Extra Nodal Research Articles

Feasibility of concurrent weekly paclitaxel and radiotherapy in node-positive breast cancer: An experience from India.

201 Background: Breast cancer patients with positive node and extra nodal spread are at a higher risk for distant metastases and they require immediate adjuvant chemotherapy. Similarly patients after breast conservative surgery or with patholgical T3, T4 disease require adjuvant radiation as early as possible. Taxanes have shown good response in node positive patients and are combined in many adjuvant chemotherapy regimens. Hence the current study was taken to assess the feasibility of concurrent weekly paclitaxel and radiotherapy. Methods: A prospective study was conducted on 22 female breast cancer patients after modified radical mastectomy or breast conservative surgery with pathologically positive node. Chest wall or whole breast radiotherapy was given on Tele Cobalt or Linac for a dose of 50 – 50.4Gy in conventional fractionation. Boost of 16 Gy was given to tumor cavity for those undergone breast conservative surgery. All patients received Inj. paclitaxel 60 mg/m2 once a week for 5 weeks. After completion of RT, paclitaxel dose was increased to 80mg/m2 for remaining 7 cycles. This was followed by anthracycline-based treatment sequentially as per standard adjuvant guidelines. Patients assessed weekly and toxicities graded based on CTC version 03. The minimum follow up was 2 months after completion of chemoradiation. Chi-Square test and Fisher exact test were used to interpret the results with literature. Results: See table. Skin reaction was more frequent and severe of all toxicities (p=0.003). With available literatures on adjuvant radiation alone the grade III and higher skin reactions are 3% but in our study it is 28% because of which 5/22 (22%) patients had interruption of both chemotherapy and radiation. Conclusions: Concurrent chemoradiation with weekly paclitaxel in adjuvant treatment of ca breast is associated with more Skin reactions which may result in significant treatment interruptions. It should be practiced cautiously which requires further randomized control studies to assess the toxicities in detail. [Table: see text]

Characteristics and outcomes of diffuse large B‐cell lymphoma presenting in leukaemic phase

Diffuse large B-cell lymphoma (DLBCL) occasionally presents with circulating malignant cells. The clinical characteristics and long-term outcomes of these patients have not been described. Twenty-nine newly diagnosed DLBCL presenting in leukaemic phase were identified between 1996 and 2010, at two institutions. Median age was 48years, and patients presented with leucocytosis, high lactate dehydrogenase levels, B symptoms, and high International Prognostic Index score. Extra nodal site involvement was observed in all patients and affected the bone marrow (100%), spleen (62%), pleura/lung (41%), liver (21%), bone (17%), bowels (7%) and cerebrospinal fluid (14%). Blood lymphomatous cells co-expressed CD19, CD20, CD22, CD38, CD45, HLA-DR and FMC7 in >90%, and kappa or lambda light chain restriction in >50%. Ninety per cent received rituximab and anthracycline-based chemotherapy. Overall, remission was complete in 54% and partial in 31%; 15% had resistant disease. Median follow-up was 47months; 13 (45%) patients remain alive in complete remission. Median progression-free and overall survivals were 11·5 and 46·7months, respectively. In summary, patients with DLBCL in leukaemic phase present with high tumour burden and frequent involvement of extra nodal sites. In this uncommon DLBCL subgroup, anthracycline-based regimens with rituximab are associated with early morbidity and mortality, but yield approximately 50% 4-year survival.

Prognostic value of the Follicular Lymphoma International Prognostic Index score in marginal zone lymphoma

In marginal zone lymphoma (MZL), clinical and follow-up data on large cohorts of patients are difficult to obtain. The objective of this single-center, retrospective analysis of a large cohort of 144 patients with MZL was to elucidate the role of prognostic markers, treatments, and outcomes in this disease. In total, 144 patients were identified who were diagnosed with MZL at the authors' institution between 2003 and 2010. Data on clinical parameters, treatments, response, and survival were analyzed. In addition, the validity of the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) prognostic scores were tested in patients with MZL. Among 144 patients with MZL, 96 patients (67%) had extralymph node (extranodal) MZL, 32 patients (22%) had lymph node (nodal) MZL, and 16 patients (11%) had splenic MZL. The 5-year progression-free survival rate was 82% in the nodal MZL group, 88% in the extranodal MZL group, and 74% in the splenic MZL group and did not different between the 3 groups (P = .60). The 5-year overall survival rate was excellent in all 3 MZL groups (nodal MZL, 89%; extranodal MZL, 92%; splenic MZL, 82%; P = .46). In our cohort, the FLIPI score was a significant prognostic marker: The 5-year progression-free survival rate for patients who had FLIPI scores of 0 to 2 (low or intermediate risk) was excellent at 92%, whereas it was only 62% for patients who had FLIPI scores of 3 to 5 (poor risk; P = .003). Similarly, the 5-year overall survival rate for patients who had FLIPI scores of 0 to 2 was 95%, whereas it was only 62% for patients who had FLIPI scores of 3 to 5 (P = .0009). The FLIPI score had strong prognostic value in patients with MZL. Patients who have low-risk or intermediate-risk FLIPI scores have an excellent prognosis, whereas patients with poor-risk FLIPI scores are candidates for novel treatment approaches.

P-0124 Outcome of Gastric Lymphoma in Elderly Patients with Reduced dose Chemotherapy Followed by Involved Field Radiotherapy

ABSTRACT Introduction NHL arises often in extra nodal tissues. Gastrointestinal lymphoma represents the largest group of extra nodal lymphoma. It accounts for approximately 40 percent of them. The most frequent type of non-Hodgkin's lymphoma is diffuse large-B-cell lymphoma. More than half of patients with diffuse large-B-cell lymphoma are over 60 years of age and the treatment of these elderly patients is a difficult challenge. Methods this study included 18 patients from 2008 to 2010 of age more than 60 years. All patients were subjected to six cycles of RCHOP followed by involved field radiotherapy. Radiation (45Gy/25#/5weeks) was given with linear accelerator (energies used 6, 15 MV) by 3DCRT technique. With Keeping in mind the toxicities associated with these drugs and the KPS of the patient, drug dosage was reduced. In most cases it was reduced by 20-25%. Results The completion rate of patients with this regimen was 100%. 5 year local control rate was 96%. Five year disease free survival was 74%. Grade III neurotoxicity was seen in one patient. Conclusion The concept of chemotherapy with reduced dosage followed by involved field radiotherapy is safe and effective in managing the Gastric lymphomas even in patients with associated geriatric co morbidities.

Central nervous system involvement in T-cell lymphomas: A single center experience.

8069 Background: Large experiences have reviewed the risk of central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL), but there are limited data on CNS involvement by peripheral T cell lymphomas (PTCL). We characterized the incidence of CNS involvement, risk factors and outcome in a large single institution dataset of PTCL. Methods: Retrospective review of the T-cell lymphoma database at Memorial Sloan Kettering Cancer Center. We identified 232 patients with any subtype of PTCL between 1994-2011 with a minimum 6 months of follow-up or an event defined as relapse or death. We excluded indolent forms of cutaneous T cell lymphoma. Results: Histologies included PTCL-NOS (31%), angioimmunoblastic (16.8%), anaplastic (ALCL), ALK negative (12%), ALCL, ALK positive (6%), extranodal NK/T cell lymphoma (7.3%), adult T cell leukemia/lymphoma (ATLL) (7.3%), and transformed MF (8.6%). Median age was 58 years with 59.9% men. CNS disease was found in 17 patients (7.32%). 8 (47%) had pathologic confirmation and 7 (41.2%) were clinically diagnosed. Two had other diagnoses at biopsy: DLBCL and glioblastoma. Median time to CNS involvement was 2.33 months (range, 0.16 to 103.1). CNS prophylaxis was given to 24 (10.34%), primarily intrathecal methotrexate. There was no difference in CNS involvement in patients who received prophylaxis vs. those who did not: 3/24 (12.5%) vs. 12/208 (5.77%) (p=0.192) respectively. Univariate analysis identified: stage III-IV (p=0.03), bone marrow involvement (p=0.018), >1 extranodal site (p<0.001), and ATLL vs. all other subtypes, 23.5% vs. 6.4% (p=0.003) as risk factors for CNS disease. On multivariate analysis, >1 extranodal site (p=0.004) and high intermediate (H-I) and high (H) IPI (IPI 3-5 & 4-5) were predictive for CNS involvement (p<0.05). The median survival of patients with CNS involvement was 2.628 months. Conclusions: Despite high relapse rates, PTCL carries a low risk of CNS involvement other than the ATLL subtype. As with other aggressive lymphomas, survival of patients with CNS involvement is poor and risk factors include: >1 extra nodal site and H-I-H IPI. In this dataset, prophylactic intrathecal chemotherapy does not appear to reduce the risk of CNS disease.

Epidemiologic, clinical, and pathologic features of lymphomas at the Peruvian hospital: Hospital Nacional Cayetano Heredia.

e12041 Background: During the decade 70’ to 90’ incidence of lymphomas in Lima, Peru increased from 3.4 to 7.5 per 100 000 females and from 6 to 8.3 per 100 000 males. We describe epidemiological, clinical and pathologic features of patients with lymphoma diagnosed at the Hospital Nacional Cayetano Heredia (HNCH), center of reference of Lima north. Methods: Retrospective study of 433 patients with lymphoma diagnosed from 1998 to 2008 at the HNCH. Results: The mean age was 44.8 years (range 1 to 93 years), the ratio was 1.5:1 for male and female respectively, 85.9% were Non Hodgkin Lymphoma (LNH). In Hodgkin diseases’ patients the mean age was 34 years and ratio male: female was 2:1; whereas, in NHL, the average age was 45.9 years and ratio male: female was 1.4:1. The more frequently symptoms were weight loss (40.5%) and lymphadenopathy (36.7%). The 55.08% were clinical stage I-II. The most frequent location was nodal (55.1%). More frequently extra nodal locations were: gastrointestinal (15.2%) and skin (10.8%). In NHL, the immunophenotype B were: B (57.8%), T (19.6%) and not determined ( 22.6%). The most common histological type was large diffuse cells lymphoma (35.8%). T-cell lymphoma adults occurs in 6.9% of cases, follicular in 4.7% and anaplastic in 4.7%.According to RECIST 1,1: 78.12% had remission completed and parcial. In Hodgkin’s disease’s treatment with ABVD was 90.97% of responses complete and parcial. During this period 23.45% of patients reported died Conclusions: Our patients with lymphoma retain the same general characteristics of the worldwide. ATLL had prevalence high relative to others series

Clinical features and therapeutic effect of 38 children with anaplastic large cell lymphoma

To analyze the clinical features and prognostic factors of children's anaplastic large cell lymphoma (ALCL), summarize the therapeutic effect and toxicities. A total of 38 ALCL patients admitted to Beijing Children's Hospital from Jan. 2003 to Apr. 2010 were treated with BCH-ALCL-2003 regimen (modified from HK-ALCL-2000). Thirty-four cases were ALK(+), male:female ratio = 2.16:1. The median age was 9 years; 86.8% had B symptoms. 94.7% evolved to Stage III and IV on admission. The median follow-up duration was 48 months (12 to 99 months). Median event-free survival (EFS) time was 43 months. Thirty-four patients (89.5%) achieved a remission. The disease relapsed in 3 patients within 20 months after diagnosis. Estimated 4-year EFS was (81.2 ± 6.4)%, estimated 4-year overall survival (OS) rate was (86.4 ± 5.7)%. Univariate analysis indicated that the unfavorable prognostic factors included: more than 3 extra nodal involvement, hepatosplenomegaly (> 3 cm), elevated lactate dehydrogenase (LDH), stage IV, hemophagocytosis in bone marrow, and age < 3 years. The major toxicity was myelosuppression and mucositis. no chemotherapy related death occurred. (1) Childhood ALCL patients often have B symptoms and extranodal involvement. (2) In the study, therapeutic effects was good. The disease relapsed mostly within the first 2 years, maintenance therapy with vinblastine is necessary. (3) The regimen is safe to patients.

Sonographic Manifestation of Thyroid's Rosai-Dorfman Disease

Rosai-Dorfman disease (RDD) is a rare and benign histiocytic proliferative disorder of unknown etiology. It can affect all age groups, particularly young adults. The typical clinical manifestation is painless, bilateral, massive cervical lymphadenopathy with or without extra nodal involvement, along with fever, weight loss, and night sweats. However, thyroid involvement is very uncommon. The ultrasonographic manifestations of RDD are rarely reported. A case of RDD involving the thyroid that was recorded in our hospital PACS system during 2002–2010 is reported here, which was initially misdiagnosed as non-Hodgkin’s lymphoma (NHL). In our case, ultrasonography revealed diffuse enlargement of whole thyroid glands with heterogeneous hypoechogenicity. Areas of linear hyperechogenicity were noted on the sonograms with multiple enlarged nodes over the cervical, supraclavicular, and submandibular areas. Though not specific, in order to avoid unnecessary surgery or a total thyroidectomy, ultrasonography and ultrasonography-guided core needle biopsy should be performed to establish an accurate diagnosis.

Clinical and histopathological factors affecting failed sentinel node localization in axillary staging for breast cancer

BackgroundSentinel lymph node biopsy (SLNB) has become the standard of care in axillary staging of clinically node-negative breast cancer patients. AimsTo analyze reasons for failure of SLN localization by means of a multivariate analysis of clinical and histopathological factors. MethodsWe performed a review of 164 consecutive breast cancer patients who underwent SLNB. A superficial injection technique was used. Results9/164 patients failed to show nodes. In 7/9 patients no evidence of radioactivity or blue dye was observed. Age and nodal status were the only statistically significant factors (p < 0.05). For every unit increase in age there was a 9% reduced chance of failed SLN localization. Patients with negative nodal status have 90% reduced risk of failed sentinel node localization than patients with macro or extra capsular nodal invasion. DiscussionThe results suggest that altered lymphatic dynamics secondary to tumour burden may play a role in failed sentinel node localization. We showed that in all failed localizations the radiocolloid persisted around the injection site, showing limited local diffusion only. While clinical and histopathological data may provide some clues as to why sentinel node localization fails, we further hypothesize that integrity of peri-areolar lymphatics is important for successful localization.

A case of Rosai-Dorfman Disease in a pediatric patient with cardiac involvement

Rosai-Dorfman disease (RDD) involves abnormal proliferations of oddly behaving histocytes that are not derived from the Langerhan's Cell linage. These collections tend to occur within lymph nodes, with occasional extra nodal presentation. While RDD is a rare entity itself, extra nodal cases are even more so, with even fewer reporting cardiac involvement, and previously only in adults. This report describes the disease in a pediatric patient who had the unique feature of an extra nodal cardiac mass. The patient, who was known to have sickle cell disease, was initially erroneously thought to have acute chest syndrome. Sudden changes in the patient's status, including development of 3rd degree heart block, demanded investigation with additional imaging. Chest CT revealed a mass arising from the cardiac interatrial septum and encircling the entire thoracic aorta. Imaging features of Rosai-Dorfman disease are nonspecific, complicating the diagnosis. We present this case with discussion of this extremely uncommon entity. We describe the diagnostic methods, the differential diagnosis, and the treatment options.

Primary extra nodal non-Hodgkin′s lymphoma of the oral cavity in a young girl

Primary Non Hodgkin s Lymphoma (NHL) usually arises within the lymphnodes, but 20-30% account for extra nodal sites. Oral cavity, as a primary extra nodal site for NHL, is relatively rare and diverse in presentation, response to therapy and prognosis. We report a 14 year old adolescent girl who presented with multiple gingival swellings, the most prominent one being in the right anterior maxilla. Gingival biopsy showed NHL- diffuse large B cell type. Child was completely cured with chemotherapy and now she is in complete remission and under regular follow up.

Imaging characteristics of diffuse large cell extra nodal non-Hodgkin's lymphoma involving the palate and maxillary sinus: a case report

Non-Hodgkin's lymphomas are a group of highly diverse malignancies and have a strong tendency to affect organs and tissues that do not ordinarily contain lymphoid cells. Primary extra nodal lymphoma of the hard palate is rare. Here, we present a case of diffuse large B cell lymphoma in a 60-year-old male patient that manifested as slightly painful ulcerated growth on the edentulous right maxillary alveolar ridge extending onto the palate, closely resembling carcinoma of the alveolar ridge. Computed tomography images showed the involvement of the maxillary sinus and right nasal cavity, along with destruction of hard palate, superiorly extending into the orbit. This case report highlights the importance of imaging to evaluate the exact extent of such large malignant lesions, which is essential for treatment planning.

Lymphomatoidgastropathy mimicking extranodal NK/T cell lymphoma, nasal type: A case report

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, exhibits aggressive tumor behavior and carries a poor prognosis. Recently, lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment. Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type, it is difficult to distinguish between the two conditions by histopathological evaluation only. Here, we report a rare case of lymphomatoid gastropathy in a 57-year-old female. Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body. Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments, at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body. Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3⁺, CD4⁻, CD5⁻, CD7⁺, CD8⁻, CD20⁻, CD30⁻, CD56⁺, CD79a⁻ and T-cell-restricted intracellular antigen-1⁺ into gastric mucosa. After treatment for Helicobacter pylori (H. pylori) eradication, the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo. Here, we report a case of H. pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation, and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type. In any case, these lesions are evaluated with biopsy specimens, the possibility of this benign entity should be considered, and excessive treatment should be carefully avoided. Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.

MRI and pet-CT in the diagnosis and follow-up of a lymphoma case with multifocal peripheral nerve involvement

Lymphoma of the peripheral nerve, particularly of the T-cell variety, is an extremely rare subtype of extra nodal lymphoma that has a variable response to current therapeutic regimens. Here, we present a patient with natural killer (NK)/T-cell lymphoma in remission who presented with a two-month history of right forearm swelling and paresthesia in the ulnar nerve distribution. Magnetic resonance imaging (MRI) showed an ulnar nerve mass identified as a nerve sheath tumor. Frozen section and postresection biopsies showed an Epstein-Barr virus-positive NK/T-cell lymphoma, nasal type. Consequently, the patient received chemotherapy following resection. Four months later, the patient developed a proximal leg mass, which was diagnosed as tibial nerve lymphoma. The patient was then treated with chemotherapy and follow-up was done by positron emission tomography-computed tomography (PET-CT). In conclusion, lymphoma should be considered in the differential diagnosis of a peripheral nerve mass. MRI is a useful imaging tool together with PET-CT, which plays a beneficial role in the follow-up of these patients on therapy as well as diagnosis of new lesions.

Soluble Interleukin-2 Receptors (sIL-2R) Is An Independent Prognostic Factor for Patients with Diffuse Large B Cell Lymphoma Treated with R-CHOP

Abstract 2678 Background:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a wide range of clinical outcomes. Rituximab added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, R-CHOP has made a marked improvement in outcome in patients with DLBCL. The International Prognostic Index (IPI), which consists of age > 60 years, stage III/IV, elevated lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) performance status (PS) † 2, and more than one extranodal (EN) site of disease, remains the most commonly used system for risk classification in DLBCL. However, recent studies suggested that new agent has altered the significance of previously recognized risk factors. Here we investigate the prognostic impact of reported risk factors in a large DLBCL patient cohort in a single institute to determine a better prognostic model in rituximab era. Patients and Methods:In total, 250 newly diagnosed DLBCL patients treated with R-CHOP regimen at the Cancer Institute Hospital of JFCR between October 2003 and December 2008 were included and analyzed. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared among risk groups using the log rank test. The Cox proportional hazards model was used to test the significance of prognostic factors. ROC curve was used to determine optimal serum level of sIL-2R and LDH as a cut off value for 4-year mortality risk. Results:The median age of patients was 65 years (range 23–88 years), 56% were male. The median follow-up time was 49 months (range 1–90 months) and 39 deaths had been recorded by the time of the last follow-up. The IPI still remains predictive with an OS ranging from 52.4% to 91.6% at 4 years; however it cannot discriminate between low and low-intermediate group. Revised IPI was valid as well with an OS ranging from 63.3% to 97%. In univariate analysis, elevated sIL-2R level, B symptom, elevated LDH level, PS>2, age>65, stage III/IV, CD5 positive, and EN>1 were significant as poor prognostic factors whereas sex, bulky mass, MIB1 index >90%, Non-GCB were not. Furthermore, multivariate analysis showed that only sIL-2R>924U/ml, CD5 expression, and EN>1 were significant with relative hazard 1.4∼17.5, 1.4∼8.9, and 1.3∼4.7, respectively. As elevated sIL-2R was the most powerful prognostic factor, we performed further analysis on this parameter. Average serum sIL-2R level was 2,775U/ml (range from 220U/ml to 43,100U/ml) with a normal limit of upper is 230U/ml. ROC curve demonstrated that serum sIL-2R was more optimal value than serum LDH to identify high risk patients for 4-year mortality after initiation of R-CHOP therapy and cutoff value of sIL-2R was 924U/ml (1.73 upper limit of normal). sIL-2R level can be divided into three distinctprognostic groups. Patients with sIL-2R<925U/ml fall into a very good group with a 4-year OS:98% and 4-year PFS:90.7%, patients with 925U/ml<=sIL-2R<4,625U/mlfall into a good group with a 4-year OS:82% and 4-year PFS:77.7%, and patients with sIL-2R>=4,625U/ml fall into a poor group with a 4-year OS:59.6% and 4-year PFS:54.7% (P < 0.001). Conclusions:sIL-2R level is an independent and powerful prognostic factor in serum level dependent manner in DLBCL patients treated with R-CHOP. This prognostic model should be reassessed on a larger scale and prospective study. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Diffuse Large B-Cell Lymphoma with Testicular Involvement: Outcome and Risk of CNS Relapse in the Rituximab Era

Abstract 780▪FN2▪This icon denotes a clinically relevant abstract Background:Testicular involvement of diffuse large B-cell lymphoma (Te-DLBCL) is associated with a poor outcome and a high risk of central nervous system (CNS) relapse. Rituximab is now routinely used into the treatment of both limited (LIM) and advanced (ADV) stage disease but it is unclear if this can reduce the rate of CNS relapse given it's limited penetration of the blood brain barrier and frequent parenchymal relapses in Te-DLBCL. A recent phase II study by the IELSG using R-CHOP, contralateral testicular radiation (RT) and IT prophylaxis in LIM stage patients demonstrated improved survival rates and a lower rate of CNS relapse compared with historical series. Herein, we evaluated the impact of R-CHOP on the natural history in all patients with Te-DLBCL Methods:The Centre for Lymphoid Cancer Database was used to identify patients with Te-DLBCL who were treated with curative intent. LIM stage was defined as stage I/II without bulk (< 10 cm) or B symptoms and also included patients with discordant involvement of the bone marrow with a low grade lymphoma whose stage was otherwise limited stage, and ADV stage included all others. Results:109 patients with Te-DLBCL treated between 1985–2011 were identified including 10 patients (11%) with discordant non-follicular low grade lymphoma in the bone marrow (9) or lymph node (1). Twenty-one patients were excluded: chemotherapy refusal (7), palliative (n=9), HIV + (2), peritesticular and not testicular involvement (2), clinical information N/A (1). Of the remaining 88 patients, 40 received CHOP-like chemotherapy and 48 received R-CHOP. The median age at diagnosis was 68 y (range 26–83 y) and half the patients had LIM stage disease. Most patients received either prophylactic contralateral testicular RT (59) or had bilateral orchiectomy (11) with few exceptions: refusal (3), PD or death on therapy (12), unknown (3). Five patients with CNS disease at presentation (R-CHOP n=4; CHOP n=1) also received HD methotrexate (HDMtx) and IT CHT. Only nine patients (7 ADV) received CNS prophylaxis (R-CHOP n=4; CHOP n=5) either IT (8) or IT + HDMtx (1)R-CHOP treated patients were more likely to have > 1 extranodal (EN) sites involved (p=0.030), and there was a trend to a greater proportion of patients with ADV disease (p=.087). With a median follow up of 60 mos, the 5 year TTP and OS for the CHOP and R-CHOP treated patients was similar (TTP 52% vs 67.5%, p=.181; OS 52.5% and 57%, p=0.262). However, an improved TTP (p=.025) and a trend to improved OS (p=.085) was observed in ADV stage patients but not LIM stage patients (TTP p=.617, OS p=.407) treated with R-CHOP. In univariate analysis, stage, EN sites > 1, IPI (0-2 v 3–5) and urinary tract (UT) involvement (kidney, adrenal or ureter) were prognostic for both TTP and OS. In multivariate analysis treatment with rituximab, > 1 EN sites and UT disease were prognostic for both TTP (rituximab p=.006, > 1 EN sites, p=.014, and a trend for UT disease p=.067) and OS (rituximab, p=.009, > 1 EN sites p=.025, UT disease p=.016)Excluding patients with CNS disease at diagnosis, there was no difference in the time to CNS relapse (TTCNS) in R-CHOP (5 y 27%) compared to CHOP treated patients (5 y 23%) (p=.789) in both LIM (5 y 16.5% vs 23.5%, p=.901) and ADV disease (5 y 27% vs 23%, p=0.386). In univariate analysis, the IPI, EN sites, PS and UT disease were associated with an increased risk of CNS relapse. In multivariate analysis, only UT disease (HR 9.18, p<.0001) was predictive of CNS relapse. CNS relapse in LIM patients (12) was typically late (≤ 2 years n=9), commonly parenchymal, (n=9 vs leptomeningeal (LM) n=2, both n=1) and usually in the absence of systemic disease (9). In contrast, CNS relapse in ADV patients (12) was usually early (< ∼ 1 year 10/12), preferentially involved the LM either alone (8) or in concert (3) with parenchymal lesions but also in the absence of systemic disease (10/12). Conclusion:Although survival has improved in Te-DLBCL patients since the introduction of rituximab, the benefit is likely primarily through systemic disease control as there remains an inherently high risk of CNS relapse. Patients with ADV stage disease and particularly with UT tract involvement, have frequent early leptomeningeal relapse and should be considered for up-front CNS treatment. Given the propensity for late parenchymal relapses in LIM stage patients, strategies to test agents with CNS penetration need further investigation. Disclosures:Villa:Roche: Research Funding. Shenkier:Roche: Research Funding. Sehn:Roche: Honoraria, Research Funding. Klasa:Roche: Research Funding. Gascoyne:Roche: Research Funding. Connors:Roche: Research Funding. Savage:Roche: Honoraria, Research Funding.

Incremental Value in Outcome Prediction with Molecular Signatures in Diffuse Large B-Cell Lymphoma,

Abstract 3687 INTRODUCTION:Multiple gene expression-based biomarkers have been identified in diffuse large B-cell lymphoma (DLBCL) that are predictive for survival outcomes. Most studies assess predictive significance based on p-value from multivariate Cox regression; few investigations have evaluated the incremental usefulness of these biomarkers in risk prediction. Using the recently developed concordance measures (e.g., C-statistics) on censored survival data, we assessed the usefulness of two published gene-based risk signatures and compared them to the known clinical prognostic factors; with an overall goal of investigating the added value. METHOD:The added value of biomarkers was assessed by C-statistic and the Integrated Discrimination Improvement (IDI). The overall C-statistic is an estimated concordance between prediction and observation (event vs. non-event) - the probability that predicted risk score is higher for subject with earlier time of event. The IDI measures overall improvement in sensitivity and specificity. The signatures we selected are a six-gene predictor by Lossos et al. (2004) and a three-component signature (∼400 genes) by Lenz et al. (2008). We used the Lenz dataset which include 233 patients with DLBCL who received R-CHOP therapy (median follow-up=2.81 yr), and focused on predicting 3-year survival outcome (42% censored). Clinical prognostic factors evaluated are the traditional IPI components (stage, performance status, age, LDH, and number of extra nodal sites). RESULTS:The C-statistic was 0.60 and 0.721 for six-gene predictor and three-component signature, suggesting good discrimination ability by molecular signature when used alone. However, the performance is inferior to IPI risk factors, with a C-statistic of 0.733. When integrating gene signatures with IPI risk factors, the C-statistic was increased to 0.744 and 0.762, an improvement of only 0.011 (95% CI, -0.049 to 0.071) and 0.029 (95% CI, -0.033 to 0.091) for six-gene predictor and three-component signature, respectively. Furthermore, assessment by IDI reveals an added value of only 0.011 (95% CI, -0.008 to 0.081) and 0.076 (95% CI, 0.013 to 0.16) for the two molecular signatures. Kaplan-Meier survival curves for the four quartile groups based on the predictor scores confirms the marginal benefit in risk prediction using molecular signatures. (Figure 1). [Display omitted] CONCLUSIONS:These results indicate that molecular biomarkers are inferior to clinical factors for risk assessment in DLBCL and provide little added value in risk prediction. These calculations suggest we will need to consider more than gene expression to develop highly discriminatory risk prediction models. However, the study of gene expression and clinical outcomes retains considerable potential to enhance understanding of disease mechanisms and uncover new therapeutic targets. Disclosures:No relevant conflicts of interest to declare.

Absolute Monocytosis At Diagnosis Is Associated with Poor Survival in Diffuse Large B-Cell Lymphoma -Possibly Related to Increase in Monocytic-Myeloid Derived Suppressor Cells

Abstract 2641 Background:monocytes and macrophages play a role in promoting angiogenesis and suppression of the anti-tumor immune response. Monocytic-myeloid derived suppressor cells (M-MDSCs) are a subpopulation of immature myeloid cells which have immune-suppressive function and play a role in cancer tolerance. Some patients with malignant lymphoma exhibit peripheral blood monocytosis (PBM) at diagnosis but its exact prevalence is not known. Aim:Recently we encountered PBM in a few patients with DLBCL who had a rapidly progressive fatal course. This observation coupled with emerging data on the role of M-MDSCs is in the tumor microenvironment, led us to undertake a retrospective study to determine prevalence of PBM and its possible prognostic significance in DLBCL. In a proportion of these patients we also quantitated the M-MDSCs pool in the peripheral blood using flow cytometry in an attempt to assess possible changes in this subpopulation of monocytic cells in DLBCL. Material and methods:Clinical and laboratory data from medical records of 91 newly diagnosed patients with DLBCL seen at our institute during 1996–2010, were evaluated for the presence of absolute PBM> 1000 cells/mm3, at diagnosis and for possible correlations with other prognostic factors including age, stage, gender, B symptoms, extra nodal involvement, serum LDH and CRP levels, bone marrow (BM) involvement and IPI score. A Cox proportional hazards regression model was used to determine significance of the prognostic factors in a multivariate analysis. In the last 23 consecutive patients flow-cytometry analysis peripheral blood cells was also performed using surface staining for CD45+CD14+ HLA DR−/LOW to define the proportion of M-MDSCs compared to 15 healthy volunteers. Statistical analysis of was done using student T-TEST. Results:The median age of the entire patient cohort was 66 years (21–87); median follow up was 30 months: (1–332 months) and 57 % were men. All patients received CHOP or R-CHOP. PBM was found in 18.3% at diagnosis. In the multivariate analysis (Cox model), only PBM, bone marrow involvement and IPI score were found to be independent prognostic factors for overall survival (OS) while age and LDH weren’t (Table). Blood samples collected at diagnosis from 23 patients showed increased numbers of M- MDSCs compared to healthy volunteers (9.59% range: 5.6–19 % and, 5.44% range 4.8–7.7 % respectively p<0.05).Levels of MDSCs decreased to within normal limits when performed 3 month following chemotherapy in patient in CR (5.76% range: 5.1–7.2 %). In conclusion:These results show that PBM is an independent factor for predicting poor survival in patients with DLCL and was as significant a risk factor as IPI score. This simple routine laboratory test can be utilized in daily practice as another indicator of poor outcome in DLBCL. The findings provide further support for the functional role of monocytes in the immune response in DLBCL. Furthermore, the consistent finding of significantly increased numbers of M-MDSC in the peripheral blood in these patients suggests that this subpopulation of immunosuppressive monocytes may contribute to the decreased tumor surveillance seen in DLBCL and may help to explain why absolute PBM is associated with poor outcome in these patients. Studies on their biological role as a marker of disease activity in DLBCL are in progress.VariablesHazard Ratio95% Hazard Ratio Confidence Limitsp. valueAge at DX1.0280.9881.0700.1685IPI3.4811.14010.6270.0285MONO >10003.3581.1889.4930.0223LDH1.0640.3013.7580.9228B.M. involved4.1891.63010.7640.0029 [Display omitted] Disclosures:No relevant conflicts of interest to declare.

A Restrospective Review of Peripheral T-Cell Lymphoma in a Single Institution Between 2000 and 2010

Abstract 1623 Background:Peripheral T-cell non-hodgkin lymphomas (NHL) comprise a heterogeneous group of malignancies, characterized by an aggressive disease course and a poor clinical outcome. T-cell lymphomas present in lymph nodes and they also frequently involve extra nodal sites. The first line treatment consists in CHOP-like regimen. Consolidation treatment in first line or in relapse is autologous stem cell transplantation (ASCT) or allogenic stem cell transplantation (SCT).Patients and methods: We retrospectively analysed the data of 189 adults who had received chemotherapy in our institution between 2000 and 2010. Results:Median age at time of presentation was 55 (range 17–89) years, 76% were <65 years. 50% had B symptoms and 50% serum elevated LDH. ECOG was 0–1 in 60% and 2–4 in 40%. According to the Ann Arbor classification, 15% were stage I-II and 85% were stage III-IV. 50% had low IPI (0-1-2) and 50% had elevated IPI (3-4-5). The histologic subtypes were 42% peripheral T-cell NHL unspecified (PTCL-U), anaplastic large cell lymphoma (ALCL), 8% had ALK+ and 10% had ALK-, 24% angioimmunoblastic lymphoma (AILT), 3% transformed mycosis fungoide, 2% instestinal T-cell lymphoma, 2% hepatosplenic γδ T-cell lymphoma and 1% adult T-cell lymphoma/leukemia. Primary extranodal lymphoma represented 17% and 8% were diagnosed with hemophagocytosis.Five-year overall survival (OS) was 28.3% (21.8–36.8%), and five-year progression free survival (PFS) was 18.4% (13.1–25.7%). On multivariate analysis, ALCL-ALK+ (p=0.008), AILT (p<0.001), extranodal involvement (p=0.01), PS>1 (p<0.001), LDH>N (p=0.003) were independent adverse factors for OS. Moreover B symptoms (p<0.01) was a significant factor for PFS.86% received CHOP-like induction treatment. The median number of chemotherapy was 2 (1–7). 59% experienced a complete response during the therapeutic procedure, while 22% were primary refractory. 44% had ASCT and 14% allogenic SCT. Only 28% of patients referred for allogenic SCT received this treatment. Conclusions:This 10-year review of patients treated in a single institution with initial conventional chemotherapy followed by more intensive treatments confirms the poor OS and PFS in the case of T-cell lymphoma. Despite a low incidence, T-cell lymphoma could be a priority area of research for new treatments with a potential to improve OS and PFS. Disclosures:No relevant conflicts of interest to declare.

The Importance of Age in Prognosis of Follicular Lymphoma: Clinical Features and Life Expectancy of Patients Younger Than 40 Years

Abstract 1593 BackgroundThe median age at presentation of follicular lymphoma (FL) is around 60 years (yrs). Despite recent reports of general improvement of overall survival (OS) in the last decade, the outcome of younger patients (pts) with FL has not been extensively investigated. Patients and methodsOur study aimed to investigate possible differences in clinical features, therapy and outcome in FL pts younger than 40 yrs compared to the older ones. Consecutive FL cases from 4 different European centers (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) diagnosed in the last 25 yrs were retrospectively analyzed. For each patient data on clinical features at diagnosis, treatment and outcome were retrieved. ResultsA total of 1003 FL pts (452 males and 551 females; median age: 56.5 yrs, interquartile range 46–67 yrs) were collected, 153 of them were ≤40 yrs at the time of diagnosis. Comparing clinical features at diagnosis of pts >40 and of pts ≤40 yrs, some differences were observed. In younger pts there was a lower incidence of elevated LDH (14% vs. 23%, p=0.02), and a less frequent primary extra nodal localization (7% vs. 13%, p=0.03), but a more frequent bone marrow involvement (57% vs. 44%, p=0.003) and involvement of more than 4 nodal lesions (43% vs. 25%, p<0.001). Information concerning first line treatment was available for >95% of pts. At a median follow-up of 9.3 yrs (interquartile range, 5–15 yrs) 91% of pts ≤40 yrs have received treatment for their lymphoma, compared to 84% of pts >40 yrs (p=0.02). An initial wait and see policy was applied in 11% of the younger pts and in 19% of the remainder (p=0.03). No differences in the two populations were observed in the type of chemotherapy given as first FL treatment, but pts >40 yrs received more frequently rituximab, alone or in combination, than younger pts (26% vs. 13%, p=0.001).At a univariate analysis younger pts had longer OS, and longer cause-specific survival (CSS, defined by deaths due to FL or acute toxicity of its treatment). In particular, the 10-yrs OS was 81% for pts ≤40 yrs (95%CI: 75–88%), vs 51% in the older ones (95%CI: 47–55%) (p<0.001). The 10-yrs CSS was 82% for pts ≤40 yrs (95%CI: 75–89%) compared to 60% in the older ones (95%CI: 56–64%) (p<0.001). 10-yr PFS was 39% for pts ≤40 yrs (95%CI: 31–48%), vs 24% in the older ones (95%CI: 21–28%) (p<0.001). Notably, when stratifying pts by age (≤40, 41–59 and ≥60 yrs) those ≤40 yrs-old at diagnosis had a CSS similar to that of pts of 41–59 yrs, but longer OS (figure 1). Even in this younger group, OS (median, 24 yrs) was, however, dramatically shorter than the life expectancy for the general population of the same age (approx. 45 yrs for males and 50 yrs for females in the UK, according to the Office for National statistics -www.statistics.gov.uk).At multivariate analysis, the features at diagnosis significantly influencing OS and CSS were B symptoms, stage ≥III, hemoglobin<12 g/dl, elevated LDH, period of diagnosis (≤1990, between 1991 and 1999, and >2000), age>60 yrs.No differences between age groups (≤40 yrs vs. >40 yrs) were observed in the incidence of second tumors (8% vs. 11%) and histological transformation (18% in both populations). ConclusionsIn this multicentre study younger pts with FL presented with different clinical features than those >40 yrs. As expected the CSS of pts >60 is strongly impaired, but interestingly the CSS of pts ≤40 yrs was similar to that of pts 41–59 yrs. Despite some limitations due to the fact that many pts were treated in the pre-rituximab era, these data suggest that FL still has a strong impact on survival duration of younger pts, who otherwise would have a long life expectation. [Display omitted] Disclosures:No relevant conflicts of interest to declare.