PubMed Health⌕ Search

Biomedical subjects

A M Alvarez

Publications and source records attributed to A M Alvarez.

At least 19 recordsLinked to original sources
PubMed2002

Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia.

A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of </=50,000 platelets/mm(3), and recent receipt of chemotherapy [16]. Children were uniformly evaluated at enrollment and were classified as having high or low risk for IBI according to a model that considers the number and type of variables present. Of the 263 febrile episodes evaluated during a 17-month period, 140 (53%) were in IBI-positive children. The sensitivity, specificity, and positive and negative predictive values of the model were 92%, 76%, 82%, and 90%, respectively. Identification of these 5 risk factors during the first 24 h of hospitalization was helpful in discriminating between children with a high or low risk for IBI.

Adolescent↗
PubMed2002

Induction of apoptosis by nitric oxide in macrophages is independent of apoptotic volume decrease.

Apoptosis occurs through a sequence of specific biochemical and morphological alterations that define the progress of cell death. The changes of the mitochondrial inner membrane potential (DeltaPsi(m)), the release of cytochrome c to the cytosol, the apoptotic volume decrease (AVD) and the activation of caspases have been measured in RAW 264.7, HeLa and Jurkat T cells incubated with molecules that induce apoptosis through the mitochondrial pathway. Our data show that NO, staurosporine, etoposide and camptothecin increased DeltaPsi(m) in macrophages but not in HeLa and Jurkat cells, that exhibited a DeltaPsi(m) decrease. Moreover, the apoptosis induced by NO in macrophages, but not that promoted by staurosporine, might occur in the absence of AVD. Analysis of the sequence of apoptotic manifestations shows that DeltaPsi(m) precedes AVD and caspase activation in RAW 264.7 cells. Inhibition of AVD abrogates apoptosis in HeLa and Jurkat T cells regardless of the stimuli used. These data suggest that the changes of DeltaPsi(m) are cell-type dependent and that AVD is dispensable for apoptosis in macrophages.

Apoptosis↗
PubMed2001

Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever.

PURPOSE: To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION: In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.

Adolescent↗
PubMed2001

Lovastatin induces apoptosis of spontaneously immortalized rat brain neuroblasts: involvement of nonsterol isoprenoid biosynthesis inhibition.

We have examined the effects of lovastatin and pravastatin (competitive HMG-CoA reductase inhibitors) on the growth and survival of rat brain neuroblasts. Lovastatin, but not pravastatin, suppressed cell growth by inducing apoptosis of neuroblasts in a dose- and time-dependent manner. Apoptosis was accompanied by a decrease in both Bcl-2 and Bcl-xL protein levels, suggesting that changes in the expression of these genes may contribute to apoptosis following lovastatin treatment. Lovastatin treatment was also associated with decreased prenylation of both Ras and Rho A proteins whereas Rac 1 geranylgeranylation was not affected. Lovastatin effects were fully prevented by mevalonate. The present data suggest that lovastatin induces apoptosis of rat brain neuroblasts by its capacity to decrease the prenylation of specific proteins involved in signal transduction pathways that control growth and survival of neuronal cells.

Animals↗
PubMed2001

Mitochondrial involvement in cocaine-treated rat hepatocytes: effect of N-acetylcysteine and deferoxamine.

The cytotoxicity of cocaine (0 - 1000 microM), was studied on parameters related to the mitochondrial role and the cascade of events that lead to apoptosis in hepatocyte cultures from phenobarbitone (PB) pretreated rats. Cytotoxicity was dose-dependent and LDH leakage was significantly enhanced above 100 microM cocaine. Apoptosis was visualized by DNA fragmentation on agarose gel, and appeared at 50 and 100 microM cocaine. Cocaine induced biphasic changes in mitochondrial transmembrane potential and significantly increased the mitochondrial release of cytochrome c, the caspase-3 like DEVDase activity and the level of 20 kDa subunit, a product of pro-caspase-3 cleavage. The protective effect of N-acetylcysteine (NAC) and deferoxamine (DFO) on all these parameters confirmed the involvement of oxygen radicals in cocaine-induced necrosis/apoptosis. We conclude: first, that the biphasic changes recorded in mitochondrial inner membrane potential by the effect of cocaine, were parallel to apoptosis; second, that caspase-3 activity and cleavage to it p20 subunit increased sharply in parallel to the translocation of cytochrome c from mitochondria to cytosol; and third, that the antioxidants, NAC or DFO exerted a noticeable protective role in counteracting the cytotoxicity of cocaine, these effects being more pronounced in the case of DFO than NAC. These findings demonstrate that cocaine cytotoxicity involves mitochondrial damage.

Acetylcysteine↗
PubMed2001

Intracellular water motion decreases in apoptotic macrophages after caspase activation.

Triggering of the macrophage cell line RAW 264.7 with lipopolysaccharide and interferon-gamma promoted apoptosis that was prevented by inhibitors of type 2 nitric oxide synthase or caspase. Using (1)H NMR analysis, we have investigated the changes of the intracellular transverse relaxation time (T(2)) and apparent diffusion coefficient (ADC) as parameters reflecting the rotational and translational motions of water in apoptotic macrophages. T(2) values decreased significantly from 287 to 182 ms in cells treated for 18 h with NO-donors. These changes of T(2) were prevented by caspase inhibitors and were not due to mitochondrial depolarization or microtubule depolymerization. The decrease of the intracellular values of T(2) and ADC in apoptotic macrophages was observed after caspase activation, but preceded phosphatidylserine exposure and nucleosomal DNA cleavage. The changes of water motion were accompanied by an enhancement of the hydrophobic properties of the intracellular milieu, as detected by fluorescent probes. These results indicate the occurrence of an alteration in the physicochemical properties of intracellular water during the course of apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by transforming growth factor beta in rat fetal hepatocytes.

Most of the morphologic changes that are observed in apoptotic cells are caused by a set of cysteine proteases (caspases) that are activated during this process. In previous works from our group we found that treatment of rat fetal hepatocytes with transforming growth factor beta1 (TGF-beta1) is followed by apoptotic cell death. TGF-beta1 mediates radical oxygen species (ROS) production that precedes bcl-xL down-regulation, loss of mitochondrial transmembrane potential, release of cytochrome c, and activation of caspase-3 (Herrera et al., FASEB J 2001;15:741-751). In this work, we have analyzed how TGF-beta1 activates the caspase cascade and whether or not caspase activation precedes the oxidative stress induced by this factor. Our results show that TGF-beta1 activates at least caspase-3, -8, and -9 in rat fetal hepatocytes, which are not required for ROS production, glutathione depletion, bcl-xL down-regulation, and initial cytochrome c release. However, caspase activation mediates cleavage of Bid and Bcl-xL that could originate an amplification loop on the mitochondrial events. An interesting result is that transmembrane potential disruption occurs later than the initial cytochrome c release and is mostly blocked by the pan-caspase inhibitor Z-VAD.fmk, indicating that the decrease in mitochondrial transmembrane potential (Delta(Psi)m) may be a consequence of caspase activity rather than the mechanism by which TGF-beta induces cytochrome c efflux. Finally, although Z-VAD.fmk completely blocks nucleosomal DNA fragmentation, it only delays cell death, which suggests that activation of the apoptotic program by TGF-beta in fetal hepatocytes inevitably leads to death, with or without caspases.

Animals↗
PubMed2001

Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (beta) in fetal hepatocytes.

Treatment of fetal rat hepatocytes with transforming growth factor beta (TGF-beta) is followed by apoptotic cell death. Analysis of radical oxygen species (ROS) content and mitochondrial transmembrane potential (Deltapsim), using specific fluorescent probes in FACScan and confocal microscopy, showed that TGF-beta mediates ROS production that precedes the loss of Deltapsim, the release of cytochrome c, and the activation of caspase 3. TGF-beta induces a decrease in the protein and mRNA levels of bcl-xL, an antiapoptotic member of the Bcl-2 family. In contrast, there is no change in the expression and/or translocation of Bax, a proapoptotic member of the same family. EGF maintains Bcl-xL, preventing Deltapsim collapse and release of cytochrome c. The presence of radical scavengers blocks the decrease in bcl-xL levels, Deltapsim collapse, cytochrome c release, and activation of caspase 3; in contrast, the presence of glutathione synthesis inhibitors such as BSO accentuated the effect. The incubation of fetal hepatocytes in the presence of ter-butyl-hydroperoxide alone produces a decrease in bcl-xL. These results indicate that during the apoptosis mediated by TGF-beta in fetal hepatocytes, ROS may be responsible for the decrease in bcl-xL mRNA levels that precedes the loss of Deltapsim, the release of cytochrome c, and the activation of caspase 3, culminating in cell death.

Animals↗
PubMed2001

Association of insulin receptor substrate 1 (IRS-1) y895 with Grb-2 mediates the insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis.

We have recently generated immortalized fetal brown adipocyte cell lines from insulin receptor substrate 1 (IRS-1) knockout mice and demonstrated an impairment in insulin-induced lipid synthesis as compared to wild-type cell lines. In this study, we investigated the consequences of IRS-1 deficiency on mitogenesis in response to insulin. The lack of IRS-1 resulted in the inability of insulin-stimulated IRS-1-deficient brown adipocytes to increase DNA synthesis and enter into S/G2/M phases of the cell cycle. These cells showed a severe impairment in activating mitogen-activated protein kinase kinase (MEK1/2) and p42-p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. IRS-1-deficient cells also lacked tyrosine phosphorylation of SHC and showed no SHC-Grb-2 association in response to insulin. The mitogenic response to insulin could be partially restored by enhancing IRS-2 tyrosine phosphorylation and its association with Grb-2 by inhibition of phosphatidylinositol 3-kinase activity through a feedback mechanism. Reconstitution of IRS-1-deficient brown adipocytes with wild-type IRS-1 restored insulin-induced IRS-1 and SHC tyrosine phosphorylation and IRS-1-Grb-2, IRS-1-SHC, and SHC-Grb-2 associations, leading to the activation of MAPK and enhancement of DNA synthesis. Reconstitution of IRS-1-deficient brown adipocytes with the IRS-1 mutant Tyr895Phe, which lacks IRS-1-Grb-2 binding, restored SHC-IRS-1 association and SHC-Grb-2 association. However, the lack of IRS-1-Grb-2 association impaired MAPK activation and DNA synthesis in insulin-stimulated mutant cells. These data provide strong evidence for an essential role of IRS-1 and its direct association with Grb-2 in the insulin signaling pathway leading to MAPK activation and mitogenesis in brown adipocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

[Causative agents of bloodstream infections in children with neoplasm, in 5 hospitals of Santiago (1994-1998)].

BACKGROUND: Pediatric patients in treatment for cancer can have fatal bacterial infections. Thus, in the presence of fever or other signs infection, antimicrobials have to be prescribed empirically. AIM: To know the causative agents of bacteremia in children with cancer, their changes with time and between different hospitals and their patterns of susceptibility. MATERIAL AND METHODS: We reviewed the blood cultores of children with cancer in five hospitals of Santiago, from 1994 at 1998. RESULTS: During the study period, 707 agents were isolated. The most frequently isolated species or genus were coagulase negative Staphylococcus (43%), Staphylococcus aureus (16%), Escherichia coli (9%), Klebsiella spp. (8%), Pseudomonas spp. (5%) and Candida spp. (4%). Coagulase negative Staphylococcus was 55% resistant to meticilin and S. aureus was 44% resistant. Enterobacteriaceae had 15% resistance to gentamicin and amikacin, 2% to imipenem, 26% to ceftriaxone, 21% to cefotaxime and 20% to ceftazidime. Among non fermenting agents resistance was 6% for imipenem, 9% for amikacin 10% for ciprofloxacin, 19% for ceftazidime and 22% for cefoperazone. The resistance of Streptococcus spp. (non pneumoniae) to penicillin reached 50% and that of Enterococcus spp. was of 33%. CONCLUSIONS: Treatment for pediatric patients with cancer must be modified and new guidelines including more active medications for patients at risk for bacteremia, should be devised.

Adolescent↗
PubMed2000

Contribution of cyclopentenone prostaglandins to the resolution of inflammation through the potentiation of apoptosis in activated macrophages.

Activation of the macrophage cell line RAW 264.7 with LPS and IFN-gamma induces apoptosis through the synthesis of high concentrations of NO due to the expression of NO synthase-2. In addition to NO, activated macrophages release other molecules involved in the inflammatory response, such as reactive oxygen intermediates and PGs. Treatment of macrophages with cyclopentenone PGs, which are synthesized late in the inflammatory onset, exerted a negative regulation on cell activation by impairing the expression of genes involved in host defense, among them NO synthase-2. However, despite the attenuation of NO synthesis, the percentage of apoptotic cells increased with respect to activated cells in the absence of cyclopentenone PGs. Analysis of the mechanisms by which these PGs enhanced apoptosis suggested a potentiation of superoxide anion synthesis that reacted with NO, leading to the formation of higher concentrations of peroxynitrite, a more reactive and proapoptotic molecule than the precursors. The effect of the cyclopentenone 15-deoxy-Delta(12,14)-PGJ(2) on superoxide synthesis was dependent on p38 mitogen-activated protein kinase activity, but was independent of the interaction with peroxisomal proliferator-activated receptor gamma. The potentiation of apoptosis induced by cyclopentenone PGs involved an increase in the release of cytochrome c from the mitochondria to the cytosol and in the nitration of this protein. These results suggest a role for cyclopentenone PGs in the resolution of inflammation by inducing apoptosis of activated cells.

Adjuvants, Immunologic↗
PubMed2000

Changes in antioxidant defence systems induced by cyclosporine A in cultures of hepatocytes from 2- and 12-month-old rats.

The in vitro effect of cyclosporine A (CsA) was studied in reference to the production of reactive oxygen species (peroxides and superoxide anion) and to cell enzyme-mediated antioxidant defence in hepatocytes isolated from rats aged 2 and 12 months. Primary cultures of hepatocytes were incubated in the presence of concentrations of cyclosporine in the range of 0 to 50 microM for 24 hr, and the release of lactate dehydrogenase into the culture medium was evaluated as a parameter of cytotoxicity and membrane lysis. Peroxides were quantified by using 2',7'-dichlorodihydrofluorescein diacetate, and superoxide anion levels were evaluated by the fluorescence of dihydroethidium. Enzyme activity and gene expression of catalase and Mn- and Cu,Zn-superoxide dismutase were also assayed. CsA cytotoxicity was significantly higher in hepatocytes from rats aged 12 months when compared to those aged 2 months. Intracellular peroxide content resulted in a dose-dependent increase, while the anion superoxide intracellular level slightly decreased as CsA increased from 0-50 microM. The progressive increase in intracellular peroxides in cell cultures in the range from 0-50 microM CsA was associated with the loss of cell viability and accompanied by significantly higher levels of Mn- and Cu, Zn-superoxide dismutase enzyme activities and mRNAs, and slight increases in catalase activity and mRNA. We conclude that, in primary hepatocyte cultures, the cytotoxicity of CsA was dose-dependent in both age groups and significantly higher in cultures from 12-month-old rats when compared to those from 2-month-old animals. The non-coordinated regulation of the gene expression of antioxidant enzyme systems, i.e. catalase and Mn- and Cu,Zn-superoxide dismutases, evidenced to a greater extent in hepatocytes from the older group of rats, could be one of the mechanisms involved in CsA toxicity.

Age Factors↗
PubMed2000

Effect of N-acetylcysteine and deferoxamine on endogenous antioxidant defense system gene expression in a rat hepatocyte model of cocaine cytotoxicity.

In the present study we investigated on cultures of hepatocytes from phenobarbital-pretreated rats, the effect of the antioxidants, 0.5 mM N-acetylcysteine (NAC) or 1.5 mM deferoxamine (DFO), previously incubated for 24 h and coincubated with cocaine (0-1000 microM) for another 24 h. Cocaine cytotoxicity was monitored by either the lysis of the cell membranes or apoptosis. Lysis of the cell membranes was evidenced by lactate dehydrogenase leakage, apoptosis was observed by detecting a hypodiploid peak (<2C) in DNA histograms obtained by flow cytometry, peroxide production was quantified with 2', 7'-dichlorodihydrofluorescein diacetate and gene expression of the antioxidant enzymes: Mn- and Cu,Zn-superoxide dismutases, catalase and glutathione peroxidase were measured by Northern blot analysis. NAC and DFO significantly decreased the extent of lysis of cell membranes and apoptosis, and the antiapoptotic effect was parallel to peroxide generation. By the effect of NAC and DFO, significant increases were detected in the levels of mRNA of catalase, manganese superoxide dismutase and glutathione peroxidase. From these results we conclude that NAC or DFO, when incubated in the presence of cocaine, exerted a protective effect against cocaine toxicity at the level of both lysis of the membranes and apoptosis. This protective effect, in the case of NAC, was directed towards an increase in antioxidant enzyme expression, and in the case of DFO against reactive oxygen species generation.

Acetylcysteine↗
PubMed2000

Noradrenaline induces brown adipocytes cell growth via beta-receptors by a mechanism dependent on ERKs but independent of cAMP and PKA.

It has been well established that the key role of noradrenaline is the induction of uncoupling-protein-1 (UCP-1) expression, the unique marker of brown adipocytes. However, its implication on proliferation and the pathways involved are not as well characterized. By using rat fetal brown adipocytes as a model, we show that, although noradrenaline activates extracellular regulated kinases (ERKs) through beta-, alpha1-, and alpha2-receptors, only beta-receptors mediate cell growth by a mechanism that requires ERKs activation but is independent of cyclic-adenosine-monophosphate/protein kinase A (cAMP/PKA). Conversely, the cAMP/PKA cascade mediates noradrenaline-induced UCP-1 expression, whereas ERKs pathway attenuates thermogenic differentiation. On the other hand, alpha1- and alpha2-receptors have an antiproliferative effect that is enhanced by ERK inhibition.

Adipocytes↗
PubMed2000

Fibronectin regulates morphology, cell organization and gene expression of rat fetal hepatocytes in primary culture.

BACKGROUND/AIMS: The extracellular matrix regulates hepatic development and regeneration, modulating the maintenance of liver architecture in the differentiated state. The aim of this work was to analyze how different extracellular matrix molecules modulate fetal hepatocyte morphology, growth and differentiation. METHODS: We cultured fetal hepatocytes either on plastic or on different extracellular matrix proteins, i.e., collagen I, fibronectin or E-C-L (entactin-collagen IV-laminin) and we analyzed cell attachment, morphological organization, proliferative response and gene expression. RESULTS: Cell attachment was increased by all the extracellular matrix proteins to a similar extent. However, only fibronectin facilitated the formation of elongated cord-like structures, reminiscent of liver plate organization. Immunocytochemical analysis of the cells in these structures revealed high levels of albumin and cytokeratin 18, phenotypical markers of parenchymal hepatocytes. Fibronectin did not block the mitogenic stimuli induced by epidermal growth factor in these cells and the elongated structures appeared either in the absence or in the presence of the mitogen. Cells cultured on fibronectin, regardless of whether epidermal growth factor was present or not, also presented the maximal levels of expression for liver specific genes, such as albumin or alpha-fetoprotein. This expression was coincident with an increased expression of hepatocyte nuclear factor (HNF)-4 and a higher HNF-1alpha/HNF-1beta ratio, when compared with those cells that were cultured on collagen or E-C-L extracellular matrix. CONCLUSIONS: These results suggest that fibronectin might play a differential role, as compared to other extracellular matrix proteins, in fetal hepatocyte organization and gene expression.

Animals↗
PubMed2000

HSP70 induction by cyclosporine A in cultured rat hepatocytes: effect of vitamin E succinate.

BACKGROUND/AIMS: The effect of vitamin E succinate was studied in vitro against cyclosporine A (CsA) cytotoxicity in reference to the induction of heat shock protein 70 (HSP70) in rat hepatocytes. METHODS: Primary cultures of hepatocytes were incubated with CsA, in the range of 0 to 50 microM, in the presence or absence of 50 microM vitamin E succinate for 24 h. Peroxides were quantified by using 2',7'dichlorodihydrofluorescein diacetate, HSP70 levels were measured by Western blot analysis and apoptosis was detected by the hypodiploid peak of propidium iodide stained DNA. RESULTS: At 24 h of incubation with CsA, intracellular peroxide content increased in a dose-dependent manner. HSP70 also increased in parallel to CsA concentration, and apoptosis showed a biphasic change, increasing at concentrations between 0 and 10 microM and decreasing from 10 to 50 microM. The effect of vitamin E was studied at 24 h of coincubation with CsA. The values obtained show that vitamin E significantly counteracted the effect of CsA, diminishing the CsA-induced increase in intracellular peroxides and the lysis of cell membrane. These vitamin E effects were accompanied by a decrease in HSP70 and an enhancement of apoptosis. CONCLUSIONS: We conclude that in primary hepatocyte cultures, peroxide generation and cytotoxicity induced by CsA was accompanied by HSP70 induction and that the CsA cytotoxicity significantly decreased in the presence of vitamin E succinate parallel to a disappearance in HSP70 and to an increase in apoptosis.

Animals↗
PubMed2000

Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma.

High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

Busulfan↗