AbstractBackgroundStandard bone marrow biopsy (BMB) and bone involvement with follicular lymphoma (FL) on positron emission tomography (PET)/computed tomography (CT) both predict early clinical failure in FL. The key clinical question is whether PET/CT findings can obviate the need for BMB. The goal of this study was to determine the value of PET/CT in determining bone involvement in FL, using posterior iliac crest BMB as the gold standard.Materials and MethodsA total of 548 patients with newly diagnosed grade 1–3A FL were included. The presence, pattern, and location of bone involvement, spleen involvement, and standardized uptake values (SUVs) in the L3 vertebral body were recorded for all patients and compared with the BMB report.ResultsExcluding patients with focal bone lesions on PET/CT, the sensitivity and specificity of PET/CT in detecting bone or marrow involvement, compared with BMB, were 53% and 88%, respectively. The sensitivity and specificity of spleen involvement on PET/CT in predicting a positive BMB were 55% and 86%, respectively. An L3 SUVmax of less than 2.0 resulted in a negative predictive value (NPV) of 96% for marrow involvement on BMB; an L3 SUVmean below 1.4 resulted in an NPV of 100%.ConclusionIn newly diagnosed FL, PET/CT-detected bone and splenic involvement is highly specific for a positive BMB, and very low SUV values (<2.0 SUVmax and < 1.4 SUVmean) in the lumbar spine have a high NPV for a negative BMB. Routine BMB may be obviated in these patients. BMB remains necessary to definitively exclude bone marrow involvement in a large majority of patients with a negative PET.Implications for PracticePredicting early clinical failure in follicular lymphoma (FL) is important but difficult. Bone marrow involvement by FL is associated with early clinical failure, and determining this involvement is a key component of the initial staging. This study highlights that in certain patients, positron emission tomography/computed tomography is sufficient in determining bone or marrow involvement, without the need for a confirmatory bone marrow biopsy (BMB). An algorithm is provided based on these findings to help clinicians determine which patients would benefit from BMB and when it can be avoided.
Cytokine Gene Polymorphisms and Overall Survival in Follicular Lymphoma: Results from a Large Population-Based Study.
Abstract Background. The strongest established prognostic factors for follicular lymphoma are age and clinical factors. Biologic studies suggest a major role for the host immunologic environment in follicular lymphomagenesis, which is in part determined by host genetic background. Cytokines are key regulators of immune function and regulation, are highly polymorphic, and have been implicated in lymphoma etiology and prognosis. We evaluated the hypothesis that inherited variability in cytokine and related immune genes impact overall survival in follicular lymphoma. Methods. We genotyped 73 single nucleotide polymorphisms (SNPs) from 44 candidate cytokine and immune genes in 278 follicular lymphoma patients who participated in a population-based case-control study conducted from 1998–2000 in the Detroit, Iowa, Los Angeles and Seattle SEER (Surveillance, Epidemiology and End Results) cancer registries. Baseline clinical data and survival through early 2005 were obtained from cancer registry files. Cox proportional hazards analysis was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for the association between individual SNPs and overall survival, adjusting for age, demographic and clinical factors. We also used parallel modeling strategies to identify the best summary multi-SNP risk score to predict survival, and applied these results in a time-dependent receiver-operator characteristics (ROC) analysis. Results. The median age at diagnosis was 57 years (range, 25–74), and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27 – 78 months) for surviving patients. In multivariate modeling, SNPs in IL8 (rs4073; HRTT=2.14, 1.26–3.63), IL2 (rs2069762; HRGT/TT=1.80, 1.06–3.05), IL12B (rs3212227; HRAA/CC=1.83, 1.06–3.06), and IL1RN (rs454078; HRAA=1.93, 1.11–3.34) were the strongest and most robust predictors of survival. A summary score of the number of deleterious genotypes from these four genes was strongly associated with survival (p=1.4 × 10−5) after accounting for demographic and clinical variables (HR=2.06 per deleterious genotype, 1.52–2.79). A combination of the four SNPs and the demographic and clinical risk scores was strongly associated with survival (p=1.8 × 10−11); the 5-year Kaplan Meier survival estimates were 96% (93%–100%), 72% (62%–83%) and 58% (48%–72%) for low, intermediate, and high risk groups respectively. In a time-dependent ROC analysis the three risk groups had an area under the curve (AUC) of 0.83 at 72 months of follow-up (95% CI 0.72–0.93). Conclusion: Host genetic variability in immune genes, particularly IL8, IL2, IL12B, and IL1RN, individually and particularly in combination, was associated with overall survival in follicular lymphoma after accounting for demographic and clinical factors. Host immunogenetics is a promising class of prognostic factors in follicular lymphoma that warrants further evaluation.
Absolute Lymphocyte Count Recovery Predicts Superior Survival and Is Independent of the International Prognostic Index in Patients Treated with CHOP or R-CHOP Chemotherapy for Diffuse Large B Cell Lymphoma.
Abstract Absolute lymphocyte count (ALC) recovery post-autologous stem cell transplantation has been documented as an independent predictor for survival in non-Hodgkin lymphoma. The effect of ALC recovery on survival during standard CHOP or R-CHOP chemotherapy for newly diagnosed diffuse large B cell lymphoma (DLBCL) is unknown. To participate in the study, patients required to receive their full treatment with complete blood count determinations at the Mayo Clinic College of Medicine. Of 1633 DLBCL cases seen at the Mayo Clinic College of Medicine between February 1994 through August 2004, 212 consecutive DLBCL patients were eligible for the study. We study ALC recovery as a prognostic factor for progression-free survival (PFS) and overall survival (OS) in DLBCL patients treated with at least 3 cycles of CHOP or R-CHOP. 57% were male and the median age was 66 years (range: 20 – 87); 42% had elevated LDH, only 11% had a PS of 2 or higher; 58% were low stage (I or II); 88% of pts achieved a complete response. ALC was evaluated at the beginning of each treatment cycle, focusing on cycles 1–3 and the 3 month post treatment sample. ALC for each of the cycles were significantly correlated with PFS and OS, with cycle 1 ALC most significantly correlated when accounting for inherent differences based on treatment (Rx) type (i.e. CHOP vs. R-CHOP) as well as high vs. low IPI (PFS: p = 0.0012; OS: p = 0.005). Also, 74 pts achieved an ALC of at least 1,000 during all three cycles, where there was no significant relationship with this incidence and Rx type; this incidence was significantly associated with higher PFS (p = 0.0007) and OS (p = 0.0006), even when accounting for Rx type and high vs. low IPI. In the 179 pts who had 3-month post-Rx ALC data, this was also significantly associated with PFS (p = 0.002) and OS (p = 0.0009), while still accounting for Rx type and IPI status. Achievement of ALC >= 1,000 post-Rx was also significant for PFS (p = 0.0014) and OS (0.003). Also of note, only cycle 1 ALC was significantly different in high vs. low IPI pts (p = 0.008). In summary, these data support the hypothesis that there is a critical role of lymphocyte (immune) recovery during CHOP/R-CHOP chemotherapy in DLBCL.
Smoking, Obesity and Overall Survival in Non-Hodgkin Lymphoma (NHL): A Population-Based Study.
Abstract Background: Several studies suggest that smoking and obesity may increase the risk of developing NHL, but the impact of these factors on survival is relatively unexplored. One recent population-based Italian study found that smoking may negatively impact overall survival. Methods: We evaluated the association of body mass index (BMI) and cigarette smoking on overall survival in 1,286 patients who participated in a population-based case-control study conducted through the Surveillance, Epidemiology, and End Results (SEER) cancer registries in Detroit, Iowa, Seattle and Los Angeles. BMI (on 1189 participants) and a smoking history (on 471 participants) were obtained through in-person interviews. Histology, stage, presence of B symptoms, first course of therapy, date of last follow-up, and vital status were derived from linkage to registry databases at each study site in the spring of 2005. Hazard Ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards models, while adjusting for demographic and clinical factors. Results: The median age at diagnosis was 58 years (range: 16 – 74), and the most common histologies were DLBCL (33%), follicular (25%), SLL/CLL (12%), marginal zone (9%), mantle cell (4%) and Peripheral T-cell (3%). The median BMI was 26.6 (range: 16.2 – 47.3), and 26% of patients were classified as obese (i.e. BMI >30). Of patients with a smoking history, 47% had never smoked, 19% were active smokers at diagnosis, and 34% were former smokers. No significant differences were observed between those with and without tobacco use data in terms of primary lymphoma characteristics. Overall survival (OS) was defined as time from diagnosis to death due to any cause. Median follow-up on all living patients was 58 months (range: 4 – 78), and 333 patients had died. When BMI was assessed as a continuous measure, it was borderline significantly associated with OS (p=0.050). An indicator of whether or not BMI > 30 was also significantly associated with OS (HR=1.30; 95% CI: 1.01 – 1.68; p=0.042). Ever vs. never smokers also exhibited a survival disadvantage (HR=1.66; 95% CI: 1.12 – 2.44; p=0.011). When broken down further, former smokers who had smoked for >10 years (HR=1.61; 95% CI: 1.02 – 2.52; p=0.039) and current smokers (HR=1.79; 95% CI: 1.07 – 3.02; p=0.028) were at a survival disadvantage over those who had never smoked. When both smoking and BMI status were included in the model, only the indicator of being a current smoker remained statistically significant (p=0.031), with a trend toward decreased survival for former smokers who had smoked >10 years (p=0.061) and those with BMI >30 (p=0.058). Conclusions: NHL patients who smoke or are obese had a poorer overall survival. These observations warrant further investigation, including whether interventions for smoking cessation or weight loss can impact NHL survival.
A Large Scale Evaluation of Genetic Variation in Immune and Inflammation Genes and Risk of Non-Hodgkin Lymphoma.
Abstract Background: Non-Hodgkin lymphoma (NHL) is a malignancy of lymphocytes, and may develop in the setting of inflammation and immune dysfunction. Small scale evaluations have suggested that common genetic variation in candidate genes related to immune function may predispose to the development of NHL. Here we report a comprehensive analysis of variants within genes associated with immunity and inflammation and risk of NHL. Methods: We used ParAllele’s Immune and Inflammation panel of 9,412 single nucleotide polymorphisms (SNPs) from 1,450 immune/inflammation genes as a discovery tool in a clinic-based study of 458 NHL cases and 484 frequency matched controls seen at the Mayo Clinic from 2002–2005. The panel included 537 coding non-synonymous SNPs (nsSNPs), with the remainder of the SNPs selected as tags from HapMap (tagSNPs) to provide coverage of the candidate genes (r2 = 0.8 and minor allele frequency >0.05). To assess the association of individual SNPs with risk of NHL, we calculated Odds Ratios (ORs) and 95% confidence intervals, adjusted for age and gender. The most prevalent homozygous genotype was used as the reference group, and each polymorphism was modeled individually as having a log-additive effect in the regression model. Associations between haplotypes from each gene and the risk of NHL were calculated using a score test implemented in HAPLO.SCORE. We also modeled the main effects for all independent (r2 <0.25) SNPs from a gene in a multivariate logistic regression model. Results: The mean age at diagnosis was 60 years for cases and 58% were male; in controls the mean age at enrollment was 61.6 years and 55% were male. In the gene analyses, the strongest findings (p≤0.001 from multiple SNP logistic regression or haplotype analysis) were for cAMP responsive element binding protein 1 (CREB1; p=0.0004), fibrinogen alpha chain (FGA; p=0.0006), TNF receptor-associated factor 1 (TRAF1; p=0.001), dual specificity phosphatase 2 (DUSP2; p=0.001), and fibrinogen gamma chain (FGG; p=0.001). In the nsSNP analyses, the strongest findings (p≤0.01) were for integrin β3 (ITGB3) L59P (OR=0.64, 0.50–0.83), Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) H328R (OR=0.72, 0.57–0.91), transporter 2, ATP-binding cassette (TAP2) T665A (OR=1.32, 1.07–1.63), HLA-B associated transcript 2 (BAT2) V1895L (OR=0.60, 0.42–0.85), and complement component 7 (C7) T587P (OR=1.39, 1.07–1.80). Conclusions. Our results suggest that genetic variability in genes associated with antigen processing (CREB1 and TAP2), lymphocyte trafficking (B3GNT3), immune activation (TRAF1, BAT2), complement and coagulation pathways (FGA, FGG, ITGB3, C7), and MAPK signaling (DUSP2) may be important in the etiology of NHL, and should be pursued in replication studies.
Absolute Lymphocyte Count Recovery during Standard Chemotherapy Predicts Superior Survival and Is Independent of the Hasenclever Index for Hodgkin’s Disease.
Abstract Absolute lymphocyte count (ALC) post-autologous stem cell transplantation is an independent predictor for survival in Hodgkin’s Disease (HD). Lymphopenia at diagnosis is associated with worse prognosis in patients with newly diagnosed HD. The role of ALC recovery during standard chemotherapy for HD is unknown. We analyzed all patients managed for HD at the Mayo Clinic from 1986 to 2003. Of the 141 consecutive patients, two patients were excluded due to missing ALC data. Of the 139 patients, 63 patients were females and 76 males. The median age of patients at diagnosis was 31 years (range 6–75 years). 118 (85%) patients presented with nodular sclerosis HD, 10 (7%) with mixed cellularity, 2 (1%) with lymphocyte predominance, 1(1%) with lymphocyte depletion, 4 (3%) with lymphocyte predominant (nodular variant), and 4 (3%) unclassified. Frontline chemotherapy included ABVD (N = 79), MOPP-ABV (N = 47), COPP-ABV (N = 8), BEACOPP (N = 3), and Stanford V (N =2). The median number of cycles was 6 (range: 2–10). The median follow-up for the cohort was 62 months (range: 4–221 months). The ALC recovery was analyzed during the first 4 cycles as 90% of the patients received at least 4 cycles of therapy. Patients with an ALC ≥ 1.3 x 109/l at any time point within the first four cycles of chemotherapy (N = 93) demonstrated improved overall survival (OS) and progression-free survival (PFS) compared to patients with an ALC < 1.3 x 109/L at all time points within the first four cycles of chemotherapy (N =46) (10 years OS and PFS: 91% vs 51%, p < 0.0001; 85% vs 52%, p < 0.0001, respectively). Both groups were balanced for the Hasenclever Index: albumin < 4g/dl (p = 0.1), hemoglobin < 10.5 g/dl (p = 0.46), male gender (p =0.21), age ≥ 45 years (p = 0.06), stage IV disease (p = 0.68), leukocytosis ≥ 15 x 109/L (p = 0.58), and lymphopenia < 600 cell/ml (p = 0.211). Multivariate analysis demonstrated ALC recovery to be independent predictor of OS and PFS when compared to the Hasenclever index. These data suggest a critical role of lymphocyte (immune) recovery during standard chemotherapy in HD.
Maintenance Rituximab after CVP Results in Superior Clinical Outcome in Advanced Follicular Lymphoma (FL): Results of the E1496 Phase III Trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B.
Abstract E1496 is a phase III trial designed to evaluate the ability of 2 years (yr) of maintenance rituximab (MR) to prolong progression-free survival (PFS) after CVP (cyclophosphamide 1 G/m2 day [d] 1, vincristine 1.4 mg/m2 [max = 2 mg] d 1, prednisone 100 mg/m2 d 1–5) chemotherapy in stage III–IV follicular grade 1 and 2 and small lymphocytic lymphoma. After CVP treatment to maximum response, (6–8 cycles), stable and responding patients (pt) were randomized to MR (375 mg/m2 weekly x 4) every 6 months x 4 or observation (OBS). Stratification factors included histology, response and residual disease after CVP. With 3-yr median follow-up, survivals (from time of randomization, one-sided logrank p values) for all pt (n=304) favored MR for PFS (p = 3 x 10–8; hazard rate {HR} = 0.38 [0.28;0.54, 95% confidence intervals]) and OS (p = 0.09; HR = 0.66 [0.36–1.22]). Because the large majority of pt have FL and because rituximab efficacy is notably greater in FL, we focused in this report on the 237 FL pt. Median age was 58 yr, 65% were stage IV, 64% had marrow disease, 64% had high tumor burden and 37% had high-risk disease by the follicular lymphoma prognostic index. PFS after randomization was significantly longer for MR vs OBS (p = 3 x 10-7; HR = 0.39 [0.27;0.57]). The estimated PFS at 4 yr (~4.5 yr after start of treatment) was 56% for MR vs 33% for OBS. Differences in PFS were significant within the predefined strata and the differences were most significant in favor of MR for pt with high initial tumor burden and minimal residual disease after CVP. Overall survival was superior for MR (p = 0.03; HR = 0.51 [0.25;1.04]. Estimated OS at 4 yr (~4.5 years after start of treatment) was 88% for MR vs 72% for OBS. Of 33 deaths, 21 occurred on the OBS arm. These data demonstrate that maintenance rituximab not only significantly delays disease progression in FL compared with OBS but that a substantial proportion of patients treated with MR remain disease-free at 4 years after the completion of CVP. These are the first data to strongly suggest a survival benefit with a therapy that includes rituximab and CVP and the first to strongly suggest a survival benefit with maintenance rituximab in FL.
Intravascular Lymphoma: Poor Outcomes May Be Improved with Aggressive Therapy.
Abstract Intravascular lymphoma is a rare subtype of extranodal DLBCL characterized by the proliferation of malignant B-cells within the lumina of blood vessels. Organ involvement is variable and diffuse. Making the diagnosis can be challenging with symptoms persisting for months prior to definitive diagnosis. Treatment to date with standard anthracycline containing chemotherapy regimens has been disappointing with variable response rates, high relapse rates, and median survival times typically measured in months. We report diagnostic, treatment, and follow-up information regarding a group of patients with intravascular lymphoma evaluated at the Mayo Clinic with special attention to those receiving rituximab and/or high dose chemotherapy with or without peripheral blood autologous stem cell rescue. Methods: The medical records of patients with intravascular lymphoma seen at the Mayo Clinic between January 1970 and May 2005 were reviewed. Patients were included if they had evidence of intravascular lymphoma at the time of diagnosis of lymphoma. Pathologic specimens were reviewed for confirmation of diagnosis. Results: Twenty patients with a diagnosis of intravascular lymphoma were identified. Their median age was 66.5 years. Thirteen (65%) had B symptoms at the time of diagnosis and 13 had a performance status ≥ 3. Nine (45%) had an IPI ≥ 4. The median time to diagnosis from the onset of symptoms was 5.5 months. All had stage IV disease with biopsy proven involvement of at least one organ. The sites of disease involvement were CNS (10), marrow (7), lung (5), adrenal (3), kidney (2), lymph node, seminal vesicle, and skin (1). Two patients had involvement of three organs, six had involvement of two organs, and twelve had involvement of one organ. Nineteen patients received chemotherapy: ProMACE/CytaBOM (3), CHOP (6), RCHOP (6), DHAP (1), high dose methotrexate (1), methylprednisolone, nitrogen mustard, rituximab (1), and hyperCVAD (1). Three patients underwent peripheral blood autologous stem cell rescue after conditioning with BEAM. With a median follow-up of 60 months for all patients, the median overall survival was 8 months. No difference in outcome was seen with regard to site of organ involvement, number of organs involved, presence of B symptoms, or IPI. With a median follow-up for those receiving rituximab of 26 months, the median survival has not yet been reached while the median survival for those receiving non-rituximab containing regimens was 6.5 months. Similarly, with a median follow-up for those receiving high dose chemotherapy (hyperCVAD or BEAM) of 9.3 months, the median survival has not yet been reached while the median survival for those not receiving high dose therapy was 7 months. Conclusion: Intravascular lymphoma is a unique and aggressive subtype of DLBCL. The clinical presentation and sites of organ involvement are variable and the time from onset of symptoms to diagnosis can be prolonged. Standard chemotherapeutic treatment leads to poor outcomes. However, survival may be improved upon with newer strategies such as the use of rituximab and/or high dose chemotherapy with or without peripheral blood autologous stem cell rescue.
A Prognostic Model of 114 Patients with Castleman’s Disease.
Abstract Background: Castleman Disease (angiofollicular hyperplasia) is a rare, lymphoproliferative disease. There has been no large study describing the natural history of this disease. Hypothesis: A retrospective analysis of clinical, pathologic, and laboratory factors predictive of outcome should be identifiable. Methods: During the period from 3/30/48 to 6/18/2002, 114 patients with Castleman Disease were seen at the Mayo Clinic (Rochester, 56; Jacksonville, 19; Arizona, 13) and at the University of Nebraska (26). Pathology, laboratory and clinical characteristics analyzed included: the presence of unicentric or multicentric disease, the pathologic variant (hyaline vascular versus plasma cell variant), co-existing POEMS syndrome, age, serum albumin, alkaline phosphatase, AST, sedimentation rate, the presence of cytopenias, organomegaly (hepatomegaly or splenomegaly), papilledema, peripheral neuropathy, sclerotic bone lesions, renal disease, B-symptoms or respiratory symptoms. The impact of these variables on overall survival from time of diagnosis was evaluated using univariate analyses, where their significance was determined based on the logrank statistic. To derive the multivariable model, the score-based model-building method was used. Based on this approach, a 3-variable model was designed, adjusting for age at diagnosis. Patients were then assigned a risk score corresponding to how many of these risk factors they possessed. A final proportional hazards model was constructed based on this risk score. Results: The median age at diagnosis was 43 (range: 5 – 78), and 48% of patients were male. Fifty-five patients had multicentric disease. Median follow-up of living patients was 5.8 years (range: 0.02 – 27). On univariate analysis, factors that predicted for overall survival included: age at diagnosis, presence of multicentric disease, presence of a monoclonal protein in the urine, co-existing POEMS syndrome, serum albumin, presence of cytopenias, organomegaly, neuropathy, thrombocytosis, and respiratory symptoms. The final multivariable model included 98 patients. Adjusting for age, the model included organomegaly, respiratory symptoms, and thrombocytosis. Patients were assigned 1 point for each risk factor they possessed based on clinical relevance and similarity of the hazard ratios for each of these 3 variables (ranging from 3.1 to 4). A final prognostic survival model was constructed using this assigned risk score. These scores were collapsed further based on observed similarities (0 factors vs. 1 or more factors). This final model yielded a hazards ratio of 5.5 (95% CI 2.3–13.4). The 10 year survival rates were 80% (95% CI: 65–98%) and 41% (95% CI: 28–59%) for the 0 factor and 1+ factor groups, respectively. The 20 year survival rates were 71% (95% CI: 52–87%) and 31% (95% CI: 19–51%), respectively. Conclusion: The most distinguishing prognostic clinical, laboratory, and pathological characteristics of Castleman’s Disease are orgnaomegaly, respiratory symptoms, and thrombocytosis. This prognostic scoring system should aid in individual cases and in assessing results of therapeutic interventions.
Tissue Is the Issue: Accuracy of PET Imaging to Detect Bone Marrow Clearance in Patients with Peripheral T-Cell Lymphoma
Abstract INTRODUCTION: Adult mature T- and NK-cell neoplasms are a heterogeneous group of aggressive lymphomas comprising approximately 10% to 20% of all non-Hodgkin lymphomas (NHL) with an estimated 5-year overall survival of 40%. Staging and treatment strategies are guided by malignant involvement on PET/CT scan and bone marrow (BM) biopsy. The Lugano Criteria, established in 2014, suggested that focal FDG uptake within the bone marrow was highly sensitive for both Hodgkin (HL) and diffuse large B-cell lymphoma (DLBCL) potentially obviating the need for a bone marrow biopsy if no lesions were seen. Limited data exist regarding the sensitivity of PET for BM involvement in T-cell lymphoma. This study compares PET/CT scans and repeat BM biopsy in patients who have undergone treatment for peripheral T-cell lymphomas (PTCL) by evaluating BM avidity on PET scans. METHODS: This is a single institution study using the Mayo Clinic Lymphoma Database between January 1, 2001 and January 1, 2015. We retrospectively identified all patients with a diagnosis of PTCL, biopsy proven BM involvement at diagnosis, and a concomitant PET for staging. Patients were then reviewed to assess completion of induction therapy and availability of both PET/CT and bone marrow results post-therapy. Evaluation for concordance and discordant BM involvement were then determined using BM biopsy as the gold standard. RESULTS: Sixteen patients had both PET/CT and BM biopsy after completing induction therapy. Median age at diagnosis was 63 years (range 34-72) and 69% were male. PTCL subtype was peripheral T-cell lymphoma, not otherwise specified in seven patients; ALK negative anaplastic large cell lymphoma in one patient; and angioimmunoblastic in 8 patients. Pre-treatment PET/CT scans demonstrated eight patients (50%) with false negative scans. Post-treatment biopsy results demonstrated that ten (62.5%) had biopsy proven residual bone marrow involvement after induction. Eight patients (50%) were found to have BM biopsy proven disease with a negative PET scan. Two patients (12.5%) had both positive BM biopsy and PET scans; 5 patients (31.3%) had negative BM biopsies and PET scans. One patient (6.25%) had a negative BM biopsy, but had a PET scan that revealed positive disease. This patient was considered to have had a false positive PET scan and indeed has remained in remission since April 2009 without any further relapse or treatment. Sensitivity of PET for BM involvement was very poor at 20% (2/10) with a specificity of 50% (2/4) (Table 1 and 2). CONCLUSIONS: This study in PTCL indicates that PET scans at the completion of therapy have a 50% false negative rate. These patients should not be assumed to have negative bone marrow involvement based solely on PET/CT scans. A bone marrow biopsy at the end of therapy is necessary in PTCL patients to confirm complete response. Table 1. Bone Marrow Involvement Pre-Therapy PET Scan Imaging PET Negative PET Positive Total Patients Bone Marrow Negative NA NA NA Bone Marrow Positive 8 8 16 Total Patients 8 (50%) 8 (50%) 16 Abbreviations: NA, not applicable. The study defined that all patients had to have a positive bone marrow at baseline to be eligible for the study. Table 2. Bone Marrow Involvement PET Negative PET Positive Total Patients Bone Marrow Negative 4 2 6 (37.5%) Bone Marrow Positive 8 2 10 (62.5%) Total Patients 12 (75%) 4 (25%) 16 Table 1 and 2. Involvement of bone marrow with peripheral T-cell lymphoma based on evaluation by PET scans versus bone marrow biopsy. Disclosures Maurer: Kite Pharma: Research Funding.