide AcSDKP or AcSDKP-NH2. No effect on proliferation was noted when cytokines were added to AcSDKP-NH2. CONCLUSION: PKH67 labelling method is a powerful tool for cell proliferation assessment in patients with AML, even in cells treated by various drugs.

Amsacrine↗
PubMed2005

Major improvement of the reference method of the French drug resistance network for P-glycoprotein detection in human haematological malignancies.

The aim of this study was to improve significantly the sensitivity and specificity of the flow cytometric assay of P-glycoprotein (Pgp) implemented and validated by the laboratories of the French Drug Resistance Network [Huet S, Marie JP, Gualde N, Robert J. Reference method for detection of Pgp mediated multidrug resistance in human hematological malignancies: a method validated by the laboratories of the French Drug Resistance Network. Cytometry 1998;34:248-56] in cells displaying low level of resistance. Fluoresceine-conjugated monoclonal antibodies (Mabs) and propidium iodide were respectively replaced by phycoerythrin-conjugated Mabs and Sytox green. The removal of erythrocytes and granulocytes by density gradient was replaced by the lysis of erythrocytes after Mab incubation. Using these conditions, Pgp could be detected in the K-H30 line, which was negative in former studies, with Mab/Control ratios increasing by 3.7- to 5.9-fold, and Mab/Control ratios in the parental sensitive K562 line still ranging between 0.8 and 1.2. When tested on 16 blood samples from patients presenting haematological malignancies, six samples presented low positivity, which was not detected with the former method, while 10 samples remained negative with the two methods. Pgp was specifically detected in pathological blood cells in the six positive samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.

The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G-CSF; (B) G-CSF during chemotherapy; (C) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes; and (D) G-CSF during and after chemotherapy. The complete remission (CR) rate was 48.9% in group A, 52.2% in group B, 48.3% in group C, and 64.4% in group D. Analysis according to the 2 x 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy (58.3% for groups B + D vs 48.6% for groups A + C; P = .009), whereas no significant difference was observed between groups A + B and C + D (50.6% vs 56.4%, P = .12). In terms of overall survival, no significant differences were observed between the various groups. Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery (median, 20 vs 25 days; P < .001) and a shorter hospitalization (mean, 27.2 vs 29.7 days; P < .001). We conclude that although priming with G-CSF can improve the CR rate, the use of G-CSF during and/or after chemotherapy has no effect on the long-term outcome of AML in older patients.

Acute Disease↗
PubMed2005

Acute myeloid leukemia in the elderly: etoposide when anthracyclins are contraindicated.

We investigated whether etoposide might be a suitable alternative to anthracyclins for the treatment of elderly patients with acute myeloid leukemia (AML) in whom anthracyclins are contraindicated. In total, 88 patients over 60 years old were treated in our department between 1988 and 2000 for de novo or secondary AML. Of these 88 patients, 21 had severe cardiac disease and received a combination of etoposide and cytosine arabinoside (group A). They were compared with 23 patients who received daunorubicin plus cytosine arabinoside (group B) and 44 patients who received mitoxantrone, cytosine arabinoside and etoposide (group C). In group A, the complete remission (CR) rate was 33% (7/21), median disease-free survival (DFS) was 365 days and median overall survival (OS) was 214 days. These results were not statistically different from those for the anthracyclin-based regimens (CR 43%, DFS 210 days, OS 150 days for group B and CR 47%, DFS 216, OS 295 days for group C). Moreover, there was no significant difference in the number of treatment-related toxic events and deaths in the 3 treatment groups. Etoposide combined with a standard dose of cytosine arabinoside is relatively safe and effective in elderly patients with AML and offers an alternative approach to patients with cardiac contraindications to anthracyclin treatment.

Aged↗
PubMed2005

Prognosis of patients with acute myeloid leukaemia admitted to intensive care.

This retrospective study assessed the prognostic factors associated with early and long-term outcome in consecutive patients with acute myeloid leukaemia (AML) admitted to the intensive care unit (ICU) over a 9-year period. A total of 83 patients were studied (age 48 +/- 16 years), among whom 60% were neutropenic on admission. For 68%, admission occurred within the first month following diagnosis of AML. The main reason for ICU admission was an acute respiratory disease in 82% of cases. Mechanical ventilation (MV) was required in 57% of patients. In-ICU mortality was 34%. Among patients discharged alive from ICU, 49% died within a year after discharge. Factors significantly associated with in-ICU death in multivariate analysis were simplified acute physiology score II and need for invasive MV (IMV). Age, performance status, AML3 subtype and complete remission were significantly associated with 1-year survival. Patients with acute respiratory failure initially supported with non-invasive MV had significantly better ICU outcome than patients initially supported with IMV. In conclusion, ICU admission is justified for selected patients with AML. The ICU mortality rate is highly predictable by the acute illness severity score. A 1-year survival is predicted by haematological prognostic factors.

Acute Disease↗
PubMed2005

Reticulated platelets: a reliable measure to reduce prophylactic platelet transfusions after intensive chemotherapy.

BACKGROUND: Reticulated platelets (RPs) are the youngest circulating platelets (PLTs). The aim of our study was to predict PLT recovery with RP percentage (RP%) and therefore to identify PLT transfusions that could be avoided after autologous peripheral blood progenitor cell (PBPC) transplantation. STUDY DESIGN AND METHODS: With a whole-blood dual-labeling flow cytometric method, RP% was prospectively assessed in 47 patients who received myeloablative chemotherapy followed by autologous PBPC transplantation. Retrospective analysis of RP evolution identified three time points: nadir of the RP% (NRP), imminent PLT recovery (IPR) corresponding to an RP% of greater than 7 percent, and PLT transfusion autonomy (PTA). RESULTS: Median occurrences of NRP, IPR, and PTA were on Days +5, +8, and +12 after transplantation, respectively. The RP% value at NRP (4%) was significantly lower compared to the IPR (15%) and PTA (14%). Thirty patients (64%) achieved PTA within 4 days after IPR. On Day +8, if RP% was greater than 7 percent, positive and negative predictive values for PTA within 4 days, specificity, and sensitivity were 79, 63, 66, and 76 percent, respectively. Fever between IPR and PTA was the only factor found to negatively influence PLT recovery (p = 0.02). All patients required at least one PLT transfusion. Among patients with rapid PLT recovery (IPR-PTA interval < 4 days; n = 30), half of them received one PLT transfusion after RP increase, which could be avoided. CONCLUSION: These encouraging results may allow us to reduce the prophylactic PLT transfusion according to patients RP% increase.

Adult↗
PubMed2005

Bacteremia caused by an undescribed species of Janibacter.

A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides.

Actinomycetales↗
PubMed2004

Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias.

PURPOSE: Recently, a new ABC protein, breast cancer resistance protein (BCRP), was described. But its prognosis is not known in acute myeloid leukemia (AML). In addition, the prognosis of P-glycoprotein (Pgp) and BCRP in patients treated homogeneously by the same anthracycline (daunorubicin, idarubicin, or mitoxantrone) during all of the treatment with aracytine is not known. Therefore, we have evaluated the relationship between drug resistance phenotype, in vitro anthracene sensitivity, and the relation to treatment outcome. EXPERIMENTAL DESIGN: We have analyzed 149 AML treated according to protocol of the European Organization for Research and Treatment of Cancer group. The prognostic value of BCRP and Pgp were analyzed in the whole population and according to intercalating agent. RESULTS: BCRP was a prognostic factor, for achievement of complete remission (43% in positive patients and 69% in negative patients, P = 0.005), the 4-year disease-free survival (12% versus 33%, P = 0.03), and the 4-year overall survival (19% versus 38%, P = 0.003). When BCRP expression and Pgp function were categorized in three groups, +/+, +/- or -/+, and -/-, the achievement of complete remission was 45%, 66%, and 90% (P = 0.0003), the 4-year disease-free survival was 8%, 26%, and 40% (P = 0.01), and the 4-year overall survival was 16%, 37%, and 48% (P = 0.001), respectively. Pgp function was a prognostic factor in patients treated by daunorubicin and idarubicin but not by mitoxantrone. In contrast, BCRP expression was a prognostic factor in patients treated by daunorubicin and mitoxantrone but not by idarubicin. CONCLUSIONS: BCRP would be implicated in the resistance to chemotherapies in AML. But these are the patients expressing both BCRP and Pgp who have the poorest prognosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial.

In myelodysplastic syndromes (MDS), anemia responds to recombinant human erythropoietin (rHuEPO) alone and in combination with recombinant human granulocyte-colony-stimulating factor (rHuGCSF) in 10% to 20% and in 35% to 40% of patients, respectively. We randomly divided 60 patients with low-grade anemic MDS and serum EPO levels lower than 500 IU/L (500 mU/mL) into 2 groups: rHuEPO + rHuG-CSF (arm A) and supportive care (arm B). After 12 weeks, those who had erythroid responses were given rHuEPO alone for 40 additional weeks. They were also given rHuG-CSF if they had relapses. A response was considered major if the hemoglobin (Hb) level was 115 g/L (11.5 g/dL) or higher and minor Hb increase was 15 g/L (1.5 g/dL) or more or if it remained stable without transfusion. Ten of 24 patients responded in arm A, and 0 of 26 responded in arm B (P =.01). Eight patients in arm A continued rHuEPO therapy alone, and 6 had relapses. Responses were always restored when rHuG-CSF was reintroduced. Mean direct costs per patient were 26,723 euros (arm A) and 8,746 euros (arm B). Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Similar percentages of patients from both arms showed significant clinical improvement. rHuEPO plus rHuG-CSF led to responses in 41.7% of MDS patients. This treatment was expensive. No effect on quality of life was demonstrated.

Adult↗
PubMed2004

Evaluation and comparison of MRP1 activity with three fluorescent dyes and three modulators in leukemic cell lines.

MRP1 activity was evaluated and compared in 11 cell lines with different levels of MRP1 expression using functional assays of calcein acetoxymethyl ester (calcein-AM), carboxyfluorescein diacetate (CFDA) and Rhodamine 123 (Rh123) in combination with the modulators cyclosporin A (CsA), probenecid and MK571. A good correlation was found between MRP1 expression and the modulatory effect of MK571 on calcein-AM uptake (P = 0.01 and probenecid effect on CFDA uptake (P = 0.02). Additionally, the combined modulatory effect of MK571 and probenecid on CFDA uptake (P < 0.0001) and on calcein-AM uptake (P = 0.0001) were highly significant. No correlation was found between MRP1 expression and the effects of three modulators on Rh123 uptake or efflux. In conclusion, calcein-AM and CFDA uptake assays are the best choices to probe MRP1 activity and combination of two modulators may improve the efficiency of these assays.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Lethal pulmonary hemorrhage caused by a fulminant Stenotrophomonas maltophilia respiratory infection in an acute myeloid leukemia patient.

Stenotrophomonas maltophilia (Sm) pneumonia in immunocompromized hosts is an increasingly common nosocomial infection. Even though resistant to multiple antimicrobials, this gram-negative bacteria usually does not present with a fulminant course leading to a fatal hemorrhagic respiratory infection in neutropenic patients. We report here the case of a 63-year-old woman treated by intensive chemotherapy for acute myeloid leukemia (AML) who presented while severely neutropenic and thrombocytopenic a Sm pulmonary infection with hemoptysis leading to death in 48 h. The bronchoalveolar lavage (BAL) performed shortly before death was highly hemorrhagic and contained a striking amount of extra- and intra-cellular pathogens. Blood and BAL cultures grew S. maltophilia. Post-mortem examination revealed bilateral extensive intra-alveolar hemorrhage (IAH) associated with a great amount of microorganisms and severe bone marrow aplasia was observed without evidence of leukemia residual disease. Sm pneumonia usually does not evolve into such a devastating clinical picture although infections due to the bacteria are known to be associated with high morbidity and mortality. So far, the present observation is the fourth similar case reported in the literature. Even though an early diagnosis and an adequate antibiotic prescription may improve Sm infection prognosis, S. maltophilia proves difficult to eradicate due to a high resistance rate in part intrinsic but also in part acquired.

Acute Disease↗
PubMed2004

Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B.

We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.

Adolescent↗