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Summary. Background:Thrombotic thrombocytopenic purpura (TTP) is a rare life‐threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS‐13 deficiency, both during the acute episode and remission, is a well‐established predictor of recurrence. The predictive value of anti‐ADAMTS‐13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established.

Rapid on-site evaluation (ROSE) of transbronchial needle aspirates has long been used during flexible bronchoscopy, but its usefulness in the diagnosis of hilar and mediastinal adenopathy is controversial. The aim of the present study was to evaluate the extent to which ROSE can be valuable in patients undergoing transbronchial needle aspiration (TBNA) for the diagnosis of hilar and mediastinal adenopathy.

Background:The aim of the study was to assess whether loss of PTEN and expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib.

The Epidermal Growth Factor Receptor (EGFR) family, including EGFR, HER2, HER3, and HER4, is implicated in the development and progression of cancer, and is expressed in many human epithelial malignancies, including Non-Small Cell Lung Cancer (NSCLC). Several molecules were synthesized to inhibit the extracellular domain of EGFR, such as cetuximab (Erbitux), the extracellular domain of HER2, such as trastuzumab (Herceptin) or the EGFR tyrosine kinase domain, such as gefitinib (Iressa) and erlotinib (Tarceva). Gefitinib and erlotinib are orally active, selective EGFR tyrosine-kinase inhibitors (EGFR-TKI) that produce objective response rates in about 10 of advanced NSCLC. More recently, erlotinib produced a significant improvement in survival when compared to placebo in pretreated NSCLCs. Among clinical characteristics, although female gender, and adenocarcinoma histology, showed to be significantly associated to TKI sensitivity, never smoking history is probably the most relevant factor. Presence of specific EGFR gene mutations or EGFR gene amplification confer a particularly sensitive phenotype, and patients with activation of the anti-apoptotic protein Akt are more sensitive, when Akt activation is sustained by a EGFR dependent mechanism. Cetuximab is a human-murine chimeric anti-EGFR IgG monoclonal antibody that has demonstrated both in vitro and in vivo antitumor activity in tumor cell lines expressing EGFR. It has shown impressive activity when combined with radiation by increasing the antitumor effect of radiation therapy. Cetuximab has a synergistic effect with cisplatin and may play a role in reversing resistance to chemotherapy. Cetuximab demonstrated to be active in pretreated NSCLCs, and its activity as first-line therapy in combination with chemotherapy is currently under evaluation. Efforts should be made for the identification of biological mechanism underlying cetuximab sensitivity and emerging data suggest that the drugs is more active in patients with EGFR gene amplification. In NSCLC, trastuzumab produced disappointing results when combined with chemotherapy, but probably patients were not properly selected. Recent findings in gefitinib treated patients support HER2 analysis by fluorescence in situ hybridization as a complementary test for selection of patient candidate for EGFR targeted therapies. Combination of EGFR targeting agents with other biological drugs is under investigation.

Transbronchial lung biopsy (TBLB) during flexible bronchoscopy (FB) is the recommended procedure for diagnosing sarcoidosis in most cases, although its yield in stage I disease is reported to be not as high as when parenchymal involvement is radiologically evident. We undertook this study to assess the diagnostic value of transbronchial needle aspiration (TBNA) in sarcoidosis presenting with hilar and/or mediastinal lymphadenopathy (stage I).

Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects of the exacerbation on ventilatory function. The mean (SD) FEV1was 45 (15)% predicted during the exacerbation and 57·8 (16)% predicted 2 months later (P=0·00001). The mean (SD) DES excretion was 25·3 (9)μg g−1creatinine at day 1;23·5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20·9 (7) μg g−1creatinine (P=0·049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3·2 μg g−1creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.

AbstractGlycoprotein 90K/MAC-2BP is a member of the scavenger receptor cystein-rich protein superfamily, which is thought to be involved in immune surveillance, defending the body against pathogens and cancer.90K serum levels are elevated in patients with cancer of various origins and in viral infections, such as human immunodeficiency virus and hepatitis C virus (HCV). Because in patients with HCV-related cirrhosis the incidence of hepatocellular carcinoma (HCC) is high, in the present paper we examined, by means of an enzyme-linked immunosorbent assay, the 90K serum levels in 103 patients with liver cirrhosis, and in 69 with HCC, and compared them to α-fetoprotein, the reference tumor marker for this neoplasm.Serum levels of 90K (cut-off 14 μg/ml) were elevated both in cirrhosis (39%) and HCC (46%) compared to controls (14.1 μg/ml vs. 10.6 μg/ml in cirrhosis, and 14.8 μg/ml vs. 9.1 μg/ml in HCC, p≤0.001). There was a significant association with the presence of anti-HCV antibodies. 90K was found to be a non-specific tumor marker which is complementary to α-fetoprotein on the basis of its probable different biological significance. In fact, 74% of HCC patients had at least one positive marker. Combined use of 90K and α-fetoprotein could improve the sensitivity of a single test in the diagnosis of HCC.

Background:Achieving a first complete remission (CR1) is the primary goal in the treatment of AML and is an important prognostic factor for transplantation outcome in general and even more so for autologous transplantation (AutoSCT). However, there are no data for AutoSCT indicating whether the number of chemotherapy courses (1 vs 2) needed to achieve CR1 is of prognostic significance for transplantation outcome.

Objectives: To assess changes in physicians' attitudes towards practice guidelines and towards the role of empirical evidence in their development.Methods: The findings from two surveys carried out in 1993 and 1997 on the same random sample from two Italian medical specialty societies were compared. In both studies, physicians were mailed a questionnaire asking their views on the goals and role of practice guidelines in influencing clinical decision-making, and the role of empirical evidence versus subjective clinical experience in their development.Results: One hundred and seventy physicians participated in both surveys. An increasing proportion of physicians accepted that cost containment could be a legitimate goal of practice guidelines (from 26% in 1993 to 40% in 1997; P= 0.010). More clinicians (43% in 1993 and 57% in 1997; P< 0.01) supported the use of empirical evidence, as opposed to subjective clinical experience, as the primary basis for practice guidelines. Although only a tiny minority of physicians (6% in 1993 and 1997) supported the view that practice guidelines should reflect patient preferences, an increased proportion of physicians supported the participation of representatives from outside the medical profession in their development. The level of support increased from 6% in 1993 to 26% in 1997 (P< 0.001) in the case of consumers, from 24% to 38% (P= 0.015) for patient involvement and from 16% to 33% (P= 0.003) in the case of health care administrators.Conclusions: The documented changes suggest that more clinicians acknowledge the role of empirical evidence and the need for a dialogue with other professionals and patient groups in the development of practice guidelines than was the case in the recent past.

In order to estimate real cost savings achievable from reductions in laboratory test volume and in order to provide a management tool to help achieve such savings, we developed a management system for our chemistry laboratory. The system estimates the fixed costs (i.e., equipment, direct overhead, and indirect overhead costs), the variable costs (i.e., labor and supplies), and the total costs for each of the 81 tests performed in our hospital's chemistry laboratory. A monthly management report compares predicted changes in total variable costs (based on test volume) to actual variable cost changes. One useful insight from the system is that substantial savings may be realized from reducing low-volume, high-variable cost tests that are not normally the target of test-reducing strategies. The savings per test not ordered was estimated to be $5.24 for the low-volume, high-variable cost tests but only $0.45 for the high-volume, low-variable cost tests, nearly a 12-fold difference. A 10 volume reduction of the former (a reduction of only 6,400 tests annually) would achieve 63 of the savings from a 10 volume reduction of the latter (a reduction of 120,000 tests annually). An effective management reporting system, which tracks actual cost savings, is probably necessary to achieve these savings.

EFFECTIVE LISTENING. 16 mm. film. 12 minutes. Sound. Black and White. Consultants: E. C. Buehler and William Conboy, both of the Department of Speech, University of Kansas. One of the Young America series. Rental: $4.00. Produced and distributed by McGraw-Hill Book Company, 330 W. 42nd Street, New York 36, New York.LISTENING IS GOOD BUSINESS and THE PSYCHOLOGY OF PERSUASION. 335 1/3 RPM. Two records, both by Dr. Ralph Nichols. Cost: $6.00 each. Available through Edward M. Miller and Associates, 518-24 McKay Tower, Grand Rapids 2, Michigan.GREAT DEBATES OF THE 1960 PRESIDENTIAL POLITICAL CAMPAIGN. 33 1/3 RPM. Three Microgroove records (Sw-167, Sw-168, Sw-169). Cost: $17.85. Code number: SW A-26. Available through The Spoken Word, Inc., 10 East 39th Street, New York 16, N. Y.FRANKLIN DELANO ROOSEVELT. FIRST INAUGURATION ADDRESS—March 4, 1933, AND SECOND INAUGURATION ADDRESS—January 20, 1937. 33 1/3 RPM Microgroove record. From the Footnotes of History Series. Cost: $5.98. Available through The Spoken Word, Inc., 10 East 39th Street, New York 16, New York.LET'S DISCUSS IT. 16mm. film. Sound. 29 minutes. Black and White. Cost: $130.00. Available through the National Film Board of Canada, 680 Fifth Avenue, New York 19, New York.HAVING YOUR SAY. 16 mm. film. 7 minutes. Sound. Black and White. Cost: $45.00. Available through the National Film Board of Canada, 680 Fifth Avenue, New York 19, New York.LET'S TALK ABOUT FILMS. 16mm. film. 18 minutes. Sound. Black and White. Cost: $90.00. Available through the National Film Board of Canada, 680 Fifth Avenue, New York 19, New York.THE PHILOSOPHY OF RUGGED INDIVIDUALISM and CROSS OF GOLD SPEECH; THE DECLARATION OF INDEPENDENCE and LINCOLN'S GETTYSBURG ADDRESS. Documentary Enrichment Records. 33 1/3 RPM. 12 inch records with 15 minutes on each side. Cost: $5.29 each. Available through Enrichment Teaching Materials, 246 Fifth Avenue, New York 1, New York.TELLING STORIES TO CHILDREN. 16 mm. film. 27 minutes. Sound. Color. Storytellers: Mark Taylor, Winnifred Moffett Crossley, Mary Ann Stevenson. Consultants: Jesse Dypha and Sarita Davis of The University of Michigan, and Frances Clarke Sayers of the University of Michigan. Purchase cost: $200.00; rental: $7.50. Available through The University of Michigan, Audio-Visual Education Center, Frieze Building, 720 E. Huron Street, Ann Arbor, Michigan.SPEECH: USING VISUALS IN YOUR SPEECH. 16 mm. film. 14 minutes. Sound. Color. Rental: $5.75. Produced and distributed by McGraw-Hill Book Company, 330 W. 42nd Street, New York. West Coast distributor: Photo and Sound Films, Inc., 116 Notoma Street, San Francisco 5, California.UNDERSTANDING AND APPRECIATION OF POETRY. 33 1/3 RPM. 12 inch record. Prepared and narrated by Morris Schreiber. Order number: FL9120. Cost: $5.95. Available through Folkways, 121 West 47th Street, New York 36, New York.JOHN CROWE RANSOM. 33 1/3 RPM. 12 inch record. Produced by The Yale University Department of English and Audio-Visual Center. Edited by Alvin B. Kernan. Yale Series of Recorded Poets. Cost: $5.95. Available through Carillon Records, 202 Davenport Avenue, New Haven, Connecticut.MARIANNE MOORE. 33 1/3 RPM. 12 inch record. Yale Series of Recorded Poets. Cost: S5.98. Available through Carillon Records, P. O. Box 1616, New Haven, Connecticut.ROBERT PENN WARREN. 33 1/3 RPM. 12 inch record. Produced by the Yale Series of Recorded Poets. Cost: $5.98. Available through Carillon Records, 520 Fifth Avenue, New York 36, New York.CONRAD AIK.EN. 33 1/3 RPM. 12 inch record. The Yale Series of Recorded Poets. Cost: $5.98. Available through Carillon Records, 202 Davenport Avenue, New Haven, Connecticut.SYMPHONY OF SPEECH. 16 mm film. 13 minutes. Black and White. Sound. Produced in 1962 and distributed by Infinity Films, P. O. Box 20-277, San Diego 20, California.

IMPORTANCE: Identifying the factors associated with premature stroke mortality and measuring between-county disparities may provide insight into how to reduce variations and achieve more equitable health outcomes. OBJECTIVE: To examine the between-county disparities in premature stroke mortality in the US, investigate county-level factors associated with mortality, and describe differences in mortality disparities by place of death and stroke subtype. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study linked the mortality and demographic data of US counties from the Centers for Disease Control and Prevention WONDER database to county-level characteristics from multiple databases. The outcome measure was county-level age-adjusted stroke mortality among adults aged 25 to 64 years in 2637 US counties from 1999 to 2018. This study was conducted from April 1, 2019, to October 31, 2020. Generalized linear Poisson regressions were fitted to investigate 4 sets of factors associated with county-level mortality: demographic composition, socioeconomic status, health care and environmental features, and population health. The Theil index score was calculated to assess the mortality disparities. MAIN OUTCOMES AND MEASURES: Stroke mortality was measured as the number of deaths attributed to stroke in the data set. Out-of-stroke-unit death was defined as any death occurring in outpatient or emergency departments or at the pretransport location. Five stroke subtypes were included in the analysis. RESULTS: Although mortality did not change substantially from 1999 to 2018 (from 12.62 to 11.81 per 100?000 population), the proportion of deaths occurring out of the stroke unit increased from 23.56% (4328 of 18 369) to 34.57% (6978 of 20 188). A large percentage of stroke of an uncertain cause was reported, with most deaths (55.20%) occurring out of the stroke unit. In the county with the highest premature stroke mortality, the incidence was 20.78 times as high as that in the county with the lowest mortality (65.04 vs 3.13 deaths per 100?000 population). The highest between-county disparities were found for stroke of uncertain cause. For out-of-stroke-unit death, county-level mortality was largely associated with demographic composition (31.6%) and health care and environmental features (25.8%). For in-hospital death, 29.8% of county-level mortality was associated with population health and 28.7% was associated with demographic composition. CONCLUSIONS AND RELEVANCE: These findings suggest that strategies addressing specific factors that underlie the mortality disparities among US counties, especially for out-of-stroke-unit death and stroke of uncertain cause, may be useful when tailored to the county-level context before implementing interventions for the neediest counties.

ABSTRACTMost studies examining correlations between the gut microbiota and disease states focus on fecal samples due to ease of collection, yet there are distinct differences when compared to samples collected from the colonic mucosa. Although fecal microbiota has been reported to be altered in cirrhosis, correlation with mucosal microbiota characterized via rectal swab has not been previously described in this patient population. We conducted a cross-sectional analysis using 39 stool and 39 rectal swabs from adult patients with cirrhosis of different etiologies and performed shotgun metagenomic sequencing. Bacterial growth studies were performed with Escherichia coli. Two asaccharolytic bacterial taxa, Finegoldia magnaand Porphyromonas asaccharolytica, were increased in rectal swabs relative to stool (FDR < 0.01). Genomic analysis of the microbiome revealed 58 genes and 16 pathways that differed between stool and rectal swabs (FDR < 0.05), where rectal swabs were enriched for pathways associated with protein synthesis and cellular proliferation but decreased in carbohydrate metabolism. Although no features in the fecal microbiome differentiated cirrhosis etiologies, the mucosal microbiome revealed decreased abundances of E. coliand Enterobacteriaceae in alcohol-related cirrhosis relative to non-alcohol related cirrhosis (FDR < 0.05). In vitrobacterial culture studies showed that physiological concentrations of ethanol and its oxidative metabolites inhibited E. coligrowth in a pH- and concentration-dependent manner. Characterization of the mucosally associated gut microbiome via rectal swab revealed findings consistent with amino acid/nitrogen abundance versus carbohydrate limitation in the mucosal microenvironment as well as unique features of alcohol-related cirrhosis possibly consistent with the influence of host-derived metabolites on the composition of mucosally adherent microbiota.

We report on the successful surgical treatment of an esophageal-bibronchial fistula originating from an iatrogenic mediastinal abscess. Endoscopic treatment had been excluded due to the extensive damage to the right main stem bronchus wall. The surgical treatment was carried out as follows: 1) Endoscopic stenting of the left main bronchus with a self-expanding metallic stent followed by selective left main bronchus intubation; 2) Laparotomic harvesting of the omentum pedicled on both gastro-epiploic vessels; 3) Right thoracotomy, complete dissection of both main bronchi and esophageal wall at the site of the leakage; 4) Harvesting of a pericardial vascularized graft; 5) Deployment of a self-expanding metallic stent from the surgical field into the right main stem bronchus; 6) Reconstruction of the right bronchus wall with the pericardial patch; 7) Positioning a T-tube in the esophageal leak; and 8) Intrathoracic transposition of the omental graft for buttressing all sutures and potential leakage points. The postoperative course was uneventful from a surgical point of view and the patient recovered completely.

The occurrence of acute myeloid leukemia (AML) within six months from a diagnosis of breast cancer (BC) is rarely reported in the literature, and it is associated with a poor prognosis. We report herein the case of a 40-year-old woman referred to our centre affected by BC and simultaneous AML. The patient proved refractory to first line therapy and achieved complete remission (CR) with a clofarabine-based regimen followed by allogeneic stem cell transplantation (ASCT). Both during salvage chemotherapy and after ASCT, the patient presented severe infectious complications ( acute cholecistytis and Nocardia pneumonia, respectively) treated with surgery, and currently she is alive in CR for both diseases after 29 months of follow-up. The case highlights the importance of a diagnostic assessment of any unexplained cytopenia in association with solid neoplasia under treatment, underlining the feasibility and priority of a timely treatment of the haematological neoplasm in order to achieve long-term survival.

Chiaretti: Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Foà:Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees.

FB, FE and SS contributed equally to the work.

Peyvandi: Novo Nordisk: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau; SOBI: Speakers Bureau; Biotest: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; Ablynx: Membership on an entity's Board of Directors or advisory committees, Other: research funding paid to Luigi Villa Foundation, Research Funding; Octapharma: Consultancy; Alexion: Other: research funding paid to Luigi Villa Foundation, Research Funding; Bayer: Speakers Bureau; Grifols: Speakers Bureau; LFB: Consultancy; Kedrion Biopharma: Consultancy, Other: research funding paid to Luigi Villa Foundation, Research Funding.

No relevant conflicts of interest to declare.

Breccia: novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Latagliata:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Shire: Consultancy.

No relevant conflicts of interest to declare.

Abstract 3322

This study shows that, with a median follow-up of 6 years, low dose IL-2 maintenance does not lead to a prolonged DFS and overall survival in pts with AML in first complete remission treated in the EORTC-GIMEMA AML12 trial.Muus: Amgen: Membership on an entity's Board of Directors or advisory committees. de Witte:Novartis: Consultancy, Honoraria, Speakers Bureau.

36 healthy controls and 36 consecutive patients affected by acquired TTP during remission (defined as the maintenance of normalization of clinical and laboratory data for at least 30 days after the last plasma therapy following the resolution of the last acute episode) were characterized by flow cytometry for the quantification of:- different peripheral B cell subsets, using labeled surface markers anti-CD19-PerCP, anti-IgD-PE, anti-IgM-FITC, anti-CD27-APC, anti-CD38-FITC;- different peripheral T cell subsets, using labeled surface markers anti-CD3-FITC, anti-CD4-PE, anti-CD8-APC, anti-CD25-FITC. For Treg cell quantification (only 17 patients were analyzed), anti-CD3-PerCP, anti-CD4-FITC, anti-CD25-PE and the intracellular marker FoxP3 were used.Patients were classified in two subgroups: those who developed at least two episodes of TTP (n=19, with recurrence) and those who experienced a single episode only and no relapse during at least one year of retrospective observational time (n=17).ADAMTS13 activity was measured by residual collagen binding assay (Gerritsen et al, Thromb Haemost 1999). The presence of anti-ADAMTS13 IgG was evaluated by Western blotting and ELISA assays, using recombinant ADAMTS13 protein as antigen and patients' plasma as a source of antibody. The presence of anti-ADAMTS13 IgA, IgM, IgG subclasses (IgG1, 2, 3, 4) were evaluated by ELISA assays.For continuous variables, differences between controls and patients and between patients with or without recurrence were evaluated by the t-test; for discrete variables, by the chi square test. P values smaller than 0.05 were considered statistically significant. Analyses were performed using the SPSS package version 17.0.1) TTP patients had an increased number of CD19+ B cells (mean ± SD 13% ± 5) compared with the control group (10% ± 3, p=0.001). No difference was observed in T cells subsets.2) The results of the characterization of the two groups of patients (with and without recurrence) are reported in the table.Patients with and without recurrence did not differ either in the amount of Treg FoxP3 or in the presence of IgA, IgM and IgG subclasses.The increased B cell numbers in acquired TTP indicates an enhanced activation of cellular immunity. Analysis of B cell subsets, particularly of memory B cells, and of T cells CD24+CD25+ during remission might provide information on the likelihood of recurrence in TTP.In conclusion, in recurrent TTP patients the higher amount of B cells might result in persistent autoantibodies production whilst the decreased level of T cells CD4+CD25+ may lead to a decreased inhibition of autoreactive T cells. These findings may explain the higher level of recurrence in these patients.Peyvandi: Archemix Corporation: Consultancy.

Muus: Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Nucleophosmin (NPM1) gene mutations represent the most common genetic alterations in adult acute myeloid leukemia (AML), accounting for about 30% of cases and 50–60% of AML with normal karyotype. In addition to their recognized prognostic value (when combined with analysis of the FLT3gene), NPM1mutations represent an ideal marker for monitoring of minimal residual disease (MRD) since they are very stable during the course of the disease. PCR quantitative monitoring of NPM1mutant copies has been mainly restricted to patients treated with conventional chemotherapy. In our study, we retrospectively analyzed, by RQ-PCR, MRD in 12 consecutive NPM1-mutated AML patients who underwent an autologous peripheral blood stem cell transplantation (PBSCT) between September 2000 and March 2008 at the Division of Hematology, “Sapienza” University of Rome. By sequencing of the region encompassing NPM1exon 12, we demonstrated the presence of a type A mutation in 10/12 patients and of a type B in the remaining 2. Moreover, at diagnosis molecular analysis of the FLT3gene revealed an internal tandem duplication (ITD) in 7/12 patients. Cytogenetic analysis showed a normal karyotype in 11/12, whereas 1 patient presented a minor karyotype aberration (trisomy 4). RQ-PCR was retrospectively performed on bone marrow samples in all patients at diagnosis, in 11/12 patients before the transplant and in 9/12 after the graft. Six of the 12 patients are at present in continuous complete remission (CCR) with a median follow-up of 54 months (range 4–89), 1 patient has died in CCR 55 months after PBSCT due to a pancreatic carcinoma and 5/12 have relapsed. Four of the latter 5 patients relapsed shortly after the transplant (range 3–10 months); 2 of them died of disease progression and 2 of salvage chemotherapy toxicity. One patient, who relapsed 92 months from PBSCT, is alive in second hematological remission following re-induction and consolidation chemotherapy. No significant differences in median levels of transcript at diagnosis were found between relapsing and non-relapsing patients (93,000 and 68,000; range: 86,000–103,000 and 37,000–116,000, respectively). Nine patients were analyzed after PBSCT: 3 persistently positive relapsed and the copy number of the transcript was always higher than at diagnosis. In the other 6 patients, the transcript was undetectable (3 of them were already in molecular remission pre-transplant): 5 are still in CCR while 1 patient relapsed 92 months after the graft. Regarding the FLT3-ITD status at diagnosis, 3/7 patients are in CCR whereas 4 have relapsed. The retention of NPM1mutations even at relapse further confirms that NPM1alterations are highly stable, pointing to this event as critical for leukemia growth and survival. Moreover, in our study long-term survival was always associated with a copy number of NPM1mutant transcripts below the detectable level of the method, suggesting that disappearance of the transcript should be the primary clinical endpoint. Prospective studies and larger case series are necessary in an attempt to identify a cut-off level during treatment which could be predictive of the clinical outcome of AML patients harboring NPM1mutations and help in therapeutic choices.