Search

Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment [gastrointestinal toxicity (36.3%) and skin rash (10.3%)]. Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.

Donor selection contributes to improve clinical outcomes of T-cell–replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

The upper age-limit for patients with hematological malignancies eligible for allo-SCT progressed to 70-75 years. As a consequence, an increase of older patients submitted to allo-SCT has been observed worldwide and in Italy as well. This registry-based retrospective study on behalf of GITMO (GITMO AlloEld) describes the transplant activity among elderly patients in Italy, between 2000 and 2017. Thiry GITMO Centers participated to the Study. 2061 allo-SCTS in patients older than 60 years were exported from PROMISE database and 1996 first transplants were analysed. The median age of the patients at transplant was 63,5 years (59,5-77,8). The most commonly transplanted diseases were acute leukemias and myelodisplastic syndromes (67,5%). 28% and 27% of the patients showed a HCT-CI of 1-2 or grater than 3, respectively. The KPS was 100% in 27,2% and 90% in 42,9% of the cases. 32% of the patients received a myeloablative conditioning regimen and 55% of the patients received an in vivo T-cell depletion (either post transplant cyclophosphamide or ATG). With a median follow up of 10,4 years, the OS at 5 years significantly improved during time, moving from 28% between 2000-2005 to 37% between 2012-2017 (p=0,012). This was related to a significant reduction in RI (45% vs 30%, p The following significant differences were observed across the years of the present study: 1) a longer 5 years OS in patients younger than 65 years (34%) vs those older than 70 years (19%) between 2000 and 2011 only (p=0,003) (Figure 1A and 1B); 2) a longer 5 years OS (p3 between 2000-2011 only (Figure 2A and 2B); 3) a different 5 years OS according to donor type between 2000 and 2011 only (19% for haplo vs 31% for sibling vs 33% for mismatch UD and 38% for MUD; p 4) a reduction in the incidence of extensive cGVHD at 1 year (15,6% between 2000 and 2005 vs 10,3% between 2012 and 2017, p=0,004) (Figure 4). Comparing 2000-2005 vs 2012-2017, the major significant differences of the patients regard: the baseline disease (more AL/MDS: 40% vs 77%; p 3 moved from 10% to 30% (p By multivariate analysis MUD donor or UCB, no response at the time of SCT and male recipient significantly impaired OS, whereas HCT-CI These retrospective data showed that the transplant procedure for elderly patients became safer and more effective over time, for a reduction of the RI related to a better selection of patients (more acute leukemias in CR) and a better selection of conditionings (more MAC and more alkylators). Nowdays, the HCT-CI score is probably not sufficient for estimate elderly patients probability of OS and NRM. Figure 1 Figure 1. Disclosures Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment.

Current treatments for non-Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2-6) lymphoma patients in an off-label setting. Bortezomib therapy was scheduled for 4-6 cycles (1.3 mg/m(2) biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non-responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B-cell lymphoma patients obtained a response. Extra-hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3-4 thrombocytopenia in nine patients and grades 3-4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated.

Minimal residual disease (MRD) of 30 adult AML patients was monitored by multiparameter flow cytometry (MFC) and WT1 expression before and after allogeneic stem cell transplantation (allo-SCT). Diagnostic performance of pre-transplant MRD measured by MFC was higher than that obtained by WT1 expression. Comparable results were displayed at day +30 post-transplant, while better values by WT1 compared to MFC were found at day +90. Positive MRD by MFC predicted a shorter disease free survival (DFS) before and 1 month after transplant (p = 0.006 and p = 0.005), while only high WT1 levels at 1 month from the transplant significantly impacted on DFS (p = 0.010). Our results support the idea that MRD monitoring by MFC should be suggested before and 30 days after the transplant, while WT1 expression should be preferred after this procedure. The assessment of MRD at day +30 from allo-SCT is recommended as post transplant check-point for the predictive role displayed, independently of the method used.

Summary Background: Peripheral B-cell lymphoma of the marginal zone (MALT, low-grade), presenting as localized, extranodal disease, usually affects the elderly. The gastrointestinal tract is the most frequently involved extranodal location, representing 70% of all MALT lymphomas. Recently, numerous other extranodal sites involved by MALT lymphomas have also been described. Patients and methods: From January 1990 to October 1995, 24 patients with untreated nongastrointestinal low-grade MALT lymphoma were submitted to treatments ranging from the local approach of radiotherapy and local a-interferon (a-IFN) administration to chemotherapy. The tumours were located in the lung (seven cases), conjunctiva (four cases), lachrymal gland and orbital soft tissue (four cases), salivary glands (three cases), skin (three cases), breast (two cases), and thyroid (one case). All patients had low-grade stage IE tumours. Results: Chemotherapy was administered in 11 patients (six with lung, three with salivary gland, one with breast, and one with thyroid locations); radiation therapy was employed in seven patients (three with lachrymal gland, three with skin, and one with breast locations); local a-IFN administration was administered in five patients (four with conjunctival, and one with lachrymal gland sites); and surgery was employed in one patient with a lung tumour. All patients achieved complete remissions; three local recurrences and two relapses in other sites were observed. The global five-year survival rate was 100% with a relapse-free survival rate of 79%. Conclusions: These data confirm the significant efficacy of different therapeutic approaches to specific sites inbes obtaining a good remission rate for nongastrointestinal localized low-grade MALT lymphomas.

Summary Background The promising results of fludarabine (FLU) in chronic lymphocytic leukemia have prompted its extensive evaluation in low-grade non-Hodgkin's lymphoma (LG-NHL). Its different mechanisms of action make FLU an attractive partner for combination with other cytostatic agents. Patients and methods We used a three-drug combination of FLU (25 mg/m2 i.v. on days one to three), mitoxantrone (10 mg/m2 i.v. on day one) and prednisone (40 mg given orally on days one to five) (FMP) to treat 48 patients with recurrent LG-NHL. Results Of the 48 patients, 17 (35%) achieved complete responses (CR), 23 (48%) partial responses, while the remaining 8 (17%) showed no benefit from the treatment. The risk of lower CR rate was significantly correlated with the presence of advanced stage (IV) (P = 0.01), the number of previous regimens (ij3) (P = 0.006), and the follicular histologic subtype (P = 0.02). The major toxic effects observed were neutropenia and infections; there was only one fatality, due to drug-related side effects. Conclusion These data confirm the significant efficacy of the FMP fiudarabine-mitoxantrone combination regimen in obtaining a good remission rate with moderate toxicity in a particular subset of recurrent LG-NHL.

Relapse represents the main cause of treatment failure after allogeneic stem cell transplant (allo-SCT). The detection of minimal residual disease (MRD) by multiparametric flow cytometry (MFC), chimerism, cytogenetics and molecular analysis may be critical to prevent relapse. Therefore, we assessed the overall agreement among chimerism (low level mixed chimerism [LL-MC] vs. complete chimerism [CC]), MFC and Wilms tumor 1 (WT1) mRNA to detect MRD and investigated the impact of MRD obtained from the three methods on patient outcome. Sixty-seven fresh bone marrow (BM) samples from 24 patients (17 acute myeloid leukemia [AML], seven acute lymphoblastic leukemia [ALL]) in complete remission (CR) after allo-SCT were investigated at different time points. A moderate agreement was found among the three techniques investigated. A higher concordance between positive results from MFC (75.0% vs. 32.7%, p = 0.010) and WT1 (58.3% vs. 29.1%, p = 0.090) was detected among LL-MC rather than CC samples. Relapse-free survival (RFS) and overall survival (OS) were found to be higher in MRD negative patients than in MRD positive patients analyzed with MFC and WT1. Our results discourage the use of low autologous signals as the only marker of MRD, and suggest the usefulness of MFC and WT1 real-time quantitative polymerase chain reaction (RQ-PCR) in stratifying patients with respect to risk of relapse.

Twenty-one patients with multiple myeloma, all relapsed after frontline autologous stem cell transplantation and all relapsed again after or resistant to thalidomide (employed as second line treatment) received bortezomib (1.3 mg/m(2) body surface twice weekly for 2 weeks followed by an interval of 10-12 days) without adjunct of steroids as third line therapy. Three patients died of progressive disease during the first 2 cycles with bortezomib. Eighteen patients received at least 2 cycles and were evaluated for response. According to EBMT criteria, two complete (negative immunofixation) and seven partial (reduction of M-component > 50-75%) remissions were achieved (ITT response rate 42.8%). Duration of response lasted from 2 to 14+ months. Grades 3-4 toxicities (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were observed in seven patients, but no patient interrupted the treatment due to side effects. We conclude that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide.

The purpose of this study was to evaluate the efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and radiotherapy in advanced Hodgkin's disease. In addition, to evaluate whether patients with slow responding tumors could profit from the early change of treatment regimen [MOPP (mechloretamine, vincristine, procarbazine, and prednisone)] followed by radiation therapy or autologous bone marrow transplantation (ABMT). Finally, to evaluate treatment options for patients with both early and late relapses. A total of 78 patients with previously untreated stages IIA bulky, IIB, III (A and B), and IV (A and B) Hodgkin's disease were treated with the ABVD regimen followed by radiotherapy. Patients with stages IIIB and IV (A and B) were re-staged after 4 ABVD courses of the treatment: slow responders (response less than 70%) underwent second-line treatment (MOPP) and eventually ABMT. Relapsed patients with a long initial complete response (> or = 12 months) were treated with second-line conventional treatment and those patients with a short initial complete response (< 12 months) underwent ABMT. The complete response (CR) rate was 91% after ABVD and radiation therapy. An additional 5 stage IIIB and IV patients whose therapy was switched after 4 cycles because of a slow response obtained a CR (3 after 2 MOPP courses plus radiotherapy and 2 after 2 MOPP courses followed by ABMT). Including these additional CRs, the overall CR rate was 97%. No episodes of clinical cardiopulmonary toxicity were observed. With a median follow-up time of 42 months, the 4-year relapse-free survival was 87%. The 4-year overall survival was 96%. Ten cases relapsed: all but one obtained a second CR with different approaches depending on the timing of relapse. The ABVD regimen appears to be effective and well tolerated confirming the validity of this four-drug regimen in the treatment of advanced Hodgkin's disease. In addition, therapeutic choices based on the timing of the relapse and the use of re-staging after 4 cycles in order to identify slow responders can play an important role in increasing the number of cured patients.

In the last decade, there have been several reports on what is now recognized as a new clinical and pathological entity termed primarily mediastinal B-cell lymphoma (PMBCL) with sclerosis. This lymphoma presents unique clinical characteristics with an aggressive outcome and, at present, the best approach seems to be a combination of chemotherapy and radiotherapy. Between June 1989 and September 1994, twenty-two previously untreated patients with PMBCL with sclerosis were treated with a combination of third-generation chemotherapy regimen (MACOP-B or F-MACHOP) and mediastinal irradiation. All the patients presented with bulky mediastinal involvement; the radiologic clinical stage with evaluation of tumor size included computed tomography and Gallium-67-citrate SPECT. Twenty-one patients (95%) achieved a complete response and only one was resistant to treatment. Regarding 67Ga SPECT, 6 patients, including the nonresponder, showed persistent abnormal 67Ga uptake after chemotherapy; however after the mediastinal radiotherapy, all the patients except for the nonresponder were 67Ga-negative. The overall survival was 87%, with a median follow-up of 24 months from the time of diagnosis. Two of the patients who achieved complete response relapsed 7 and 10 months after completion of treatment, respectively. The relapse-free survival rate was 89% at 62 months (median 20 months). In patients presenting with bulky mediastinal PMBCL with sclerosis combined modality treatment using third-generation chemotherapy regimens and radiotherapy induces a good remission rate with greater than 80% chance of surviving disease-free, at 2 years. A longer follow-up before definitive conclusions are drawn is still warranted.

Abstract 1971 Introduction. Relapse represents the main cause of treatment failure after allogeneic stem cell transplantation (allo-SCT). Thus, monitoring of minimal residual disease (MRD) in allografted patients allows an early detection of recurrence and a subsequent intervention prior to florid relapse. Multiparameter Flow Cytometry (MFC), chimerism, cytogenetics and molecular analysis have been widely used for this purpose, although the gold standard needs to be established yet. The evaluation of fusion transcripts represents the most sensitive method but more than 65% of patients do not demonstrate a molecular target. WT1 mRNA is over expressed in > 90% of patients with acute myeloid leukemia (AML) but it is not so expressed in acute lymphoblastic leukemia (ALL). On the MFC analysis instead, the complexity of maturational patterns and phenotypic shifts after therapy may underestimate residual leukemic cells. Finally, previous papers reported that a state of mixed chimerism (MC) in RT-PCR may identify higher risk of relapse in patients with AML. However, the test has a low sensitivity (from 0,1% to 1%) and recipient cells are not necessarily linked to disease recurrence. Hypothesizing the presence of blast cells in the low-level mixed chimerism (MC, 1% Methods. Fresh BM samples from 24 patients (17 AML and 7 ALL) in both morphological CR and CC or low-level MC status after allo-SCT were investigated. MRD with MFC, WT1 mRNA expression and chimerism analysis was evaluated at different time points: +1, +3, +6,+12,+18,+24 months after allo-SCT. The immunophenotypic analysis was performed using a six-color combinations and acquiring 250.000 events. RQ- PCR to test WT1 mRNA expression was made according to the standardized and quality-controlled method. Chimerism studies were performed with a multiplex amplification of 16 (STR). The agreement between two methods in monitoring MRD after allo-SCT was assessed by Kappa statistic. Moreover, time-to-event analyses were performed using Cox proportional-hazard models with time-dependent covariates. Risks were reported as hazards ratios (HR) along with their 95% confidence interval (95% CI). Results. Comparisons among results of MFC, RQ-PCR for WT1 mRNA and Chimerism were performed in all 67 serial samples obtained from 24 patients. A significant moderate agreement between MFC and WT1 mRNA evaluations was found (k= 0.463, p Conclusions. According to our study MFC, WT1 mRNA and CC or low-level MC displayed an overall agreement in monitoring MRD. In particular, the agreement on the low-level MC may suggest the presence of leukemic cells. The detection of a positive MRD by MFC and WT1 mRNA similarly identified higher risk of relapse in patients with acute leukemia (AL) undergone to allo-SCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 5032 Introduction. Combining bortezomib with pegylated liposomal doxorubicin for the treatment of Multiple Myeloma (MM) may reciprocally increase their efficacy in vitro and appears to offer higher overall response rates in vivo. With the aim to verify the synergistic interaction towards myeloma cells we planned a prospective study with bortezomib, non-pegylated liposomal doxorubicin and dexamethason in patients with relapsed/refractory multiple myeloma (R/R MM). In this setting of patients, showing a poor outcome because of multi-drug resistance, low-performance status and toxicity to previous chemotherapy, bortezomib, by inhibiting proteasome function, may enhance chemosensitivity to doxorubicin and overcome drug-resistance. Thus, to improve outcome minimizing therapy-related toxicity, bortezomib was added to non-pegylated liposomal doxorubicin and dexamethason (PAD regimen). Patients and Methods. From November 2005 and January 2012, 50 patients with R/R MM (relapsed n= 37 and refractory n= 13) referred to the our Institution received PAD regimen. Male/Female ratio: 27/23; Median age: 61 years (range 34–79); median time from diagnosis: 32 months (range 4–121); median of previous therapy lines: n= 3 (range 1–5); patients previously underwent to autologous and allogeneic hemopoietic stem cell transplantation (auto- and allo-HSCT): 22 and 5, respectively. Planned treatment: bortezomib 1, 3 mg/mq iv days 1, 4, 8, 11; non-pegylated liposomal doxorubicin 30 mg/mq on day 1 and dexamethason 40 mg days 1–4 of a 28-day cycle up to 6 cycles. Results. Forty patients (80%) received the planned treatment schedule whereas 10 patients did not complete it because of toxicity (1 patients) and resistant or progressive disease (9 patients). Median time to best response was 3 months (range 2–6). The overall response rate was 74% with 10 CR (20%), 15 vGPR (30%) and 12 PR (24%). Fifteen of the responder patients underwent HSCT (auto-HSCT: 9; allo-HSCT: 6). The previous use of anthracyclines (35 patients) and bortezomib (3 patients) did not seem influence the response. Median duration of response was 24 months (range 6–57 months). After a median follow-up of 58 months, 14 (28%) patients were alive and, of these, 7 (14%) in Continue CR. The safety profile was manageable: the hematologic grade 3/4 toxicity (neutropenia, thrombocytopenia and anemia) was 28%; non-hematologic grade 3/4 toxicity (sensory or motor neuropathy, infections, fever, fatigue, diarrhea) was 36%. Despite heavy previous treatments, including anthracycline-based, no significant cardiac toxicity was observed. Conclusion. According to our study, the PAD regimen appears feasible and effective in both elderly and heavily pre-treated R/R MM patients. In fact a significant improved clinical outcome in our cohort of patients was observed. Disclosures: No relevant conflicts of interest to declare.

Background: Despite the popularity of splenectomy has decreased dramatically in the past few years, the surgical approach remains the best therapy for patients with refractory Immune Thrombocytopenic Purpura (ITP) in terms of high and durable rate of response (Vesely et al, Ann Intern Med2004; 140: 112). The recent introduction of anti-CD20 antibodies and thrombopoietins of second generation such as AMG 531 and Eltrombopag may have a relevant role (Kuter et al, Lancet2008; 371: 362) but their long-term safety and efficacy have not been still established. In parallel with new drugs, there has been an evolution in the surgery of splenectomy as well (Dolan et al, Am J Hematol2008; 83: 93). Actually, the laparoscopic surgery is considered the standard approach and the ITP represents the most common indication in 50–80% of all the laparoscopic splenectomies. Methods: The aim of this study is to evaluate the long-term complete and partial haematological response (CR + PR), as well as the short and long-term complications, of 40 patients (30 females and 10 males; median age: 38 years - range 6–71) with unresponsive ITP after one or more medical approaches and underwent laparoscopic splenectomy at our Institution from 1999 through 2006. The 40 patients accounted for 22.2% of 181 patients diagnosed in those years. An abdominal CT scan to evaluate the presence of accessory spleens was performed in all cases. All patients received meningococcal, pneumococcal and haemophilus influenzae vaccine one week before splenectomy. For 4 or 5 days before splenectomy the patients were treated with high doses of intravenous Immunoglobulins. Anti-thrombotic prophylaxis was performed with low molecular weight heparin (LMWH) for 10 days and afterwards with cardioaspirin (ASA) if the platelet count exceeded 500x10E9/L. Results: No cases required conversion to laparotomic splenectomy. An accessory spleen was found in 2 patients (5%). Immediate haematological response rate was of 100%. At date, after a median follow-up of 78 months (range 28–112 months), 36 patients (90%) remain in CR or PR with a platelet count more than 50x10E9/L and 2 patients are taking ASA. Four patients (10%) relapsed; out of which, 2 patients have a platelet count less than 10x10E9/L. Short and long-term mortality rate was 0%. Immediate postoperative complications rate was 5%: we observed 2 cases of hemoperitoneum related to a trocar’s tube and to an active bleeding, respectively, both resolved with new laparoscopic approach. The mean postoperative hospital stay was 4,5 days (range 4–8). Neither cases of bacterial sepsis in the postoperative or during the follow-up time, nor cases of splenic-portal vein thrombosis (SPVT) and no cases of neoplasms occurred. Conclusions: Our experience suggests that laparoscopic splenectomy is an excellent approach to patients with refractory ITP in terms of safety, efficacy and costs. With respect to laparotomic splenectomy, the use of laparoscopy is likely to make the splenectomy even safer and therefore suitable for a larger number of patients. Undoubtedly there is a great expectation for the new drugs (Rodeghiero et al, Am J Hematol2008; 83: 91) and we agree that only controlled comparative clinical trials (Vianelli et al, Haematologica2005; 90: 72) will be able or not to say a final word and to challenge the role of splenectomy.

Background: Autologous Transplantation with intermediate or high doses of Melphalan is the most effective therapy in patients with Multiple Myeloma being < 65 years old, although this procedure is limited by an high percentage of relapses. Recent advances knowledge of the molecular mechanisms, allowed the development of novel targeted therapies. Several studies have shown that the synergic effect of Bortezomib and Talidomidomide, in association with conventional chemotherapies, induces a more pronounced reduction of tumour mass, an enhancement of global responses and an improvement of Progression Free Survival (PFS). Aims: The present study is aimed at the evaluation of effectiveness and toxicity of MVTD conditioning therapy with stem cell support in Multiple Myeloma relapsed patients. Patients and Methods: From January 2005 to August 2007, 15 patients (7 males and 8 females: median age 62 yrs (46–70)) have been subjected to Autologous Transplantation therapy with MVTD conditioning therapy (Melphalan 100 mg/sqm days - 6 and - 3, Bortezomib 1.3 mg/sqm days - 6 and - 3, Talidomide 200 mg from day - 6 to day - 2, Desametazone from day - 6 to day - 3, CSP infusion at day 0). All patients were in CS III A; median performed therapies 3 (1–5); all had received previously a therapy with Talidomide, two Talidomide + Velcade, one PEG-IFN. Results: 100% of patients obtained a response: 4 patients (26.7%) obtained CR, 5 (33.3%) a nCR, 4 (26.7%) a VGPR and 2 (13.3%) a PR. One patient in CR was subjected to 2 therapeutic lines and 3 patients in CR were subjected to more than 1 therapeutic lines, 5 in nCR from 2 to 4, 4 in VGPR from 2 to 4 and 2 in PR more than 2. At the moment, with a median of 7.5 months (1–21), 11 (73%) are alive, 8 (53%) still keep the obtained response, 3 (20%) after progression are in rescue therapy, 4 patients (27%) died because of progression. PFS median since MVTD beginning is of 6 months (1–24). None of the patients have developed a significant neurotoxicity. All patients have developed grade 4 thrombocytopenia and neutropoenia, with a median of 3 days (1–10) and 6 days (4–12), respectively. 54% of patients had neutropoenia with fever with a median of 2 days (0–8). The median units of platelets and red cells infused was 3 (2–11) and 2 (0–11), respectively. Conclusions: In our experience, Autologous Transplantation therapy with MVTD conditioning, appeared to be effective in relapsed patients with Multiple Myeloma. Although in a small series of patients the response obtained was independent from the number and type of previous therapies, from the clinical state, and β2 microglobulin. No significant neurotoxicity has been observed, whether the haematological toxicity was overlapping to that due to conventional Autologous Transplant. Further studies, in larger series of non pluritreated patients are required.

The role of ASCT in AML appears to be appropriate in patients with favorable cytogenetic features whereas allogeneic SCT is appropriate in those with high-risk cytogenetic features. Gemtuzumab ozogamicin (GO), a monoclonal antibody conjugated to the calicheamicin, targets the CD33+ cell surface marker that is expressed on cells in the majority of AML patients. Clinical trials currently underway are investigating the role of GO in consolidation therapy. We hypothesized that GO could have beneficial effects as maintenance therapy after hematopoietic SCT in high-risk patients. Here we report data on 4 AML patients in CR who received 4 doses of GO as maintenance therapy following ASCT. Our approach differs from previous reports in the literature in that, instead of using GO to induce a first remission or re-induce a second remission after relapse, we administered GO to patients while they remained in remission, two months after undergoing ASCT. Patient #1 was a 64 year-old male with 88% CD33 expression at diagnosis. This patient had previously undergone an ASCT using a conditioning regimen of Bu+Cy. He was in second CR following an induction regimen of 2 cycles of fludarabine + cytarabine + idarubicin. Patient #2 was female, aged 67 years and had 90% CD33 expression at diagnosis. She was in first CR following an induction regimen of 2 cycles of etoposide + cytarabine + idarubicin. Patient #3 was a 69-year old male with 95% CD33 expression at diagnosis. He was in first CR following an induction regimen of 2 cycles of fludarabine + cytarabine. Patient #4 was a 59 year-old male with 93% CD33 expression. He was in first CR after a second line treatment with mitoxantrone, cytarabine and etoposide. Histocompatible donors were not available for any of the patients. Three months after attaining CR, all 4 patients received a myeloablative conditioning regimen with B(A)VC, Bu+Cy, Bu+Cy and TBI+Melphalan, respectively, and underwent ASCT. Two months after the ASCT procedure, patients initiated treatment with GO: GO was administered alone for 4 doses with 28 days between doses (two patients received 6 mg/mq for the two first doses and 3 mg/mq for the two last doses; two patients received 3 mg/mq for four doses). All four patients remain alive and in CR at +17, +13, +11and + 5 months. Overall survival at the time of reporting is +35, +15, +13 and +8 months in patients 1, 2, 3 and 4, respectively. There were no cases of grade 3 or 4 liver toxicity and bleeding was not observed in any of the patients. Thrombocytopenia (50,000–100,000 cells/μL) occurred in all four patients and neutropenia (500–1000 cells/μL) in two patients. In conclusion in our small series GO demonstrated good efficacy when administered in fractionated doses as maintenance therapy after ASCT in patients with CD33+ AML in first or second CR. GO showed an acceptable tolerability profile, with no severe hepatotoxicity and no bleeding. Thrombocytopenia occurred in all three patients and in all cases there was a rapid platelet recovery. A GO dose of 3 mg/m2 appeared to be better tolerated than the higher dose (6 mg/m2) and will be used in future studies. If confirmed in a study involving a larger number of patients, our results could support a new therapeutic role for GO, namely as a maintenance therapy for patients in CR following hematopoietic SCT.

The Lymphomatous Meningitis (LM) is an uncommon event, either as an initial diagnosis and in the course (or as an outcome) of a front line treatment. In the latter cases the LM has a poor prognosis and a median survival of few months in untreated patients. Its occurrence is tightly related to the histology, the response to the therapy and the introduction of a proper prophylaxis. Currently, high doses of Methotrexate (HD-MTX) (3 g/sqm) followed by radiotherapy (WBRT: 50 Gy) represents the elective treatment. The role of the intrathecal therapy (IT-T) isn’t well defined: as a matter of facts, it doesn’t seem more effective than the systemic treatment with HD-MTX and it is burdened by a higher neurotoxicity. Furthermore, more frequent intrathecal administrations, a proper concentration and a prolonged exposition to the drugs are required. Recently, an important role both in the prophylaxis and in the therapy of LM is played by the IT-T of Cytarabine in liposomal formulation (DepoCyte): the slow release from the multivescicular lipidic particles improves the distribution in the liquor, allows a lesser number of IT-T, reduces the undesired effects due to the treatment and increases the compliance of patients. Randomized studies have shown a significant better effectiveness and a reduced toxicity of liposomal formulation treatment with respect to the traditional one. In the present work 9 cases of LM treated with systemic chemotherapy and with DepoCyte (50 mg IT every 15 days x 6 times) are shown. Male/Female ratio is 6/3; average age is 46 years (range 24–78). In all patients neurological symptoms were present; lymphomatous cells were identified in the CSF of 5 patients and Central Nervous System (CNS) localizations were detected by NMR in 7 patients. The 5 CSF-positive cases were heterogeneous, as follows: B-lineage CD10+ ALL meningeal relapse (after two marrow relapses), already undertaken to allogeneic stem cells transplantation, treated only with DepoCyte; Lymphoblastic T-Cell Lymphoma meningeal localization, with mediastinic mass, treated with DepoCyte associated to LSA2L2 Protocol and autologous stem cells tranplantation; DLBCL meningeal localization treated with DepoCyte associated to R-CHOP Protocol; LM at diagnosis in a 78 years old patient with inadequate compliance to systemic therapy, treated with DepoCyte; Mantle Cell Lymphoma meningeal (and systemic) relapse treated with DepoCyte associated to Codox-M Protocol. In patients 1) to 4) the CR was obtained and they are still alive; only the latter patient, namely, case 5), died for disease progression. The remaining 4 CSF-negative cases had been diagnosed as DLBCL (3 at diagnosis and 1 at relapse) CNS solitary localizations. In all cases L-VAMP Protocol (modified with HD-MTX) was associated to IT-T with DepoCyte. With the only exception of the relapsed patient, the remaining 3 patients had a good response to therapy and they are still alive and in CR.Overall, DepoCyte was shown to be mostly effective, well tolerated by all patients and devoid of undesired side effects. The association with various systemic chemotherapy protocols had been demonstrated to be suitable and endowed with synergic effects. Studies with higher number of patients might validate the effectiveness of DepoCyte also in those CSF-negative cases with solitary CNS localization.

Treatment of both Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL) with bulky presentation at diagnosis frequently results in residual masses detected radiologically. Conventional diagnostic radiology and computed tomography (CT) are generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate (67Ga) SPECT and magnetic resonance imaging (MRI) can potentially differentiate residual active tumor tissue and fibrosis. Thirty-three patients with HD or HG-NHL presenting with bulky mediastinal disease were studied with CT, 67Ga SPECT, and MRI (only for 16 patients) at diagnosis, after two-thirds of their chemotherapy, at the end of chemotherapy, and after radiotherapy in order to evaluate the mediastinal region on the basis of persistence of residual masses and activity of pathological tissue. After treatment, all patients with 67Ga-negative (30/33) disease are still in continuous complete response. Among the three 67Ga-positive patients, 2 relapsed within one year and another one is still alive without evidence of disease. Regarding MRI, two patients were found to be positive, one of them concomitant with 67Ga-positivity; both patients survive in complete response. In lymphoma patients with bulky mediastinal presentation, the 67Ga SPECT remains the preferable imaging technique for monitoring and differentiating the eventual active residual tumor. In combination, CT and 67Ga SPECT represent a suitable complete imaging approach to the radiological diagnosis which may be useful in these particular patients. MRI could probably be considered as a second-line method and from our data would be used only in selected cases because of the high cost, accessibility, and lower specificity as opposed to 67Ga SPECT in evaluating potentially active residual disease.