Search

Introduction: Neurolymphomatosis (NL) is an extremely rare neurological manifestation of non-Hodgkin lymphoma (NHL) in which peripheral nerve infiltration of lymphoma cells is a dominant feature both clinically and pathologically. Previously, we reported a high frequency of NL as a relapse disease of intravascular large B cell lymphoma (IVL), although NL could present as an initial disease as well as relapsed disease in other types of NHL. In addition, the clinical features and treatment outcomes of NL are largely unknown. However, the recent increase in use of PET/CT in lymphoma has facilitated the diagnosis of NL. Here, we report our experience with NL at our hospital over the period from January 2006 to July 2014. Methods: We reviewed the clinical records at the Hematology/Oncology Department of Kameda Medical Center. The diagnosis of NL required: 1) clinical symptoms and neurological examination findings related to the cranial or spinal nerves; and 2) histological confirmation of malignant lymphoma cells within the peripheral nerve, nerve root/plexus, or cranial nerve; or 3) CT/MRI demonstration of nerve enhancement and/or enlargement of peripheral nerve(s) or nerve root that were also demonstrated by the accumulation of FDG by FDG-PET/CT. Patients with stomach limited mucosa-associated lymphoid tissue (MALT) lymphoma and leukemic infiltration of peripheral nerve due to acute leukemia were excluded from the study. Results: Over the past 7 years, there were 514 patients diagnosed with NHL. Among them, we identified 9 patients (1.8%) diagnosed as having NL. The patients consisted of 2 men and 7 women with a median age of 72 years (range: 63 – 83 years). All 9 patients were histologically diagnosed as a diffuse large B-cell lymphoma (DLBCL). NL occurred as part of the presenting disease in 3 patients and as a relapse disease in the remaining 6 patients. 4 NL patients presented as a relapse disease of IVL, 2 as a relapse disease of nodal DLBCL, and 3 as a concomitant extranodal DLBCL (stomach, ileum, and uterus). CD5 was positive in 7 cases (78%). Diagnosis of NL was made by neurological findings, enlargement and enhancement of affected cranial or peripheral nerves by MRI, and FDG-uptake of affected nerve demonstrated by PET/CT in all patients. Autopsy also confirmed the lymphoma infiltration in 1 patient. The affected nerves included the lumbosacral nerve (5 patients), brachial plexus (2 patients), peroneal nerve (1 patients), cranial nerves (4 patients), especially oculomotor nerve (2 patients), trigeminal nerve (2 patients). Cerebrospinal fluid cytology was positive in 4 cases (44%). All 9 patients received a treatment regimen including high-dose methotrexate (MTX) in addition to rituximab containing systemic chemotherapy. Six patients received involved nerve irradiation, 4 patients at relapse and 2 at presentation. Neurological symptoms of the all patients responded promptly. Six patients subsequently developed CNS involvement despite the prophylactic use of high-does MTX. Six patients died due to progressive NL with a median of 11.3 months after NL development. Three patients are still alive 8, 9, and 92 months from the diagnosis. Two patients received autologous stem cell transplantation (auto-SCT), one survived for more than 7 years but the other relapsed 4 months after auto-SCT and being treated with radiation and chemotherapy. Conclusions: NL occurs in a minority of patients (1.8%) and can present in diverse ways, both at initial diagnosis of lymphoma or after treatment. All of them were DLBCL and 78% were CD5-positive. IVL is a most common type of lymphoma subtype in which develop NL. Contemporary imaging techniques including MRI and PET/CT, can often detect relevant neural involvement. Prognosis remains poor once patient developed NL despite the use of high-dose MTX and rituximab containing aggressive chemotherapy included auto-SCT. Only involved nerve irradiation was effective for the relief of neurologic symptoms. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) is considered the procedure of choice for the diagnosis and staging of intra-abdominal non-Hodgkin’s lymphoma (NHL) without accessible peripheral lymphadenopathy. However, diagnosis and subclassification lymphoma by FNAB is often challenging due to variable cellularity and lack of architecture. Recent advances of ancillary techniques such as immunohistochemical staining, flowcytometry (FCM), fluorescence in situ hybridization (FISH) analysis and molecular analysis allowed classify lymphoma more precisely, although sufficient information can be obtained through this procedure remained undetermined. The present study was performed to evaluate the yield of EUS-FNAB using a standard 19 or 22-gauge needle for diagnosis and subclassification of lymphoma, assessing the feasibility of immunohistological, FCM, molecular and cytogenetic assessments. Methods: Between April 2008 and July 2014, 90 patients with malignant lymphoma who had an intra-abdominal mass without accessible peripheral lymphadenopathy underwent EUS-guided fine needle aspiration biopsy at our hospital. All patients received positron emission tomography/computed tomography and had 2-deoxy-2-(18F)fluoro-D-glucose-avid lesions in abdomen before examination. The aspirated materials were processed for flowcytometry (FCM), molecular analysis of immunoglobulin heavy (IgH) and T-cell receptor (TCR) gene rearrangement, cytogenetic analysis by conventional G banding, and FISH analysis, in addition to standard histopathological studies. Patients’ baseline data, including age, sex, laboratory examinations, imaging studies, and final diagnosis of lymphoma, were collected and examined to determine the feasibility and sensitivity for diagnosis and subclassification of lymphoma. Results: The mean of the diameter of mass was 37mm (9.7-149mm). Among the 90 patients, conventional G banding, FCM analysis, standard cytogenetic analysis, and FISH were successfully performed in 67 (74%), 78 (87%), 44 (49%), and 58 (64%) cases, respectively. G banding analysis were successful in 45 patients (67%) that showed normal karyotype in 5 cases (7%), t(14;18)(q32;q21) in 7 cases (10%), t(8;14)(q24;q32) in one case, and complex abnormality in 32 cases (48%), respectively. FCM analysis showed immunoglobulin light chain restriction in 48 cases (62%) and were diagnosed as B-cell lymphoma. FCM could not determine the T-cell clonality. Molecular analyses for TCR and/or IgH receptor rearrangements were successful in 35 patients (83%), 31 rearranged in IgH and 4 rearranged in TCR, respectively. There were 32 cases with IgH/Bcl2 fusions by FISH analysis, 26 cases in follicular lymphoma (FL) and 6 cases in diffuse large B-cell lymphoma (DLBCL), respectively. IgH/Bcl6 fusion was seen in 2 case of DLBCL and IgH/C-myc fusion was seen in 1 case of Burkitt lymphoma (BL). Finally, our cohort included 82 B-cell lymphomas (91%) and 8 T-cell lymphomas (9%). Subclassification of lymphoma in accordance with WHO system included 40 cases of FL, 39 cases of DLBCL, one case of BL, 2 cases of lymphoblastic lymphoma, 7 cases of peripheral T cell lymphoma not specified, and one case of angioimmunoblastic lymphoma. Although all of the outpatients were hospitalized until the day after biopsy, there were no serious complications related to this procedure like bleeding, perforation, ileus, and infection. Conclusions: EUS-FNAB using a standard 19 or 22-gauge needle is safe and feasible and has high diagnostic value for subclassification of intra-abdominal lymphoma without accessible peripheral lymphadenopathy. With the use of simultaneous immunophenotyping, molecular, and cytogenetic studies, lymphoma subclassification was possible in most of the cases. Disclosures No relevant conflicts of interest to declare.

Introduction: With the development of novel therapeutic agents, more than 30% of patients with multiple myeloma (MM) achieve complete response (CR) as defined by the International Myeloma Working Group (IMWG). However, most patients that achieve CR ultimately die due to relapse, suggesting the presence of minimal residual disease (MRD) in these patients. Multicolor flow cytometry (MFC) allows the detection of Methods: Among the 164 patients treated at our hospital between April 2005 and July 2014, 83 patients that achieved more than VGPR were included in this study. The study population consisted of 49 males and 34 females with a median age of 71 years. All patients received at least one course of novel agent-containing therapeutic regimen. Autologous stem cell transplantation was performed 43 patients. Maintenance treatment was not systematically given, but patients failed to achieve CR continued to receive treatment until CR was obtained. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the course of disease was assessed by simultaneous analysis by serum immunofixation, sFLC measurements, and MFC analysis of bone marrow plasma cells. Identification of plasma cells MFC requires at least two markers (CD38 and either CD45 or CD138) by single-tube 6-color flow-cytometry. Neoplastic plasma cells were further identified from normal plasma cell based on differential expression of CD19 and CD45 characteristics. Patients were considered MRD negative (IR) when ≤ 50 neoplastic plasma cells were detected by MFC in the bone marrow samples at the sensitivity limit of 10-4. Overall survival (OS) and Time to next treatment (TNT) differences between curves were calculated by two-sided log-rank test. Subjects were classified into three categories, i.e., CR with MRD positive or negative and VGPR, and TNT and OS were compared between groups. Results: At a median follow-up of 44.8 months, 83 patients obtained better than VGPR, ie; CR, 55 patients, VGPR, 28 patients. Among the 55 patients who obtained CR, normalization of sFLC k/l and IR were achieved in 48 (88%) and 28 (51%) patients, respectively. Conversely, normal sFLC k/l ratio was achieved in 66 patients, 50 were in CR and 16 were in VGPR. IR was obtained in 34/83 (41%) patients. Among 48 CR patients with normal sFLC k/l (stringent CR), IR was obtained 27 patients (56%). All of the 7 CR patients with abnormal sFLC k/l (non-stringent CR) did not achieve IR. Kaplan–Meier estimated 3- and 5-year OS were 94% and 80% in patients with CR, 90% and 71% in patients with VGPR. No significant differences were observed at 3- and 5-year OS between patients achieved CR and VGPR. Among the patients with VGPR or better response, patients with IR showed significantly longer TNT compared to those without IR. However, The patients who achieved CR and IR showed significantly longer TNT compared to those with VGPR (P=0.004), but CR patients without IR showed similar TNT curve with VGPR patients. Patients with both CR and IR showed longer TNT than those CR but without IR, although difference between the 2 groups was marginally significant (P=0.06). Although, patients with IR and normal sFLC showed significantly longer TNT compared to those with VGPR, it was not translated to longer OS reflecting the continuous maintenance treatment for VGPR patients. Conclusion: Although both achievement of CR, normalization of sFLC k/l, and IR appeared to confer on longer TNT and OS, obtaining IR seems to have greater implications for longer survival compared to CR or FLC k/l normalization. MFC analysis is a rapid, affordable, and easy performable method for measurement of MRD, and IR could be considered as a goal of treatment for patients with MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: Monitoring of multiple myeloma (MM) patients is required to assess and determine the treatment response. The serum immunoglobulin (Ig) heavy/light chain immunoassays are a new method that enables separate quantification of the different light chain types of each Ig class, i.e., IgGk, IgGl, IgAk, and IgAl. Although the contribution of these tests to disease evaluation has been assessed, available data are still limited. Here, we compared the serum Ig heavy/light chain immunoassays with the conventional methods for disease evaluation. PATIENTS AND METHODS: Three hundred and three samples were obtained from a total of 101 patients with IgG and IgA type MM recruited at Kameda Medical Center and Kanazawa University Hospital. The median age of the patients was 68 years (range: 44 – 89). The median follow-up was 36 months (range: 2.5 – 189.6). The proportions of patients in International Scoring System (ISS) stages I, II, and III were 25%, 35%, and 40%, respectively. Paraprotein type was IgG in 64 patients (44 Gk, 20 Gl) and IgA in 37 (20 Ak, 17 Al). Samples were taken at various times after treatment and analyzed retrospectively with serum Ig heavy/light chain immunoassays (Hevylite®; Binding Site, Birmingham, UK) on a SPAPLUS® turbidimeter. The heavy/light chain ratio (HLCR) was calculated with the Ig' k (either G or A) as the numerator and compared to normal ranges (IgGk:3.84-12.07g/L; IgGl:1.91-6.74g/L; IgGk/IgGl: 1.12-3.21; IgAk:0.57-2.08g/L; IgAl:0.44-2.04g/L; IgAk/IgAl:0.78-1.94). Results were compared to serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain immunoassays (FLC). HLC-pair suppression was defined as the uninvolved immunoglobulin of the same isotype 50% below the lower limit of the normal range (IgGk, IgGl, IgAk, IgAl). Residual neoplastic plasma cells (MM-PCs) in bone marrow samples were assessed by multicolor flow cytometry (MFC) simultaneously in 140 samples from 64 patients at very good partial response (VGPR), complete response (CR), and stringent CR (sCR). The MFC negativity was defined at a level of RESULTS: Myeloma responses were assessed serially after induction therapy and were assigned according to international response criteria. Patients' samples at various responses were: sCR, n = 86 (28%); CR, n = 31 (10%); VGPR, n = 116 (38%); and PR, n = 70 (23%). Normal HLCR was obtained at sCR, CR, and VGPR in 73 (85%), 28 (90%), and 69 (59%) cases, respectively. Discordance in the depth of response between standard electrophoretic methods and HLCR was more commonly seen in IgG compared to IgA MM; possibly reflecting the dose dependent half life of IgG immunoglobulins. In the sera from patients who achieved a CR or better, abnormal HLCR and FLC ratio were seen at rates of 12.8% and 26.5%, respectively. Discordance between normalization of HLCR and FLC ratio was seen in 42% of patients with a CR or better; however, a good correlation between normalization of HLCR and FLC ratio was still observed (Fisher's exact test, P = 0.004). Among the 71 sera from patients with a CR or better in which simultaneous MFC data were available, 16 (22.5%) sera were MFC-negative. Among the patients who achieved a VGPR or better, patients with a normal HLCR had fewer MM-PCs than those with an abnormal HLCR (median 9.8x10-4vs. 46.0x10-4, respectively, P=0.062), although the difference was not statistically significant. Abnormal HLCR in CR samples was seen more frequently in patients with IgA type (19%) than IgG type (7.7%). Longer PFS and OS were observed in patients who achieved HLCR normalization at best response than in those who did not (PFS; 83.8 months vs. 41.8 month, respectively, P = 0.016 and OS; not reached vs. not reached, P = 0.018). When patients at best response were divided into with or without uninvolved HLC pair suppression, the latter group showed significantly better OS compared to the former group (not reached vs. not reached, P=0.019). CONCLUSIONS: The findings presented here suggest the potential usefulness of heavy/light chain immunoassays for monitoring of myeloma response in patients with IgA myeloma and residual MM-PC assessment at VGPR or better. Presence of abnormal HLCR at best response and HLC pair suppression were also associated with poorer survival. Disclosures No relevant conflicts of interest to declare.

Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) comprise a heterogeneous group of bone marrow failure disorders. As both show profound hypocellular marrow with minimal morphological atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the early 20s. Although an abnormal distribution of red marrow in AS has previously been reported in small numbers of patients with MDS, along with leukemia and lymphoma by MRI, there have been no further reports to date. Here, we examined the distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationships between the abnormal medullary pattern in AS and laboratory variables, subsequent development of leukemic transformation, and survival in MDS patients. Patients: We performed low-dose MDCT of the humerus and femur in 103 untreated adult patients with AA (n = 32) and MDS (n = 71). We retrospectively reviewed the medical records of patients with AA and MDS diagnosed in the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from July 2008 to June 2014. A retrospective review of clinical and laboratory features, including complete blood count, % bone marrow blasts, chromosomal analysis, and International Prognostic Scoring System (IPSS), was performed. WHO classification of MDS patients was as follows: RA (n = 22), RARS (n = 2), RCMD (n = 17), RAEB 1 (n = 18), RAEB 2 (n = 11), and MDS unclassified (n = 1). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 71 MDS patients by the Kaplan–Meier method and differences between curves were calculated by two-sided log-rank test. CT image acquisition and image analysis: Non-enhanced CT examinations were performed from the base of the skull down to the knee joint with an MS-CT scanner (AQUILION 64; Toshiba, Tokyo, Japan). The bony canals of the humeral and femoral bones were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole-body MD-CT was 10.1 mSv (ICRP 26). The dose was comparable to whole-body CT (2.4 mSv). Medullary CT density of the humerus and femur were measured and the results are expressed in Hounsfield units (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by a low-density CT value between –30 and –100 HU. A value above –30 HU observed in long bony canals was considered to indicate a high-density lesion. The medullary pattern of the appendicular skeleton was categorized as follows: (1) fatty, showing a low signal density marrow; (2) focal, showing abnormally focal high-density lesions; (3) diffuse, showing uniformly high-density marrow. Results: All 15 patients with AA showed a fatty (n = 12, 37.5%) or focal (n = 20, 62.5%) pattern in medullary AS on MDCT, and none showed a diffuse pattern. Among the 71 patients with MDS, 22 (30.9%) had a fatty pattern, 32 (45.1%) had a focal pattern, and 17 (23.9%) had a diffuse pattern. Seventeen patients with diffuse infiltration pattern on MDCT had significantly shorter LFS (P Conclusions: This study showed that MDCT imaging of the appendicular skeleton provided important information for the diagnosis and prognosis of patients with MDS and AA. In patients with MDS, a diffuse pattern on MDCT emerged as an independent negative prognostic indicator on LFS and OS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Background Modern imaging techniques such as whole body multidetector CT (MDCT) and 18F-fluorodeoxyglucose-positron emission tomography CT (PET-CT) are increasingly playing an important role in the diagnosis, staging, and treatment response monitoring of patients with MM because of limitations in hematological parameters. To date, however, few studies have evaluated the roles of MDCT and PET-CT in determining clinical outcome. This study was conducted to compare these two modalities for assessment of tumor burden and prognostic relevance in patients with symptomatic MM. Patients and methods Between December 2008 and November 2012, MDCT scans were performed in 64 newly diagnosed symptomatic MM patients as an initial evaluation of lytic bones and abnormal medullary and/or extramedullary lesions. Among them, PET-CT scan was performed in 56 patients. MDCT and PET-CT image acquisitions were as follows. MDCT was performed in a non-enhanced manner (acquisition time ∼45 s) and CT values (CTV) were measured using circular regions of interest for abnormal medullary lesions of the appendicular skeleton (AS; humerus and femur). The results were expressed in Hounsfield Units (HU). Since the normal CTV of yellow bone marrow ranges between -30 HU and -100 HU, we defined abnormal MDCT findings as marrow infiltration with CTV ≥ –30 HU, and the highest CTV among abnormal AS lesions was recorded in each patient. PET-CT was carried out according to the standard procedure. Data acquisition was performed in 3D mode. Field of view included the skull, upper limbs, and knees. The standardized uptake value (SUV) was calculated by the standard formula and the highest SUV (SUVmax) and SUV in the AS were collected. Visible areas of either focal or diffuse FDG uptake in bone were considered positive for myelomatous lesions. The numbers of abnormal lesions detected by these two modalities were investigated. CTV in MDCT and SUVmax in PET-CT were compared in relation to clinical variables and survival outcome. Statistical analyses were performed using STATA software ver. 12.0. Results Among 64 consecutive patients (36 male and 28 female, median age 71 yr, range 44 – 90), IgG, IgA, light chain only, and non-secretory subtypes were 34, 19, 10, and 1, respectively. Fifty-one patients and 34 patients were disease stage III according to the Durie-Salmon staging system (D-S) and International Staging System (ISS), respectively. Abnormal findings of AS were detected in 53 of 64 patients (82.8%) by MDCT. However, such findings were detected only in 15 patients (26.8%) by PET-CT. Patients with D-S stage III had significantly higher CTV on MDCT than those with D-S stage I or II (mean CTV: 16.94 HU vs -9.59 HU, p = 0.032). In correlation analysis between CTV, SUVmax, serum beta-2-microglobulin, the amount of M protein, and abnormal serum lactate dehydrogenase, a positive correlation was found between CTV and M protein (r = 0.36, p = 0.003), however, SUVmax by PET-CT was not significantly correlated with any variables. All patients were treated with bortezomib and/or lenalidomide-containing regimens. Based on IMWG response criteria, the numbers of patients achieving complete remission, very good partial response, partial response, and stable disease or less were 27, 14, 20, and 3, respectively. With median follow-up duration of 18.9 months (range: 2.9 – 52.7), one-year progression-free survival (PFS) and overall survival (OS) was 46.3% and 90.2%, respectively. With the cut-off value of CTV ≥ -10 HU, high CTV had significantly shorter PFS and OS (median PFS, 9.3 months vs. 19.5 months, p = 0.041, Figure 1; median OS, not reached, p = 0.018, Figure 2). However, with the cut-off value of SUVmax ≥ 6, high SUVmax was not associated with shorter PFS or OS. Conclusions MDCT had higher sensitivity for detection of abnormal medullary lesions in AS than PET-CT. As CTVs in MDCT were significantly associated with the amount of M protein and D-S stage, CTVs may reflect tumor burden of MM. Although the follow-up duration was relatively short, our results suggest that the presence of medullary lesions in AS with high CTV may be associated with poorer outcome in patients with symptomatic MM. Disclosures: No relevant conflicts of interest to declare.

Abstract 4051 BACKGROUND: Imaging is playing an increasing role in the diagnosis, staging and treatment response monitoring of patients with multiple myeloma (MM) because of limitation of hematological parameters and uneven distribution of MM lesions in the bone marrow. Although MRI and 18F-FDG-PET/CT have been utilized for visualization of medullary and extra-medullary lesions in patients with MM, both are too time-consuming and expensive for routine clinical use. Whole body Low-dose multidetector CT (WBLD MD-CT) can provide information on the degree of myeloma cell infiltration, especially in the appendicular skeleton. This study was performed to determine the incidence and prognostic implications of abnormal medullary lesions in the appendicular skeleton detected by WBLD MD-CT in patients with monoclonal gammopathy of undetermined significance (MGUS), and asymptomatic and symptomatic MM. We also compared the various hematological parameters with the development of these abnormalities. PATIENTS AND METHODS: Between January 2008 and July 2012, WBLD MD-CT was performed in 89 patients with MM and MGUS as an initial evaluation of lytic bone lesion and medullary and extra-medullary MM lesions. CT image acquisition and analysis were as follows. WBLD MD-CT was performed in an non-enhanced manner on a 16—Salmon staging system (DS), and were 11, 26 and 37 in International Staging System (ISS), respectively. Medullary abnormalities were found in 61 of 73 patients (83.6%). Patients with symptomatic MM had significantly higher mean HU than patients with MGUS/asymptomatic MM (−5.64 vs. −69.99, p < 0.001, Fig. 1). In the symptomatic MM, laboratory variables such as albumin, hemoglobin, creatinine, beta-2-microglobulin and presence of poor cytogenetic abnormalities (del17p, IGH-FGFR3, or IGH/MAF on FISH) were not correlated with the mean HU values. Positive correlations between the mean HU value and the amount of intact immunoglobulin (Ig) with IgG and IgA subtypes were observed (correlation coefficient: 0.330 and 0.694, p = 0.049 and 0.005, respectively), but it was not observed in patients with light chain only MM (correlation coefficient: 0.133, p = 0.598). Patients with DS stage 3 showed significantly high HU values compared to those with DS stage 1 and 2 (−35.30 vs. 1.11, p < 0.001, Fig. 2) whereas the mean HU value was not significantly different between ISS 3 and 1 or 2 (p = 0.186). Patients with abnormal medullary lesions occupying >25% of boney canals had significantly poorer progression-free survival compared to those with < 25% (12.5 vs. 15.1 months, p = 0.011, Fig. 3). Moreover, patients with mean HU value >0 had significantly shorter median overall survival (40.6 months vs. not reached, p = 0.040, Fig. 4) and tended to have shorter progression-free survival (9.8 vs. 15.7 months, p = 0.106, Fig. 5) compared to those with mean HU value CONCLUSIONS: This study indicated that medullary abnormalities in the appendicular skeleton detected by WBLD MD-CT might be associated with high tumor burden of MM independent of ISS stage and laboratory variables. In addition, it also has possible prognostic relevance in patients with newly diagnosed MM. Disclosures: No relevant conflicts of interest to declare.

Abstract 2969 Purpose: Although stringent complete response (sCR) defined by paraprotein negativity on immunofixation and serum free light chain (sFLC) ratio normalization are considered deeper responses in the IMWG criteria, recent report indicated that Multiparameter flow cytometry (MFC)-dased immunophenotypic response (IR) is a more relevant prognostic factor in MM patients. However, data on the prognostic impact of IR and sFLC ratio (sFLCκ/λ) normalization are still scarce. We investigated the prognostic impact of IR and sFLCκ/λ normalization in MM patients treated with novel agents. Patients and Methods: A total of 124 consecutive patients (M:F=68:56; median age, 71 yr) were treated by chemotherapy regimens containing at least one novel agent (thalidomide, bortezomib, lenalidomide)from April 2005 to May 2012. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the clinical course was assessed by simultaneous serum immunofixation, sFLC measurements, and MFC analysis of bone marrow (BM) plasma cells. Normalization of sFLCκ/λ was defined 2 consecutive normal sFLCκ/λ apart from at least 4 weeks. MFC-defined minimal residual disease (MRD) was evaluated by single-tube 6-color MFC, CD45-CD38 gating strategy, and combination CD19, CD56, and cytoplasmic κ-λ analysis. Clonal plasma cell (PC) negativity by MFC (MFC-negative) was defined as Results: At a median follow-up of 25.8 months, 3- and 5-year OS of all patients were 61.0% and 42.4%, respectively. CR was obtained in 25% (31/124), very good partial response (VGPR) in 33.5% (41/124), partial response (PR) in 30.5% (38/124), and stable disease or less (SD) in 11% (14/124). Normal sFLCκ/λ was achieved in 81% of CR, 56% of VGPR, 13% of PR, and 0% of SD or less response of patients. K-M estimated 3- and 5-year OS were 100% in CR patients; these were significantly better than in VGPR (75.8% and 43.2%, respectively) and PR patients (63% and 26.7.%, respectively). There were no significant differences in 3- or 5-year OS between VGPR and PR patients. Normal sFLCκ/λ and MFC negativity were achieved in 25 (81%) and 18 (58%) of 31 CR patients, respectively. Among 25 CR patients with normal sFLCκ/λ (stringent CR), 15 (60%) were MFC-negative and 10 (40%) were MFC-positive; three of 6 CR patients (50%)without normal sFLCκ/λ were MFC-positive. Twenty-three of 41 VGPR patients (56%) obtained normal sFLCκ/λ, while only 5 (12%) became MFC-negative; all 5 MFC-negative patients also obtained normal sFLCκ/λ. Among 52 patients with less than PR, only 5 (9.6%) obtained normal sFLCκ/λ and none achieved MFC negativity. Patients with MFC-negative CR showed significantly better PFS than patients with MFC-positive CR (p, age >70 yr, and abnormal LDH had negative prognostic impacts on attaining normal sFLCκ/λ, but none of these factors remained significant on multivariate analysis. Cox analysis showed that sFLCκ/λ normalization was an independent prognostic factor for longer PFS and OS in patients with CR, VGPR and PR (P=0.001). Conclusions: This study confirmed that magnitude of CR and VGPR response defined by IMWG criteria was heterogeneous in terms of sFLCκ/λ normalization and MFC negativity. Although MFC and sFLC analysis frequently gave discrepant results among patients with CR and VGPR, both analyses appeared to give important complementary information for assessing the depth of CR and VGPR category. Disclosures: No relevant conflicts of interest to declare.

Abstract 2817 Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are the heterogeneous group of bone marrow failure disorders. AS both shows profound hypocellular marrow without minimal morphologic atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion is occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the age of early 20s. Although abnormal distribution of red marrow in appendicular skeleton has previously reported in small series of patients with MDS, leukemia and lymphoma by MRI, no further study has published so far. Here, we examined distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationship between the abnormal medullary pattern in AS with laboratory variables, subsequent development of leukemic transformation and survivals MDS patients. Patients: We performed a low-dose MDCT of humerus and femurs in 64 untreated adult patients with AA (N=15) and MDS (N=49). Retrospective review of clinical and laboratory features including complete blood count, % of bone marrow blast, chromosomal analysis, and International Prognostic Scoring System (IPSS) was performed. WHO classification of MDS patients was as follows: RA (N=17), RARS (N=2), RCMD (N=9), RAEB (N=19) and MDS unclassified (N=2). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 49 MDS patients by the Kaplan-Meier and differences between curves were calculated by two-sided log-rank test. Multivariate analysis was Used to assess the effects of prognostic factors - hemoglobin, platelet, bone marrow blast, cytogenetic abnormalities, IPSS score, WHO classification, and MDCT patterns. CT image acquisition and Image analysis: Non-enhanced CT examinations were performed from the base of skull down to the knee joint by MS-CT scanner (AQUILION 64, Tohshiba, Tokyo, Japan). Bony canal of humeral and femoral bone were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole body MD-CT was 10.1 mSv. (ICRP 26). The dose was comparable to whole body CT (2.4 mSv.). Medullary CT density of humerus and femurs were measured and the results were expressed as Hounsfield unit (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by low density CT value between −30 to −100 HU. The value above −30 HU observed in long bony canals was considered as high density lesions. Medullary pattern of appendicular skeletons were categorized as follows: (1) fatty; showing a low signal density marrow (2) focal; showing abnormally focal high density lesions: (3) diffuse; showing uniformly high density marrow. Results: All 15 patients with AA showed a fatty (N=10, 66%) or focal (N=5, 33%) pattern in medullary AS on MDCT and none of them showed diffuse pattern. Conversion from fatty to focal marrow was observed in 9 of 15 AA patients after successful immunosuppressive treatment. Among the 49 patients with MDS, 15 (31%) had fatty pattern, 21 (43%) had focal pattern, and 13 (27%) had diffuse pattern. Patients with diffuse infiltration pattern on MDCT had a significantly low hemoglobin concentration (p Conclusions: This study showed that MDCT imaging of the appendicular skeletons provided important information for the diagnosis and prognosis of patients with MDS and AA. Disclosures: No relevant conflicts of interest to declare.