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High-dose chemotherapy with autologous stem cell transplantation (ASCT) has been shown effective in the control of relapsed/refractory follicular lymphoma. We evaluate the long-term outcome of patients with relapsed or refractory follicular lymphoma treated with ASCT with in vivo purged progenitors cells. We report the long-term results of a prospective multicenter phase 2 trial on 124 relapsed/refractory follicular lymphoma patients treated with a program of anthracycline-based debulking chemotherapy, immunochemotherapy, mobilization of in vivo purged PBSC followed by ASCT. Median age was 52 years; 14% of patients had grade 3A histology. Debulking chemotherapy produced CR in 16% and PR in 71%, while 13% of patients progressed. After rituximab, cyclophosphamide, vincristine, prednisone (R-COP), CR was obtained in 60% and PR in 35%; 118 patients successfully mobilized PBSC and 117 proceeded to ASCT. The harvest in all the 32 molecularly informative patients was bcl-2 negative. TRM was 0%. The 5-year PFS was 54% and the 5-year OS was 83%. After a median f-up of 6.7 years (range 1.5-13.6), 54% are still in CR. These data show that prolonged PFS is achievable in relapsed/refractory patients with high dose autologous transplantation of in vivo purged progenitor cells.

Background. Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms that can progress to secondary myelofibrosis (MF), named post-PV (PPV) MF and post-ET (PET) MF. While outcome of primary myelofibrosis is defined on the basis of the IPSS models, information on outcome of secondary myelofibrosis (SMF) is scant. The objective of this study is to develop a prognostic model to predict survival of SMF. Patients and Methods.A total of 718 patients from 16 international Centers were included in this study. Diagnosis of PPV-MF and PET-MF was according to the IWGMRT criteria. Since survival varied among centers, statistical analyses took into account this cluster effect. Survival was calculated utilizing Kaplan-Meier estimates for univariate categorical risk factors and Cox proportional hazard regression, when performing multivariate analysis. The log-rank test was applied to compare Kaplan-Meier curves. Survival was censored at date of stem cell transplant, splenectomy or trial enrollment. Results. Among 718 SMF, 364 (51%) were PET-MF and 354 (49%) PPV-MF. The median follow-up was 2.4 years (range, 0.6-20.1). Median age was 64 years (range, 25-96), 370 were males (52%). Median time from PV/ET diagnosis to SMF diagnosis was 10.6 years (range, 2.5-41). Median values of hemoglobin, white blood cell count and platelet count were 11.2 g/dL (range, 5-17), 10.2 x10(9)/L (range, 1.1-98.4) and 343 x10(9)/L (range, 16-1908), respectively. Splenomegaly was present in 606 patients (87%) and constitutional symptoms in 329 (47%). Cytogenetic profile (N= 338) was normal in 222 (66%), unfavorable in 40 (12%), abnormal but favorable in 76 (22%), and the JAK2 (V617F) mutation (N=679) in 73%. Anemia, leukocytosis, thrombocytopenia, advanced age, circulating blasts, JAK2(V617F), constitutional symptoms, time to SMF, history of thrombosis negatively affected survival in univariate analysis (maximum P values, 0.043), while type of diagnosis (PPV, PET), splenomegaly, spleen size, cytogenetics, and cardiovascular risk did not. Since survival did not differ between PPV and PET, multivariable analysis was carried out on a subset of 493 SMF patients randomly selected and stratified by diagnosis from the original cohort of 718 patients to generate the MYSEC-PM. The remaining 225 were used as validation cohort. By multivariable analysis, age over 65 years (Hazard Ratio –HR- 2.6, 95%CI: 1.5-4.4; p65 years (3 points), time to SMF >15 years (2 points), history of thrombosis (2 points), constitutional symptoms (2 points), hemoglobin = 1% (2 points). To facilitate the use in clinical practice, the MYSEC-PM was recoded into three broader categories: low-risk (score, 0 to 2), intermediate-risk (score, 3 to 6), high-risk (score >6). Survival was significantly different among the risk groups (Figure 1, p< 0.0001): median survival and its 95% CI was not reached in low-risk, 7.9 years (95% CI: 6.7-9.3) in intermediate and 3.8 (95% CI: 2.2-5) in high-risk. The predictive value of MYSEC-PM was confirmed in the validation cohort (N=190) with the maximum p value in pairwise comparisons of 0.01. In the validation cohort, by Akaike information criterion, MYSEC-PM model better predicted survival than the IPSS/DIPSS models (N=190, AIC, 330.5 vs. 336.5 vs. 334.3, respectively) and also compared to the DIPSS-plus (N=91, 103.8 vs. 106.5, respectively): lower score implies better prediction. Conclusions. The MYSEC prognostic model, based on age >65 years, time to SMF >15 years, previous thrombosis, constitutional symptoms, hemoglobin 1%, clearly distinguishes outcome of patients with SMF and outperforms PMF risk models among those patients. This model can be considered for tailoring treatment according to disease risk in SMF. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

CVC-related complications were retrospectively analysed for 373 CVCs inserted in 261 hematologic pts consecutively admitted to our Hematology Department between January 2002 and March 2004. Pts diagnosis comprised AML (96 pts, 36.8%), ALL (19 pts, 7.3%), lymphoproliferative disorders (74 pts, 28.3%), MM (51 pts, 19.5%), CML (13 pts, 5%), others (8 pts, 3.1%). The CVCs were polyurethane Plastimed three lumen 7 Fr (193 cases) for chemotherapy and polyurethane Arrow three lumen 12 Fr (173 cases) for chemotherapy and peripheral blood stem cell (PBSC) apheresis. CVCs were inserted, according to physician’s judgement, either at bedside (369 cases) or in the operating room (4 cases) and were used for drug infusion in 309 cases (82.8%), for total parenteral nutrition in 19 cases (5.1%), for blood transfusions in 226 cases (60.6%), for PBSC apheresis in 152 cases (40.7%). Fifty five CVCs were inserted in neutropenic pts ( N < 1 x 109/L); severe thrombocytopenia (Plts < 30 x 109/L) was present in 33/373 cases. Antithrombotic prophylaxis with low molecular weight heparin because of previous thrombosis was instituted in 33 cases (8.8%). At univariate and multivariate analysis the following risk factors for catheter-related bloodstream infections were considered: pt age, number of days/catheter, haematological disease, catheter lumen, administration of chemotherapy (standard- vs high-dose), presence of neutropenia. The median duration of CVCs after placement was 22.7 days (range 2–70) for the 7 Fr lumen, and 9 (range 1–39) for the 12 Fr. Major hemorrhagic complications related to the insertion procedure were observed in 4 cases of whom 2 were severely thrombocytopenic. CVC occlusion were observed in 24 cases (6.4%). Thrombotic complications developed in 7 cases (1.87% of inserted CVCs) and in 2/7 were complicated by pulmonary embolism; thrombophilia tests were negative in all 7 pts who developed thrombosis. Among febrile pts the frequency of bacteriemias was 19.6% (73/373 cases) of which 52/373 were CVC-related (13.9%). Approximately 6% of cases (23/373 CVCs) had CVC exit point infection with or without associated bacteriemia. Gram positive bacteria were isolated in 49 cases (67.1%), 38 of which were CVC-related (19 S. epidermidis, 4 S. pneumoniae, 3 S. aureus, 3 Enterococci species, 9 others). Gram negative bacteria were isolated in 23 cases, of which 13 were CVC-related (5 E.coli, 4 E. cloacae, 2 P. aeruginosa, 2 K pneumoniae). Candida was isolated in one case. Overall mortality in our patient population was 4.2% (11/261 pts); one patient only died of infection (P. aeruginosa sepsis) not CVC-related. At univariate and multivariate analysis significant risk factors for infection (p

Polycythemia vera (PV) is a chronic myeloproliferative disorder with a propensity to develop myelofibrosis, a condition named post polycythemia vera myelofibrosis (post-PV MF). Survival and prognostic factors after transition to MF remain to be defined. We studied 68 patients with post-PV MF to define survival and prognostic factors for survival at diagnosis of post-PV MF. We also developed a dynamic prognostic model to predict survival at any time from diagnosis of post-PV MF. The median interval between the diagnosis of PV and that of post-PV MF was 13 years (range, 4–29.6 years). Patients with post-PV MF were observed for 181 person-years of follow-up. At diagnosis of post-PV MF, 43 (63%) of 68 patients had less than 65 years. During the follow-up, the incidence of thrombosis was 42 × 1000 person-years (95% CI: 19–93.5) and the incidence of leukemia was 50.3 × 1000 person-years (95% CI: 26–115). The median survival was 5.7 years. Multivariable Cox proportional hazard regression including age, hemoglobin value, platelet count, leukocyte count, and spleen size, showed that hemoglobin < 10 g/dL (P < .001) and platelet count < 100 × 109/L (P= .026) were independent risk factors for survival. We stratified patients at diagnosis of post-PV MF, according to these factors, obtaining two risk groups with significantly different survival (P = .003): low risk (Hb > 10 g/dL and platelet count > 100 × 109/L) with a median survival of 7 years, and high risk (Hb < 10 g/dL or platelet count < 100 × 109/L) with a median survival of 2 years. The prognostic model retained significance after adjustment for age in a multivariable Cox proportional hazard regression (HR: 4.3, 95% CI: 1.6–11.4; P= .003). To assess whether this prognostic model may predict survival at any time from diagnosis of post-PV MF, we evaluated in a time-dependent analysis 64 patients who had longitudinal blood cell counts during follow-up. As first step, we evaluated univariate survival analysis with hemoglobin value < 10 g/dL and platelet count < 100 ×109/L as time-dependent covariates. Both time-dependent parameters affected survival (HR for hemoglobin 5.8, 95% CI: 2.2–15.2, P < 0.001; HR for platelets 4.5, 95% CI: 1.67-12, P=.002). As second step, we evaluated the prognostic model assessed at diagnosis as time-dependent covariate, to define whether the acquisition of one risk factor during follow-up may affect survival. The HR was 7.5 (95% CI: 2.4-23.4; P < .001). The time-dependent prognostic model retained statistical significance after adjustment for age (P < .001). In conclusion, in patients developing post-PV myelofibrosis, a prognostic model based on hemoglobin level < 10 g/dL and platelet count < 100 × 109/L may predict survival at diagnosis of post-PV MF and at any time thereafter.