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In light-chain (AL) amyloidosis, prognosis is dictated by cardiac dysfunction. N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn) are used to assess the severity of cardiac damage. We evaluated the prognostic relevance of a high-sensitivity (hs) cTnT assay, NT-proBNP, and cardiac troponin I in 171 consecutive patients with AL amyloidosis at presentation and 6 months after treatment. Response and progression of NT-proBNP were defined as more than 30% and more than 300 ng/L changes. All 3 markers predicted survival, but the best multivariable model included hs-cTnT. The hs-cTnT prognostic cutoff was 77 ng/L (median survival 10.6 months for patients with hs-cTnT above the cutoff). After treatment, response and progression of NT-proBNP and a more than 75% increase of hs-cTnT were independent prognostic determinant. In AL amyloidosis, hs-cTnT is the best baseline prognostic marker. Therapy should be aimed at preventing progression of cardiac biomarkers, whereas NT-proBNP response confers an additional survival benefit.

Using quantitative fluorescence in situ hybridisation and flow cytometry (flow-FISH), we investigated the biological and clinical relevance of telomere length in 55 patients affected by myelodysplastic syndromes (MDS) compared with 55 sex- and age-matched controls. We found that telomere fluorescence in MDS granulocytes, and CD34+ cells did not decline with age as in normal controls and that MDS granulocytes and CD34+ cells had significantly shorter telomeres than healthy controls. A significant higher incidence of cases with intermediate-unfavourable cytogenetics and International Prognostic Scoring System (IPSS) int-2/high-risk group was observed among patients with lower telomere fluorescence. We also found that apoptosis in CD34+ cells was significantly higher in IPSS int-1 low-risk patients when compared with IPSS int-2 high-risk cases and healthy controls and that CD34+ cell telomere fluorescence directly correlated with CD34+ cell apoptosis. Reduced telomere fluorescence was associated with a history of occupational exposure to toxic agents and with worse survival in univariate and multivariate analyses. Our results suggest that flow-cytometry assessment of telomere dynamics may represent a valuable tool in the biological and clinical–prognostic characterisation of MDS disorders.

The in vivo effect of recombinant human erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) combined treatment on CD34(+) cells was evaluated by fluorescence in situ hybridization (FISH) in 13 myelodysplastic syndrome (MDS) patients with known cytogenetic abnormalities. After treatment, responsive patients presented a significantly lower proportion of FISH abnormal CD34(+) cells than before treatment (P = 0.003), and in comparison with unresponsive cases (P = 0.007). Response to treatment was associated with a reduced degree of apoptosis in CD34(+) cells (P = 0.021): however, no difference in telomere length was observed in responsive patients after growth factor administration. Although the number of patients analysed was relatively small, the present data suggest that, in MDS patients, response to rHuEpo and G-CSF may be related to the proliferation of karyotypically normal but potentially defective CD34(+) progenitor cells.

In a rare case of follicluar dendritic cell sarcoma, malignant cells were isolated and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF-α). After 14 d, 15% of neoplastic cells differentiated into myeloid-dendritic cell-like elements as demonstrated by immunological and functional characteristics. These cells showed the same cytogenetic abnormality of the malignant clone (fluorescence in situ hybridisation analysis performed on CD1a+ cells) and were able to induce allogenic T-cell proliferation in the mixed leucocyte reaction. These data may indicate that antigen presenting capacity could be a functional state inducible in cellular elements which are believed not to be of hemopoietic origin. Further studies are warranted to confirm these findings and to clarify the possibility to use these cells to generate specific anti-tumoral immune responses.

The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0.038), CD38 (P = 0.058) and CD138 (P = 0.054) and CD45bright positivity (P = 0.014). suPAR levels correlated positively with soluble serum CD138 (P = 0.001), creatinine (P = 0.001), beta2-microglobulin (P < 0.001), disease stage (P = 0.017) and extra-BM involvement (P = 0.002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0.0214) and disease stage (P = 0.0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0.0278), high soluble serum CD138 (P = 0.0201) and high suPAR (P = 0.0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM.

Sequential nasopharyngeal aspirates from patients without respiratory symptoms undergoing hematopoietic stem cell transplantation (HSCT) were tested for genomic RNA of human metapneumovirus (hMPV). Persistent hMPV infection was documented in most of them and confirmed by virus isolation. hMPV infection etiology was also evaluated during the same period in samples from pediatric patients with acute respiratory diseases (ARDs). Sequence analysis of hMPV in HSCT recipients documented infection by hMPV genotype A and strong interhost similarity; this pattern differs from that observed in pediatric patients with ARDs. The data indicate that HSCT recipients may frequently develop symptomless hMPV infection.

Aims There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI). Methods and results Twenty patients with STEMI (mean age, 61±10 years), of whom 14 were submitted to primary percutaneous coronary intervention, were randomized to G-CSF (5 µg/kg/day s.c. for 4 consecutive days) or placebo. At entry and then at months 3 and 6, 99mTc-sestamibi gated-SPECT was performed to estimate extension of perfusion defect (PD) and LV function. The study drug was well tolerated and induced a significant increase of white blood count, CD34+ cells, and CD34+ cells coexpressing AC133 and VEGFR-2. At follow-up, treated and placebo groups did not differ for the angiographic coronary late loss and showed a similar pattern of PD recovery, whereas in the former at 6 months LVEF and especially LVEDV tended to be relatively higher ( P =0.068) and lower ( P =0.054), respectively. Conclusion G-CSF administration in acute MI patients was feasible and did not lead to any clinical or angiographic adverse events and resulted in CD34+ and CD34+AC133+VEGFR2+ cell mobilization.

Using quantitative fluorescence in situ hybridisation and flow cytometry (flow-FISH), we investigated the biological and clinical relevance of telomere length in 55 patients affected by myelodysplastic syndromes (MDS) compared with 55 sex- and age-matched controls. We found that telomere fluorescence in MDS granulocytes, and CD34+ cells did not decline with age as in normal controls and that MDS granulocytes and CD34+ cells had significantly shorter telomeres than healthy controls. A significant higher incidence of cases with intermediate-unfavourable cytogenetics and International Prognostic Scoring System (IPSS) int-2/high-risk group was observed among patients with lower telomere fluorescence. We also found that apoptosis in CD34+ cells was significantly higher in IPSS int-1 low-risk patients when compared with IPSS int-2 high-risk cases and healthy controls and that CD34+ cell telomere fluorescence directly correlated with CD34+ cell apoptosis. Reduced telomere fluorescence was associated with a history of occupational exposure to toxic agents and with worse survival in univariate and multivariate analyses. Our results suggest that flow-cytometry assessment of telomere dynamics may represent a valuable tool in the biological and clinical-prognostic characterisation of MDS disorders.

The in vivo effect of recombinant human erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) combined treatment on CD34(+) cells was evaluated by fluorescence in situ hybridization (FISH) in 13 myelodysplastic syndrome (MDS) patients with known cytogenetic abnormalities. After treatment, responsive patients presented a significantly lower proportion of FISH abnormal CD34(+) cells than before treatment (P = 0.003), and in comparison with unresponsive cases (P = 0.007). Response to treatment was associated with a reduced degree of apoptosis in CD34(+) cells (P = 0.021): however, no difference in telomere length was observed in responsive patients after growth factor administration. Although the number of patients analysed was relatively small, the present data suggest that, in MDS patients, response to rHuEpo and G-CSF may be related to the proliferation of karyotypically normal but potentially defective CD34(+) progenitor cells.

Background— Peripheral blood CD34 + cells and circulating endothelial progenitor cells (EPCs) increase in myocardial infarction and vascular injuries as a reflection of endothelial damage. Despite the occurrence of endothelial dysfunction in heart failure (HF), no data are available on EPC mobilization in this setting. We investigated the pattern of CD34 + cells and EPC mobilization during HF and their correlation with the severity and origin of the disease. Methods and Results— Peripheral blood CD34 + cells (n=91) and EPCs (n=41), assessed both as CD34 + cells coexpressing AC133 and vascular endothelial growth factor (VEGF) receptor-2 and as endothelial colony-forming units, were studied in HF patients (mean age 67±11 years) and 45 gender- and age-matched controls. Tumor necrosis factor-α (TNF-α) and its receptors (sTNFR-1 and sTNFR-2), VEGF, stromal derived factor-1 (SDF-1), granulocyte-colony stimulating factor (G-CSF), and B-type natriuretic peptide were also measured. CD34 + cells, EPCs, TNF-α and receptors, VEGF, SDF-1, and B-type natriuretic peptide were increased in HF. CD34 + cells and EPCs were inversely related to functional class and to TNF-α, being decreased in New York Heart Association class IV compared with class I and II and controls. No role was found for the origin of the disease. Conclusions— CD34 + cells and EPC mobilization occurs in HF and shows a biphasic response, with elevation and depression in the early and advanced phases, respectively. This could be related to the myelosuppressive role of TNF-α.

In a rare case of follicluar dendritic cell sarcoma, malignant cells were isolated and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF-alpha). After 14 d, 15% of neoplastic cells differentiated into myeloid-dendritic cell-like elements as demonstrated by immunological and functional characteristics. These cells showed the same cytogenetic abnormality of the malignant clone (fluorescence in situ hybridisation analysis performed on CD1a+ cells) and were able to induce allogenic T-cell proliferation in the mixed leucocyte reaction. These data may indicate that antigen presenting capacity could be a functional state inducible in cellular elements which are believed not to be of hemopoietic origin. Further studies are warranted to confirm these findings and to clarify the possibility to use these cells to generate specific anti-tumoral immune responses.

The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0.038), CD38 (P = 0.058) and CD138 (P = 0.054) and CD45bright positivity (P = 0.014). suPAR levels correlated positively with soluble serum CD138 (P = 0.001), creatinine (P = 0.001), beta2-microglobulin (P0.001), disease stage (P = 0.017) and extra-BM involvement (P = 0.002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0.0214) and disease stage (P = 0.0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0.0278), high soluble serum CD138 (P = 0.0201) and high suPAR (P = 0.0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM.

Abstract 3062 In the last few years the therapeutic armamentarium for AL amyloidosis has substantially increased with the introduction of new agents, such as bortezomib and immunomodulatory drugs. Although the probability of responding to the potent first line regimens also increased, still several patients are refractory to 2 or more agents, including new drugs. These patients often develop severe cardiac involvement, which further reduces the therapeutic options and portends a dismal prognosis. Given its toxicity profile, lenalidomide is an appealing therapeutic option for subjects with advanced disease. The efficacy of lenalidomide in AL amyloidosis has been reported by the Mayo Clinic (Dispenzieri et al, Blood 2007; 109: 465-70) and Boston (Sanchorawala et al, Blood 2007; 109: 492-96) groups. Overall, 56 patients were reported in these studies, 44 of whom were previously treated. However, prior exposure to bortezomib was not reported, and the median number of previous regimens was 1. In the present study we describe the outcome of 24 patients with advanced AL amyloidosis, refractory to both melphalan and bortezomib, who were treated with the combination of lenalidomide and dexamethasone (LDex). The patients received lenalidomide (15 mg on days 1–21 with dose reductions for renal failure) and dexamethasone (dex, 20 mg on days 1, 8, 15 and 22) in 28 days cycles, between July 2007 and July 2009. Prophylactic aspirin and omeprazole were also administered. Response was assessed after 2 cycles according to the 2005 International Society of Amyloidosis criteria (Gertz et al, Am J Hematol 2005; 79: 319-28). All the patients were refractory to prior melphalan (autologous stem cell transplant in 7 cases and oral melphalan plus dex in 17) and bortezomib plus dex. Moreover, 19 patients (79%) were also refractory to thalidomide (administered in association with cyclophosphamide and dex in 10 subjects and with dex alone in 9). The median number of prior treatments was 3 (range 2–5). Sixteen patients (67%) had heart involvement as assessed by echocardiography. According to the cardiac staging system based on NT-proBNP (cutoff 332 ng/L) and troponin I (cutoff 100 ng/L), 6 patients (25%) were stage 1 (both markers below the cutoff), 3 (13%) were stage 2 (only 1 marker elevated), and 15 (62%) were stage 3 (both markers elevated). Six patients (25%) had glomerular filtration rate Our results indicate that treatment can be continued in patients with advanced AL amyloidosis refractory to 2 or more prior regimens and that LDex is a valuable option in this setting. Disclosures: Off Label Use: Lenalidomide for systemic AL amyloidosis.

Abstract 3889 Poster Board III-825 Oral melphalan and dexamethasone (MDex) has been adopted in many referral centers as standard therapy for AL amyloidosis, particularly in patients who are not eligible for high dose melphalan (M) and autologous stem cell transplant (ASCT). A randomized trial failed to demonstrate the superiority of ASCT over MDex, and phase III trials are being designed to compare MDex with regimens including new drugs. However, only few small series of patients treated with MDex have been published so far. We report the outcome of 126 consecutive patients with AL amyloidosis who received first line MDex between January 2004 and December 2007. All the patients who were not eligible for ASCT with high dose M, due to any of the following conditions: age >60 years, N terminal natriuretic peptide type B (NT-proBNP) >332 ng/L, troponin I (cTnI) >0.1 ng/mL, glomerular filtration rate (eGFR) ≤50 mL/min, were included. Patients were given M (0.22 mg/Kg, or 0.16 mg/Kg if eGFR was 3% of body weight or complex ventricular arrhythmias at 24 h Holter ECG) on days 1-4 q28 days for up to 9 cycles. Treatment was discontinued if complete remission (CR) or partial hematologic response (PR) plus organ response (OR) was reached after 6 cycles, or in case of lack of response after 3 cycles. The International Society for Amyloidosis (ISA) consensus criteria for hematologic and organ response and progression were used. Progression free survival (PFS) was defined as the time to death or hematologic or organ progression according to the ISA criteria. Response and progression of NT-proBNP were defined as 3300 ng/L and 330% modifications. The median number of organs involved was 2 (range 1-5), 92 patients (73%) had heart involvement, with New York Heart Association (NYHA) class ≥2 heart failure in 66 cases (60%) and 93 patients (74%) had renal involvement, with eGFR 0.1 ng/mL in 27 patients (22%) and NT-proBNP was >332 ng/L in 99 (79%). Twenty-four patients (19%) experienced severe, though non fatal, adverse events. The most common was fluid retention (12%), that was significantly associated with NYHA class (p=0.02) and cTnI concentration (p Disclosures: No relevant conflicts of interest to declare.

Abstract 1782 Poster Board I-808 The heart is involved in approximately two thirds of patients with AL amyloidosis and the prognosis of the disease is largely dependent on the severity of cardiac damage. Heart dysfunction can be assessed by measuring the serum concentrations of N terminal natriuretic peptide type B (NT-proBNP) and of cardiac troponins (cTn). The combination of these biomarkers allows an accurate prognostic stratification of patients with AL amyloidosis. Recently, new generation of more sensitive assays for cTn, characterized by low limits of detection and low imprecision, have been developed, aiming at identifying minimal cardiac damage. We report the impact of a highly sensitive (hs) cTnT assay on detection of heart involvement, prognosis and response to therapy in 109 consecutive newly diagnosed patients with AL amyloidosis. The hs-cTnT was measured on the Modular E instrument with a precommercial immunoassay from Roche Diagnostics on frozen sera collected at the time of diagnosis and stored at -80°C. The 99th centile of hs-cTnT concentration in sera from 546 healthy volunteers is 14 ng/L (95%CI 12.4-24.9 ng/L). NT-proBNP and cTnI were measured with commercially available assays. The upper reference limit of NT-proBNP is 332 ng/L and for cTnI is 40 ng/L. Heart involvement was defined according to the International Society of Amyloidosis consensus criteria as a mean left ventricular wall thickness (mLVW) >12 mm in the absence of other causes. Sixty-nine of the 109 patients (63%) fulfilled the echocardiographic criteria of heart involvement. Among these patients, 74% had elevated cTnI, 96% had high hs-cTnT and 100% had elevated NT-proBNP. Fifteen patients who did not have echocardiographic heart involvement at presentation reached a mLVW >12 mm within 6 months from diagnosis. Among them, cTnI was elevated at presentation in 33% of cases, hs-cTnT in 80% (p=0.01 compared to cTnI) and NT-proBNP in 73%, indicating that hs-cTnT and NT-proBNP can detect amyloid cardiac involvement when it is still unapparent by conventional echocardiographic criteria. Thirty-seven (34%) patients died and the median follow-up of living patients was 38 months (range 14-67 months). Survival was reduced in patients with hs-cTnT >14 ng/L (58% vs. 84% surviving at 3 years, p=0.01) and NT-proBNP >332 ng/L (58% vs. 86% surviving at 3 years, p=0.02) and cTnI >40 ng/L (52% vs. 75% surviving at 3 years, p=0.007). At multivariate analysis ln(hs-cTnT) was the only variable significantly associated with survival (HR 1.576, 95%CI 1.048-2.371, p=0.03). All the patients were treated with melphalan-dexamethasone and 66 (60%) reached hematologic response. The hs-cTnT cutoff best predicting survival after treatment was 68 ng/L (45% vs. 80% surviving at 3 years, p=0.0003). This cutoff, in combination with hematologic response to therapy, could differentiate the patient population into 3 groups with significantly different survival. Estimated survival at 3 years was 30% in non responders with hs-cTnT >68 ng/L, 51% in those who obtained either hematologic response or had hs-cTnT Cardiac troponin measured with a high-sensitivity assay significantly improved the sensitivity, compared with commercially available troponin assay, for cardiac damage caused by AL amyloidosis and represents now the most powerful prognostic determinant. Patients who obtain hematologic response and a hs-cTnT concentration below the threshold of 68 ng/L enjoy prolonged survival. Disclosures No relevant conflicts of interest to declare.

From 1996 to 2003, 113 consecutive patients with multiple myeloma were treated with four different high dose approaches rescued by autologous peripheral blood progenitor cells (PBPC) after four cycles of VAD or other combinations. The median age was 53 years 31–68), 58% were male and 42% female, the median interval from diagnosis to transplant was 252 days (range 160–3116 days). Twenty-five patients received as preparative regimen Carmustine, Etoposide and Melphalan (BVM) at the total dose of 600 mg/m2, 900mg/m2 and 140–180 mg m2 respectively. Nineteen pts had as preparative regimen Thiotepa and Melphalan at the total dose of 10 mg/kg and 140–180 mg/m2 respectively, 38 pts received a double transplant with Melphalan given as a single agent at the dose of 200 mg/m2, while 31 pts received a single transplant with Melphalan 200 mg/m2. In patients with poor performance status at transplant or previous history of infection or renal impairment, the dose of melphalan was reduced by 20% respect to the standard planned dose. in the group of 25patients treated by BVM, 10 had progressive disease, 6 stable disease (SD), 7 partial remission (PR), 1 very good partial remission (VGPR). At day +90 from transplant, 17 patients were in CR or PR (68%). The actuarial probability of overall survival and event free survival at 5 years were 40% and 20%, respectively. One pt died of transplant, one developed a solid tumor 24 mos after transplant. in the group of 19 pts treated with TT and Mel (TT-Mel), 3 pts were with progressive disease, 3 with stable disease, 6 in partial remission, 3 with minimal response, 3 in VGPR, 1 in CR. At day +90, 15 pts were in CR or PR (78%). The actuarial probability of survival was 50% at 5 years, and event free survival 28%. in the group of 38 pts who received a double transplant, 7 pts were with progressive disease, 3 with stable disease, 14 in PR, 12 in VGPR or CR. At day +90 after the second transplant, 31 of 38 patients (81%) were in CR or PR. Overall survival and event free survival was respectively 48% and 20% at five years. in the group of 31 pts receiving a single transplant with Melphalan alone, 8 were with progressive disease, 1 with stable disease, 6 in VGPR, 1 in CR, 13 in PR. At day +90, 21 of 31 patients (67%) were in CR or PR. Overall survival and event free survival was respectively 45% and 22% at five years. In conclusion, double transplant seems better than one transplant with melphalan alone in terms of EFS and OS (p

The human metapneumovirus (hMPV) has been described as possible cause of respiratory disease in pediatric and adult subjects. There are not, however, data concerning the epidemiology and or the clinical impact of hMPV infection in adults receiving allogeneic hemopoietic stem cell (HSC) transplant. We report the results of a prospective study aimed to asses the incidence of hMPV infection in patients undergoing allogeneic HSC transplant. We analyzed by reverse transcription PCR assay, the presence of hMPV in nasopharingeal aspirate (NPA) collected before transplant and on day 0, +15, +30, +60, +90, +180, +360 from transplant. Detection of hMPV RNA was based on two set primers pair located in the L and N genes. Amplified hMPV RNA was sequenced for genotyping in region N. Twenty patients with a median age of 37 yrs (range 25–58), receiving allogeneic HSC for hematological disorders (AML 11 pts, ALL 5 pts, MDS 2 pts, NHL and MM 1 pt each), entered the study. Six pts received transplant from an HLA identical sibling and 14 from an unrelated donor (MUD). As preparative regimen, 15 pts had a standard myeloablative conditioning regimen, and 5 received reduced intensity conditioning with Thiotepa and Fludarabine. Acute graft-versus-host-disease prophylaxis consisted of Cyclosporine A and Methotrexate. In 6 pts receiving MUD transplant, in vivo T depletion by ATG was performed. At transplant, all patients were in good performance status and none had signs of active acute respiratory disease. Of 20 patients, four had a prior history of pulmonary infection from agents different from hMPV. Of 49 NPA samples analyzed so far, 29 (59%) resulted hMPV-positive. Sequence analysis performed in 12 patents detected a virus genotype-A. Of 12 pts in whom 3 or more NPA samples were collected, 9 (45%) resulted positive for hMPV RT-PCR, with persistence of infection for a period ranging from 14 to 84 days. No patient, however, showed clinical signs of respiratory disease. These data indicate an high prevalence and a long persistence of asymptomatic hMPV infection in adults receiving allogeneic HSC transplant.

Abstract 2863 Poster Board II-839 Despite significant toxicity, thalidomide is effective in AL amyloidosis. A study of the United Kingdom National Amyloidosis Centre showed that the association of cyclophosphamide, thalidomide and dexamethasone produced a high hematologic response rate. Lenalidomide is a potent analogue of thalidomide and two independent phase II trials by the Mayo Clinic and the Boston groups demonstrated its activity, alone and in combination with dexamethasone, in AL amyloidosis. In both studies the dose of 25 mg/day, commonly used in multiple myeloma, showed significant toxicity. A lower dosage of 15 mg/day was generally better tolerated. In the present trial (NCT00607581) we evaluated the combination of cyclophosphamide, lenalidomide and dexamethasone (CLD) in previously treated patients with AL amyloidosis. Main exclusion criteria were overt multiple myeloma, having both N terminal natriuretic peptide type B (NT-proBNP) >332 ng/L and troponin I (cTnI) ≥0.1 ng/mL, New York Heart Association (NYHA) class 4 heart failure, glomerular filtration rate 3. The patients received up to 9 cycles of C (500 mg on days 1, 8 and 15), L (15 mg on days 1-21), and D (40 mg on days 1, 8, 15 and 22) every 28 days. The protocol was amended to allow starting with D 20 mg in patients who presented with severe fluid retention (>3% of body weight). The patients received prophylactic aspirin (100 mg/day) and omeprazole (20 mg/day). Treatment was discontinued if complete remission or partial hematologic response plus organ response was reached after 6 cycles, or in case of lack of response after 3 cycles. Twenty patients were enrolled. Organ involvement was cardiac (60%), renal (80%), hepatic (25%) and nerve (20%). Median (range) NT-proBNP was 872 ng/L (62-2778 ng/L) and cTnI was 0.02 ng/mL (0-0.09 ng/mL). Eleven patients (55%) received 1 previous treatment line, 6 (30%) had 2 prior treatments and 3 patients (15%) underwent to 3 previous therapies. All the patients were exposed to melphalan, 5 (25%) to thalidomide and 3 (15%) to bortezomib. Twelve subjects (60%) were refractory to previous treatment and the remaining had relapsed. Twelve patients (60%) experienced severe adverse events (grade 3 in all cases): neutropenia in 6 cases (30%), fluid retention in 2 (10%), renal failure in 2 (10%), thrombocytopenia and rash in 1 patient (5%) each. Treatment was discontinued only in the patient who experienced skin rash. Fluid retention, though not severe, was common and D was reduced to 20 mg in 11 of the 18 patients who started with full dosage. Six patients (30%) required L dose reduction. Notably, NT-proBNP increased by at least 30% and 300 ng/L (median 220% and 2024 ng/L) in 14 patients (70%) after cycle 1. This increase occurred in all the 12 patients with heart involvement, was accompanied by an increase by at least 0.05 ng/mL in cTnI in 6 cases, was asymptomatic and was not associated with modifications in NYHA class, ejection fraction, creatinine, fluid retention, hematologic response and survival. Four patients (20%) died after a median of 8 months (range 6-11 months) due to heart failure (2) and sudden death (2). Median survival was not reached. With a median follow-up of 9 months, 8 patients (40%) obtained a hematologic response that was complete in 1 case (5%). Median time to response was 1.9 months (range 0.8-3.9 months). Organ response was reached in 3 patients (proteinuria in 2 cases and neuropathy in 1). Treatment with CLD proved effective in this cohort of heavily pretreated patients and warrants further investigation. Adverse events were frequent but not fatal and they could be managed by dose adjustments. Treatment with CLD causes an asymptomatic increase in cardiac biomarkers that should be considered when evaluating organ response. Disclosures: No relevant conflicts of interest to declare.