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  • 1
    ISSN: 0006-3525
    Schlagwort(e): Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The secondary structure of human fibrin from normal donors and from bovine and suilline plasma was studied by Fourier transform ir spectroscopy and a quantitative analysis of its secondary structure was suggested. For this purpose, a previously experimented spectrum deconvolution procedure based on the use of the Conjugate Gradient Minimisation Algorithm with the addition of suitable constraints was applied to the analysis of conformation-sensitive amide bands. This procedure was applied to amide I and III analysis of bovine and suilline fibrin, obtained industrially, and to amide III analysis of human fibrin clots. The analysis of both amide I and III in the first case was useful in order to test the reliability of the method. We found bovine, suilline, and human fibrin to contain about 30% α-helix (amide I and III components at 1653 cm-1, and 1312 and 1284 cm-1, respectively), 40% β-sheets (amide I and III components at 1625 and 1231 cm-1, respectively) and 30% turns (amide I and III components at 1696, 1680, 1675 cm-1, and 1249 cm-1, respectively). The precision of the quantitative determination depends on the amount of these structures in the protein. Particularly, the coefficient of variation is 〈 10% for percentage values of amide I and III components 〉 15 and 5%, respectively. The good agreement of our quantitative data, obtained separately by amide I and amide III analysis, and consistent with a previous fibrinogen (from commercial sources) study that reports only information about fibrin β-sheet content obtained by factor analysis, leads us to believe that the amounts of secondary structures found (α-helix, β-sheets, and turns) are accurate. © 1997 John Wiley & Sons, Inc. Biopoly 41: 545-553, 1997.
    Zusätzliches Material: 4 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2009-11-20
    Beschreibung: Abstract 3945 Poster Board III-881 Introduction Non Hodgkin Lymphoma could be clinically divided as low grade/indolent NHL (LG NHL) and high grade/aggressive NHL (HG NHL). These diseases are chemo and radio-sensitive and improvements have been achieved by immunotherapeutic approaches. However some patients will relapse and a follow up strategy has to be planned in order to detect and treat them. Several aspects should be considered in planning a follow up including safety, specificity, sensitivity, costs and impact on the patient's psychology: an optimal follow up should mediate between these ones. The more diffuse follow up have been planned years before the introduction of innovative methods and imaging techniques, suggesting the opportunity to revise these programs. Methods We collected data about 418 NHL patients -both low and high grade- treated at our institution from 1990 to 2005 who achieved a complete remission according to Cheson criteria and who entered a follow up program which schedule is planned for 5 years divided in two periods: first two years evaluation every 3 months and in the following three years every sixth month. At each visit physical examinations, blood testing (blood count, chemistry) are performed; for imaging techniques we alternate a whole body CT scans to ultrasounds and chest X-ray coupled. Analyzing time to relapse (TTR), we tried to optimize our follow up schedule trough a computation application known as multi-objective analysis. The first step of this method has been to choose and try to quantify the costs of a follow up which reflect its effectiveness. We considered as costs the expected time between relapse and its detection (Ca) and the expected number of performed examinations before failure or censoring occurs (Cb). The total follow up costs could be summarized in a vector Cref: (Ca,Cb). After doing that we described survival analysis, relapse rate and their onset time in order to be suitable for the informatic analysis. We used a log logistic parametric model to do that. Next we shaped our ideal follow up as a structure based one, which is currently the most used in medical practice: a first period where examinations are more tightly spaced, followed by a second period where they are performed further apart. We describe such follow-up schedule “S” as (d1, k, d2) : d1 is the time between the first k examinations; d2 is the time between the remaining examinations. Applying the log-logistic model we calculated the Cref and schedule for our follow up: Cref was (Ca,Cb)=(8.5,6.2); this means that, on average, every patient entering the follow-up will perform 6.2 examinations, and among those who incur in a relapse, the relapse will be detected 8.5 units of time (eg. weeks) after its onset. The follow up structure was (13,8,26). We then calculated all the possible combination of (d1, k, d2) values from 1 to d1 = 25, k= 24 and d2 = 60. Results 360000 follow up schedules had been detected after searching all the possible combinations for d1, k and d2. For each one Ca e Cb costs have been calculated and than compared by multi-objective analysis to those of the current schedule, We look for both follow up structured and “free” follow up, where “free” means that intervals between examination is continuously variable. When comparing follow-up schedules, we apply the rule of Pareto-dominance: the schedule S1 is superior to the S2 schedule if and only if the cost values for S1 are both lower than the cost values for S2. The method then takes into account only those schedules which improve the current one, with respect to both the Ca and the Cb costs. After multi-objective analysis six follow up were detected. These were as following: (16,10,22), (15,8,20), (15,6,19), (16,8,19), (16,5,18), (16,4,18) and are shown in Fig. 1. Conclusions no differences in follow up schedules emerged when we considered separately LG and HG lymphoma patients. Maximum improving of our follow was just 4% and all the new schedules had wide time frequency visit in the first period and a narrow one in the second period: this was a consequence of the higher relapse distribution in the first period and this follow up organization lead to a lower total number of visit without risk of lose any relapse. This is the first application of this analysis to hematological patients confirming the validity of a follow up schedule should be shaped in two different period. Disclosures: No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 3
    Publikationsdatum: 2009-11-20
    Beschreibung: Abstract 1221 Poster Board I-243 Introduction A subset of Multiple Sclerosis (MS) patients shows a clinical trend to a fast deterioration of disability despite the use of approved drugs. New immunosuppressive agents are currently employed only in the early phase of the disease but in almost 10% of patients they either do not show any clinical/ radiological improvement or have to be halted for different reasons. Autologous HSCT has been reported as a promising approach for MS patients unresponsive to the available therapies but long term clinical and laboratory follow-up with a stringent MRI monitoring are not yet available. We report here the long term follow-up of a prospective phase II multicenter trial of the Italian GITMO-Neuro cooperative network. Method 21 MS patients (4 Relapsing Remitting and 17 Secondary Progressive) were enrolled between 1999 and 2004 in a prospective trial, aimed to monitor both clinical outcome and MRI imaging. Patients were shown to be refractory to conventional treatments, had a EDSS between 5.0 and 6.5 and at least 1 Gadolinium (Gd) enhancing area in brain MRI. PBSC were mobilized with Cyclophosphamide (4g/m2 ) and Filgrastim; patients were conditioned with BEAM plus rabbit ATG (Thymoglobulin®, Genzyme) and infused with unmanipulated graft. The effect of HSCT was evaluated with serial monthly Gd-enhanced brain MRI for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI imaging for the following 6 months. Subsequently, MRI scans were carried out at, +9, +12, +18 + 24 and at the last follow-up. Clinical outcome was evaluated by both EDSS assessment and number of clinical relapses after the transplant. The same MRI scanning protocol was used at each neuroradiological examination: T1 and T2 total lesion load, new T2 lesions, new hypointense lesions, Gd enhancing activity and progression of brain atrophy were evaluated. Results All patients showed a sustained engraftment with modest early side effects, as previously reported (Saccardi R. et al. Blood 2005 105:2601-07). At a median follow up of 7 years (range 4-10 years) no late effects were reported. Two patients had a clinical relapse 5 years after the HSCT, spontaneously recovered. Nine patients showed a clinical progression at a median of 30 months (16 – 66) after transplant, while the others are either stable (7) or improved (5), as compared with baseline. No patients received any immunosuppressive treatment after HSCT. At MRI examination total lesion load assessed by T2 and T1 sequences remained stable through the follow-up, and only 5 new T2 lesions appeared after HSCT. No Gd enhancing activity was ever observed after transplantation in the examined cases. Brain atrophy progression was higher in the first 2 years after transplantation and then decreased significantly in the following years Conclusions The clinical and MRI results of this prospective study are extremely positive, considering that the majority of cases remained stable at a median of 7 years after transplantation. MRI activity, as evaluated with Gd enhancing areas and the appearance of new lesions, was absent or negligible. Also brain atrophy, rapidly progressing early after the transplant probably due to the suppression of the inflammation, was thereafter shown to be in the range of MS patients. The duration of the follow-up and the stringent MRI methodology provide an evidence of the efficacy of this procedure in this subset of aggressive MS patients. Disclosures No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 4
    Publikationsdatum: 2009-11-20
    Beschreibung: Abstract 4772 Introduction Non Hodgkin Lymphomas (NHL) are commonly divided in two large groups known as high grade (HG) and low grade (LG) lymphomas. Specific therapeutic strategies are potentially curative, but a tailored treatment should be planned from the diagnosis on the basis of the prognostic features. Some clinical features at the diagnosis or relapse may be grouped to build prognostic indexes. These indexes are “build” starting from features present at diagnosis and related to patients and disease onset, but lacks to give any information about disease history and chemosensitivity. For these purposes others methods have been evaluated and probably the two that gave major help to detect slow responders or resistant patients are minimal residual disease (MRD) and PET scans. Here we develop and apply a partitioning recursive algorithm, known as HCS, by which possibly detect new possible prognostic factors. Methods Our dataset comprised 651 NHL patients followed at our Institution from 1990 to 2005, divided in High grade (HG NHL, n=343; 52,7%) and Low grade Lymphoma (LG NHL, n= 308; 47,3%). Only patients who enter in a follow up program were considered: therefore patients with at least a partial response. We considered as variables for algorithm analysis: age, sex, histological subtype, IPI status and bone marrow involvement, treatment approaches (poli-chemotherapy, mono-chemoterapy, radiotherapy, surgery, purine based chemotherapy, monoclonal antibodies, transplant approach, oral chemotherapy), response to therapy, previous successful treatments, previous relapses, previous failed therapies. Data were analyzed by a recursive partitioning algorithms. A partitioning recursive algorithm. This tool is thought to splits data in different subgroups that behave in a different way. It works starting from data and utilized them to create all the possible combinations of splits available. Among them it chooses the best one by statistics and finally applies it to patients' datasets. For these reason it is defined as “partitioning”. Afterwards the algorithm starts again the analysis on the subset previously detected and that's because it is called “recursive”. Results The most important split emerged to be the quality of response: patiets were splitted between patients in partial remission (PR) and complete remission (CR). Among PR patients, one subset (subset 1) with worse prognosis were found: both comprised patients with HG NHL not treated with monoclonal antibodies and/or transplant. Therefore the remaining PRs patients, treated by transplant approach and immunotherapy, had a better outcome. In CR group subset 2 has been detected, comprising HD NHL patients not treated by oral chemo alone were detected. Those patients, who had a better outcome, had been treated aggressively with polichemotherapy and/or autologous transplant. Differences between detected groups are statistically significant with p. value 0,03 maximum. Splits are shown in Figure 1 and 2. Conclusion Application of computer science analysis to NHL patients has been successfull. Quality of response emerged as the most important prognostic factor but among both PRs and CRs patients those with better outcome had HG NHL diagnosis and were treated by autologous transplantation or/and immunotherapy. This analysis confirms data available about transplant as a good approach for NHL patients. Disclosures: No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 5
    Publikationsdatum: 2009-11-20
    Beschreibung: Abstract 4493 Introduction Acute GVHD involving the gastrointestinal tract is now the major cause of non-relapse mortality following allogenic transplant. Diagnosis remains problematic for some patients with pathology in the mid-gut; there is significant sampling error with mucosal biopsy; we lack objective measures of physiologic improvement or worsening in the gut; and duration of immune suppressive therapy remains imprecise. To address these issues, we have serially evaluated intestinal pathology in patients with acute GVHD using a reproducible ultrasound technique as a proof of principle study. Specifically, we examined the hypothesis that contrast-enhanced ultrasound (CEUS) could detect an enhancement of microcirculation during active intestinal acute GVHD as a diagnostic tool and that CEUS could be used to serially assess physiologic changes after treatment. Methods Four patients (pts) with hematologic malignancy (1 each with ALL, AML, mantle cell lymphoma, and myeloma) received a matched unrelated donor allogenic transplant after a myeloablative (N=2), reduced intensity (N=1), or non-myeloablative (N=1) conditioning. GVHD prophylaxis consisted of cyclosporine with either short course methotrexate (N=3) or mycophenolate mofetil (N=1). All patients developed biopsy-proven intestinal GVHD that was steroid refractory in 2 patients. At GVHD onset, patients were scanned with transabdominal ultrasonography and subsequently by CEUS using a linear phased-array 7.5-MHz transducer. A second generation echo-contrast agent (SonoVue®, Bracco), which consists of microbubbles stabilized by phospholipids and filled with sulphur hexafluoride, was injected i.v. as a bolus (2.4 mL) followed by 5 mL saline flush. Microbubbles have a mean diameter of 2.5 μm and remain within the vascular space allowing real-time imaging of microcirculation. Results In all patients, routine ultrasonography revealed mucosal edema involving the terminal ileum in 3 patients (wall thickness 5.1, 5.8 and 7.9 mm) and the colon in 4 patients (ascending colon 5.8, 6, 8.4 and 18 mm; transverse colon 6 and 12.6 mm; descending colon 11 mm). CEUS at GVHD onset showed an arterial phase (AP) complete enhancement of the entire wall section from the mucosal to the serosal layer (terminal ileum) in 2 patients. There was absence of enhancement only in the outer border of the muscularis propria in 1 patient (pt); there was absence of enhancement both in the outer and in the inner border of the colon wall and enhancement only of the intermediate layer in 1 pt. All patients showed late parenchymal phase (PP) wash out. These enhancement patterns have previously been described in active Crohn's disease (Serra C. et al; 2007). CEUS follow-up findings on serial examinations: 1) allowed us to monitor residual disease in one pt after Infliximab, showing persistent AP enhancement of microcirculation suggesting residual GVHD activity which required further treatment with eventually complete remission; 2) CEUS showed normalization and/or decreased microcirculation enhancement in pts responding to treatment (N=2); 3) CEUS showed AP microcirculation enhancement when GVHD flared (N=2); 4) CEUS showed persistence of AP enhancement of microcirculation after Rituxan (4 doses 375mg/m2/weekly) despite a decrease in ileum wall thickness and in agreement with only a slight improvement of symptoms in one pt when GVHD flared, 5) CEUS showed no improvement of intestinal microcirculation wall enhancement in steroid refractory aGVHD patients who eventually died (N=2). In one of them there was persistence of AP phase enhancement despite improvement of symptoms suggesting still active disease. Conclusions Contrast enhanced US showed intestinal microcirculation wall enhancement and delayed washout at the onset of GVHD symptoms in areas of the intestine inaccessible to endoscopic evaluation. CEUS findings on serial examinations correlated with incomplete responses and flares of GVHD symptoms (microcirculation enhancement) and responses to therapy (decreased microcirculation activity). CEUS may be useful for both diagnosis and prognosis, as it provides both anatomic and physiologic information about intestinal GVHD. These findings prompted us to design a prospective study to evaluate clinical usefulness of CEUS in diagnosis and follow-up of intestinal acute GVHD. Disclosures: No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 6
    Publikationsdatum: 2011-11-18
    Beschreibung: Abstract 334 Background: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease believed to be mediated by autoreactive lymphocytes that invade the Central Nervous System and cause oligodendrocyte, axonal and neuronal damage as well as glial scarring.to and resulting in demyelination, neuronal death and brain atrophy. Hematopoietic Stem Cell Transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with a poor prognosis autoimmune disease not responding to conventional treatments. Worldwide ≥600 patients with MS have been treated with HSCT, most of them having been recruited in small, single center, phase 1–2 uncontrolled trials. Clinical and MRI outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted earlier in the relapsing-remitting phase. The intensity of the immunosuppression from transplant treatment may be determined by several factors, such as the use of chemotherapy in the mobilization regimen, the intensity of the conditioning regimen and ex-vivo T-cell depletion. Methods: We report here the Italian multi-center experience on 74 MS patients treated with AHSCT between 1996 and 2008, all mobilized with Cyclophosphamide/G-CSF and conditioned with BEAM and rabbit ATG. Clinical and MRI outcomes were reported to the Italian Registry; the median follow-up is 48.3 (range 30–210) months. All patients clinically deteriorated in the year prior to HSCT, with an increase of Extended Disability Scale (EDSS) of at least one point (average EDSS change=1.5 points, range=1–9), Results: Two patients (3.3%) died for transplant-related causes. At 5 years after the transplant, 66% of patients remained stable or improved. Progression free survival (PFS) was slightly better in relapsing-remitting (RR) (5 years PFS=71%) than in secondary-progressive (SP) forms (5 years PFS=62%, p=0.28). Amongst patients with a follow up longer than 1 year, 8 out of 25 RR subjects (31%) had a 6–12 months confirmed EDSS improvement 〉 1 point as compared to 1 out of 36 (3%) SP patients (p=0.009), Figure 1. Out of 18 cases with a follow up longer than 7 years, 8 (44%) remained stable or had a sustained improvement whilst 10 (56%), after an initial period of stabilization or improvement with a median duration of 3.5 years, showed a slow progression of disability. Conclusions: This study shows in a large cohort of patients with a long follow-up that AHSCT with BEAM/ATG conditioning regimen has a profound effect in suppressing disease progression in aggressive MS cases, unresponsive to conventional therapies. Indeed it results in a sustained improvement of the disability, free of immunosuppression, in a significant amount of RR patients. Clinical improvement is scarcely reported in MS literature as it is rather infrequent with conventional treatments; nevertheless it results in a stable increase of the quality of the life in this subset of young patients and should be considered in the choice of a therapeutic strategy in the early phase of MS. Disclosures: Cuneo: Roche: Consultancy, Speakers Bureau.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 7
    Publikationsdatum: 2009-11-20
    Beschreibung: Abstract 5007 Introduction Non Hodgkin Lymphoma represent a category of hematological malignances which are chemo and radio-sensitive; improvements in their treatment had been achieved by immunotherapeutic approaches. However some patients will relapse after achieving complete remission (CR). Obviously, in order to detect and possibly treat them as soon as possible, a follow up strategy has to be planned. The more diffuse follow up have been planned years before the introduction of innovative methods and imaging techniques, suggesting the opportunity to revise these programs. In particulary it is not still clear which is best techniques useful to properly follow this patient. Recently new interesting methods are available like PET, CT-PET and minimal residual disease (MRD) monitoring. Methods 418 NHL patients -both low and high grade- treated at our institution from 1995 to 2005 who achieved a CR status according to Cheson criteria have been evaluated. LH NHL included follicular lymphoma, lymphoplasmocytic lymphoma, Marginal zone lymphoma, and small lymphocytes lymphoma. In the HG NHL, we included T-cells lymphomas, diffuse large cell lymphoma, lymphoblastic lymphoma, Mantle cell lymphoma, anaplastic lymphoma, Burkitt lymphoma. Patient characteristics are summarized in Table 1. Follow up is planned for 5 years divided in two periods: in the first two years patients are evaluated every 3 months and in the following three years every sixth month. At each visit physical examinations, blood testing (blood count, chemistry) are performed; for imaging techniques we alternate a whole body CT scans to ultrasounds and chest X-ray coupled. Bone marrow samples for both pathological and molecular analysis are collected every six months in the first period and once a year afterwards. PETs were usually performed when CT showed uncertain findings. Results There were 431 events, with 188 first relapses, 86 second, 18 third, 4 fourth and 1 fifth relapses. Relapse rate was similar among high and low grades, (37% and 35 % respectively) but time to relapse was longer for low grades (18.2 months vs 8.9 months). There was not relationship between IPI status and relapse rate. 72 % of relapse was at the same site of diagnosis. Relapses were detected by ultrasound in 139 cases (32 %), CT scans in 110 (25.5%) and by physical examination in 62 (14.4%). Remaining patients' relapse were diagnosed with other techniques (lab test, gastroscopy, NRM) New techniques as MRD monitoring, PET or PET/CT were not available for many patients, anyway MRD monitoring was able to detect disease re-appearance in 2%, and we had a total of 28 cases (6,5%) of relapse diagnosis with PET, but we noted a total of 18,5 % of false positive. Discussion and conclusions Many papers from literature raised many questions about which is the best techniques to follow patients. Many authors showed how symptoms onset and clinical findings appeared to be the more important for relapse detection compared to imaging before and during CT era. Some works pointed out also that even when CT detected earlier a relapse that do not translate in a survival advantage. Recently much interest has been focused on PET, CT-PET and MRD. They two appeared to be very important as prognostic tolls but their role for follow up purpose is still debatable. On the basis of clinical data and of these consideration routine PET is not recommended during follow up. Unfortunately PETs and MRD monitoring were not available for the majority of our patients, diagnosed in the nineteen's. In conclusion in our experience we observed some usefulness of CT scans and ultrasounds but we must recall that the majority of literature is not consistent with our results. Considering our experience and data from literature probably imaging should be performed routinely at the end of therapy, and during follow up only on the basis of presentation and clinical suspicion. As a matter of fact NCCN reviewed its guidelines do not suggesting a wide use of routine imaging. Further investigation by clinical and randomized trials are certainly needed to better understand, in particular the role of PET-PET/CT for follow up purpose. Disclosures No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Publikationsdatum: 2005-11-16
    Beschreibung: Previously untreated mantle cell lymphoma (MCL) are consistently associated with poor prognosis when treated with CHOP-like regimens. Typically the CR rate is 20–30%, median FFS = 10–16 months and median OS = 3 years. In the attempt to improve outcome we used a high dose intensity regimen such as Hyper-CVAD (HCVAD) with autologous stem cell transplant (ASCT). Twenty patients entered the study but only 10 up to now are valuable. Patients were apheresed after 2nd course of HCVAD and if apheresis (LPH) were PCR positive (Bcl1+/JH+) a second set of LPH were performed after completion of 4th cycle. To perform an in vivo purging Rituximab 375 mg/m2 was added at day +1 and +9 after last dose of ARA-C; GCSF 10μg/kg was commenced on day +5 until LPH was ultimated. Rituximab maintenance (375 mg/m2 once weekly for 4 consecutive weeks) started 2 month post-ASCT and was repeated every 6 months. Ten patients have completed 4 HCVAD and 7 /10 underwent ASCT and were conditioned with BEAM. After 4 HCVAD 7/10 patients were in CR and 3/7 in PR. After ASCT 1 PR obtained a CR, 1 PD obtained a VGPR and 5 CR maintained CR. Only 4CR post ASCT have received Rituximab maintenance and maintain CR. Two patients (1 CR blastic variant and 1 PR) refused ASCT and after 4 HCVAD received Rituximab maintenance and both are in CCR. Overall with a median follow up of 28.6 months (range 12–51) median survival is not reached. At 4 years 77.8% of patients are alive and PFS is 87.9%. Patients were monitored for bone marrow-MRD by PCR. Eight out of 10 were PCR+ at diagnosis and 7/8 were PCR negative after 4 HCVAD. After ASCT one PCR+ converted to PCR- and 1 PCR+ patient after 4 HCVAD converted to PCR- with Rituximab maintenance (refused ASCT). Conclusions: high dose intensity regimen HCVAD + Rituximab as in vivo purging and for maintenance allowed to collect tumor free grafts in 70% of PCR+patients at diagnosis and to reach an ORR of 100%, 7/10 CR and PR 3/10 (included 1 blastic variant). PCR negativity was obtained in 7/8 patients. One patient from PR converted to CR after ASCT and one after Rituximab maintenance (without ASCT); thus we might speculate that both high doses (BEAM) and Rituximab do play a role to increase the probability to obtain a CR and PCR-. Survival and PFS of 77.8% and 87.9% respectively at 4 years are encouraging. Further follow up and a higher enrolment of patients are needed to better define the role of HCVAD + Rituximab and ASCT to increase CR,PCR- PFS and OS in MCL.
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    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2009-11-20
    Beschreibung: Abstract 4742 Introduction Neutropenic enterocolitis (NEC) is a life threatening complication of chemotherapy in leukemic and solid tumor patients with an incidence ranging from 2.6% to 33%. It is a necrotizing inflammatory disease that most commonly involves the ileo-cecal region. The cecum is almost invariably affected likely due to its distensibility and limited blood supply. Macroscopically the involved bowel segments show oedematous and thickened walls, with varying degrees of ulceration and haemorrhage. Perforation occurs in 5%-10% of cases. Early diagnosis is crucial to start conservative medical treatment which appears the optimal strategy. Criteria for prompt surgical treatment have also been proposed (Shamberger RC et al, 1986) so that a careful clinical evaluation by both the physician and the surgeon is mandatory (Davila ML et al, 2004). NEC should be always suspected in neutropenic patients with abdominal pain, fever and diarrhea. Ultrasound (US) has been used to evaluate bowel-wall thickening (BWT). One study correlated BWT with clinical outcome: 60% of patients with BWT 〉 10 mm died from NEC as compared with 4.2% of those with BWT 〈 10 mm (Cartoni C. et al, 2001). Overall, despite aggressive treatment, mortality rate is up to 21-48% and patients may die within hours from the onset of acute symptoms. Because of the risk of early death, a swift diagnosis is imperative. We investigated if US could detect early signs of NEC and lead to prompt treatment. We analyzed two patients cohorts (A and B). In cohort A US was performed later in the course of the disease whereas, in cohort B US was immediately performed at the onset of a single symptom (diarrhea and/or abdominal pain whichever occurred first with/without fever). Underlying haematological diagnoses were Hodgkin Disease (N=10), acute leukemias (N=9), multiple myeloma (N=3) and non-Hodgkin lymphomas (N=10). Treatments consisted of standard chemotherapy (N=10), myeloablative allografting after busulfan/cytoxan (N=1) and cytoxan/total body irradiation (N=1); autografting after busulfan/cytoxan (N=1), BEAM (N=16) and melphalan (N=3). Results All 32 patients showed grade 4 neutropenia at the onset of symptoms. Thirty-one/32 (97%) complained of abdominal pain whereas diarrhea was present in 30/32 (94%). Positive stool (for Clostridium Difficilis and Escherichia Coli) and blood cultures (62% Gram negative and 38% Gram positive bacteria) were found in 4/32 (12.5%) and 8/32 (25%) respectively. Trans-abdominal real-time US scanning of the bowel was performed using a 3.5-5 MHz convex probe and a 7 MHz linear transducer. A portable sonographer (Esaote model My Lab 25) was used for bed-side US. Both trans-abdominal axial and transverse US scans were performed on the colon. US signs of NEC were defined as thickening or dilation of small and/or large intestine. The intestinal involved areas were ileum, 21%, last terminal ileum, 21%, cecum 7%, ascending colon, 16%, transverse colon, 16%, descending colon, 14% and jejunum, 4%. US revealed signs of NEC in 8/14 in cohort A and 18/18 in cohort B. In cohort B, early US detected signs of NEC in 7 patients with abdominal pain and diarrhea without fever. Complete response to prompt medical treatment occurred in 6. Three/7 patients developed fever 48 hours after the US-guided diagnosis of NEC. Two patients, at risk of wall rupture by US imaging (confirmed by CT scans), underwent successful colon surgery within 12 hours from diagnosis. Except for these 2, all patients received medical treatment (broad spectrum antibiotics for gram-negative, gram-positive and anaerobic coverage, and antifungal drugs, granulocyte transfusions, bowel rest and granulocyte colony stimulating factor as per internal protocol). Overall 3/32 patients died. Conclusions Early bed-side intestinal US in neutropenic patients performed at the onset of a single symptom suggestive of NEC led to timely and successful treatment of this life threatening complication even before the development of fever. Disclosures: No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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