ALBERT

Description: Background Acute promyelocytic leukemia (APL) in the elderly has a favourable outcome in a significant proportion of patients (pts). Elderly and frail pts are usually treated with attenuated treatment schedules, mostly "according to medical judgment". The combination of all-trans retinoic (ATRA) and anthracycline-based chemotherapy (CT) has been the mainstay of treatment for many years. Alternative approaches, such as arsenic trioxide (ATO) and gentuzumab ozogamicin (GO) have recently been tested with success in this setting, even though no large series of elderly pts treated with CT-free first-line treatment have been published yet. Moreover, neither a "standard of care approach" nor a specific prognostic score system have been developed to guide physician in choosing the most adequate treatment schedule in this setting. Objective Aim of the present preliminary survey was to assess genetic and clinical features of APL in pts over 60 yrs. This cut off reflects the definition of "elderly patient" in most Italian APL GIMEMA trials. Moreover, both the real life outcome and safety data after either conventional anthracycline-based CT or alternative CT-free approaches were analysed. OS, response rate to either regimens and adverse event occurrence were collected. Methods This retrospective multicenter REL (Rete Ematologica Lombarda) survey, enrolled a total of 101 consecutive APL pts aged ≥60, treated between 2000-2018. Demographics, clinical data and therapy outcome data were recorded in a dedicated patient's report form. Statistical analysis was performed using the Kaplan Maier method, Log-rank test and Cox regression. Results For analysis, pts were grouped into different categories according to age and fitness. Tables 1 and 2 summarise clinical charcteristics and treatment administered. Performance status (PS) and number of comorbidities increase with age. Twentynine of 102 (28,4%) and 9/102 (8,8%) pts had a history of or subsequently developed a solid tumor respectively. High frequency of additive cytogenetic abnormalities was observed as well. CT+ATRA was preferentially administered, mostly with attenuated intensity, to younger pts with better PS, while ATO+ATRA was preferred in pts with reduced cardiac function and ATRA monotherapy was reserved to frail or over 80 yrs old pts. Rates of differentiation syndrome or infections or cardiac events were similar in the different treatment groups. Overall, complete remission (CR) rate after induction therapy was 94.16% [CI95%: 87,5%-97,8% ]. At a median follow-up of 40 mos (range 0-199), the overall relapse rate was 24%. Median time to relapse was 7 mos in 1/8 (12,5%) ATRA monotherapy treated pts and 13 mos (range 5-66) in the 23/68 (33,8%) pts receiving CT+ATRA. No relapse occurred among the 22 pts treated with ATO+ATRA (p 0.005). OS and EFS were significantly associated with pts' age (HR 9% and 7.6%; p

Description: AML patients (pts) with a normal chromosome pattern and the “Internal Tandem Duplication” (ITD) of the FLT3 gene have an overall and event-free survival (OS, EFS) inferior than those of pts with a FLT3 “wild-type” gene because of a higher relapse risk, are placed in the intermediate-1 prognostic category, and when in complete remission (CR) are candidates to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of allo-HSCT in ITD+ pts is still debated and a recent retrospective analysis has stated that FLT3/ITD adversely affected allo-HSCT outcome in the same direction as it does after chemotherapy. Thus, the present study was aimed to compare the OS, EFS and relapse risk of pts submitted to allo-HSCT in first CR or in initial relapse, defined by a 5-10% bone marrow blast cell percentage, with those of pts submitted to chemotherapy alone. The study cohort consisted of 54 chromosomally normal, ITD+ consecutive non-M3 AML pts who were included in 168 AML pts aged 18-66 years who came to our observation in the period January 2007-December 2013. At diagnosis median age was 48.6 years (range 18-66), 25 pts were males and 29 females. Median follow-up was 16.2 months (0.4-68.8): median follow-up for responsive pts was 7.15 months (range 0.26-27.6), for relapsed pts was 18.1 (range 1.9-68.8) and for transplanted pts was 9.1 months (range 2.9-26.8). All pts received the same induction treatment that consisted of standard Idarubicine+Ara-c “3+7” followed by two consolidation courses with high-dose Ara-c. Those who failed induction received other treatment schedules among which Fludarabine+Ara-c+Idarubicine was the most common. At the end of consolidation 38 pts were in first CR, achieved after 3+7 in 27 pts and after a second different course in 11. Sixteen pts had a resistant disease. After a median time of five months (range 1-21) 21/38 pts (55.2%) relapsed. All received a re-induction and 8/21 (38.1%) attained a second CR. Allo-HSCT was performed in a total of 23 pts: 12 first CRs, 6 second CRs and 5 initial relapses. The donor was a sibling in 7 pts, an unrelated donor in 13 and an haplo-identical donor in 3; the HSC source was the marrow in 6 pts, the peripheral blood in 16 and the cord blood (CB) in one. The Conditioning regimen was myeloblative (mainly Busulfan+Fludarabine) in 21 and non-myeloblative in 2; GvHD prophylaxis consisted of Cyclosporine A, steroids and methotrexate “short course”. The median number of CD34+ cells infused was 5.14x106/kg (1.3-12.7). All pts except that who received CB engrafted after a median time of 15 days (12-28); 21 were complete chimeras, two partial chimeras. Thirteen pts developed acute GvHD (grade I in 3 pts, grade II in 5, grade III in 2 and grade IV in 3) which totally/partially recovered after high dose steroids along with different immunosuppressive drugs in 4 and 9 pts respectively. Eleven pts developed a chronic GvHD which was the evolution of an aGvHD in 9, targeted different organs, was stable in 3 pts and completely/partially recovered in 4 and 2 pts respectively. Post-transplant relapse occurred in 3/12 first CRs, in none second CRs and in 3/5 initial relapse. The estimated response rate for CR pts submitted to allo-HSCT was 422.1 (95% CI: 262.4-679.1) versus 64.6 (95% CI: 40.7-102.6) for those submitted to chemotherapy alone with a median survival time of 7.2 months (range 5.3-8.8) versus not reached (1.9-not available); on univariable Cox model the HR of allo-HSCT pts was 37.9 (95% CI: 9.4-152.0) with p=0.0000. The estimated relapse rate for CR pts submitted to allo-HSCT was 8.6 (95% CI: 2.1-34.4) versus 44.3 (95% CI: 25.7-76.3) for those submitted to chemotherapy alone with a median survival time not reached (range not available) versus 13.2 (7.2-not available); on univariable Cox model the HR of allo-HSCT pts was 0.5 (95% CI: 0.2-1.1) with p=0.06. The estimated death rate for CR pts submitted to allo-HSCT was 28.7 (95% CI: 13.7-60.4) versus 49.7 (95% CI: 32.1-77.1) for those submitted to chemotherapy alone with a median survival time of 18.3 months (range 14.2-not available) versus 12.2 (8.8-18.9); on univariable Cox model the HR for allo-HSCT pts was 0.48 (95% CI: 0.2-1.1) with p=0.09. In conclusion, our series suggests that in ITD+ pts allo-HSCT significantly strengthens CR in pts who had already responded to conventional chemotherapy, but it presents only a trend towards significance when its superiority to prevent relapse was considered. Disclosures Castagnola: Gilead Sciences: Research Funding.

Description: Abstract 3037 Fotemustine (Muphoran), a nitrosourea alkylating agent approved for use in the treatment of metastatic melanoma, has proven to be effective as single agent in relapsed/refractory multiple mieloma (MM). We report preliminary data of a phase II single centre study exploring the feasibility and the efficacy of the combination bortezomib (B) + fotemustine (Mu) + dexamethasone (D) (B-MuD) in relapsed/refractory MM patients. This study has been approved by local ethical committee; all patients (pts) signed written informed consent before the enrolment. MM pts relapsed or refractory after at least one therapy were eligible for the study. Pts who received prior bortezomib-containing regimen were included only if not considered bortezomib-refractory. Fotemustine at the escalating doses of 80 and 100 mg/m2 i.v. on day 1 was associated to Bortezomib 1,3 mg/m2 i.v. on days 1,4,8,11 + Dexamethasone 20 mg orally on days 1–2, 4–5, 8–9, 11–12 of 21-day cycle for a total of 6 cycles. Protocol was amended after the enrolment of the first five pts due to a considerable toxicity. We observed 3 grade 3–4 peripheral neuropathy, 1 grade 3 pneumonia, 4 grade 4 thrombocytopenia and two pts dropped-out (one for grade 3 pneumonia at 2° cycle, and one for grade 4 peripheral neuropathy at 3° cycles). Thus the schedule was modified as following: Fotemustine at escalating doses of 80 and 100 mg/m2 i.v. on day 1, Bortezomib 1,3 mg/m2 i.v. once weekly on days 1, 8, 15, 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, 22 for six 35-day cycles. An interim analysis of feasibility and efficacy was planned after the inclusion of the first two cohort of 6 pts each, treated with escalating dose of Fotemustine according to the amended schedule. Up to now, 18 pts have been enrolled (5 pts before and 13 after the amendment): M/F 10/8, median age 69 years (44-82), median number of previous therapies 2 (1-5). Previous treatments included autologous transplant in 10 pts (59%), bortezomib in 8 pts (44%), oral melphalan in 7 pts (41%) and thalidomide in 12 (71%). After the inclusion of 12 pts the MTD for Fotemustine was established to be 100 mg/m2. No drop-outs were registered after the amendment. Preliminary data on response are available in 10 pts. Nine pts (90%) obtained at least a PR, 8 pts (80%) registered ≥VGPR (CR 10%). At time of this analysis 79 cycles were delivered: 14 before, 65 after the amendment. Eighty-nine AE of any grade were observed, 43 hematological and 46 non-hematological. Thrombocytopenia was the most common AE either before and after the amendment. Need for dose reduction was significantly lower after the amendment. In detail fotemustine was reduced in 14% of cycles before and never after the amendment (p=0.0001), bortezomib dose reduction were performed in 36% of cycles before and 15% after the amendment (p=0.08), dexamethasone dose reduction occurred in 64% of cycles before and 13% after the amendment (p=0.0001). In conclusion, this interim analysis shows that fotemustine in combination with bortezomib and dexamethasone is safe and gives encouraging results in relapsed/refractory myeloma patients with 80% of ≥VGPR. Updated results will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Bisphosphonates (Bi) have been proven to be effective in preventing or delaying skeletal complications in multiple myeloma (MM) with a significant improvement of the quality of life. The 2002 ASCO guidelines indicate that once initiated intravenous Bi should be continued until an evident substantial decline of performance status. Recently, osteonecrosis of the jaw (ONJ) has been reported as complication of intravenous Bi treatment, with an incidence ranging between 6 and 13% and a greater occurrence in patients (pts) receiving zoledronic acid (Zol) than in those treated with pamidronate (Pam). Aim. In this retrospective study we evaluated the incidence of ONJ and of skeletal related events (SRE) in a cohort of MM pts divided in two groups according to the schedule of administration of Bi; group A: monthly administrations until tolerated (standard), group B: monthly administrations during the first year and then every 3 months (reduced). Methods: One hundred and six MM pts (M: 63, F: 43) were included in this study: 51 pts received a standard treatment (group A) and 55 a reduced schedule (group B). Pam 90 mg i.v. was administered as a three hour infusion and Zol 4 mg i.v. as a 15 minutes infusion. SRE was defined as: pathologic fracture, radiation to bone, spinal cord compression with vertebral fracture, hypercalcemia. Results: No difference was found between the two groups concerning pts characteristics at the onset: age, sex, extension of bone disease, status of the disease (progressive or responsive). Twenty pts received only Pam, 42 only Zol and 44 pts Pam followed by Zol. The distribution of the different type of Bi was not different in the two groups. ONJ occurred in 7 pts (6.6%) with a significant difference between the two groups: 6 pts in standard schedule (11.7%) and 1 in the reduced (1.8%), p=0.01, after a median time of 22.8 months in group A, and 37.8 months in the case of group B. Four of out 7 ONJ occurred during the second year of treatment (12–24 months): that period resulted significantly related (p=0.000) to the occurrence of ONJ with respect to the others (24–38 months, 40–100 months). All ONJ occurred in pts treated with Zol alone (5 pts) or with Zol after Pam (2 pts), whereas no cases were observed in Pam alone pts (p= 0.005). The median number of infusions was 20 with comparable results in the two groups (20 in group A, 19 in group B). SRE was observed in 38 pts (35.8%): 16 pts in group A and 22 pts in group B without statistical difference (p=0.6), after a median time of 9.8 months. Conclusions: These results suggest that the reduced schedule of Bi is associated with a significant lower incidence of ONJ and, although the sample size is limited, the appearance of ONJ seems delayed with respect to the standard treatment. Moreover, the incidence of SRE is similar in the two groups. In conclusion, the reduced schedule, could be applied in order to combine the antiresorptive efficacy of Bi with a higher safety and a better compliance.

Description: Introduction: The European Leukemia Net (ELN) stratification classifies as favorable prognosis four different subgroups of acute myeloid leukemia (AML) with specific cytogenetic/molecular abnormalities. These forms are potentially curable with standard chemotherapy, even though about 30% of patients (pts) still relapse. Overall survival (OS) of 60% at 5 years is reported but it is not clear if all different subgroups show an homogeneous outcome. The purpose of this study was to assess, in a real life setting, the response rate and the outcome of newly diagnosed AML patients with favorable prognosis based on ELN classification. Data were collected from six hematological centers of the regional network REL (Rete Ematologica Lombarda). Methods: Between 2007 and 2014 we analyzed adult AML patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1(group1), inv(16)(p13q22) or t(16;16)(p13q22)/CBFbeta-MIH11(group 2), normal karyotype and mutated NPM1 and negative FLT3-ITD (group 3) or double mutated CEBPA (CEBPA dm) (group 4). All patients received induction, mainly standard 3+7 chemotherapy (or reduced 1+5 in older pts) in 66% of cases, followed by high dose cytarabine based consolidation in 77% of pts. Clinical and molecular data were analyzed at diagnosis and at different time points during treatment and follow up with qualitative and quantitative PCR. The Kaplan-Meier product-limit method was used to estimate survival curves, and the log-rank test was adopted to evaluate differences between groups of pts. Results: We studied 177 AML pts (96 males and 81 females) with a median age of 55 years (range 20-80): 27 of group 1, 35 of group 2, 98 of group 3 and 17 of group 4. Complete hematological response (CHR), assessed in 176 pts, was achieved in 161 pts (92%): 23(85%), 32(91%), 90(93%), 16(94%) respectively in group 1, 2, 3, 4 without significant difference (p=0.26). Molecular complete remission (mCR), evaluated in 152 pts out of 161 in CHR, was documented in 102 pts. Forty pts entered mCR after induction and 62 pts at the end of consolidation or later (1-40 months); therefore, mCR rate was 67%. Considering the type of the method, 48 pts resulted in mCR with qualitative PCR, the remaining 54 (53%) with qualitatitive and quantitative PCR. Median time to mCR was 4 months and was different among groups (p=0.03); in particular, t(8;21) pts obtained mCR later than NPM1 pts (8 versus 2.6 months) (p=0.01). The relapse rate was 41% and the median time to relapse was 10.2 months, without any difference among groups (respectively p=0.5 and p=0.8). Five years overall survival (OS) and disease free survival (DFS) were 65% and 47% with no significant difference among groups (respectively p=0.3 and p=0.9). Age (

Description: Abstract 1223 Poster Board I-245 Introduction This study aimed at evaluating the impact of three different pre-transplant therapies on the outcome of patients (pts) eligible for high-dose therapy. Methods two-hundred sixty eight newly diagnosed MM pts aged £65 years, Durie-Salmon stage III, II, or I in progression, were consecutively enrolled from 2000 to 2007 in three different protocols, with three different pre-transplant therapy: Group 1: (145 pts) 3 pulse-VAD cycles; Group 2: (67 pts) 3 pulse-VAD cycles plus 3 Thal-Dex cycles (thalidomide at the dose of 100 mg/day orally at bedtime, continuously for 3 months, oral dexamethasone at the dose of 20 mg on days 1-4 and 14-17 every 28 days); Group 3: (57pts) 4 Vel-Dex courses (Bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, 11; oral Dexamethasone 40 mg on days 1-4 and 8-11 every 3 weeks). After induction all pts received two DCEP-short cycles as mobilization (oral Dexamethasone 40 mg/day on days 1-4 + Cyclophosphamide 700 mg/m2/day i.v., Etoposide 100 mg/ m2/day i.v., cisPlatin 25 mg/m2/day for 2 days) with peripheral blood stem-cell (PBSC) collection prompted by G-CSF followed by one or two transplants (Tx) with melphalan 200 mg/m2 as conditioning regimen. Response was defined according to IMWG uniform criteria. Pts were considered responsive when obtaining at least a PR. Results pts in the three group were similar for age, gender, Ig type, ISS stage. A significant higher percentage of Durie and Salmon stages III was found in group 3 (83% vs 68% in group 1 and 67% in group 2, p=0.0002). The median follow-up was 46 (1-150) months for group 1, 43 (1-68) months for group 2, and 29.7 (1-79) months for group 3. At the time of this analysis in the three groups 51%, 65%, 90% of transplanted pts respectively were still alive, and progression after transplant was registered in 84%, 80%, 50% respectively. Patient flow before Tx was similar (p=0.45): 19% in group 1, 27% in group 2, 23% in group 3. In group 1, 2% of pts went off-study after VAD, and 17% after mobilization phase. In group 2, patient flow was equally distributed: 7% after pulse VAD, 10% after thal-dex, 9% after DCEP. In group 3, 12% of the pts went off-study after Vel-Dex, 11% after DCEP. Table 1 summarized responses. In group 3 (Vel-Dex) response was better along all protocol phases with respect to group 1 or 2 (p

Description: Introduction. In a modern context of improved management of acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement at diagnosis remains an obstacle towards long-term cure. We have previously reported that flow cytometry (FCM) is better than conventional cytology (CC) in demonstrating the presence of leukemic cells in patients' (pts) cerebrospinal fluid (CSF), especially in samples with low cell counts. In the framework of the national Campus ALL program aimed at improving the management of adult ALL patients enrolled in the GIMEMA protocols, we retrospectively evaluated the incidence of occult CNS positivity and its impact on outcome in 221 adult pts with newly diagnosed ALL from 11 centers. Methods. Ninety-four patients (42%) were females and 127 (58%) males, with a median age of 44 years (range 17-80), a median white blood cell (WBC) count of 10.6x109/L (range 0.1-457). One hundred and seventy pts (77%) had B-lineage ALL. Cytogenetic/genetic data were available in 167 (75%) pts: 58 (35%) had a BCR/ABL rearrangement, 14 (8%) a complex karyotype and 11 (6%) a MLL rearrangement. Pts were treated according to the GIMEMA/NILG ALL protocols or with the Hyper-CVAD program. Ninety-eight pts underwent an allogeneic stem cell transplant (ASCT). Median follow up was 26.8 months (range 1-136.6). All CSF samples were evaluated both by CC and FCM. The presence of ≥10 clonally restricted or phenotypically abnormal events was regarded as a FCM positivity. Based on the results of CSF examination, three different categories were recognized: manifest CNS+ (CC+FCM+), occult CNS+ (CC-FCM+) and CNS- (CC-FCM-). Results. Overall, 16 (7%) pts had manifest CNS+, 39 (17%) occult CNS+ and 166 (75%) were CNS-Median age, WBC count, B/T lineage, cytogenetic/genetic features did not differ significantly between the three categories. A complete remission (CR) was achieved in 178 (80%) pts, 9 (4%) died early in induction and 104/178 (58%) experienced a relapse. The frequency of CR rate did not vary significantly across the three identified categories. In univariate analysis, the CNS status correlated significantly with the incidence of relapse (p=.004) and with censor (45 years (RR:1.45, 95% CI 1.47-2.43, p=0.04)were independently associated with a lower OS. Conclusions. Our large, multicenter CAMPUS ALL study showed that i) in ALL adult pts, FCM allows to detect occult CNS disease, even in conditions of low spinal fluid leukemic count; ii) the presence of occult CNS disease is associated with an unfavorable outcome. Further prospective studies on larger series are needed to confirm these data. Figure. Figure. Disclosures Del Principe: Gilead: Membership on an entity's Board of Directors or advisory committees. Fracchiolla:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Foà:NOVARTIS: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau.

Description: Introduction. Acute leukemia (AL) and high-risk myelodysplastic syndromes (HR-MDS) are relatively uncommon among HIV-positive (HIV-pos) patients (pts) and epidemiologic studies are very limited. A dismal outcome for these patients has been reported in the past; however more recently an improvement of prognosis was observed using intensive approaches, such as allogeneic stem cell transplantation (alloSCT) (Kwon, AIDS 2019). In order to better define the clinical characteristics of AL/HR-MDS HIV-pos pts, the feasibility of any specific treatment and the outcome in this setting, we evaluated all HIV-pos AL and HR-MDS pts diagnosed at 5 Hematology Centers participating to Rete Ematologica Lombarda (REL). Patients and Methods. We asked to the Centers to retrospectively report all cases of HIV-pos adult pts with AL or HR-MDS. We sent a database asking information about the characteristics of hematological disease, HIV infection, therapy, toxicities and outcome of pts. AL and MDS were classified according to WHO classification. The response to therapy was defined by European Leukemia Net criteria. Results. Between 1994 and 2019, 23 pts have been retrieved: 3 affected by HR-MDS, 15 by acute myeloid leukemia (AML) and 5 by acute lymphoblastic leukemia (ALL). Median age at AL/MDS diagnosis was 49y (range 28-67), M/F ratio 17/6. Median CD4 count was 336/mcl (range 50-2048). HIV infection was antecedent to AL/MDS diagnosis in 20/21 evaluable cases, with a median duration of 115 months (range 0-396); these pts were already on HAART at AL/MDS diagnosis. In 6 (29%) pts AIDS was also documented (1 Kaposi sarcoma, 1 P. jirovecii pneumonia and 4 non Hodgkin B-cell lymphoma). Six (30%) of the 20 evaluable cases had an adverse cytogenetics (complex karyotype), while only 1 pt showed a favorable karyotype (inv16). NPM1 mutation was observed in 2 AML cases, FLT3 ITD and p53 mutation in 1 case each. No bcr/abl rearrangement was observed in ALL cases. Three pts (13%) did not receive any treatment due to poor performance status (1 ALL, 2 AML) and died of progressive disease after a median of 2 months (mo, 0.5-2). Two HR-MDS pts received azacytidine but they rapidly progressed after 2 courses and died at +7 and +8mo respectively. Eighteen pts were treated with intensive therapy: 17 underwent induction chemotherapy (cht) and 1 alloSCT upfront. All the pts received HAART during AL/MDS treatment. Eleven out of the 17 pts (65%) receiving induction cht achieved a complete remission (CR); 4 pts received further induction cht, which was successful in 2/4 (50%) the overall CR rate being therefore 76.5%. A further pt received venetoclax+azacytidine as fourth-line treatment and achieved a morphological CR. Ten pts (9 AML and 1 HR-MDS) underwent stem cell transplantation at first-line: 3 autologous (ASCT) and 7 allogeneic. Overall 5 out of 13 (38%) pts achieving CR after induction cht relapsed; only one of the 5 receiving salvage treatment achieved a durable CR and proceeded to salvage alloSCT. Five pts (22%) died of toxicity: 2 (1 P, jirovecii pneumonia and 1 septic shock) during induction cht (2/17, 12%), 1 during aplastic phase after ASCT (hemorrhagic stroke), 2 after alloSCT (1 aGVHD, 1 infection); overall, SCT therapy-related morality was 3/10 (30%). After a median follow up of 21mo, 10 pts are alive in CR, with a median overall survival (OS) of 17mo and a 2y OS of 41.2±22.7SEM. A trend for a better OS was observed in pts with AL/HR-MDS diagnosis in the last years (2y OS: 2011-2019: 64.2% vs 1994-2010 27.3%, p=0.12) (Fig.1), even if median age was significantly higher in the second period (55.5y vs 44.5y, p=0.02). A complex karyotype was predictive of poor outcome in pts evaluable for cytogenetics (45% vs 10%, p=0.04), whereas no correlation between age, CD4 count, HIV duration and OS was observed. Conclusions. Intensive chemotherapy and stem cell transplantation are feasible and effective in AL/HR-MDS HIV-pos pts, with an acceptable toxicity profile, similar to the HIV-neg counterpart. The more frequent curative intent approach to AL HIV-pos pts is probably the main responsible for the improved survival in the last years also in the elderly; antiviral, antibiotic and antifungal prophylactic strategy, together with a prompt diagnosis and a careful management of infectious events, should be carefully considered in this setting of pts. HIV infection responsive to HAART should no longer be considered a contraindication to standard AL/HR-MDS treatment. Disclosures Rossi: Sandoz: Honoraria; Daiichi-Sankyo: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria.

Description: Extramedullary myeloma (EMM) at diagnosis or during the course of the disease is rare and often anecdotal. We reviewed the records of 965 consecutive MM pts diagnosed and followed from 1969 to July 2007 in order to evaluate: the overall incidence of EMMs and the changes over time clinical presentation, response to treatment and outcome of EMM pts divided into two subgroups according to the time of appearance, at diagnosis or during the course of the disease. We considered three periods: 1969–1989 (conventional chemotherapy, CCT); 1990–1999 (introduction of high-dose therapy, HDT); 2000–2007, (era of novel agents). The overall incidence of EMM was of 13% (129/965 pts), 87/42 M/F, median age 58 (31–80) years. A prior MGUS was present in 24 pts and a solitary plasmacytoma in 10 (8%). Characteristics at the time of EMM were: 77 pts IgG (60%), 23 IgA (18%), 2 IgM (2%), 16 light chain (12%), 11 not secretory (8%); 29 pts were in stage I, 14 in stage II, 86 in stage III; 30/129 pts (23%) were asymptomatic. More frequently involved sites were: paravertebral (40%), rib cage (32%), pelvis (10%). Multiple localizations were present in 27 pts (21%). A plasmacytic leukemia was observed during the follow-up in 9 pts (7%). The overall median follow-up was 24.4 (2.5–148) months. Seventy-three pts presented EMM at the time of diagnosis with different incidences in the 3 periods: 1969–1989 4.5%, 1990–99 4.3%, 2000–07 12.7%. These pts were treated with HDT in 43 cases (59%) and CCT in 30 (41%). Radiotherapy (RT) was associated in 38 pts (52%). A partial response (PR) was achieved in 49 pts (67%). Progression or relapse were observed in 46 pts (63%) and the median time to progression (TTP) and overall survival (OS) in this subgroup of pts were 17.3 and 21.5 months respectively. The other 56 pts showed an EMM during the course of the disease after a median time of 20 (2–144) months from diagnosis. EMM incidence varied as follows: 1969–1989 2.7%, 1990–99 7.2%, 2000–07 7.4%. Median number of previous lines of therapy was 1 (range: 1–7), including HDT in 22 pts (39%), thalidomide or lenalidomide in 18 (32%), bortezomib in 5 (9%). The median time from HDT to EMM was 17 (2–125) months. Treatment of these pts consisted of CCT in 36 cases (64%), thalidomide in 3 (5%) and bortezomib in 8 (14%). RT was given in 29 cases (52%). Response rate in this subgroup was low, only 30% of pts obtained a PR. The median TTP and OS from the time of appearance of EMM were 4.7 and 6.5 months respectively and the overall survival from the diagnosis was 29.9 months. The two groups of EMM pts were also compared for all the clinical characteristics, response to therapy and outcome. EMM pts at diagnosis showed higher levels of monoclonal component and haemoglobin, and lower bone marrow plasmacytosis with respect to the others. OS from diagnosis was similar in the two groups. In conclusion, our study shows an increased incidence of EMM over time. The more recent increase of EMM at diagnosis might be due to the wider use of more sensitive imaging techniques as CT scan and magnetic resonance, while during the course of the disease after 1990 could be related to the longer survival of pts thanks to the new therapeutic approaches. Anyway, the presence of EMM whether at diagnosis or at progression seems to negatively affect the outcome of pts since the OS is shorter than MM pts without EMM.

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