ALBERT

Description: Sezary syndrome (SS) and advanced tumor-stage mycosis fungoides (MF) have an aggressive clinical course, ultimately leading to a very short survival. Because patients are often elderly and show poor clinical conditions, conventional allogeneic hematopoietic stem cell transplantation is associated with a undesirable high TRM; therefore, allogeneic reduced-intensity conditioning (RIC) HSCT represent an attractive and worth-investigating strategy of cure in this disease setting. In our Institutions, from September 2000 to May 2006, fifteen patients with advanced mycosis fungoides or Sezary Sindrome underwent RIC allogeneic hematopoietic stem cell transplantation either from HLA-identical sibling, or from HLA-matched unrelated donor, or from unrelated cord blood. Conditioning regimens for patients with HLA-identical sibling included fludarabine/cyclophosphamide/TBI200 up to 2001, then pentostatin/TBI200. Patients who underwent unrelated transplants were treated with melphalan/CP1H/Fludarabine/TBI200 combination. All patients (10 males and 5 females) had a clinical diagnosis of MF (10 pts) or SS (5 pts) confirmed by histopathology, immunohistochemistry and molecular biology. Median age was 48 years (range 38–65). Median time from diagnosis to transplant was 48 months (range 13 to 252). Disease stage for all patients was from IIIB to IVB. GVHD prophylaxis included oral Cy-A from day 0 to day +100 and oral MMF from day 0 to day +27, then tapered within 2 weeks. The source of donor stem cells was peripheral blood and bone marrow for siblings and MUD, respectively. A complete clinical remission was achieved in 10 patients, whereas 2 patients obtained a VGPR. Five patients died from various complications (3 with progressive disease, 1 in CR e 1 in PR) within a period ranging from 33 days to 8 months after transplant. A full donor chimerism was achieved within 6 months in 8 out of 10 evaluable patients, whereas no engraftemnt was observed in 2 patients (1 MUD and 1 UCB). 5 patients experienced acute GVHD of grade I–II, while limited chronic GVHD occurred in 7 patients. With a median follow-up of 38 months (range 2–70), ten patients were alive with an estimated overall survival greater than 60% at five years (Figure 1), whereas 7 patients were alive and disease-free at the last follow-up. Based on these highly encouraging results, we conclude that RIC allogeneic HSCT represents a feasible and effective treatment for advanced mycosis fungoides and Sezary Syndrome. Further studies in larger patient populations are warranted to confirm the curative potential of this strategy. Overall Survival in MF/SS following RIC allo-HSCT Overall Survival in MF/SS following RIC allo-HSCT

Description: Introduction. Multiresistant (multiR) bacteria are emerging pathogens in hematologic cancer patients (pts) and may negatively impact on the outcome of bloodstream infections (BSI). The antibiotic pressure, including fluoroquinolones (Fq) prophylaxis, may be one of the factors responsible for this phenomenon. In order to better define the very recent epidemiology and outcome of BSI in a real-life setting, we planned a prospective study collecting all consecutive febrile/infectious episodes occurring in acute leukemia (AL) pts admitted to 9 hematological institutions participating to REL, representing about 75% of the entire AL population treated in Lombardy. Patients and Methods. From Dec-2012 to Jul-2014, all febrile/infectious episodes were recorded. The following data concerning BSI were analysed: age, gender, type and phase of leukemia, neutropenia, Fq prophylaxis, presence of central venous catheter (CVC), concomitant pulmonary infiltrates, antibiotic resistance. Results. In 218 AL pts (M/F 131/87; median age 54y, range 17-80; AML/ALL 181/37), 314 BSI were diagnosed. In 180 (57.3%) BSI occurred in pts on Fq prophylaxis. In 71 (22.6%) pneumonia was also present. Gram-positive cocci (GPC) were isolated in 145/314 BSI (46.2%); Gram-negative rods (GNR) in 117 (37.3%), polymicrobial (PMB) aetiology in 48 (15.3%) and fungi (F) in 4 (1.3%). Coagulase-negative staphylococci (CoNS) were the most frequent GPC (105/314, 33.4%); S. aureus, S. viridans and enterococci were observed in 7 (2.2%), 17 (5.4%) and 37 (11.8%) cases, respectively. Methicillin-resistant strains accounted for 75.9% of all staphylococci and vancomycin-resistant strains for 2.7% of enterococci. CVC-related BSI, which accounted for 31.4% of BSI occurring in pts with CVC, was independently correlated with GPC aetiology (OR 1.9, CI 1.1-3.1, p=0.01). Considering GNR, Enterobacteriaceae were isolated in 113/314 BSI (36%) and P. aeruginosa in 31 (9.9%). GNR occurred more frequently during consolidation cycles (45.8% vs 31.1%) and in pts not on Fq prophylaxis (44.2% vs 32.2%). Both conditions were independent risk factors at multivariate analysis (p=0.002 and p=0.02, respectively). Frequency of Enterobacteriaceae BSI was also higher during consolidation cycles in comparison with other AL phases (48.1% vs 27.3%, p=0.0005), but Fq prophylaxis was no longer a protective factor (35% vs, 37.3%). Fq resistance was observed in 63/113 (55.7%) of Enterobacteriaceae; in 84.1% of cases were detected during Fq prophylaxis. ESBL+ strains, which accounted for 24.8% of Enterobacteriaceae, were also associated with Fq prophylaxis (OR 2.8, CI 1.1-7.1, p=0.02) at multivariate analysis. Carbapenemase producing (CP) strains occurred in 8.8% of Enterobacteriaceae. Among P. aeruginosa strains, 19.4% were multiR. Thirty-day mortality was 7.6% (24/314); it was lower for GPC (5.5%) in comparison with GNR (9.4%) and PMB BSI (11.6 %). CP Enterobacteriaceae or multiR P. aeruginosa BSI (30d mortality: 33.3%; OR 21.3, CI 4.4-102.4, p=0.0001) but not ESBL+ strains were independent predictors of death. Furthermore, having relapsed/resistant AL (18.2%; OR 9, CI 2.7-30.7, p=0.0004), and the presence of concomitant pulmonary infiltrates (26.8%; OR 15, CI 4.8-46.8, p

Description: Abstract 4949 Mantle Cell Lymphoma (MCL) is a rare lymphoma that accounts for 3–10% of all non Hodgkin's Lymphoma in adults. Being associated with rapid progression and high recurrence rate, although some treatment improvements during the last years, it is still considered an incurable disease. In order to overcome the poor outcome obtained with conventional chemotherapy, new treatment strategies using high dose chemotherapy supported by autologous stem cell transplantation (ASCT) have been developed in young patients. In particular the use of high dose cytarabine and rituximab prior to ASCT has been demonstrated to improve outcome in terms of response and disease free survival. The present study is a restrospective analysis conducted in our centre in order to evaluate the outcome of 16 MCL patients treated upfront with sequential high dose immunochemotherapy followed by double ASCT. From 2000 to 2011, 16 MCL patients, eligible for ASCT, have been consecutively treated as follow: a) standard dose phase: APO: doxorubicin, 75 mg/sqm i.v., day 1; prednisone, 60 mg/sqm orally, day 1 to 5 and day 9 to 12; vincristine, 1.4 mg/sqm i.v., day 1 and 8; DHAP: cisplatin 70 mg/sqm, day 1; cytarabin 1500 mg/sqm i.v., days 2–3; dexametasone 40 mg i.v., days 1 to 3; b) rituximab high dose sequence: high dose cyclophosphamide (CTX 5 g/sqm) and high dose cytarabine (Ara-C 2 g/sqm every 12 hours for 6 consecutive days) followed by peripheral blood stem cell (PBSCs) collection; c) high dose melphalan (180 mg/sqm) and high dose mitoxantrone plus melphalan (60 mg/sqm and 180 mg/sqm, respectively) followed by PBSCs infusion. Rituximab (375 mg/sqm) was infused twice after CTX, cytarabine and double autologous transplantation (modified from Gianni et al, Blood, 102, 749, 2003). All patients (9 female and 7 male) had a histological diagnosis of MCL according to the WHO classification criteria; molecular rearrangement of bcl-1 locus was detected by PCR in the bone marrow of 8 patients. The median age at diagnosis was 57 years (range 50–68); 14 patients were in stage IV and 2 in stage III; 2 patients had bulky disease at presentation. Four patients were in overt leukemic phase and 2 had extranodal localization. According to MIPI score, 14 patients (87%) were classified as low risk and 2 (13%) as intermediate risk. Double transplant was performed in all patients except one (who refused it). The standard dose phase, including a median number of 4 cycles (range 3–5), was generally well tolerated, with only one patient experiencing tumor lysis syndrome. After induction, clinical CR was achieved in six patients. PBSCs were successfully collected after both the CTX/rituximab (1.8-9.7×10̂6/Kg) and the Ara-C/rituximab (7.1- 40.0×10̂6/Kg) cycles. At the end of these phases, 7 patients (44%) were in CR while 9 (56%) were in PR. Following transplants, median times to ANC 〉500/μL were 11 days (range 10–14) in both the procedures, whereas median times to platelet recovery (〉50000/μL) were 19 days (range 10–44) after the first transplant and 24 days (range 11–298) after the second one. After a median follow-up of 38 months (range 14–111), 10 patients (62%) were alive (8 in CR, 2 in relapse), whereas 6 died from disease progression. Our study confirmed that in MCL the use of sequential high dose immunochemotherapy including rituximab and high dose cytarabine followed by double autologous transplantation is associated to high remission rates with long-term disease-free survival in a significant proportion of patients. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication after hematopoietic stem cell transplantation (HSCT) with a variable incidence depending on different diagnostic criteria adopted in the past. Patients and Methods The current study enrolled 551 consecutive patients (pts) (314 males, median age 29 years) undergoing HSCT from January 2000 to April 2005 from HLA match (m) or mismatch (mm) family donor (350/551) and unrelated donor (201/551) for malignant (501/551) or non malignant diseases (50/551). The diagnosis of TTP was performed on the basis of homogeneous five clinical and seven laboratory criteria. Univariate (by chi square test and Fisher’s exact test) or multivariate (by logistic regression method) analyses were performed to evaluate the effect of some candidate risk factors on both TTP occurrence and outcome. Results Sixty four of 551 pts presented TTP (11,6%) at a median time of 47 days post-HSCT; 59/64 were affected by malignant and 5/64 by non malignant diseases. Multivariate analysis showed GVHD 〉II° (p=0,0001), stem cell donors (m/mm unrelated or mm related) (p=0,024), female gender (p=0,0186),TBI-based conditioning regimen (p=0,03) and status of hematological remission (p=0,03) as factors influencing the occurrence of TTP. Only three predicting factors for TTP outcome have been demonstrated statistically significative by multivariate analysis: age (p=0,0186), stem cell donors (m/mm unrelated or mm related) (p=0,01) and TTP index (p=0,018). The TTP mortality rate was 40% while the outcome after TTP diagnosis was partially influenced by TTP treatment. In particular, Defibrotide seemed to be a promising drug in univariate analysis compared with alternative therapies for 34 alive and good responders pts out of 64 TTP pts. Conclusions The study underlines the possibility to identify those patients who are more prone to develop post-HSCT TTP, complication still frequent (11,6%) when homogeneous diagnostic criteria are adopted. TTP outcome seems to be conditioned by some peculiar risk factors as adult age, m/mm unrelated or mm related donors HSCTs. Prospective randomized therapeutic trials, focusing on the possible advantage of Defibrotide versus other treatments, should be encouraged.

Description: Metabolic syndrome (MS), formerly known as X-syndrome, is a clinical and laboratory entity involving obesity, hypertension, and borderline fasting glucose, high triglyceride and low HDL cholesterol levels, that is considered to be a counterpart of insulin resistance with overweight playing a key role; increased insulin, leptin, adiponectin and resistin levels link its various features and some common flanking findings such as hypercholesterolemia, hyperuricemia and hyperferritinemia. Clinical and laboratory data reminiscent of metabolic syndrome are commonly observed after hematopoietic stem cell transplantation (HSCT). We evaluated the body mass index (BMI), routine lipid and glucidic markers, and common endocrinologic parameters in 37 HSCT recipients (19 males; median age 45 years, range 26–60; 22 autologous, 15 allogeneic) whose continuous CR lasted at least five years; insulin (baseline and after an oral glucose test), leptin, resistin, TNF-alpha and adiponectin levels were also detemined. Diabetic HSCT recipients were excluded. The control group consisted of 23 healthy volunteers of comparable age and sex without a family history of diabetes. In comparison with the controls, the HSCT recipients had significantly increased levels of TNF (median 10.05 vs 9.3 pg/mL, p=0.034), insulin (13.6 vs 10.1 mIU/mL, p=0.029) and leptin (13.71 vs 3.69 ng/mL, p= 0.02); there were no significant differences in adiponectin and resistin levels, BMI or the other considered parameters. In comparison with the other HSCT recipients, the 16 patients with higher baseline insulin levels (〉15 mIU/mL) had significantly higher leptin levels (median 23.665 vs 8.3, p