ALBERT

Description: Background: Allogeneic hematopoietic stem cell transplantation (allo SCT) has two potential advantages over autologous SCT: a tumor-free graft and graft-versus-myeloma (GVM) effect. Allo SCT’s potential to induce long term remission has, however, been offset by high rates of transplant-related non-relapse mortality (TRM). Reduced-intensity conditioning (RIC) regimens for allo SCT are associated with lower TRM without compromising the GVM effect. Methods: We retrospectively analyzed our experience in 69 patients (30 females and 39 males) with heavily pretreated, relapsed myeloma, who received allo SCT at our institution between1985 and 2007. Eighteen patients received myeloablative regimens (MA), while 51 received RIC regimens. MA regimens were TBI-based in 5 patients, high-dose busulfan-containing in 6 patients and high-dose melphalan containing (180–200 mg/m2) in 7 patients. RIC regimens were a combination of fludarabine (90–120 mg/m2) and melphalan (100–140 mg/m2). Median age of patients at allo SCT in both groups was 51 years. Median interval from diagnosis to allo SCT was 35.4 months in MA group, and 34.2 months in RIC group. Eight (44%) patients in MA group and 36 (70%) patients in RIC group had prior autologous SCT. Six patients (33%) in the MA group and 11 (25%) in the RIC group received allo SCT from unrelated donors (p=0.3). Median number of prior treatment regimens were 5 (range 1–10) in both groups. Stem cell source was peripheral blood in 3 patients in MA group and 41 patients in the RIC group (p=0.0001). Results: Median follow-up in surviving patients was 27 months (3–98). All patients achieved engraftment. Cumulative TRM at 1 year was 56% in the MA group and 25% in the RIC group (p=0.03). Overall response rates in evaluable patients were 69% (CR=15%, PR= 54%) in MA group, and 79% (CR=23%, PR=56%) in the RIC group (p=0.47). Disease progression at 2 years was seen in 8 patients (44%) in the MA group and 25 patients (49%) in the RIC group (p=0.78). Median progression-free survival (PFS) in MA vs. RIC groups was 4.1 and 6.8 months, respectively (p=0.003) and median overall survival (OS) ) in MA vs. RIC group was 5.3 and 13.9 months, respectively (p=0.001). Cumulative Incidence of grade II–IV acute graft-vs.-host (GVHD) in MA vs. RIC groups disease was 33 vs. 27% (p=0.76); cumulative incidence of chronic GVHD in MA vs. RIC group was 54% vs. 47% (p=0.41) in evaluable patients. At the time of this analysis, 13 patients (25%) were still alive in RIC group, 7 of whom (14%) were in remission for up to 6 years post allo SCT. The most common causes of death were recurrent disease (30 patients; 43%), acute or chronic GVHD (16 patients; 23%) and opportunistic infections (5 patients: 7%). Conclusions: Allo SCT after RIC regimens is associated with longer PFS and OS and lower TRM. There was no increase in the risk of relapse, or acute or chronic GVHD. These regimens can safely replace MA regimens and may offer greater benefit if utilized earlier in the course of disease. Figure Figure

Description: Abstract 3945 Poster Board III-881 Introduction Non Hodgkin Lymphoma could be clinically divided as low grade/indolent NHL (LG NHL) and high grade/aggressive NHL (HG NHL). These diseases are chemo and radio-sensitive and improvements have been achieved by immunotherapeutic approaches. However some patients will relapse and a follow up strategy has to be planned in order to detect and treat them. Several aspects should be considered in planning a follow up including safety, specificity, sensitivity, costs and impact on the patient's psychology: an optimal follow up should mediate between these ones. The more diffuse follow up have been planned years before the introduction of innovative methods and imaging techniques, suggesting the opportunity to revise these programs. Methods We collected data about 418 NHL patients -both low and high grade- treated at our institution from 1990 to 2005 who achieved a complete remission according to Cheson criteria and who entered a follow up program which schedule is planned for 5 years divided in two periods: first two years evaluation every 3 months and in the following three years every sixth month. At each visit physical examinations, blood testing (blood count, chemistry) are performed; for imaging techniques we alternate a whole body CT scans to ultrasounds and chest X-ray coupled. Analyzing time to relapse (TTR), we tried to optimize our follow up schedule trough a computation application known as multi-objective analysis. The first step of this method has been to choose and try to quantify the costs of a follow up which reflect its effectiveness. We considered as costs the expected time between relapse and its detection (Ca) and the expected number of performed examinations before failure or censoring occurs (Cb). The total follow up costs could be summarized in a vector Cref: (Ca,Cb). After doing that we described survival analysis, relapse rate and their onset time in order to be suitable for the informatic analysis. We used a log logistic parametric model to do that. Next we shaped our ideal follow up as a structure based one, which is currently the most used in medical practice: a first period where examinations are more tightly spaced, followed by a second period where they are performed further apart. We describe such follow-up schedule “S” as (d1, k, d2) : d1 is the time between the first k examinations; d2 is the time between the remaining examinations. Applying the log-logistic model we calculated the Cref and schedule for our follow up: Cref was (Ca,Cb)=(8.5,6.2); this means that, on average, every patient entering the follow-up will perform 6.2 examinations, and among those who incur in a relapse, the relapse will be detected 8.5 units of time (eg. weeks) after its onset. The follow up structure was (13,8,26). We then calculated all the possible combination of (d1, k, d2) values from 1 to d1 = 25, k= 24 and d2 = 60. Results 360000 follow up schedules had been detected after searching all the possible combinations for d1, k and d2. For each one Ca e Cb costs have been calculated and than compared by multi-objective analysis to those of the current schedule, We look for both follow up structured and “free” follow up, where “free” means that intervals between examination is continuously variable. When comparing follow-up schedules, we apply the rule of Pareto-dominance: the schedule S1 is superior to the S2 schedule if and only if the cost values for S1 are both lower than the cost values for S2. The method then takes into account only those schedules which improve the current one, with respect to both the Ca and the Cb costs. After multi-objective analysis six follow up were detected. These were as following: (16,10,22), (15,8,20), (15,6,19), (16,8,19), (16,5,18), (16,4,18) and are shown in Fig. 1. Conclusions no differences in follow up schedules emerged when we considered separately LG and HG lymphoma patients. Maximum improving of our follow was just 4% and all the new schedules had wide time frequency visit in the first period and a narrow one in the second period: this was a consequence of the higher relapse distribution in the first period and this follow up organization lead to a lower total number of visit without risk of lose any relapse. This is the first application of this analysis to hematological patients confirming the validity of a follow up schedule should be shaped in two different period. Disclosures: No relevant conflicts of interest to declare.

Description: Background: There is a role of novel preparative regimens to further improve the outcome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma. Arsenic trioxide (ATO) has synergistic activity with melphalan and ascorbic acid (AA) both in vitro and in vivo, and this 3-drug combination was found to be safe and feasible in both conventional and high-dose settings. Bortezomib, a proteasome inhibitor, is an active agent in newly diagnosed or relapsed multiple myeloma in conventional therapy setting. We conducted a randomized phase II trial to determine the safety and efficacy of a combination of ATO, AA and melphalan with or without bortezomib as preparative regimen in patients with myeloma. Methods: Sixty patients were enrolled and 58 patient received ASCT between October 2006 and September 2007. One patient developed respiratory failure and another developed extensive pulmonary embolism after enrollment and did not proceed to ASCT. All 58 evaluable patients received melphalan 100 mg/m2 IV on days -4 and -3, AA 1000 mg/day IV on days -9 to -3 and ATO 0.25 mg/kg IV on days -9 to -3. Patients were randomized to 3 arms; no bortezomib (arm 1), bortezomib 1 mg/m2 on days -9, -6 and -3 (arm 2), and bortezomib 1.5 mg/m2 on days -9, -6 and -3 (arm 3). Patients were also asked to fill out a standardized Quality of Life (QOL) questionnaire at enrollment and at 6 months post-ASCT. Results: Median age of patients in arms 1, 2 and 3 were 61, 59 and 64 years, respectively (p=0.08). Median interval between diagnosis and ASCT were 12.2, 9.6 and 8.8 months, respectively (p=0.3). Cytogenetic abnormalities were detected in 2, 5 and 8 patients in arms 1, 2 and 3, respectively (p=0.08). With a median follow up of 11.4 months (range 5 to 20) post ASCT in surviving patients, cumulative non-relapse mortality was1.7%. Grade 3–4 toxicity was seen in 6 patients in arm 1 (mucositis 3, dyspnea 1, acute renal failure 1, pleural effusion 1), 6 patients in arm 2 (mucositis 3, diarrhea 1, pneumonia 1 and hydronephrosis 1) and 6 patients in arm 3 (pulmonary edema 2, mucositis 1, intestinal obstruction 1, low back pain 1, elevated transaminases 1) (p=0.9). The most common adverse events were nausea, diarrhea and pedal edema. Grade 1–2 weight gain due to fluid retention was seen in 84, 70 and 95% of patients in arms 1, 2 and 3, respectively (p= 0.1). Median time to neutrophil engraftment (ANC 〉500/dl) was 10 days in each arm. Complete response rates in arms 1, 2 and 3 were 26, 10 and 16%, respectively (0=0.4). Kaplan-Meiers estimates of progression-free survival (PFS) and overall survival (OS) are shown in Figures 1 and 2. Median PFS and OS have not been reached. There was no significant difference in CR, PFS or OS between the 3 arms (p = 0.4, 0.62 and 0.4, respectively). Relapsed disease at ASCT (p=0.003), 〉12 months interval between diagnosis and ASCT (p=0.05), and cytogenetic abnormalities at diagnosis (p=0.005) predicted a shorter PFS. On a subset analysis, there was no significant difference in PFS or OS between the 3 arms in patients undergoing ASCT in first remission. Fifty-patients submitted their responses to the QOL questionnaire. More patients at 6-month post ASCT reported better overall health (56% vs.12%, p=0.0001). In contrast, more patients at study enrollment reported moderate to severe pain (44% vs. 27%, p=0.09) and debilitating emotional problems (42% vs. 23%, p=0.07). Conclusions: Adding bortezomib to ATO, AA and high dose melphalan is safe and well tolerated as preparative regimen for ASCT in patients with multiple myeloma. Patients with chromosomal abnormalities were predominantly treated in the bortezomib arms without an adverse impact on PFS or OS. Overall QOL indicators showed improvement at 6-month post ASCT. Longer follow up is needed to assess the efficacy of this combination. FIGURE 1 FIGURE 1. FIGURE 2 FIGURE 2.

Description: Abstract 5033 The pharmacology of pegylated liposomal doxorubicin (PLD) gives rise to a compound with major advantages that could potentially improve response and decrease toxicity. PLD comprises doxorubicin incorporated into polyethylene-glycol-coated liposomes, resulting in a longer circulation time in the body compared with the conventional formulation and a unique toxicity profile. The lower toxicity, especially less cardiotoxicity, is also related to the encapsulation of doxorubicin into microscopic liposomes, which preferentially penetrate and accumulate in tumour vasculature. Because increased angiogenic activity occurs in the bone marrow of patients with multiple myeloma, this pegylated formulation can enhance the delivery of doxorubicin to the tumour site. In addition, because myeloma cells divide slowly, the increased exposure of these cells to doxorubicin has the potential of overcoming resistance and increasing tumour cell killing capacity, theoretically resulting in improved response rates. Between December 2008 and May 2010, we treated a total of 39 MM resistant/refractory patients with two different scheme including PLD. Twenty-five patients were resistant/relapsed after at least one prior therapy including conventional doxorubicin. The scheme therapy was based on VMD: bortezomib (Velcade®: 1.3 mg/m2) as intravenous bolus twice a week for 2 weeks (on days 1, 4, 8 and 11 of each cycle) in a 28-day cycle for a total of 4 cycles; oral dexamethasone (40 mg) on the day of each bortezomib dose and the day after, and PLD (Myocet® 30 mg/m2) on day 4 of each cycle, 1 h after bortezomib infusion. Baseline characteristics are shown in table 1. All 25 patients were evaluable for response. Response rates following VMD showed: 2 patients in nCR (10%), 4 in VGPR (20%), 14 in PR (70%) resulting in an overall response rate (ORR) of 80% (20 patients). Global toxicities were lower and included neutropenia (12.5%), fatigue (25%), thrombocytopenia (25%) and neuropathy (37.5%). In the other group, fourteen patients were treated with RMD a combination regimen of lenalidomide (Revlimid®), PLD (Myocet®) and dexamethasone and 11 patients were eligible for evaluation. All the patients had multiple myeloma resistant or progressed after 1 to 5 previous anti-myeloma regimens including at least one doxorubicin containing scheme. RMD was administered for six 28-day cycle. Lenalidomide 25mg d1-21, Liposomal doxorubicin 30 mg/m2 d4, Dex 40 mg d1-4 and d17-20. Eight of eleven patients (73%) achieved an objective response to the therapy. Respectively, 2 patients (25%) obtained a VGPR and additional 6 patients (75%) a PR. The most common side effects was haematological toxicity with grade neutropenia (32%), thrombocytopenia (32%) and anaemia (18%). Under thrombosis prophylaxis with aspirin 100 mg per day we observed thrombembolic complications in only in one patients. Other non haematological side effects were pain (9%), diarrhoea (9%). Neither neurotoxicity nor constitutional symptoms of grade 3/4 were found. In both of groups no cardiovascular events were reported. Additionally 12 patients of RVM group and 4 patients of RMD group underwent to high dose chemotherapy and successfully collected an adequate number of peripherals stem cells at the first attempt. The introduction of pegylated liposomal doxorubicin, in bortezomib or lenalidomide based regimens, can play a key role in overcoming anthracycline resistance and improving the quality of response without limiting toxicity, especially in patients who have already received at least one prior therapy. We believe that there is a rational basis for the use of PLD as a second-, third-, or fourth-line therapy in patients with advanced MM. Table I. Characteristics of MM Patients undergoing VMD or RMD therapy Characteristics Cases Age at diagnosis (median and range) 65 (44–76) Number of patients     VMD 25 (14M, 11F)     RMD 14 (10M, 4F) Stage at diagnosis     Durie-Salmon (II/III) 10/29 Prognostic Markers     b2-microglobulin (m/L.) 2.2 (1.1–35)a     Creatinin (mg/dl.) 0.9 (0.5–4.4)a     Albumin (g/dl)) 4.0 (2.1–4.9)a     Hemoglobin (mg/dl) 11.3 (5.7–16.4)a a Median (Range) Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4772 Introduction Non Hodgkin Lymphomas (NHL) are commonly divided in two large groups known as high grade (HG) and low grade (LG) lymphomas. Specific therapeutic strategies are potentially curative, but a tailored treatment should be planned from the diagnosis on the basis of the prognostic features. Some clinical features at the diagnosis or relapse may be grouped to build prognostic indexes. These indexes are “build” starting from features present at diagnosis and related to patients and disease onset, but lacks to give any information about disease history and chemosensitivity. For these purposes others methods have been evaluated and probably the two that gave major help to detect slow responders or resistant patients are minimal residual disease (MRD) and PET scans. Here we develop and apply a partitioning recursive algorithm, known as HCS, by which possibly detect new possible prognostic factors. Methods Our dataset comprised 651 NHL patients followed at our Institution from 1990 to 2005, divided in High grade (HG NHL, n=343; 52,7%) and Low grade Lymphoma (LG NHL, n= 308; 47,3%). Only patients who enter in a follow up program were considered: therefore patients with at least a partial response. We considered as variables for algorithm analysis: age, sex, histological subtype, IPI status and bone marrow involvement, treatment approaches (poli-chemotherapy, mono-chemoterapy, radiotherapy, surgery, purine based chemotherapy, monoclonal antibodies, transplant approach, oral chemotherapy), response to therapy, previous successful treatments, previous relapses, previous failed therapies. Data were analyzed by a recursive partitioning algorithms. A partitioning recursive algorithm. This tool is thought to splits data in different subgroups that behave in a different way. It works starting from data and utilized them to create all the possible combinations of splits available. Among them it chooses the best one by statistics and finally applies it to patients' datasets. For these reason it is defined as “partitioning”. Afterwards the algorithm starts again the analysis on the subset previously detected and that's because it is called “recursive”. Results The most important split emerged to be the quality of response: patiets were splitted between patients in partial remission (PR) and complete remission (CR). Among PR patients, one subset (subset 1) with worse prognosis were found: both comprised patients with HG NHL not treated with monoclonal antibodies and/or transplant. Therefore the remaining PRs patients, treated by transplant approach and immunotherapy, had a better outcome. In CR group subset 2 has been detected, comprising HD NHL patients not treated by oral chemo alone were detected. Those patients, who had a better outcome, had been treated aggressively with polichemotherapy and/or autologous transplant. Differences between detected groups are statistically significant with p. value 0,03 maximum. Splits are shown in Figure 1 and 2. Conclusion Application of computer science analysis to NHL patients has been successfull. Quality of response emerged as the most important prognostic factor but among both PRs and CRs patients those with better outcome had HG NHL diagnosis and were treated by autologous transplantation or/and immunotherapy. This analysis confirms data available about transplant as a good approach for NHL patients. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4493 Introduction Acute GVHD involving the gastrointestinal tract is now the major cause of non-relapse mortality following allogenic transplant. Diagnosis remains problematic for some patients with pathology in the mid-gut; there is significant sampling error with mucosal biopsy; we lack objective measures of physiologic improvement or worsening in the gut; and duration of immune suppressive therapy remains imprecise. To address these issues, we have serially evaluated intestinal pathology in patients with acute GVHD using a reproducible ultrasound technique as a proof of principle study. Specifically, we examined the hypothesis that contrast-enhanced ultrasound (CEUS) could detect an enhancement of microcirculation during active intestinal acute GVHD as a diagnostic tool and that CEUS could be used to serially assess physiologic changes after treatment. Methods Four patients (pts) with hematologic malignancy (1 each with ALL, AML, mantle cell lymphoma, and myeloma) received a matched unrelated donor allogenic transplant after a myeloablative (N=2), reduced intensity (N=1), or non-myeloablative (N=1) conditioning. GVHD prophylaxis consisted of cyclosporine with either short course methotrexate (N=3) or mycophenolate mofetil (N=1). All patients developed biopsy-proven intestinal GVHD that was steroid refractory in 2 patients. At GVHD onset, patients were scanned with transabdominal ultrasonography and subsequently by CEUS using a linear phased-array 7.5-MHz transducer. A second generation echo-contrast agent (SonoVue®, Bracco), which consists of microbubbles stabilized by phospholipids and filled with sulphur hexafluoride, was injected i.v. as a bolus (2.4 mL) followed by 5 mL saline flush. Microbubbles have a mean diameter of 2.5 μm and remain within the vascular space allowing real-time imaging of microcirculation. Results In all patients, routine ultrasonography revealed mucosal edema involving the terminal ileum in 3 patients (wall thickness 5.1, 5.8 and 7.9 mm) and the colon in 4 patients (ascending colon 5.8, 6, 8.4 and 18 mm; transverse colon 6 and 12.6 mm; descending colon 11 mm). CEUS at GVHD onset showed an arterial phase (AP) complete enhancement of the entire wall section from the mucosal to the serosal layer (terminal ileum) in 2 patients. There was absence of enhancement only in the outer border of the muscularis propria in 1 patient (pt); there was absence of enhancement both in the outer and in the inner border of the colon wall and enhancement only of the intermediate layer in 1 pt. All patients showed late parenchymal phase (PP) wash out. These enhancement patterns have previously been described in active Crohn's disease (Serra C. et al; 2007). CEUS follow-up findings on serial examinations: 1) allowed us to monitor residual disease in one pt after Infliximab, showing persistent AP enhancement of microcirculation suggesting residual GVHD activity which required further treatment with eventually complete remission; 2) CEUS showed normalization and/or decreased microcirculation enhancement in pts responding to treatment (N=2); 3) CEUS showed AP microcirculation enhancement when GVHD flared (N=2); 4) CEUS showed persistence of AP enhancement of microcirculation after Rituxan (4 doses 375mg/m2/weekly) despite a decrease in ileum wall thickness and in agreement with only a slight improvement of symptoms in one pt when GVHD flared, 5) CEUS showed no improvement of intestinal microcirculation wall enhancement in steroid refractory aGVHD patients who eventually died (N=2). In one of them there was persistence of AP phase enhancement despite improvement of symptoms suggesting still active disease. Conclusions Contrast enhanced US showed intestinal microcirculation wall enhancement and delayed washout at the onset of GVHD symptoms in areas of the intestine inaccessible to endoscopic evaluation. CEUS findings on serial examinations correlated with incomplete responses and flares of GVHD symptoms (microcirculation enhancement) and responses to therapy (decreased microcirculation activity). CEUS may be useful for both diagnosis and prognosis, as it provides both anatomic and physiologic information about intestinal GVHD. These findings prompted us to design a prospective study to evaluate clinical usefulness of CEUS in diagnosis and follow-up of intestinal acute GVHD. Disclosures: No relevant conflicts of interest to declare.

Description: The optimal conditioning regimen for patients older than age 55 years with myeloid leukemia receiving allogeneic HSCT remains to be determined. Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) are of intermediate sensitivity to the graft-versus leukemia effect, and preparative regimen dose intensity is an important part of the treatment. Commonly, however, age 50–55 years has been used as the upper limit for the use of myeloablative doses of chemotherapy due to perceived high rates of morbidity and mortality. Herein, we report our results using the myeloablative preparative regimen of intravenous (IV) BuFlu in patients older than age 54 years with the diagnosis of AML or MDS. Methods: Seventy-four patients ages 55 years and older with AML (n=60; 8 had secondary AML) or MDS (n=14) were transplanted from 9/2001 to 6/2008. Eligibility for transplant included adequate hepatic, renal, cardiac and pulmonary functions, and a diagnosis of MDS with a high IPSS or AML with high or intermediate risk cytogenetics in first complete remission (CR1), or with disease beyond CR1. The preparative regimen consisted of IV Flu 40 mg/m2 and IV Bu 130 mg/m2 given once daily over 3 hours on pre-transplant days −6 to −3. Tacrolimus and methotrexate was used for graft-versus-host disease (GVHD) prophylaxis, with pentostatin in 13 cases (18%). Thymoglobulin (ATG) (4 mg/kg) was administered to those who received unrelated donor grafts. Results: Median age was 58 years (range 55–66); 18 patients (24%) were older than 59 years, and 64% were male. Disease status at HSCT was complete remission (CR) in 54% of the cases; 32% were in first CR (CR1) and 22% were in second CR (CR2), while 46% of the patients had active disease at transplant. Sixty eight percent and 28% of patients had intermediate and poor risk cytogenetics, respectively. Donors were HLA compatible related (50%) and unrelated (50%). Source of stem cells was bone marrow in 36 patients (49%) and peripheral blood in 38 patients (51%). All patients engrafted. Grade II–IV and III–IV acute GVHD was diagnosed in 41% and 7% of the patients, respectively. Chronic GVHD rate was 42%. Median follow-up is 22 months (range 1–82 months). Actuarial 2-year overall survival (OS) is 70%, 48%, and 35% for patients in CR1, CR2, and with active disease at time of transplant, respectively. Actuarial 2-year event free survival (EFS) is 65%, 45%, and 30% for patients in CR1, CR2, and with active disease at time of HSCT, respectively. Actuarial 2-year OS for unrelated and related transplants is similar at 50% and 45% respectively (p=0.7). Survival was not influenced by stem cell source. Thirty-two percent of the patients have relapsed (n=24). Causes of death were disease progression (n=22), GVHD (n=8), infection (n=3), and organ failure (n=3). TRM and survival are shown in Table and Figure. Conclusion: In this cohort of patients with high-risk AML and MDS in the 6th and 7th decades of life receiving BuFlu, TRM rates were low. In addition, long-term follow up indicates that responses with this regimen are stable in a significant proportion of patients. Our results would suggest that age in itself should not be used as the primary reason to exclude patients from receiving myeloablative transplants. Table. Cumulative Incidence of Transplant-Related Mortality by Pre-Transplant Disease Status TRM 30 days 100 days 1-year All patients None 4% 21% All CR (n=40) None 5% 18% CR1 (n=24) None 4% 15% Persistent Disease (n=34) None 3% 27% Figure. Survival Probability by Pre-Transplant Disease Status (median follow-up is 22 months). Figure. Survival Probability by Pre-Transplant Disease Status (median follow-up is 22 months).

Description: Achievement of complete remission (CR), with 100K/ml remains the gold standard achievement of chemotherapy for AML. A significant fraction of patients proceed to HSCT with 100K/ml (CRp). It is possible that with new AML therapies, the proportion of patients in such a situation will increase. We hypothesized that achievement of CRp has a worse prognostic connotation than ‘classically’ defined CR, and sought to investigate this hypothesis in a cohort of AML patients transplanted between 7/1995 to 12/2007 at our institution (N=427). Methods: Patients were eligible for this analysis if they were in the following disease status at transplantation: compete remission (CR); first CR (CR1; 100K/ml); second CR (CR2); first CRp (CRp1): patients that had 5% and no platelet recovery); CRp2: patients that after first relapse achieved

Description: INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate 〉 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Description: Abstract 5007 Introduction Non Hodgkin Lymphoma represent a category of hematological malignances which are chemo and radio-sensitive; improvements in their treatment had been achieved by immunotherapeutic approaches. However some patients will relapse after achieving complete remission (CR). Obviously, in order to detect and possibly treat them as soon as possible, a follow up strategy has to be planned. The more diffuse follow up have been planned years before the introduction of innovative methods and imaging techniques, suggesting the opportunity to revise these programs. In particulary it is not still clear which is best techniques useful to properly follow this patient. Recently new interesting methods are available like PET, CT-PET and minimal residual disease (MRD) monitoring. Methods 418 NHL patients -both low and high grade- treated at our institution from 1995 to 2005 who achieved a CR status according to Cheson criteria have been evaluated. LH NHL included follicular lymphoma, lymphoplasmocytic lymphoma, Marginal zone lymphoma, and small lymphocytes lymphoma. In the HG NHL, we included T-cells lymphomas, diffuse large cell lymphoma, lymphoblastic lymphoma, Mantle cell lymphoma, anaplastic lymphoma, Burkitt lymphoma. Patient characteristics are summarized in Table 1. Follow up is planned for 5 years divided in two periods: in the first two years patients are evaluated every 3 months and in the following three years every sixth month. At each visit physical examinations, blood testing (blood count, chemistry) are performed; for imaging techniques we alternate a whole body CT scans to ultrasounds and chest X-ray coupled. Bone marrow samples for both pathological and molecular analysis are collected every six months in the first period and once a year afterwards. PETs were usually performed when CT showed uncertain findings. Results There were 431 events, with 188 first relapses, 86 second, 18 third, 4 fourth and 1 fifth relapses. Relapse rate was similar among high and low grades, (37% and 35 % respectively) but time to relapse was longer for low grades (18.2 months vs 8.9 months). There was not relationship between IPI status and relapse rate. 72 % of relapse was at the same site of diagnosis. Relapses were detected by ultrasound in 139 cases (32 %), CT scans in 110 (25.5%) and by physical examination in 62 (14.4%). Remaining patients' relapse were diagnosed with other techniques (lab test, gastroscopy, NRM) New techniques as MRD monitoring, PET or PET/CT were not available for many patients, anyway MRD monitoring was able to detect disease re-appearance in 2%, and we had a total of 28 cases (6,5%) of relapse diagnosis with PET, but we noted a total of 18,5 % of false positive. Discussion and conclusions Many papers from literature raised many questions about which is the best techniques to follow patients. Many authors showed how symptoms onset and clinical findings appeared to be the more important for relapse detection compared to imaging before and during CT era. Some works pointed out also that even when CT detected earlier a relapse that do not translate in a survival advantage. Recently much interest has been focused on PET, CT-PET and MRD. They two appeared to be very important as prognostic tolls but their role for follow up purpose is still debatable. On the basis of clinical data and of these consideration routine PET is not recommended during follow up. Unfortunately PETs and MRD monitoring were not available for the majority of our patients, diagnosed in the nineteen's. In conclusion in our experience we observed some usefulness of CT scans and ultrasounds but we must recall that the majority of literature is not consistent with our results. Considering our experience and data from literature probably imaging should be performed routinely at the end of therapy, and during follow up only on the basis of presentation and clinical suspicion. As a matter of fact NCCN reviewed its guidelines do not suggesting a wide use of routine imaging. Further investigation by clinical and randomized trials are certainly needed to better understand, in particular the role of PET-PET/CT for follow up purpose. Disclosures No relevant conflicts of interest to declare.