ALBERT

Description: In the article "Increase in Circulating Stem Cells in Patients With Myeloflbrosis" By Paul A. Chervenick (Blood, Vol. 41, No. 1, January 1973, pages 67-71) in Table 3 on page 70, the word "myeloblasts" should head column 3 and the word "myelocytes" should be included in column 4.

Description: Abstract 5082 Background: Prognosis for survival in mantle cell lymphoma (MCL) has recently been characterized using the MIPI algorithm. Using a retrospectively generated dataset of 150 patients with MCL seen at the H Lee Moffitt Cancer Center we sought to validate this approach in a more heterogeneous population. Methods: Patients were identified by physician survey, and through the use of our pathology and Total Cancer Care databases. Retrospective analysis was conducted with approval of our Institutional Review Board. In total 150 patients with MCL were identified, among whom MIPI data was available for 85 patients with a median followup of 36.8 months. Survival (expressed in months) was verified using our institutional records and the Social Security Death Index. Exploratory analysis of progression (n=79) and survival from the time of relapse (n=43) as stratified by MIPI were also conducted among evaluable patients. Data were compared using Kaplan-Meier survival analyses. Results: Median age was 65y (range 31–87), 73% male, 3% ECOG 〉1, 88% stage III/IV disease, 36% with extranodal involvement, and 38% with splenomegaly. Evaluation of the entire cohort shows median OS 57 (95% CI: 48, 70.9), median PFS 21.8 (95% CI: 14.2, 25.6), and median survival after relapse 27.6 (95% CI 25.4, 30.8). No benefit in OS was observed among patients receiving Cytarabine (HR 1.04, p=0.91) and/or Rituximab (HR 1.31, p=0.61) with initial chemotherapy. Relationship between PFS and survival after relapse demonstrated rho=0.51 (p

Description: Abstract 4162 Background: Plasmablastic lymphoma (PBL) is a distinctive B-cell lymphoma that shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts and having an immunophenotype of plasma cells. It was originally described as a rare variant of diffuse large B cell lymphoma involving the oral cavity and occurring in the clinical setting of HIV and latent EBV infection (Delecluse et al. 1997). However, the natural history of this disease in HIV-negative (HIV-) patients is poorly understood due to its rarity. Methods: Patients with a histologic diagnosis of PBL from January 1999 to June 2010 at Moffitt Cancer Center were identified and their charts were reviewed. Relevant clinical, pathologic, laboratory data and treatment variables were recorded and analyzed. Results: A total of 16 patients with PBL were evaluated including 9 HIV- cases, 5 HIV positive (HIV+) cases and 2 cases with unknown HIV status. The mean age at diagnosis was 39.8 and 58.4 years for HIV+ and HIV- patients (p=0.01) respectively. Flow cytometry and/or immunohistochemical staining analyses showed all cases phenotypically expressed at least one plasma cell marker (CD138 12/14; bright CD38 8/8; MUM1 8/8) and were negative for B-cell markers tested (CD20 16/16; PAX-5 3/3). All 5 HIV+ patients had CD4 count less than 100 (range 5–82). All 4 patients that had documented EBV status were positive. They all presented with advanced stages ranging from IIIB to IVB. Two patients received treatment, but did not have any response. All the HIV+ patients died within 6 months from diagnosis. HIV- cases (9) were more heterogeneous (summarized in Table 1). The stage at diagnosis varied from IE to IV. The list of common disease sites in the order of the frequency was following: oral-facial structures (5), lymph nodes (LN) (4), bone marrow (BM) (2), bone (1), GI tract (1). EBV was associated with 4 out of 7 cases while in 2 patients, the EBV status was unknown. Patient #5 developed PBL secondary to EBV reactivation 5 months post umbilical cord blood allogeneic stem cell transplant (HSCT) for MDS. Seven out of 9 patients received CHOP as a front-line therapy and 2 were treated with hyper-CVAD. Six out of 8 patients with assessed responses achieved complete response (CR), while one had very good partial response adequate for HSCT consolidation and the other one required salvage therapy. Four patients underwent autologous HSCT after achieving CR1. Three of them were stage IV at diagnosis and 1 was stage IIB. Two of these 4 patients were alive and disease-free (A-NED) at the end of the follow-up. The remaining 2 patients (#2 and #3) had disease recurrence at 2 and 14 months post HSCT, respectively. Interestingly, the patient #3 was treated with bortezomib/dexamethasone and achieved CR2. Despite consolidation with allogeneic HSCT, this patient recurred in 5 months post HSCT and died. The mean overall survival for our HIV- patients was 46.6 months with median survival not reached. Conclusion: Our study suggests that HIV- PBL is a heterogeneous disorder in terms of etiology and clinical course. A limited understanding of pathobiology and a lack of active biological agents for this subtype of B-cell lymphoma due to absence of cell surface CD20 expression might result in unfavorable prognosis in patients with advanced stages. Currently, more aggressive induction chemotherapy and consolidation with HSCT in CR1 have been offered to this group of patients at our center. A role of bortezomib in the front-line or relapse treatment settings needs to be tested on a larger cohort of patients. Disclosures: Off Label Use: Bortezomib use in this type of disease is considered off-label. Similarly, rituximab use is also off-label since CD20 is negative in this disease.

Description: Introduction Mantle-cell lymphoma (MCL) is a rare B-cell malignancy associated with high rates of relapse and poor survival. Aggressive treatment strategies, including dose-intensified chemotherapy and hematopoietic stem cell transplantation, are commonly utilized in an attempt to improve outcomes in this disease. The MCL international prognostic index (MIPI) is a validated tool for estimating survival risk; however, the role of risk-adapted therapy in MCL has not been defined. To better understand the role of treatment intensity in patients with lower risk MCL, we conducted a retrospective analysis of survival outcomes by treatment intensity in patients with low or intermediate risk MIPI scores. Purpose To assess the impact of treatment intensity on survival outcomes in newly diagnosed patients with lower risk MCL. Methods Patients with MCL and low or intermediate risk MIPI scores diagnosed between 1992 and 2012 were identified through our institutional databases. Clinical variables were collected and MIPI scores were calculated for each patient. Frontline treatment modalities were categorized into 4 groups: watchful waiting, low intensity (splenectomy, radiation, or rituximab monotherapy), moderate intensity (CHOP, bendamustine, lenalidomide, or equivalent), and high intensity therapy (at least 4 cycles of HyperCVAD or equivalent and/or stem cell transplant). Median progression free survival (PFS) and overall survival (OS) for each treatment group were estimated using the Kaplan-Meier (KM) method and compared using the log rank test. Cox regression was used to identify univariate predictors of survival. Results A total of 154 patients with low or intermediate risk MCL were identified. Watchful waiting, low, moderate, and high intensity treatment accounted for 8.4%, 11.7%, 40.9%, and 39.0% of patients, respectively. Intensively treated patients were more likely to be young, male, and have a higher B2-microglobulin (Table 1). With a median follow-up of 52 months, the median PFS was 31.48 mo (95% CI, 24.03-38.93) and the median OS was 111.35 mo (95% CI, 70.28-154.42). There was no statistically significant difference in OS by treatment strategy (p=0.665)(Figure 1). This lack of survival difference was true for all pairwise log-rank comparisons between treatment groups. There was a significant improvement in PFS for high intensity versus moderate intensity chemotherapy (median PFS 55.92 mo versus 18.55 mo, p

Description: Abstract 3720 Background: A Phase I study revealed that vaccination of cancer patients with irradiated autologous tumor cells and GM.CD40L bystander cells (engineered to secrete GM-CSF and express CD40L) is safe, recruits/activates dendritic cells, and elicits tumor-specific T cell responses. We report the long term followup using this vaccine strategy in patients with MCL, an aggressive and incurable B-cell malignancy. Methods: After lymph node resection for autologous tumor harvest, 4–6 cycles of chemotherapy, and restaging (CT, endoscopy, bone marrow biopsy), patients with usable vaccine who achieved a PR or CR lasting 1 month were vaccinated x4 at 28-day intervals with IL-2 (0.5 × 106 U SC BID × 14 d/cycle). Patients were monitored for toxicity, tumor response, tumor-specific immune responses, and EFS/OS. Results: 43 were enrolled, including 21 with relapsed MCL, 20 with int/high MIPI, and 6 with blastoid MCL. Twenty never received vaccine: 2 withdrew consent, 1 progressed rapidly prior to lymph node harvest, 7 had insufficient or contaminated specimens, and 10 progressed/died during chemotherapy. The unvaccinated were older (68.4y vs 62.8y; p=.026) but otherwise did not differ significantly by stage, LDH, MIPI, de novo status, or number of prior treatments. Among 23 treated, 10 had relapsed disease, 10 had an int/high MIPI, and 2 had blastoid MCL. Pre-vaccination response following chemotherapy included 7 CR, 15 PR, and one SD. At 6 months after vaccination, 2 pts in PR had resolution of MRD within the bone marrow, 10 progressed (including 3 who progressed after only 1–2 vaccines), and 11 had no change. Two are still in CR at 49 & 50 months. Median EFS and OS are calculated from receipt of first vaccine. Median EFS is 9 mo, however, this high risk cohort continues to show a prolonged median OS, which has not yet been reached (median follow-up 43 mo, range 4–79 mo). An increase in interferon gamma secretion as measured by ELISPOT assays was observed in 15 of the 23 patients (65%). Additionally, this was accompanied by an increase in EFS among those with a positive response. Conclusions: These phase 2 data are analogous to what we have seen among 4 patients with relapsed MCL treated on our phase 1 trial (EFS 6.5 mo, OS 82 mo), and support the need for further studies using GM.CD40L bystander vaccination. Similar discrepancies in EFS and OS have also been observed with other approved immunotherapeutics, ipilumumab & sipleucel-T (Hodi et al. 2010, Kantoff et al. 2010). Disclosures: No relevant conflicts of interest to declare.

Description: The time of onset and rate of self-replication in the irradiation depleted pluripotential hematopoietic stem cell compartment of mice was measured by a split-dose irradiation method. Mice were irradiated to reduce the compartment size and at daily intervals thereafter were again irradiated; 10 days after the second irradiation the number of endogenous spleen colonies was determined. As irradiation interval was lengthened, colonies increased in an exponential fashion with no apparent lag interval after the first irradiation. The doubling time of the colony-forming cell compartment was calculated as 16 hr if severely reduced in size by 300 R or more but was slower if less irradiation was given. The time of resumption of erythropoiesis following irradiation was measured after 100-900 R by determining uptake of radioactive iron into marrow, spleen, and circulating red cells each day after irradiation. With 200 R or less, erythropoiesis was not abolished. With higher doses there was an interval of no apparent erythropoiesis which increased by 1.6 days for each increment of 100 R. These results are compatible with a pluripotential stem cell compartment, which (1) begins self replication almost immediately following compartment size reduction, and (2) will not differentiate if reduced in size below approximately 10% of normal.