ALBERT

Description: Background In younger and fit multiple myeloma (MM) patients (pt), autologous stem cell transplantation (ASCT) remains the gold standard treatment. Mobilization chemotherapy is usually administered in an inpatient regimen and Cyclophosphamide (CY) at different doses is the most used chemoterapy for collecting peripheral blood stem cells (PBSC) in MM. Clinical trials have demonstrated that intermediate dose CY (3 and 4 g/m2, ID-CY) combined with G-CSF, is an efficient mobilizing regimen with less toxicity compared with high dose CY (7 g/m2, HD-CY) in term of neutrophil recovery, thrombocytopenia, need of transfusions and IV antibiotics. (Fitoussi et al, BMT 2001; Goldschmidt et al, BMT 1996). Objective To evaluate the safety of mobilization therapy administered in an outpatient regimen, with the prospect to lower costs and minimize patient inconvenience, maintaining an optimal yield. Methods 92 pt with newly diagnosed MM underwent outpatient stem cell mobilization between 2002 and 2016 with CY 3 g/m2 (82%) or 4 g/m2 (18%) + G-CSF after induction therapy with bortezomib-based (79%) or VAD-like (21%) regimens. No antibiotics prophylaxis was routinely used. Day 0 was defined as the CY infusion day. CY was administered in 2-4 consecutive 1h infusions (depending on total dose). Hyper-hydration (3.5/4 l), antiemetics and the uroprotectant Uromitexan were began IV 1 hour before CY infusion. Subsequently, Uromitexan was continued at home orally in the next 12h. Furthermore, the patient was advised to drink 2.5/3 l of water in the next 24h. G-CSF 10 mcg/Kg was started by day +5 and continued until completion of apheresis. Blood count was monitored at day + 4 and daily from day +7. CD34+ cells were counted on peripheral blood by day 7; apheresis was started at leukocyte rise and with a value of at least 20 CD34+/μl. Number of apheresis depended on the number of CD34+ cells collected to obtain al least 4x106 CD34+/Kg. Results Median age at diagnosis of was 56y (range 34-68). MM isotype was IgA, IgG and micromolecular respectively in 18%, 58% and 24%. Prior MGUS was present in 37 cases (43%). LDH was elevated in 7 pt (11%), whereas ISS was 1/2/3 in 47%/30%/23%. Bone disease was detectable in 74% of pt, with 56% having 3 or more osteolysis. Median bone marrow plasma cell at diagnosis was 60% (range 10-95%). Pt received induction with bortezomib-based regimens (79%) or chemoterapy, mostly VAD (21%). 8 pt (9%) required second line therapy before mobilization. Response prior of mobilization was CR/sCR in 15%, VGPR in 59%, PR in 24%, and SD in 2%. Stem cell collection was successful in 98% of pt, with a median CD34+ harvest of 9.8x106/Kg. Chemotherapy was very well tolerated. Most frequently observed adverse events (AEs) were nausea and vomiting of grade 1-2. 2 pt experienced cystitis (one grade 1, one grade 2), 2 pt infections, 2 pt hyperthermia regressed rapidly without therapy, 1 patient diarrhea. 3 pt had neurological symptoms: in 2 cases they were aspecific (headache, instability); the other case presented a sudden appearance of 7th cranial nerve deficit at the end of mobilization chemotherapy infusion with negative imaging and successively regressed in few hours, interpreted as transient ischemic attack not correlated with Cy. Only 2 patient required hospitalization for AEs: 1 patient for fever grade 3 without microbiological findings, rapidly regressed with IV antibiotics; the second one for 7th cranial nerve deficit. These were the only grade 3 AEs, no grade 4 AEs verified. There were no other significant AEs related to chemotherapy. All pt except 2 proceeded to stem cell harvest and reached CD34+ target, but 5 pt required administration of Plerixafor on demand. The 2 pt not reaching CD34+ target successfully mobilized afterwards, 1 with different chemoterapy and the other with G-CSF and Plerixafor. After mobilization, 88 pt proceeded to single (45%) or double (55%) ASCT. Conclusion In conclusion, outpatient mobilization with ID-CY appears to be an efficient and safe procedure, with minimal and manageable side effects and low rate of hospitalization. Outpatient mobilization could ameliorate the quality of life of pt and reduce costs, avoiding or minimizing the hospitalization rate, without compromising the safety profile and the success of PBSC collect. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2876 Background: HCV infection has been demonstrated to be involved in clonal B cell proliferation and in the subsequent development of non-Hodgkin's lymphoma (NHL). The regression of NHL after antiviral treatment is considered an indirect evidence of this pathogenetic relationship. Aim: to evaluate clinical course of patients affected by HCV infection (serology and HCV RNA positive) and low grade B-cell NHL (LG-NHL), not needing immediate treatment (absence of B symptoms, bulky disease or symptomatic tumor mass and lymphocyte doubling time less than 6 months) and treated upfront with antiviral therapy alone. Method: From 2006 to 2010, 13 patients, affected by LG- NHL at diagnosis have been treated with pegylated interferon (PegIFNa2a, 100–180 mcg weekly) and ribavirin (Rbv, 800–1200 mg daily) for a median treatment period of 6 months (6-18 months). Two patients are still in treatment. M/F ratio was 1.6 and median age was 59 years (range 51–73). The study included 9 marginal zone lymphomas (MZL: 2 splenic MZL, 7 extranodal non gastric MZL), 3 LG-NHL NOS and 1 lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL). Cryoglobulin were present in five patients. 7 pts had genotype 2, 5 pts genotype 1b, one not assessed; HCV infection was detected before lymphoma diagnosis in 9 pts and at lymphoma onset in 4 pts. Only 2 patients have previously received other combinations of antiviral therapy. Virologic response was assessed monthly by HCV-RNA polymerase chain reaction (PCR) and hematologic response was evaluated according to International Working Group response criteria (Cheson et al. J Clin Oncol. 2007) at the end of antiviral therapy. Results: Eleven patients completed the planned treatment course. Sustained virologic response (SVR) was achieved in 9 patients (6 with genotype 2); viremia clearance was achieved in a median period of 2 months (1-6). Among patients that gained a SVR, 5 achieved a complete response (CR) (3 genotype 2, 1 1b, one not assessed), one (genotype 2) partial response (PR), and 3 (2 genotype 2 and one genotype 1b) presented stable disease (SD). The remaining patients obtained only a reduction of viremia: one presented a SD and one was in PR. The treatment was well tolerated without any WHO grade III-IV toxicity. Among patients that completed treatment program, more frequent toxicity was haematological (one patient developed a WHO grade 1 anemia and one patients developed WHO grade 1 anemia and grade 2 neutropenia). After a median follow up of 17 months from the end of therapy (range 3–44), considering the 9 patients in SVR, only 2 (1 CR and 1 PR) progressed, maintaining SVR and one lost SVR maintaining SD. Patients that obtained only a reduction of viremia, maintained their hematologic status. Conclusion: We described a high CR rate in patients that obtained SVR after antiviral therapy (55%); the relationship between hematologic and viral response during follow up is not always stringent. We confirm that antiviral therapy could be considered as frontline therapeutic option in cases of HCV-related LG-NHL not requiring immediately immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Lenalidomide (Len) and low-dose Dexamethasone (dex) (Rd) in continuous is a new standard of care for elderly newly-diagnosed multiple myeloma (NDMM) patients (pts), as established by FIRST trial (Facon et al, Blood 2018). Methods and results This is a retrospective, multicentric study conducted in Italy with the aim of evaluating efficacy and tolerability of Rd in a real-life population. Thirty-seven centers were involved and data of 429 pts are available. Pts were considered eligible for the study when completing at least 2 cycles of Rd regimen. Table 1 summarizes the characteristics of pts at time of MM diagnosis. Median age was 78 years (range 57-92), 36.6% had an ECOG PS≥2, creatinine clearance (ClCr) was ULN (P=0.01) and ClCr2 still impact on OS (p

Description: Abstract 2878 Primary plasma-cell leukemia (pPCL) is an aggressive, rare variant of plasma cell (PC) dyscrasia characterized by extra-medullary proliferation of PCs, high genomic instability and very poor prognosis. The present study was aimed at investigating global genomics in 17 pPCL recruited in an open-label, exploratory, single-arm, two-stage study from the GIMEMA myeloma network designed to evaluate the safety and antitumor activity of lenalidomide in combination with low dose dexamethasone as first-line therapy in pPCL. All the samples were characterized for the main chromosomal aberrations by Fluorescence In-Situ Hybridization (FISH). Specifically, 13q and 17p deletions have been identified in 13 (76.5%) and 6 (35.3%) cases, respectively; the presence of t(11;14) translocation was found in 7 patients (41.2%), t(4;14) in 2 (11.8%) and t(14;16) in 7 (41.2%). To better define the chromosomal alterations of this set of patients, we further investigated them by means of Human Mapping 250K Nsp SNP-array (Affymetrix). SNP-array data were fully concordant with FISH results as regards 13q and 17p deletions in the analyzed patients. Among the copy number alterations identified by mapping analysis the most frequently gained chromosomal region was represented by 1q (9 cases, 52.9%); 1p, 8p, 14q, and 16q arms were affected by loss of DNA material in more than 40% of cases. Moreover, four patients showed gain at 7q (23.5%), one case displayed a near tetraploid karyotype and another one had a hyperdiploid-like pattern. Most of the minimally altered regions identified on the different chromosomes encompassed genes that have been reported to be deregulated in PC dyscrasia, such as CDKN2C (mapped to 1p32.3), FAM46C (1p12), CKS1B (1q21.2), PARK2 (6q26), PPP2R2A (8p21.2), RB1 and MIR-15A/16-1 (13q14.2), TRAF3 (14q32.32), CYLD (16q12.1), WWOX (16q23.3-q24.1), and TP53 (17p13.1). The mutational analysis of the most frequently mutated exons (5–9) of TP53 gene revealed the presence of coding mutations in 4 patients (23.5%), three of which carried a monoallelic deletion including the gene locus. This supports the knowledge that the prevalence of TP53 mutations increases in more advanced disease and is strongly associated with hemizygosity. Genome-wide profiling data were then integrated with the transcriptional profiles generated on Gene 1.0 ST array (Affymetrix). Our analysis (Wilcoxon rank-sum test at a P

Description: Abstract 107 BACKGROUND: ASCO and EORTC guidelines recommend granulocyte colony-stimulating factor (G-CSF) primary prophylaxis for cancer patients with a ≥20% overall risk of febrile neutropenia (FN), and to support delivery of dose-dense regimens. CHOP-like regimens (with rituximab [R]) are the current standard of care for the management of aggressive non-Hodgkin lymphoma (NHL), but they are often associated with significant myelosuppression. Neutropenic events, particularly febrile neutropenia (FN), can be life-threatening and may lead to dose delays or reductions that compromise the efficacy of chemotherapy. In IMPACT NHL, we evaluated current practice in FN risk assessment and use of G-CSF prophylaxis in patients receiving (R)CHOP. METHODS: IMPACT NHL is a retrospective and prospective observational study conducted in 14 European countries and Australia. Physicians assessed the overall FN risk of NHL patients and their need for G-CSF prophylaxis. This analysis focuses on patients with diffuse large B-cell lymphoma (DLBCL) receiving either 2-weekly R-CHOP-14 or 3-weekly R-CHOP-21. FN risk was assessed according to EORTC guidelines (i.e. the total risk from the chemotherapy regimen plus individual patient risk factors). The primary outcome measure was the proportion of patients assessed as being at ≥20% risk of FN and who were planned to receive primary prophylaxis with a G-CSF (defined as G-CSF initiation within days 1-7 of cycle 1). RESULTS: Data were available for 1829 patients who initiated chemotherapy between 01/2005 and 08/2008; 1136 had DLBCL. The mean age±SD of patients receiving R-CHOP-21 (N=704) was 62.6±13.8 years, 51% were aged ≥65 years and 53% had Stage III-IV disease. For R-CHOP-14 patients (N=409), the mean age was 58.4±14.7 years, 41% were ≥65 years and 59% had Stage III-IV disease. In total, 434 R-CHOP-21 patients were assessed as being at high risk for FN and 47% of them actually received G-CSF primary prophylaxis (with either pegfilgrastim or daily G-CSF) (see Table). Furthermore, almost a fifth of patients assessed as being at

Description: Introduction Hematologic neoplasms are associated with an increased incidence of autoimmune events, particularly evident in non‐Hodgkin lymphomas (NHL) and especially chronic lymphocytic leukemia (CLL); until now only few cases have been described in patients affected by multiple myeloma (MM) and other plasma cell disorders. The introduction of new drugs, in particular immunomodulatory drugs (IMiDs), could increase the risk of these complications. Herein we describe four cases of immune thrombocytopenia (ITP) occurred during Lenalidomide (LEN) therapy in 3 patients affected by MM and 1 with light‐chain amyloidosis. Case reports Case 1. A 66‐year old woman with relapsed IgGk MM started 2th line treatment with LEN/DEX 25 mg/d-20 mg/w. During the first 5 cycles she presented moderate hematologic toxicity which resolved after dose reduction (LEN 15 mg/d). A severe and isolated thrombocytopenia appeared after 5th cycle with patient in good partial remission (PR) for MM. A bone marrow evaluation showed absence of plasma cells and abundant megakaryocytes leading to a diagnosis of ITP. LEN was interrupted and steroid therapy (prednisone 1 mg/Kg) and IV Ig infusion administered, obtaining a transient good response (from 17 to 114 x 109/l). LEN was then restarted at lower dosage but a month after, while myeloma still was in good response, ITP relapsed complicated by intracranial hemorrhage and was successfully treated with IV Ig; Len was definitely interrupted. At the third relapse Rituximab (750 mg/w x 4 weeks) was administered with only minimal increase of platelet count (Fig 1). Afterwards, the patient died due to rapid MM progression. Case 2. A 76‐year old woman with relapsed IgGλ MM started 2th line treatment with LEN 15 mg. After the 3rd cycle, having obtained a very good partial remission (VGPR), she presented with grade 3 thrombocytopenia which did not ameliorate with LEN suspension and resolved only after introduction of steroid, thus supporting ITP diagnosis. She underwent a 4th cycle of LEN/DEX maintaining a normal platelet count but then LEN was interrupted due to rapid MM progression. (Fig 2). Case 3. A 78‐year old woman with renal amyloidosis in IgAλ gammopathy started a 2nd line treatment with LEN/DEX 15 mg/d-20 mg/w with a significant reduction in proteinuria. During the 6th cycle she presented with diffuse purpura and a platelet count of 18x109/L. She received platelet transfusion and bone marrow evaluation showed abundant megakaryocytes supporting the diagnosis of ITP. Furthermore anti‐platelet antibodies search resulted positive. Steroid therapy was started with partial response on platelet count but the patient remained steroid‐therapy dependent. Case 4. A 66‐year‐old woman affected by MM started a 2th‐line treatment with LEN‐DEX 25 mg/d-20 mg/w. After the third cycle, being the patient in PR, a isolated grade 3 thrombocytopenia developed, persisting despite discontinuation of LEN. Viral infections were excluded and antiplatelet antibodies search resulted positive. Therefore she started steroid therapy (prednisone 1 mg/Kg) with an progressive increase of platelet count from 44 to 80x109/L after a month of therapy, that is ongoing. Lenalidomide has not yet been restarted. Discussion We report four cases of ITP developing during LEN therapy with the characteristics of ITP. None of these patients had a history of previous autoimmune events, the decline of platelet count was rapid and other causes of thrombocytopenia were excluded or unlikely in all the cases. Furthermore diagnosis was supported by consistent bone marrow evaluation in two cases. Considering the temporal association in these four cases, the ITP mechanism may be related to the immunomodulation and T‐cell activation caused by LEN. Even if further other studies are needed, it seems reasonable to consider a possible association between LEN and autoimmune phenomena, in particular ITP. Disclosures No relevant conflicts of interest to declare.

Description: Background: CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy is standard treatment for aggressive Non-Hodgkin’s Lymphoma (NHL), and frequently results in myelosuppression. The resulting febrile neutropenia (FN) and chemotherapy-induced anaemia (CIA) may be treated with Granulocyte Colony Stimulating Factor (G-CSF) and Erythropoiesis-Stimulating Agents (ESAs), respectively. IMPACT is an observational study, ongoing since February 2007, to examine supportive care management practices in NHL patients undergoing CHOP chemotherapy. Since the beginning of this study, European treatment guidelines for use of ESAs in CIA changed: from initiation at 11 g/dL with the goal to achieve hemoglobin (Hb) within 11–13 g/dL, to, as of February 2008, initiation at 10 g/dL and target range of 10–12 g/dL. This planned interim analysis describes anaemia and transfusion outcomes from this ongoing study as of April 2008. Methods: European patients with diffuse large-B-cell lymphoma (DLBCL), planning at least 3 cycles of CHOP-14 or -21 +/− rituximab were included in the study. This subset analysis evaluated only those patients not participating in a clinical trial. Patients were retrospectively or prospectively followed up to the end of chemotherapy treatment to a maximum of 8 chemotherapy cycles. CIA treatment was according to local standard of care, either with or without ESAs. Data were collected on Hb at ESA initiation, reasons for ESA treatment, Hb achieved during the ESA treatment phase, Hb level at first transfusion, and transfusion incidence. Results: For this interim analysis, data were available for 454 patients (mean age 60.5 [SD 14.8] years and 54% male), of whom 64% received CHOP-21; 35% of patients received treatment for CIA comprising ESA and/or transfusion. Among patients who received ESAs (N=112), the most frequent reasons for initiating treatment included Hb level (79%) or perceived risk of CIA (24%). Forty-one percent of ESA-treated patients had Hb levels

Description: PURPOSE: The presenting clinico-hematologic features of 1283 patients with IgG and IgA class monoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of malignant transformation to evaluate the most important variables prognostically associated with its evolution into multiple myeloma (MM). PATIENTS AND METHODS: Two IgG MGUS patient populations were evaluated: a study sample (553 pts) and a test sample (378 pts). The IgA MGUS population included 352 cases. RESULTS: Considering IgG cases the median follow-up was 6.7 yrs in the study group vs 3.6 yrs in test group; in the first 47/553 pts developed MM vs 22/378 in the latter. At multivariate analysis serum monoclonal component (MC) £1.5 g/dl, absence of BJ proteinuria, normal serum polyclonal Ig levels and age less than 70 defined a prognostically favourable subset of patients. On the basis of these four variables, pts could be stratified into 3 different 10 yrs-evolution risk groups (HR 1.0, 4.28, 11.6; P

Description: Bendamustine (B) is an alkylating agent with unique chemical structure (purine-like benzimidazole ring) and high cytotoxic activity. In the last decade, the association of B and rituximab (BR) emerged as the worldwide most popular standard treatment of patients (pts) with indolent non-Hodgkin lymphomas (iNHL), in both relapsed/refractory (R/R) and untreated setting. Autologous stem-cell transplant (ASCT) is the standard option in young fit pts with R/R iNHL and has been recently demonstrated to improve survival of follicular lymphoma (FL) pts with early treatment failure (ETF: within 2 years [yrs] of frontline immunochemotherapy [I-CT], Casulo et al, BBMT 2018). The structure similarity with fludarabine, which is associated with a well-known peripheral blood stem cell (PBSC) mobilization impairment, may limit the use of B in younger pts with iNHL potentially candidates for ASCT. Moreover, the effectiveness of CD34+ cells collection in pts treated previously with B is essentially still unknown and based on few small series. We retrospectively analyzed rates of CD34+ cells collection in consecutive pts with iNHL undergoing PBSC mobilization attempt, who had previously received treatment with B (in the same or in a previous line of therapy) in 12 centers of the Fondazione Italiana Linfomi. The primary endpoint was the rate of pts who were able to obtain a successful harvest of PBSC (≥2 x106/Kg of body weight). Overall, we collected complete data about 45 pts with iNHL undergoing PBSC mobilization attempt after previous treatment with B (Table 1). The majority of pts had FL (n=39). Median age at diagnosis was 52 yrs (35-66). Frontline treatments comprised R-CHOP in 27 pts (60%) and BR in 11 (24%). All but 2 pts, who were mobilized during 1st line therapy, experienced disease relapse and initiated 2nd line treatment, including reinduction I-CT, PBSC mobilization and ASCT consolidation. Among pts with FL, 13 (33%) relapsed within 24 months (ETF). Median lines of therapy at PBSC mobilization were 2 (1-4). Eleven pts (24%) received B in 1st line, 29 (65%) as part of 2nd line (n=29, 65%), and 5 (11%) in 3rd or 4th line of therapy. The most frequent mobilization strategy (40 cases, 88%) was CT plus G-CSF (including R-HD-AraC in 27), with "on demand" plerixafor adjunction in 4 cases (10%). Then, two pts (4%) underwent PBSC mobilization with G-CSF only (+ plerixafor in 1) while 3 pts (7%) received G-CSF (+ plerixafor in 1) immediately after a BR course. At first mobilization attempt, 38 out of 45 pts (84%) collected ≥2 x106 CD34+/Kg (Table 2), including 2/2 (100%) in G-CSF only, 35/40 (88%) in CT + G-CSF and 1/3 (33%) in BR cohort (p=0.039), with a median of 1 (1-4) apheresis procedure. Five out of 7 pts who failed first mobilization underwent a second attempt (1 with G-CSF + plerixafor, 3 with CT + G-CSF and 1 with CT + G-CSF + plerixafor) collecting all ≥2 x106 CD34+/Kg. Considering all mobilization attempts, 43/45 pts (96%) reached successful harvest of PBSC (≥2 x106/Kg) and 38/45 (84%) obtained an optimal PBSC collection (≥5 x106/Kg). Median number of PBSC collected was 6.46 x106/kg (3-18). Pre-mobilization bone marrow involvement significantly affected PBSC mobilization (p=0.03), as well as response at mobilization (CR 92%, PR 60%, SD 50%, p=0.02) while cumulative dose of B (〉720 mg/m2, p=0.9) or timing from last B administration (≤3 months, p=0.34) did not. At multivariable analysis, mobilization type (p500/μl and PLT 〉20000/μl: 11 and 13 days). We observed 1 case of MDS (EB-2) and 1 sarcoma after ASCT. At a median follow-up of 6.3 yrs (0.7-14), only 3 pts died (2 for progression and 1 for viral encephalitis), with 8-yrs OS of 89.6% (Fig. 1) and a median PFS from ASCT of 8.1 yrs. Notably, FL pts experiencing ETF did not exhibit worse OS (85.7 vs 87.1% at 8-yrs, p=0.7). High rate of success in PBSC collection reported in this large real-world study supports the evidence that pre-treatment with B does not affect PBSC mobilization in iNHL pts, although we confirmed that B does not display per se a mobilizing capacity. Salvage strategy including ASCT resulted in overall favorable outcome in young pts with R/R iNHL and seemed able to overcome the negative prognostic impact of ETF in FL. Disclosures Luminari: Celgene: Consultancy; Roche: Consultancy; Gilead: Consultancy; Servier: Consultancy; Sandoz: Consultancy. Passamonti:Celgene: Consultancy, Speakers Bureau; Roche: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.

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.