The current study presents a case of primary pulmonary lymphoma (PPL) mimicking refractory lung abscess that was diagnosed at autopsy. An 80-year-old male with clinically inapparent aspiration presented with a large cavitated mass and pleural effusion. A lung abscess and empyema was diagnosed, therefore, antibiotics were administered and the pleural effusion was drained. Various examinations, including a biopsy, yielded no specific diagnosis. The lesion was considered inoperable due to the poor general condition of the patient. Subsequently, the mass that had been diagnosed as a refractory lung abscess became enlarged and a repeat biopsy resulted in a diagnosis of diffuse large B-cell lymphoma. The patient succumbed to sudden respiratory failure, and the final diagnosis of PPL was confirmed at autopsy. PPL is a rare disease that accounts for 0.45% of all pulmonary malignant tumors and is difficult to diagnose in inoperable cases. Therefore, patients with PPL who do not undergo surgery can be misdiagnosed and consequently treated inappropriately. PPL should therefore be considered in the differential diagnosis of a refractory lung abscess.

Abstract Introduction Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) has an indolent clinical course, with overall patient survival at 5 years after diagnosis of more than 85%. Although the cause of death in a significant proportion of MALT lymphoma patients is not the lymphoma itself, some patients experience early relapse or refractory disease. However, the risk factors capable of predicting aggressive disease in MALT lymphoma have not been clearly defined. Patients and Methods This is a retrospective pooled analysis of pathologically confirmed extranodal MALT lymphoma patients treated at our institute. Patients with nodal or splenic marginal zone lymphoma were excluded. The primary endpoint was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. Results From January 2000 to June 2013, 52 extranodal MALT lymphoma patients (26 females and 26 males) were referred to our institution. The median age of the patients was 68 years (range, 43–89 years). Thirty-three (63%) patients had limited stage disease (stage I/II) and 48 (92%) patients had an ECOG performance status of less than 2. The cumulative numbers of patients who were diagnosed with orbit, thyroid, salivary gland, stomach, lung, and intestine disease were 7 (13%), 5 (10%), 9 (17%), 16 (31%), 16 (31%), and 4 (8%), respectively. Fifteen (29%) patients had a prior history of autoimmune disease, and a serum electrophoresis study detected M-protein in 9 (17%) patients (5 patients had IgG, 3 patients had IgM, and 1 patient had IgA). There was no significant correlation between the presence of M-protein and prior history of autoimmune disease (Fisher's exact test, p=0.46). Of the 32 patients who underwent cytogenetic studies, 9 (28%) had cytogenetic aberrations involving MALT1. Histological transformation to diffuse large B-cell lymphoma (DLBCL) was confirmed in 3 patients. After a median follow-up time of 53 months (range, 1–142 months), 16 patients had relapsed (MALT lymphoma relapse or transformation to DLBCL), and 1 patient had died due to lymphoma. The 4-year PFS and overall survival rate were 76.3% (95% confidence interval (CI), 60.0–86.7%) and 98.0% (95% CI, 86.6–99.7%), respectively. Among the clinical variables measured at diagnosis, univariate analysis found that advanced stage, three or more extranodal sites, serum soluble IL-2 receptor concentration higher than 700 IU/L, lymphocyte count higher than 1x10^9/l, hemoglobin concentration lower than 12.5 g/dl, and the presence of M-protein adversely affected PFS (p<0.05). In multivariate analysis including these six variables, only the presence of M-protein remained as a poor prognostic factor for PFS (hazard ratio (HR), 14.5; 95% CI, 1.47–142; p=0.021). The 4-year unadjusted PFS for patients with M-protein was 14.8% (95% CI, 7.36–47.6%), which was significantly poorer than that of patients without M-protein (90.9% [95% CI, 74.0–97.0%]; HR, 11.9; 95% CI, 3.46–41.1; log-rank, p<0.001). Seven of the 9 patients who had M-protein received rituximab-containing combination chemotherapy (R-CHOP 5 and R-CVP 2), and 5 patients relapsed in a relatively short time (median, 10 months; range, 2–54 months). Conclusion Extranodal MALT lymphoma patients with M-protein had an increased risk of early disease progression. Patients with M-protein were more likely to had advanced stage disease (p=0.005) and more than three extranodal sites (p=0.02) compared to patients without M-protein. However, multivariate analysis showed that the prognostic impact of M-protein was better than that of advanced stage disease and the number of extranodal sites. Further studies are required to determine differences between the biological backgrounds of patients with and without M-protein, and a novel treatment strategy to obtain a durable disease control. Disclosures: No relevant conflicts of interest to declare.

Abstract Objectives Prospective clinical trials show that 5-Azicitidine (5-Aza) is superior to conventional care regimens in prolonging the survival of patients with high-risk myelodysplastic syndromes (MDS) (pts). To confirm the survival benefit of 5-Aza in daily clinical practice, we compared the survival of high-risk MDS patients who received parental treatment before 5-Aza approval to those who could be initially treated with 5-Aza. Methods In Japan, 5-Aza was approved in January 2011. We collected data of consecutive adult patients (pts) with high-risk MDS, namely refractory anemia with excess blasts-1 (RAEB-1), RAEB-2, and acute myeloid leukemia with MDS related features (AML/MRF), who received the first parental chemotherapy between January 2000 and April 2013. Survival was not calculated from the day on which the first chemotherapy was delivered, but from the day on which the diagnosis of high-risk MDS was established. Survival analysis was done by the Kaplan-Meier method. The Cox regression model was used for the analyses. A total of 107 pts with high-risk MDS were identified. They were divided into two groups (grps) on the basis of whether or not they could be initially treated with 5-Aza. In brief, pts who received the first parental treatment before January 2011 were categorized into the conventional care (CC) grp (N=75), and pts for whom treatment began after January 2011 were categorized in the 5-Aza grp (N=32). The following variables were also considered to affect survival in multivariate analysis: sex, age (>=65 years (yrs) old or < 65 yrs old), WHO classification, and IPSS at diagnosis of high-risk MDS. Results Median follow-up times of CC and 5-Aza grp were 43 and 11 months, respectively. As shown in Table 1, the distributions of sex, age, WHO classification and IPSS were nearly the same in both grps. As for initial treatment, pts in the CC group mainly received low-dose cytarabine (ld-AraC), whereas most pts in the 5-Aza grp were treated with 5-Aza. Unadjusted survival curves of the two grps are shown in Figure 1. The unadjusted 2-yr survival rate was 33% in the CC grp and 52% in 5-Aza era grp. Median survival times were 11 and 24 months in CC and 5-Aza grps, respectively. Uni-variate analysis of overall survival revealed a trend for improved survival in younger pts, but this was contradicted by the results of multi-variate analysis. In uni- and multi-variate analyses, the 5-Aza group showed an overall, and statistically significant higher survival benefit (Table 2). Removing the 26 patients allografted after parental treatment (10 in 5-Aza grp and 16 in CC grp) at the time of alloSCT from the analyses did not modify the survival advantage of the 5-Aza grp. Conclusion This retrospective analysis confirms that the introduction of 5-Aza has certainly improved the outcome of high-risk MDS in daily clinical practice. Disclosures: No relevant conflicts of interest to declare.

Abstract Background About 70-80% of adult patients (pts) with acute myeloid leukemia (AML) achieve complete remission (CR); however, around a half of them experience a relapse. For the purpose of creating accurate decision-making process of post-consolidation strategy, stratification system using karyotype and recurrent gene mutations have been widely utilized. As is confirmed in childhood acute lymphocytic leukemia, however, the information of minimal residual disease (MRD) status would substantially improve the reliance of decision-making process of adult AML pts. Unfortunately, approximately a half of AML patients lack molecular targets suitable for MRD monitoring. The aims of this study are to evaluate the applicability of MRD detection using multiparametric flow cytometry (MPFC) and to estimate the impact of MRD measured with MPFC at the end of consolidation therapy in improving decision-making process. Patients and Methods We retrospectively studied 81 consecutive pts with newly diagnosed AML who received induction therapies and achieved CR in our institute between January 2007 and March 2013. Pts with acute promyelocytic leukemia were excluded. We routinely analyzed the bone marrow specimens with MPFC for the detection of leukemia-associated immunophenotypes (LAIPs) at diagnosis. Since April 2010, RT-PCR assay examined FLT3-ITD mutation in the same specimens. In pts who had traceable LAIPs, the relationships of the levels of MRD at the end of consolidation therapy with relapse free survival were analyzed. Positive MRD was defined as the detection of 0.2% and more LAIPs-positive cells with MPFC. We compared two patient groups: those with MRD at the end of consolidation (MRDp group) and those without (MRDn group). Relapse-free survival (RFS) was analyzed using the Kaplan-Meier method and the log-rank test was used for comparison between each group. A multivariate Cox regression analysis for RFS was fit to assess the effect of the followings: age at diagnosis (≥ vs. < 65 years old), the number of induction regimens required for achieving CR (≥ vs. < 2 times), cytogenetic risk groups of SWOG (unfavorable vs. favorable/intermediate). Results In 57 / 81 pts, MPFC could detect LAIPs in the bone marrow specimens at diagnosis (70.4% of all subjects; 15-82 years-old; follow-up time [median] 98-2211[517] days). FLT-ITD mutations were found in 13 pts, but not in 39 pts (the remaining 5 pts were not examined). The rate of detection of LAIPs with 6-color MPFC was significantly superior to 3-color MPFC (82.1% vs. 61.0%, p<0.05). Induction chemotherapies the pts received were anthracyclin-containing regimens, such as idarubicin and cytarabin (3+7), in 52 pts (91.2%), low-dose cytarabin-based regimen in 4 pts (7.0%) and azacitidine in 1 pt. (1.8%). The MRDp and the MRDn groups were comprised of 20 and 37 pts (35.1% and 64.9%) , respectively. One-year RFS of the MRDp group was significantly inferior to the MRDn group (28.3% vs. 75.2%; log-rank p<0.0005). In the multivariable analysis using the model above, MRD positivity at the end of consolidation remains a significant predictor (HR, 2.93, 95% CI 1.16-7.45, p<0.05). In addition, the 1-year RFS in the MRDp group with FLT-ITD was significantly shorter than that in the MRDp group without FLT3-ITD (0% vs. 47.6% with positive and negative FLT3-ITD, log-rank p<0.05). In the MRDn group, however, the negative impact of FLT3-ITD was not documented (85.7% vs. 69.3% with positive and negative FLT3-ITD, log-rank p=0.954). Conclusion Our retrospective study confirmed that LAIPs as MRD targets were applicable to the majority of pts with AML; MRD positivity measured with LAIPs was a promising predictor for early relapses at the end of consolidation, as was previously reported. When combined with FLT-ITD status, it might become a more sensitive prognostic factor. Disclosures: Takahashi: celgene: Research Funding.

Abstract Background Recent reports have suggested that allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors improves the outcome of elderly acute myeloid leukemia (AML) patients in first complete remission (CR1) (Kurosawa et al BBMT 2011). However, the efficacy of allo-HSCT from alternative donors for the management of elderly AML patients in CR1 remains to be clarified. In this study, we examined the efficacy of allo-HCST for the management of elderly AML patients. Methods We retrospectively collected the data of consecutive AML patients who were aged 50-70 years and diagnosed in our hospital between January 1, 2000 and May 31, 2013. Patients with acute promyelocytic leukemia (APL) and patients who could not receive intensive therapy or died within 60 days after diagnosis were excluded. The primary endpoint of this study was overall survival (OS), which was defined as the interval between diagnosis and the last follow up. The unadjusted probabilities of OS were estimated using the Kaplan-Meier method. To compare OS between the treatment groups, the log-rank test was used. Multivariate analysis were performed with Cox proportional hazard regression models and 95% confidence intervals (CIs) were calculated. Results A total of 131 elderly AML (non-APL) patients were identified. Except for 14 patents, all received chemotherapy. 12 patients who died within 60 days were excluded from the study. Among the remaining 105 patients, 41 could not be induced into complete remission (CR) and showed a dismal outcome; the probabilities of 2 years (2y)-OS were 0% and 4.4% for 5 patients who received allo-HSCT and 36 patients who did not, respectively. In contrast, the probability of 2y-OS of 64 patients who achieved CR1 was 48.5%. Of these 64 patients, 20 proceeded to allo-HSCT. 13 patients were transplanted in CR1, 3 in second CR (CR2), and 4 in relapse. The probabilities of 2y-OS were 56.1% and 45.0% for patients who received and who did not receive allo-HSCT, respectively (p=0.27). When the disease status at allo-HSCT was considered, the 2y-OS of patients who received allo-HSCT in CR1 reached 83.3%, whereas that of patients transplanted in CR2 or relapse reached only 14.3%. Next, we performed univariate and multivariate analysis of OS of patients who achieved CR1. In addition to whether allo-HSCT was performed in CR1 or not, the following factors were also considered as covariates: age and leukocyte counts at diagnosis, cytogenetic classification according to National Comprehensive Cancer Network guidelines, presence or absence of preceding hematological diseases, and the number of induction regimens required for achieving CR1. Univariate analysis showed that allo-HSCT in CR1 was associated with improved OS (2y-OS: 83.3% vs 40.6%, p=0.013) (figure1). Multivariate analysis also showed that allo-HSCT in CR1 was the only favorable prognostic factor for OS (Hazard ratio=0.25, 95%CI: 0.077-0.82, p=0.022). Stem cell sources of allo-HSCT done in CR1 were 1 HLA-matched related donor and 12 unrelated donors including umbilical cord blood from 1 donor. Conclusion Allo-HSCT, even from an unrelated donor, improves the outcome of elderly AML patients in CR1. However, allo-HSCT for those with relapsed or refractory disease could hardly extend their survival. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1591 Introduction The use of fluorodeoxyglucose-positron emission tomography (PET) to aid the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) after treatment with rituximab-containing combination chemotherapy was investigated. Several studies report that less than 20 % of patients who are PET-negative and more than 85 % of PET-positive patients will experience lymphoma recurrence. Since therapy for DLBCL recurrence remains a major problem, the ability to accurately predict the risk of relapse in PET-negative DLBCL patients after chemotherapy would be extremely beneficial. In this study we focused on levels of serum soluble interleukin-2 receptor (sIL-2R) since several reports indicate that sIL-2R at the time of diagnosis is closely linked to the prognoses of DLBCL patients. We measured sIL-2R levels in DLBCL patients shortly after R-CHOP therapy and investigated whether there was any correlation with patient prognoses. Patients and Methods This was a retrospective pooled analysis of DLBCL patients treated with R-CHOP in our institute. Patients were included if they were under the age of 80, had an International Prognostic Index (IPI) score of more than two, and had received R-CHOP with curative intent. Patients who received salvage chemotherapies due to insufficient responses to R-CHOP were also included. We excluded patients with low IPI scores as their sIL-2R levels at the time of diagnosis were usually in the normal range. Patients were also excluded if R-CHOP could not be continued for reasons other than disease progression. sIL-2R and PET analyses were performed when patients first visited the institute after completing 6–8 cycles of R-CHOP. Patients were divided into three groups: Group A consisted of patients who had completed R-CHOP, were PET-negative and whose sIL-2R levels had returned to normal (<600 mg/dl); Group B consisted of patients who had completed R-CHOP and were PET-negative, but whose sIL-2R levels had remained high (>=600mg/dl); Group C consisted of patients who had switched to salvage therapies as well as those who remained PET-positive after completing R-CHOP. Overall survival (OS) was assessed using the Kaplan-Meier method and the log-rank test was used for comparisons within each group. A multivariate Cox regression analysis was used to adjust for IPI scores. Results From January, 2006 to January, 2012, a total of 178 DLBCL patients aged less than 80 years were referred to our institution, and 70 of these patients were included in this analysis. The median age of patients was 68 years (range 37–79 years), 96 % had advanced stage DLBCL, and 77 % had elevated lactate dehydrogenase levels. 30% of patients had ECOG performance status (PS) less than 2. The median sIL-2R level at the time of diagnosis was 2676 mg/dl (range 612–48000 mg/dl). The numbers of patients assigned to groups A, B, and C were 28 (40 %), 18 (26 %), and 24 (34 %), respectively. A Fisher's exact test showed no significant differences in IPI scores between the three groups (p=0.453). A Mann-Whitney test showed no significant differences in sIL-2R levels at the time of diagnosis between the three groups (A; median 2660 mg/dl, range 612–19000 mg/dl, B; 2905 mg/dl, 970–37100 mg/dl, C; 4347 mg/dl, 734–48000 mg/dl). Patients in groups A and B received 6–8 cycles of R-CHOP (median 7 cycles). Patients in group C received 1–4 salvage treatments (median 2 treatments) before or after completion of R-CHOP (median 6 cycles, range 2–8 cycles). After a median follow-up time of 36 months (range 5–60 months), 24 deaths had occurred (including 20 due to lymphoma), and the 3 year OS rate for the entire cohort was 65.5 % [95 % confidence interval (CI), 51.7–76.2 %]. The 3 year unadjusted OS rate of patients in groups A, B, and C was 95.2% [95%CI, 70.7–99.3%], 60.7% [95%CI, 31.3–80.6%] and 30.6% [95%CI, 12.5–51.0%], respectively (log-rank, p<0.001), (group A vs B; hazard ratio (HR), 10.8; 95%CI, 1.33–88.1; p=0.026, group B vs C; HR, 2.24; 95%CI, 0.91–5.54; p=0.079). Multivariate analysis including IPI score, revealed that 3 year OS for patients in group B was significantly inferior to that for patients in group A (HR, 6.26; 95%CI, 1.29–30.4; p=0.023), but was comparable with that for patients in group C. Conclusion DLBCL patients with an IPI score of more than 2 had an increased risk of relapse if their sIL-2R levels failed to return to normal following R-CHOP treatment, even if they completed 6–8 cycles of R-CHOP and were PET-negative. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1578 Introduction: It is known that advanced disease in diffuse large B-cell lymphoma (DLBCL) confers a poor prognosis, and staging investigations are routinely performed at diagnosis, including a bone marrow biopsy. Several studies have suggested that histologically proven bone marrow involvement with DLBCL is an independent predictor of a poor prognosis. However, the clinical role of flow cytometry in staging bone marrow in DLBCL, especially its impact on outcome, remains uncertain. The aim of this study is to evaluate the incidence of occult bone marrow involvement which is detectable only by flow cytometry, and examine the significance of occult bone marrow involvement in patients treated with R-CHOP. Patients and Methods: This is a retrospective pooled analysis of unselected patients with DLBCL treated with R-CHOP in our institute. Patients were included in the analysis if they were with a biopsy proven diagnosis of DLBCL and had undergone a pretreatment bone marrow aspiration, which was examined both by immunohistochemistry and by flow cytometry. By using flowcytometry, DLBCL involvement was defined by the significant bias in the ratio of kappa and lambda harboring large cells in CD19-gated lymphocytes, indicating occult bone marrow involvement of DLBCL. All patients were divided into three groups; those with histologically apparent bone marrow involvement, those with occult bone marrow involvement and those with a negative bone marrow. This was an intention-to-treat analysis, including all patients treated with curative intent who received at least one cycle of R-CHOP. Clinical characteristics between each group were analyzed. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and the log-rank test was used for comparison between each group. A multivariate Cox regression analysis was used to adjust for IPI score. Results: From April 2005 to February 2011, 105 consecutive patients with DLBCL received staging bone marrow aspiration. Among them, 25 (23.8%) had histologically apparent lymphoma involvements and 65 (61.9%) showed undetectable lymphoma cells. In remaining 15 patients (14.3%), examination of smear preparation and clot section could not find lymphoma cells, however, flow cytometry revealed significant bias in the ratio of kappa and lambda harboring cells in CD19-gated lymphocytes. At the time of analysis, median follow-up time for living patients was 26 months (range, 2–61). PFS and OS in those with histologically apparent bone marrow involvement were significantly inferior than in those with negative bone marrow involvement (3-year PFS 44.3% for apparent group vs 82.5% for negative group, log-rank P < 0.001; 3-year OS 78.2% for apparent vs 94.1% for negative, log-rank P = 0.035). Difference in 3-year PFS and OS between occult (53.5% and 84.6%, respectively) and negative bone marrow involvement groups were not significant, but there was a tendency for occult bone marrow involvement group to have a shorter PFS and OS when compared to negative bone marrow group (log-rank P = 0.084 and 0.075, respectively). Moreover, when occult cases were included with apparent cases as a positive bone marrow group, difference in OS between positive and negative bone marrow groups was significant (3-year OS 80.9% for positive vs 94.1% for negative group, log-rank P = 0.022), whereas when occult cases were included with negative cases as negative bone marrow group using the conventional definition by morphology alone, difference in OS between histologically positive and negative bone marrow groups was not significant (3-year OS 78.2% for positive vs 92.3% for negative group, log-rank P = 0.095). In a multivariate analysis, apparent but not occult bone marrow involvement remained a significant prognostic value in PFS independent of IPI score (relative risk 3.0, 95% CI 1.1–8.5, P = 0.0296). Conclusion: Taking all into account, occult bone marrow involvement has potentially adverse impact on the outcome in DLBCL treated with R-CHOP. The threshold of the ratio of lymphoma cells among bone marrow nucleated cells which have great impact on clinical outcome should be defined. Disclosures: No relevant conflicts of interest to declare.