Introduction: The WHO classification recommends the subdivision of follicular lymphoma (FL) into three grades based on the average number of centroblasts per high-power field in the neoplastic follicles. However, we have encountered cases of FL in which the follicles are comprised predominately of large cells with cleaved nuclei (large centrocytes), but without enough centroblasts to meet the WHO criteria for grade 3 FL (FL3), and have classified such cases as follicular large cleaved cell lymphoma (FLC). The objective of this study was to describe the pathologic and clinical features of a large series of patients with FLC. Methods: The pathologic features of 72 cases of FLC were evaluated, including morphometry, immunostaining, and cytogenetic studies. Clinical features were tabulated and compared to a series of patients with the other subtypes of FL (332 FL1/2, 181 FL3), and survivals were compared for those treated with anthracycline-based chemotherapy plus rituximab. Results: FLC has a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells (centrocytes) with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1 μ, similar to centroblasts and approximately twice that of small lymphocytes. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high (≥30%) Ki67 proliferation (81%). However, almost one-half of the cases of FLC were misdiagnosed as low-grade FL. The clinical features of patients with FLC were similar to those with the other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. The 5-year overall survival (OS) of these patients was 95% and the 5-year event-for survival (EFS) was 90%. No significant differences in OS were found between FLC, FL1/2, FL3A, or FL3B. However, FLC and FL3A had significantly better EFS than either FL1/2 (P = .05) or FL3B (P = .028). Conclusions: FLC is a distinctive variant of follicular lymphoma, which should be recognized in future lymphoma classifications. The correct diagnosis of FLC is critical for the selection of appropriate therapy. Keywords: B-cell lymphoma; follicular lymphoma (FL); R-CHOP

A phase I/II trial was designed to evaluate the safety and activity of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and ASCT. Eligible patients (pts) had relapsed/refractory indolent or transformed NHL or MCL that was relapsed/refractory or in first partial (PR1) or complete remission (CR1). Pts received bortezomib on D-11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (0.8, 1, 1.3, and 1.5 mg/m2) and 3 pts were accrued to each. Any non-hematological ASCT-related toxicity > 2 on the Bearman scale occurring between D-11 and engraftment defined the maximum tolerated dose (MTD). Once the MTD has been reached, another 20 pts were enrolled at this dose to determine a preliminary overall response rate (ORR). Pts who were in CR or PR at D+100 were considered responders. The study enrolled 42 pts until 8/14/2009. The median age was 58 (34-73) years; with 33 males and 9 females. The commonest diagnoses were MCL (23 pts) and FL (7 pts). The median number of prior therapies was 1 (0-6). The median follow-up was 36 (12-55) months. 13 pts were treated in phase I and 29 pts in phase II. The MTD was initially determined to be 1.5 mg/m2 but it was later decreased to 1 mg/m2 because of excessive GI toxicity and peripheral neuropathy (PN). ORR was 91% at 100 days and 87% at 1 year (y). For all 38 evaluable pts at 1y, responses were CR 84%, PR 3%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI of 68-92%) at 1y, and 60% (41-75%) at 3y. Overall survival (OS) was 93% (95% CI 79-98%) at 1y and 80% (62-90%) at 3y. The commonest NCI grade 3 toxicities were neutropenic fever (20), infection (11), anorexia (9), PN (7), hypotension (6), hypokalemia (5), syncope (5), and 1 pt had a grade 4 prolonged neutropenia. Compared to 23 MCL in CR1 historic controls treated with BEAM and ASCT, ORR was 85% in the BEAM group vs. 96% for the V-BEAM group (p = 0.54). PFS was 85% (64-94%) vs. 85% (65-96%) at 1y and 70% (46-84%) vs.73% (49-87%) at 3y (log- rank p =0.71) for BEAM vs V-BEAM respectively. OS was 88% (68-96%) vs. 96% (73-99%) at 1y and 84% (62-94%) vs. 80% (55-92%) at 3y (log-rank p = 0.74) for BEAM vs. V-BEAM respectively. Toxicities were comparable between groups except for some excess of neutropenic fever and PN in the V-BEAM group. In conclusion, the addition of bortezomib to standard BEAM (V-BEAM) and ASCT is feasible. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial.

e18509 Background: Advanced stage FL 1-2 is considered incurable with conventional therapies. Randomized trials over the past decade have demonstrated a survival advantage associated with the use of R in combination with chemotherapy compared to chemotherapy alone. We performed an analysis of pts in the Nebraska Lymphoma Study Group database to evaluate the impact of the use of R on survival over the past three decades. Methods: All pts diagnosed with FL 1-2 between June 1981 and January 2008 were included. Patient and treatment related variables were collected for analyses. Treatment related variables included the use of radiation therapy, use of autologous stem cell transplantation (ASCT), and use of R. Pts were classified as having never received R (R-N), those who received R with salvage (R-S), and those who received R with initial therapy (R-I). Overall survival was calculated from the date of diagnosis to date of death from any cause. Univariate comparison of survival probability was conducted using Kaplan-Meier estimates with log rank testing. Multivariate analysis used the Cox proportional hazards regression to control for other prognostic factors. Results: The median duration of follow-up for survivors was 10 yr, 11 yr and 6 yr (R-N, R-S, R-I). The median age at diagnosis was 60, 53, and 52 yrs for these groups, respectively. The 5-year probability of survival for R-N, R-S, and R-I groups was 72%, 90%, ad 89% respectively (p<0.001 by log rank). In multivariate analysis, compared to R-N, R-S and R-I had a significantly lower risk of death (Hazard ratio [HR]; 95% confidence interval [CI] = 0.60; 0.41-0.89 for R-S and 0.33; 0.17-0.64 for R-I. The follicular lymphoma international prognostic index (FLIPI) score was also independently predictive of survival (HR; 95% CI =1.69; 1.11-2.58 for the intermediate risk group vs low, and 3.39; 2.31-4.96 for the high risk group vs low). Conclusions: In this analysis, pts in the Nebraska Lymphoma Study Group database with FL 1-2 treated with R had prolonged survival compared to those who never received R. This effect was independent of FLIPI score and the effect size was greatest for pts who received R starting with their initial therapy.

A 37-year-old man developed high fever with expectoration of blood and dyspnea.On examination, he had mild conjunctival injection.He was diagnosed with pneumonia and treated with empiric IV antibiotics.One week later, he developed dysarthria and ataxia; brain CT showed normal results and he was discharged.In the next month, he developed apneas and mild snoring, with frequent awakenings, nonrestorative sleep, choking, and shortness of breath.He was diagnosed with central sleep apnea.At this point brain MRI was performed (figure) to reveal a heterogeneous process that was hyperintense on T2 and fluid-attenuated inversion recovery sequences with signs of perifocal edema located in medulla oblongata and caudal part of the pons, more pronounced on the left side and spreading to the middle cerebellar peduncle.After contrast application there was inhomogeneous postcontrast enhancement indicating disruption of the blood-brain barrier.Neurologic examination revealed dysarthria, dysphagia, absent palatal reflexes, left hemiparesis (muscle strength 4/5) with brisk reflexes 3ϩ, and positive Babinski sign.He had severe dysmetria of all 4 limbs and truncal ataxia.Laboratory examination revealed normal erythrocyte sedimentation rate and C-reactive protein, complete blood count, electrolytes, and liver function tests.CSF analysis showed normal cell count, mildly elevated proteins (0.52 g/L), and positive oligoclonal bands, which were identical in serum and CSF.Serology for syphilis, HIV, hepatitis B and C, Candida, Aspergillus and Cryptococcus, Borrelia burgdorferi, morbilli, rubella, varicella zoster virus, herpes simplex virus 1 and 2, human herpesvirus 6, mumps, Epstein-Barr virus, cytomegalovirus, adenoviruses, Toxoplasma, Mycoplasma pneumoniae, and tuberculosis were unremarkable in both serum and CSF.Extensive testing for tumor markers and immunologic tests were negative.The patient was treated with corticosteroids, but without any improvement.In the next 2 years, mild worsening of the symptoms occurred, but repeated brain MRIs were without changes.He was empirically treated with antimycotics, without any improvement.Upon careful review of the patient's history, we found the patient was working in the Agency for Water Figure Brain MRI (A) Fluid-attenuated inversion recovery (FLAIR) coronal sequences.(B) T2 transverse sequences showing a heterogeneous process hyperintense on T2 and FLAIR sequences with signs of perifocal edema.

8534 Background: Little data has been published describing treatment results in pts with NHL ≥ 80 years of age. Methods: A retrospective study of pts with NHL treated by the NLSG between December 1982 and January 2005. Results: Two hundred forty-nine pts were evaluated/treated. Median age was 83 years (yrs) (range 80–96 yrs). Karnofsky performance status was ≥ 80 in 20% of pts. Ninety percent of pts had aggressive histology. Forty-nine percent of pts had advanced stage disease at diagnosis; 47% had masses ≥ 5 cm; 27% had B symptoms; 34% had elevated LDH values; 63% had extranodal disease. Fifty six percent of pts received ≥ 4 cycles of chemotherapy. Ninety percent of pts received CAPBOP or CNOP/CHOP± rituximab. Twenty four percent of pts received combined modality therapy. Thirty percent were not evaluable for response because of early withdrawal of therapy or lack of follow-up. The response rate for evaluable pts was 86%. With a median follow-up of 54 months (2–161 months) the five year probabilities of progression-free and overall survival are 22% and 28% respectively. Including 206 evaluable pts completing planned therapy the five year probabilities of progression-free and overall survival are 25% and 29% respectively. For pts completing all planned therapy a high age adjusted International Prognostic Index (IPI) score was independently associated with a higher risk of treatment failure (relative risk [RR]=1.84, 95% confidence interval [CI]=1.20–2.80, P=0.005) whereas treatment which included radiation (RR=0.35, 95% CI=0.21–0.56, P<0.001) and reception of ≥ 4 cycles of chemotherapy (RR=0.25, 95% CI=0.13–0.48, P<0.001) were associated with decreased risks of treatment failure. The same factors were independently associated with the risk of death (RR=1.77, 95% CI=1.16–2.71, P=0.009 for high age adjusted IPI, RR=0.36, 95% CI=0.22–0.59, P<0.001 for treatment that included radiation, and RR=0.29, 95% CI=0.15–0.56, P<0.001 for reception of ≥ 4 cycles of chemotherapy. The five year probability of progression was 42%. Conclusions: Anthracycline-based therapy in pts ≥ 80 years is feasible and results in long-term disease-free survival in a good proportion of pts. This intensity of therapy precludes completion of treatment in a sizeable number of pts. No significant financial relationships to disclose.

The management of squamous cell carcinoma arising in the lung is markedly different than squamous cell carcinoma of the skin, cervix, or larynx. Likewise, the optimal management of diffuse large B-cell lymphoma sometimes varies by the primary site of involvement. Knowledge of the unique clinical behavior of lymphoma arising in certain extranodal sites is necessary. Examples of this include the requirement for specialized evaluation and treatment of diffuse large B-cell lymphoma arising in the eye, brain, and testicle. It has also been questioned whether primary diffuse large B-cell lymphoma of the breast is another entity that requires management that is different than localized diffuse large B-cell lymphoma that occurs in nodal or other extranodal locations. The report by Ryan et al. [1.Ryan G. Martinelli G. Kuper-Hommel M. et al.Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group.Ann Oncol. 2008; 19: 233-241Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar] from the International Extranodal Lymphoma Study Group (IELSG) in this issue of the journal attempts to answer this question. This analysis adds to the valuable information provided by other studies from the IELSG that have examined non-Hodgkin’s lymphomas occurring in other sites [2.Zucca E. Conconi A. Mughal T.I. et al.Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group.J Clin Oncol. 2003; 21: 20-27Crossref PubMed Scopus (356) Google Scholar, 3.Zucca E. Conconi A. Pedrinis E. et al.Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.Blood. 2003; 101: 2489-2495Crossref PubMed Scopus (418) Google Scholar, 4.Pileri S.A. Zinzani P.L. Gaidano G. et al.Pathobiology of primary mediastinal B-cell lymphoma.Leuk Lymphoma. 2003; 44: S21-S26Crossref PubMed Scopus (58) Google Scholar]. Large multi-institutional reviews of this type are designed to eliminate some of the reporting bias in other smaller series of primary breast lymphoma. Nevertheless, patients in this cohort were diagnosed over a 23-year period beginning in 1980 and this analysis is also subject to problems associated with a lack of central pathology review and standardized management. In addition, patients were treated in the ‘Pre-PET’ (positron emission tomography) and ‘Pre-rituximab’ era. Despite these limitations, this is the largest series of primary diffuse large B-cell lymphoma of the breast that has been reported and the observations from this study will assist in the management of these patients. The first question addressed is whether the clinical behavior of primary diffuse large B-cell lymphoma of the breast is different than diffuse large B-cell lymphoma arising at other sites. Although the final answer is not known, the propensity for disease to occur and recur in the opposite breast and other extranodal sites indicates that primary diffuse large B-cell lymphoma of the breast has distinct clinicopathological characteristics. As the authors note, a similar situation occurs in testicular lymphoma. Mechanisms of lymphocyte homing to tissues such as skin and gut are well described [5.Pals S.T. de Gorter D.J.J. Spaargaren M. Lymphoma dissemination: the other face of lymphocyte homing.Blood. 2007; 110: 3102-3111Crossref PubMed Scopus (135) Google Scholar]. Future studies will be required to determine whether specific adhesion molecules, chemokine receptors, or chemokines are involved in the behavior of diffuse large B-cell lymphoma in the breast. The authors also address the issue of central nervous system (CNS) relapse, which has been reported to occur at increased frequency in patients with diffuse large B-cell lymphoma of the breast. The presence of extranodal disease is a risk factor for CNS relapse in other patients with diffuse large B-cell lymphoma, and it is not surprising that this risk might also be higher in patients with lymphoma occurring in the breast [6.van Besien K. Ha C.S. Murphy S. et al.Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma.Blood. 1998; 91: 1178-1184Crossref PubMed Google Scholar, 7.Hollender A. Kvaloy S. Nome O. et al.Central nervous system involvement following diagnosis of non-Hodgkin’s lymphoma: a risk model.Ann Oncol. 2002; 13: 1099-1107Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar, 8.Haioun C. Besson C. Lepage E. et al.Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin’s lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients.Ann Oncol. 2000; 11: 685-690Abstract Full Text PDF PubMed Scopus (173) Google Scholar]. Relapse in the CNS was noted in only 5% of patients and no CNS relapses were noted in the small fraction of patients who received prophylactic intrathecal chemotherapy. A recent series of breast lymphoma from Stanford identified a single parenchymal brain recurrence among 37 patients with breast lymphoma identified in a retrospective analysis [9.Ganjoo K. Advani R. Mariappan M.R. et al.Non-Hodgkin lymphoma of the breast.Cancer. 2007; 110: 25-30Crossref PubMed Scopus (77) Google Scholar]. It was concluded that routine intrathecal prophylaxis was not warranted. At our institution, no CNS relapses have been noted in 11 patients with primary breast lymphoma diagnosed from 1984 to 2004 M. L. Villanueva (unpublished data). The authors of the IELSG study conclude that routine CNS prophylaxis is not required for patients with primary diffuse large B-cell lymphoma of the breast. Nevertheless, additional study is required to determine whether some patients may benefit from this approach, such as those with other risk factors for CNS recurrence [10.Bierman P. Giglio P. Diagnosis and treatment of central nervous system involvement in non-Hodgkin’s lymphoma.Hematol Oncol Clin North Am. 2005; 19: 597-609Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar]. It is not surprising that outcome was related to the International Prognostic Index and that survival was improved in patients who received anthracycline-based therapy. Survival was also longer in patients who received radiation therapy in addition to chemotherapy. The survival of patients treated in this manner was similar to that of other patients with limited-stage diffuse large B-cell lymphoma from other series [11.Miller T.P. Spier C.M. Rimsza L. Diffuse aggressive histologies of non-Hodgkin lymphoma: treatment and biology of limited disease.Semin Hematol. 2006; 43: 207-212Crossref PubMed Scopus (9) Google Scholar], and comparable to gastric diffuse large B-cell lymphoma, the most common extranodal site of disease [12.Ferrucci P.F. Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years?.Br J Haematol. 2006; 136: 521-538Crossref PubMed Scopus (121) Google Scholar]. It is still unknown whether patients can be treated with an abbreviated course of therapy, or whether a full 6–8 cycles are required. It is also unknown whether radiation is required for all patients. It is possible that PET imaging might help with these decisions. As noted, the impact of adding rituximab to chemotherapy has not been studied for primary breast lymphoma, although the combination of anthracycline-based chemotherapy with rituximab should be considered standard. It appears that the addition of rituximab improves the outcome of all clinical and molecular subtypes of CD20-positive diffuse large B-cell lymphoma [13.Armitage J.O. How I treat patients with diffuse large B-cell lymphoma.Blood. 2007; 110: 29-84Crossref PubMed Scopus (114) Google Scholar, 14.Fu K. Perry K.D. Smith L.M. et al.Effect of addition of rituximab to CHOP on survival of patients in both the GCB and non-GCB subgroups of diffuse large B-cell lymphoma. ASCO Annual Meeting Proceedings Part I.J Clin Oncol. 2007; 25 (Abstr 8040)PubMed Google Scholar, 15.Lenz G. Wright G. Sandeep D. et al.Gene expression signatures predict overall survival in diffuse large B-cell lymphoma treated with rituximab and CHOP-like chemotherapy.Blood. 2007; 110 (Abstr 348): 209aCrossref Google Scholar]. Although the most common lymphoma involving the breast is diffuse large B-cell lymphoma, other histologic subtypes including marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma have been described [9.Ganjoo K. Advani R. Mariappan M.R. et al.Non-Hodgkin lymphoma of the breast.Cancer. 2007; 110: 25-30Crossref PubMed Scopus (77) Google Scholar]. The management of these lymphomas will usually differ from the management of diffuse large B-cell lymphoma. Although we do not have all the answers, the article by Ryan et al. [1.Ryan G. Martinelli G. Kuper-Hommel M. et al.Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group.Ann Oncol. 2008; 19: 233-241Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar] provides treatment guidance for patients with this rare lymphoma presentation and it provides a framework for future studies.

9026 Background: HSCT carries an increased risk of mortality. Thus, patients are encouraged to have ACP. However, discussions about ACP is not a casual process since it may elicit undue anxiety to the patients and their families. Anecdotally, pts fear that discussion of the possibility of death is inconsistent with hoping for the best outcome. We therefore compared the outcomes of pts with or without ACP who received HSCT for cancer. Methods: ACP was defined as having living will, power of attorney for health care, or life-support instructions conducted prior to transplant. ACP were reviewed in pts who were at least 19 yo and received first allogeneic or autologous HSCT for cancer between 2001 and 2003. Pts were classified into: 1) No ACP, 2) ACP prior to cancer dx, 3) ACP after cancer dx but prior to HSCT. Multivariate analysis (MVA) was done to evaluate the relative risk of mortality at 1 year according to ACP while adjusting for other prognostic factors. Results: 343 pts were included in the study: 172 (50%) did not have ACP, while 171 (50%) pts had ACP. Of those with ACP, 127 pts (74%) were available for review. Characteristics were similar between pts with and without reviewable ACP. 28 pts had ACP prior to cancer dx, 87 had ACP prior to HSCT, while 12 had ACP after HSCT. 64% of pts with ACP had both power of attorney and a living will, 16% had a living will alone and 19% had power of attorney alone. Older pts (p <0.001) and Caucasians (p = 0.04) were more likely to have ACP. MVA were confined to the 172 pts with no ACP and 115 who had ACP before HSCT and showed that pts with ACP prior to HSCT had a significantly lower risk of mortality (see table ). Conclusions: Despite a diagnosis of cancer and hospitalization for HSCT, only 50% of patients had engaged in ACP. ACP at any time before HSCT was associated with higher one-year survival. Engagement in ACP is not necessarily inconsistent with hoping for the best outcome in HSCT. Further study is warranted to explore the reasons for engaging or not in ACP. No significant financial relationships to disclose. [Table: see text]

Background/Patients and Methods: NST is increasingly being used as a means of establishing a graft-versus-malignancy (GVM) effect with less regimen related toxicity. Between 9/01 and 7/04, 39 patients (pts) with high risk/relapsed/refractory HM who were not candidates for full intensity allogeneic stem cell transplantation underwent NST using Pentostatin/TBI. The median age of pts was 52 years (range 22–70). The median number of prior therapies was 4 (range 0–8) including prior autologous stem cell transplantation in 22 pts. Diseases transplanted included chronic lymphocytic leukemia/indolent non-Hodgkin’s lymphoma (NHL, n=6), aggressive NHL (n=8), mantle cell lymphoma (n=3), Hodgkin’s disease (n=6), myeloproliferative disorders (n=4), myelodysplastic syndromes (n=4), and acute myelogenous leukemia (AML, n=8). Conditioning consisted of Pentostatin 4 mg/m2 daily on day −21, −20, and −19, followed by 200 cGy TBI on day −1. Post-grafting immunosuppression consisted of cyclosporine/mycophenolate mofetil. Results: Stem cell transplantation was from matched related (n=14) or unrelated (n=25) donors. Death prior to 100 days post transplant occurred in 7 patients. Grade III/IV toxicities included hematologic (n=10 pts), infectious (n=5) and other non-infectious (n=4). The median nadir values (day −21 to day 0) for hemoglobin, neutrophil count and platelet count were 10.7 g/dl (range 7.8–12), 1056/mm3 (range 0–5336), and 174/mm3 (range 24–523) respectively. Three pts failed to engraft; two patients with myelofibrosis (both of whom had autologous reconstitution) and one patient with high risk AML (who died of complications of fungal sepsis without hematologic recovery). The median chimerism values for CD3+ cells and WBC at day 28 are 80% and 95% donor cells respectively. The median chimerism values for CD3+ and WBC at day 70 are 95% and 95% respectively. There have been no late graft failures. The cumulative incidence of all grades of acute graft-versus-host disease at day 100 was 40% and was more common in unrelated donor transplants (60% vs. 15%, P=0.012). Chronic graft-versus-host disease has developed in 69% of patients. The cumulative incidence of relapse for all patients is 30%, and is lower for unrelated donor transplants than matched related donor transplants (46% vs. 20%, P=0.02). The probability of event-free and overall survival at two years is 52% and 56% respectively. Conclusions: This regimen is associated with acceptable toxicity. Engraftment has not been an issue with the exception of two pts with myelofibrosis. Pts receiving unrelated donor grafts have a higher incidence of graft-versus-host disease and a lower relapse rate. This represents indirect support for the presence of a GVM effect. A prospective study using a modified Pentostatin schedule (starting at day − 10) is ongoing based on the nadir of host T-cells identified in this study.

Introduction: Quality of life (QOL) is an important outcome in the treatment of malignancy, including hematopoietic stem cell transplant (HSCT). QOL is conceptualized as multi-dimensional including physical, psychosocial, emotional, and spiritual well-being (SWB). Purpose: A longitudinal QOL study of post-HSCT recipients is being conducted at the University of Nebraska Medical Center (UNMC) to evaluate changes over time in QOL and to examine the relationship between patient, disease, and transplant characteristics and QOL. Methods: Participants complete the Medical Outcomes Survey SF-36, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and City of Hope (COH) Medical Center-BMT survivor questionnaires at baseline (pre-HSCT), day 100, and yearly post-HSCT. For each subscale, the sample was dichotomized as ≤80th percentile versus > 80th percentile of the baseline score, and clinical outcomes compared between the two groups. Results of the baseline COH SWB subscale, which includes questions regarding uncertainty, purpose, hope, and peace, are reported here. Results: Between September 2001 and June 2004, 172 participants received autologous HSCT for hematologic malignancy. Most (97%) were white, non-Hispanic, 55% were male, and the median age at transplant was 52 years (range 20-75). Median follow-up of surviving patients is 24 months (range 12-49) and 44 (25%) patients had progressed prior to analysis. The 3 year overall survival (OAS) rate for patients with high (>9.0) SWB was 93% compared to 79% for patients with lower SWB (P = .05, log rank test). However, baseline SWB was not a statistically significant predictor for event-free survival or relapse rate. No other COH subscale scores were significantly related to clinical outcome nor were any FACT subscale scores. Discussion: In this initial analysis, SWB at baseline is a significant predictor of OAS. Multivariate analysis is needed to determine if the impact of SWB can be explained by other patient characteristics such as co-morbidities or disease status at HSCT. Implications: Additional studies focusing on longitudinal spiritual assessment and intervention are needed to determine the long-term impact of SWB on QOL and survival. Introduction: Quality of life (QOL) is an important outcome in the treatment of malignancy, including hematopoietic stem cell transplant (HSCT). QOL is conceptualized as multi-dimensional including physical, psychosocial, emotional, and spiritual well-being (SWB). Purpose: A longitudinal QOL study of post-HSCT recipients is being conducted at the University of Nebraska Medical Center (UNMC) to evaluate changes over time in QOL and to examine the relationship between patient, disease, and transplant characteristics and QOL. Methods: Participants complete the Medical Outcomes Survey SF-36, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and City of Hope (COH) Medical Center-BMT survivor questionnaires at baseline (pre-HSCT), day 100, and yearly post-HSCT. For each subscale, the sample was dichotomized as ≤80th percentile versus > 80th percentile of the baseline score, and clinical outcomes compared between the two groups. Results of the baseline COH SWB subscale, which includes questions regarding uncertainty, purpose, hope, and peace, are reported here. Results: Between September 2001 and June 2004, 172 participants received autologous HSCT for hematologic malignancy. Most (97%) were white, non-Hispanic, 55% were male, and the median age at transplant was 52 years (range 20-75). Median follow-up of surviving patients is 24 months (range 12-49) and 44 (25%) patients had progressed prior to analysis. The 3 year overall survival (OAS) rate for patients with high (>9.0) SWB was 93% compared to 79% for patients with lower SWB (P = .05, log rank test). However, baseline SWB was not a statistically significant predictor for event-free survival or relapse rate. No other COH subscale scores were significantly related to clinical outcome nor were any FACT subscale scores. Discussion: In this initial analysis, SWB at baseline is a significant predictor of OAS. Multivariate analysis is needed to determine if the impact of SWB can be explained by other patient characteristics such as co-morbidities or disease status at HSCT. Implications: Additional studies focusing on longitudinal spiritual assessment and intervention are needed to determine the long-term impact of SWB on QOL and survival.

7585 Background: Bulky disease in DLBCL has been linked to adverse outcomes. Tumor bulk was not included in the IPI due to lack of uniform data availability. Radiation to sites of bulky disease may result in improved outcomes. We evaluated the impact of tumor bulk as a prognostic factor combined with the IPI in predicting overall survival in DLBCL. Methods: A retrospective review of adult patients with newly diagnosed DLBCL from October 1982 through February 2000 was done, and data pertaining to tumor size, age, Ann Arbor stage, performance status (PS), lactate dehydrogenase level (LDH), extranodal involvement, radiation therapy and overall survival was collected. Surviving patients were followed through December 2005. Bulky disease was defined as largest tumor mass of ≥10 cm. Statistical analysis was performed using Cox proportional hazards regression. Results: Complete data was available on 669 patients. All patients received anthracycline or mitoxantrone based chemotherapy. Bulky disease was found in 27% of patients, while radiation was employed in 22% of patients. There was no significant association between use of radiation and tumor bulk. IPI was calculated as low risk—37%, low-intermediate—28%, high-intermediate—20% and high—14%. Median follow-up of survivors was 100 months (range <1 - 263). In univariate analysis, bulky disease alone was a significant predictor of inferior survival (RR 1.27, p = 0.044), however when combined with the IPI it was not a significant predictor of poorer overall survival as compared with non-bulky disease (RR 1.10, p = 0.36). Radiation therapy was associated with a significant increase in overall survival (RR 0.70, p = 0.005). Conclusions: Bulky disease is an important independent prognostic factor for overall survival in patients with DLBCL, however when combined with IPI it does not result in improved prediction. It is unclear whether this is due to insufficient power or due to possible inter-relation between tumor size, LDH and PS, the latter of which are included in the IPI. Radiation therapy to some patients with bulky disease may also have mitigated the adverse effect. Larger prospective studies may shed light on the utility of tumor bulk combined with IPI and possible alterations in management. No significant financial relationships to disclose.

BACKGROUND:The aim of the study was to determine the outcome and clinical features predictive of survival in patients with follicular lymphoma (FL) treated aggressively and to determine the rate of disease-specific mortality in patients with grade 3 FL (FL3). MATERIALS AND METHODS:Four hundred and twenty-one patients with FL who were treated with various anthracycline-based chemotherapy regimens were included in this retrospective study. RESULTS:Patients with FL3 and a diffuse component of >50% had the worst outcome, with a hazard ratio of dying of 2.2 (95% CI 1.4-3.4) compared with patients with FL1 or FL2, and a ratio of 1.6 (95% CI 1.02-2.5) compared with FL3 with a diffuse component of < or =50% by multivariate analysis (P = 0.0026). Patients with FL3a had an outcome similar to those with FL3b. In patients with FL3 and a diffuse component of < or =50%, the overall and event-free survival curves showed a plateau for patients younger than 60 years of age. However, there were no differences in the cumulative incidence of relapse/progression or lymphoma-specific/treatment-related mortality between the two age groups. CONCLUSIONS:Less than half of the patients with FL3 and a diffuse component of < or =50% treated with anthracycline-based combination chemotherapy will relapse and relapses are uncommon after 6 years. Older patients should be offered the same aggressive chemotherapy as younger patients.

BACKGROUND:Patients with mantle cell lymphoma (MCL) have in general, lower response rates and overall survival (OS) than those with other B-cell non-Hodgkin's lymphomas. The role of hematopoietic stem cell transplantation (HSCT) in MCL is unclear. Hence we decided to study the clinical course of patients who received autologous and allogeneic HSCT for MCL. METHODS:Ninety-seven patients, (80 patients-autologous; 17 patients-allogeneic) who received a HSCT for mantle cell lymphoma were included in the study. RESULTS:The complete response rates at day 100 between the two groups were similar (73% vs. 62%). Day-100 mortality was higher in the allogeneic HSCT group (19% vs. 0%) (P < 0.01). The estimated 5-year relapse rates, 5-year event-free survival (EFS) and 5-year OS among the allogeneic HSCT patients were 21%, 44% and 49%, respectively, similar to 56%, 39% and 47% in the autologous group. Ten patients received HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone + high-dose methotrexate and cytarabine) +/- rituximab prior to transplant. There have been no relapses or deaths amongst these patients at a median follow-up of 16 months. CONCLUSIONS:Patients treated with allogeneic HSCT had a lower relapse rate, but similar EFS and OS to autologous HSCT. Treatment of MCL with HyperCVAD +/- rituximab followed by HSCT seems promising.

The prognosis of mantle cell lymphoma (MCL) is poor with a median survival of generally less than three years. In an attempt to improve on the outcome of this disease, high dose therapy in the form of both autologous and allogeneic stem cell transplantation (SCT) has been explored. However, recurrences following autologous transplantation are common. Allogeneic SCT offers the potential benefits of an uncontaminated stem cells and a graft versus lymphoma effect. Thirty-seven patients with MCL underwent allogeneic SCT at five institutions between 1994 and 2003. The median age at transplant was 48 (range 34–59) years; 6 patients were female and 31 male. The median interval from diagnosis to transplant was 11 months (range 4–144 months). Seventy percent of patients had received at least two prior chemotherapeutic regimens and 9% had failed an autologous SCT. Donor source was matched related donor (MRD) in 33 (89%) and matched unrelated donor (MUD) in 4 (11%). Conditioning regimens varied by center; overall 26 patients (70%) received TBI-based conditioning. Donor source was bone marrow in 14 (38%) and peripheral blood in 23 (62%). Fourteen grafts (38%) were T-cell depleted and of these, 7 received T-cell add-back. With a median follow-up for surviving patients of 42 months (range 4–98 months), sixteen patients remain alive post SCT. The cumulative incidence of non-relapse mortality is 32% at day 100 and 41% at one year post transplant, with the vast majority of deaths occurring by one year post transplant. Thirty four of 37 patients were evaluable for acute graft-versus-host disease (GVHD). The cumulative incidence of acute GVHD was 62% at 100 days. Of 20 patients evaluable for extensive chronic GVHD, the cumulative incidence was 30% at one year. Three year estimates of event-free and overall survival are 39% (95% CI 23%–55%) and 45% (95% CI 28%–61%) respectively. Progressive disease has been documented in six patients. This data demonstrates that allogeneic SCT in MCL can result in prolonged disease control in selected, pretreated patients, although nonrelapse mortality remains a significant problem with this approach.

Between 9/01 and 8/03 13 patients with relapsed/refractory lymphoid malignancies have undergone NST. The median age at transplantation was 52 years (range 21–63). The median number of prior therapies was 5 (range 1–7). Diseases transplanted represented a broad variety of lymphoid malignancies including Hodgkin's disease (n = 3) and non-Hodgkin's lymphoma (n = 10). The conditioning regimen consisted of Pentostatin 4 mg/m2/day IV on days -21, -20, and -19, followed by low dose total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine/mycophenolate mofetil. Stem cell transplantation was from matched related (n = 5) or matched unrelated (n = 8) donors. All toxicities were minimal. At day +28 the median values for donor chimerism were 90% (range 55%–100%) for CD3+ cells and 95% (range 50%–100%) for WBC. At day +70 the respective median values were 95% (range 50%–100%) and 100% (range 80%–100%) respectively. Sustained engraftment has been observed in all cases to date and no patients have required donor leukocytes. Acute GVHD has been seen in 6/13 patients, and chronic GVHD in 6/8 evaluable patients. Treatment related mortality is 15% (one death from intracranial hemorrhage, one death from chronic GVHD). With a median follow-up for surviving patients of 11.2 months, the event-free survival and overall survival are presently projected at 73%. Of six patients who underwent autologous stem cell transplantation as their immediate prior therapy (excluding salvage therapy prior to NST), five have had remission durations which have exceeded their prior remission duration with autologous transplantation (P = 0.07 by logrank). An additional patient with Waldenstrom's macroglobulinemia had evidence of minimal residual disease (persistent marrow disease and an elevated IgM) for six months post transplant, and with no further therapy at one year post transplant has a normal marrow and IgM levels. The use of Pentostatin/TBI as a preparative regimen for NST in patients with refractory/relapsed lymphoid malignancies is associated with minimal toxicity, sustained engraftment, and an acceptable treatment related mortality given the patient population. The observation that a number of patients have had remission inversions (compared with immediately prior high-dose chemotherapy/autologous stem cell transplantation) and the occurrence of a late remission in the absence of other therapy offers indirect evidence of a graft-versus-lymphoma effect.