Median Duration Of Remission Research Articles

Clinical characteristics, treatment, and outcome of dogs with presumed primary hepatic lymphoma: 18 cases (1992–2008)

OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis. DESIGN-Retrospective case series. ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical records were reviewed for information on signalment, treatment, and outcome. RESULTS-8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.

A phase II trial of bortezomib plus lenalidomide for relapsed/refractory mantle cell lymphoma (MCL) (CALGB 50501).

TPS223 Background: Despite high response rates to MCL induction therapy, relapse is common. Stem cell transplant (SCT) is often utilized, though not curative in most patients (pts), and many are not candidates due to age or comorbidities. Thalidomide and bortezomib have demonstrated activity in MCL. In a phase II trial of rituximab+thalidomide, including thalidomide maintenance, in relapsed/refractory MCL pts, overall/complete response rate (ORR/CR) was 81/31%; median progression free survival (PFS) was 20.4 months; 3-year overall survival (OS) was 75%. In a phase II bortezomib trial with 141 evaluable MCL pts, ORR/CR was 33/8%, with median remission duration (MRD) 9.2 months (mos), and median time to progression (TTP) 6.2 mos. Grade (gr) 3/4 toxicities were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). Bortezomib+lenalidomide has been studied in relapsed/refractory myeloma pts, with 61% achieving >minimal response, with MRD of 10.8 mos and acceptable tolerability. Methods: Eligibility criteria: histologically-documented MCL (CD5+, CD23-, cyclin D1+); measurable disease; prior therapy with >1 regimen, including autologous, but not allogeneic, SCT; age ≥18 yrs; no prior radioimmunotherapy; no ≥gr 3 peripheral neuropathy; performance status 0-2. Treatment: Induction: bortezomib 1.3 mg/m2 IV, d1,4,8,11; lenalidomide 20 mg/day PO, d1-14; 21d cycle, 8 cycles. Maintenance (for responders): bortezomib 1.3 mg/m2 IV, d1,8; lenalidomide 15 mg/day PO, d1-14; 21d cycle, till disease progression. Primary endpoint is ORR/CR; secondary endpoints are TTP, disease-free and OS, and correlation of changes in NK/T-cells and plasma cytokines with response. The protocol was modified in 9/09 with separate dose reductions by agent (e.g., myelosuppression-lenalidomide; neuropathy-bortezomib). Accrual: Accrual goal is 54 (49 evaluable) pts. The study was activated in 11/07; a planned interim analysis occurred after 19 patients, with >10 responses required to continue the trial. As of 1/11/11, 48 pts are accrued, with completion anticipated for 6/2011.

Chemo-immunotherapy with bendamustine hydrochloride (BH) and alemtuzumab (ALZ) in T-prolmphocytic leukemia (T-PLL): A clinico-in-vitro correlative study.

e18557 Background: T-PLL is a rare, but chemo-resistant malignancy, associated with a dismal median survival of about 7.5 months.The optimal treatment for T-PLL is still unknown. Preliminary data indicated high induction response rate with the human CD52 antibody, ALZ. The median remission duration of 7 months however, is short. Moreover, use of ALZ is frequently complicated by infectious complications, thereby limiting the prolonged use of ALZ as a single agent. The results with conventional chemotherapy are disappointing. There is an unmet need to define better treatment strategies for T-PLL. Methods: A 55-year-old female with advance T-PLL presenting with leukocytosis, bicytopenia, hepatosplenomegaly and lymphadenopathy was treated with ALZ for 3 cycles with only minor response attained. BH at 90mg/m2 for 2 days was subsequently given and resulted in remarkable response, with normalization of blood counts within a week and reduction in size of tumor masses. As T-PLL cell lines are not commercially available, T-PLL cells (CD4+CD8+) from peripheral blood frozen at diagnosis were enumerated by flow cytometry via staining with AnnexinV and 7AAD after incubation with BH, ALZ and the combination of both agents at various achievable serum concentrations for 2, 6 and 24 hours. Results: ALZ alone did not result in any significant cell death at all concentrations and time-points.Incubation with BH at concentration above 30µg/ml for 24 hours resulted in cell death in a concentration dependent manner. Combination of BH and ALZ resulted in a time and concentration dependent increase in cell death contributed by both apoptosis and necrosis (Table). Conclusions: BH is an active agent in T-PLL and synergizes with ALZ in tumor cell killing. This study provides an important proof of principle for frontline clinical trials exploring this novel chemo-immunotherapy combination in treating T-PLL. Total percentage cell death over control with different concentrations of BH and ALZ at 6 and 24 hours. Agents Total % cell death (mean±SD) 6 hours 24 hours 10 µg/ml BH + 5 µg/ml ALZ 5.2±3.1 8.51±0.5 30 µg/ml BH + 10 µg/ml ALZ 7.3±1.9 28.7±3.6 100 µg/ml BH + 30 µg/ml ALZ 13.4±2.2 57.6±1.1

Evaluation of factors associated with second remission in dogs with lymphoma undergoing retreatment with a cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol: 95 cases (2000–2007)

To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol. Retrospective case series. 95 dogs with lymphoma. Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined. Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days. Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.

Phase 2 Results of Clofarabine In Combination with Etoposide and Cyclophosphamide In Pediatric Patients with Refractory or Relapsed Acute Lymphoblastic Leukemia

Phase 2 Results of Clofarabine In Combination with Etoposide and Cyclophosphamide In Pediatric Patients with Refractory or Relapsed Acute Lymphoblastic Leukemia

Phase II Study of Velcade® Plus Mabthera® In Relapsed Follicular Lymphomas

AbstractAbstract 1801 Background:Velcade ® (V) and Mabthera ® (M) have demonstrated an individual considerable efficacy in the treatment of non Hodgkin's lymphoma. The aim of this study was to evaluate the efficacy and safety of the combination of V and M in patients with relapsed Follicular lymphoma (FL). Methods:Patients (pts) with histologic documentation of CD20+ FL, measurable and active disease, received : 1.3 mg/m2 of V on days 1–4-8-11 every 21 days for 6 cycle and M 375 mg/m2 on day 1 of each cycle from cycle III to VI. Two additional doses of M were administered alone after cycle VI, every 21 days (cycle VII and VIII). Response was assessed after 2 and 8 cycles using the NCI recommendations for Non-Hodgkin's Lymphomas. Results:At the time of current analysis, initial planned accrual of 41 evaluable pts was not completed. From 2007 to now 37 pts entered into the trial. The pts characteristics at baseline were: median age 66 years (range: 46–84), male 51%, stage IV 43 % elevated values of LDH, 27%, and of Beta2microglobulin 41%. The FLIPI score was calculated in 34 pts (92%) and 11 pts (31%) had a poor prognostic score (> 3). The median number of previous immuno/chemotherapy regimens was 2 (range:1-3), and the median duration of last remission before registration into trial was 23 months (range: 3–67).In four out of the 37 pts who entered into the trial, the treatment is ongoing and thirty-three pts were evaluable for response. The overall response rate in the intent to treat analysis was 58% (19 pts), of which 16 pts (49%) obtained complete response (CR) and 3 (9%) partial response (PR). Stable disease was seen in 1 pt (3%). Eight pts (24%) had progressive disease and 2 (6%) pts were lost at follow-up. Three pts (9%) had to stop the treatment: one pt (3%) for grade IV peripheral neuropathy, one pt (3%) refused to continue the treatment after 2 cycle and one pt (3%) died during the treatment for toxicity . After a median follow up of 14 month (0-44), the median overall survival and the event free survival were not reached. Overall, 2 pts relapsed (10 %) and 1 pt (5 %) showed a progression of disease. A total of five pts died, four because of lymphoma progression, and one for toxicity during treatment.Complete response are ongoing in 14 pts .Toxicity was evaluable in 33 patients. We observed the following grade 1/2 adverse events: neuropathy (10 pts), neutropenia (2 pts), infection (5 pts), constipation (4 pts), rash (2 pts), fatigue (1 pt). Further we saw the following grade 3/4 adverse events: thrombocytopenia (5 pts), neuropathy (5 pts), neutropenia (1 pt) and infection with fever(1 pt). Three patient interrupted the treatment due to severe neuropathy. Conclusions:The combination of V+M is associated with acceptable toxicity and a promising percentage of response. Further follow-up is required to evaluate the response duration and survival in the whole group of patients Disclosures:Sacchi:Janssen-Cilag: Research Funding. Off Label Use: Velcade is not approved in Italy for the treatment of Follicular lymphomas. However,we have perfomed with study has I have thought that the association with Mabthera could have efficacy and low toxicity in the treatment of NHL.

Treatment of Molecular and Clinical Relapse of Acute Promyelocytic Leukemia (APL) with Arsenic Trioxide: Results of the European Registry of Relapsed APL

AbstractAbstract 15Arsenic trioxide (ATO) is presently regarded as the best treatment option in relapsed PML-RARA+ acute promyelocytic leukemia (rAPL). However, given the relative rarity of relapses following standard front-line APL therapy, the optimal management of this group of patients remains to be firmly established. For this reason, and in order to ensure homogeneity in patient data collection and gain insights into the epidemiology and clinical aspects of rAPL, a European registry of rAPL was established in 2008 under the auspices of the European LeukemiaNet (ELN). Patients with a genetically confirmed (PML-RARA+) molecular or clinical relapse of APL occurring from January 2003 onwards were eligible for registration using uniform CRFs. Management of relapse was at the discretion of the treating physician, but could be based on the treatment recommendations developed by an expert panel provided on the ELN website (www.leukemia-net.org/content/). By 15 July 2010, 122 cases of rAPL had been registered by participants of 7 European countries (Spain, Italy, UK, France, Germany, Greece, Poland) representing the starting group of this ongoing initiative open for participation. In 80 pts (69 in first, 11 in 2nd and later relapse), information was available on ATO salvage therapy. At time of first diagnosis median age was 43 years (14-77); all pts had received all-trans retinoic acid (ATRA) and anthracyclines ± ara-C as first-line therapy. No patients received ATO as part of front-line therapy. According to Sanz Score, 26% were low risk, 45% intermediate and 29% high risk. 39% of pts had the bcr1/2 and 61% the bcr3 isoform of PML-RARA. Median duration of first remission was 493 days (93d to 5.7 years). The usual dosage of ATO was 0,15mg/kg/day, or regimens with the same cumulative dose were used. ATO induction therapy was combined with ATRA (45 mg/m2/day) in 40% of pts and during the consolidation cycle in 50% of pts, respectively. The median duration of ATO (± ATRA) for induction was 30 days and for consolidation 25 days. CNS relapses were treated with intrathecal application of methotrexate ± ara-C ± hydrocortisone and ATO. Among the 69 pts with first relapse, there were (Group A) 25 molecular and (Group B) 42 hematological relapses (bone marrow), in three pts combined with CNS involvement. Two pts had isolated CNS or extramedullary relapse. Main characteristics of pts at start of induction therapy in Group A vs. B were: median WBC count (x109/L) 4.4 (1.9-6.2) vs. 2.3 (0.5-102) (p=0.015); median platelet count (x109/L) 178 (40-392) vs. 87 (9-273) (p=0.0007); median Hb (g/L) 14 (10.6-15.7) vs. 12 (7.6-14.8) (p=0.0008). In Group A, none of the pts had coagulopathy compared to 8 of 25 (32%) pts with coagulopathy in Group B (p=0.004). In Group A, ATO therapy was not complicated by hyperleukocytosis and no episodes of differentiation syndrome were observed. In Group B, 9 (21%) pts had suspected or manifest differentiation syndrome (p=0.02), and additional chemotherapy was administered in 14 (33%) pts to control hyperleukocytosis. Other toxicities were rare and had no significant influence on therapy. In Group A, the rate of 2nd molecular remission after induction was 52% (13 of 25 pts) and after consolidation therapy 64%. No pt died. In Group B, 39 (88%) pts achieved 2nd CR, 2 (5%) pts were resistant and 3 (7%) pts died early from cerebral bleeding. Second molecular remission was reached in 12 of 32 (38%) pts after induction and in 62% after consolidation. Information on postconsolidation therapy was available in 45 pts of Group A and B. Of these, 14 pts underwent allogeneic, 18 pts autologous transplantation and 13 pts further therapy with ATO ± gemtuzumab ozogamicin. 11 of the 45 (24%) pts relapsed (median 2nd remission duration 10 months, 4 to 26), and 9 deaths were reported between 9 and 14 months after the end of consolidation therapy. In pts with 2nd and later relapse, despite previous exposure to ATO, further responses with this agent were observed. Conclusions:ATO is an effective therapy for all stages of relapsed APL. The results argue in favor of serial PML-RARA monitoring in front-line therapy of APL to allow early treatment of emergent relapses, avoiding hyperleukocytosis and risk of death due to bleeding and differentiation syndrome. Furthermore, the favorable toxicity profile of ATO seems to benefit the feasibility of subsequent transplantation. Disclosures:Lengfelder:Cephalon: Research Funding. Fenaux: CELGENE, JANSSEN CILAG, AMGEN, ROCHE, GSK, NOVARTIS, MERCK, CEPHALON: Honoraria, Research Funding.

Allogeneic Hematopoietic Stem Cell Transplantation with Clofarabine/Busulfan × 4 (CloBu4) Conditioning Exhibits Significant Anti-Tumor Activity In Non - Remission Hematologic Malignancies, Especially In AML

AbstractAbstract 35Patients with hematologic malignancies who are not in remission prior to allogeneic hematopoietic stem cell transplantation (HSCT) have a poor prognosis. In an effort to improve the anti-tumor activity of conditioning without added toxicity, we combined clofarabine, which is known to have a significant anti-leukemia activity, with myeloablative doses of busulfan in a phase I/II study in non-remission hematologic malignancies. Busulfan was administered as a single daily dose of 3.2 mg/kg IV × 4d (days -5 to -2) and clofarabine as a single daily dose of 20, 30 or 40 mg/m2 IV × 5d (days -6 to -2) with the specific dose determined by the Time to Event-Continuous Reassessment Method (TITE-CRM). All pts received dexamethasone 12 mg IV on the days of clofarabine to prevent capillary leak syndrome. Graft-versus-host-disease (GVHD) prophylaxis was tacrolimus/MMF in all but one patient (tacrolimus/methotrexate).Forty six pts were enrolled. Characteristics of pts are shown in table 1. Prior to HSCT, pts failed an average of 3 regimens (range: 1–5), none were in remission, and 68% of leukemic pts had peripheral blasts. The majority received unrelated and / or HLA mismatched grafts. CloBu4 was generally well tolerated. Grade 3–4 non-hematological toxicities observed from initiation of conditioning to day +30 include: transient transaminitis (50%), mucositis (26%), hand-foot syndrome (13%), transient hypoxia (13%), nausea/vomiting (11%), diarrhea (11%), hypertension (7%), veno-occlusive disease (4%), hyperbilirubinemia (4%), hypersensitivity (2%), joint pain (2%) and seizure (2%). There were no cases of renal insufficiency and all cases of transaminitis resolved to ≤grade 1 within 14 days. All patients engrafted (median 11 days for neutrophils [range: 9–16]; 10 days for platelets [range: 1–20]. Lineage specific chimerism was analyzed at day 30, 100, 180, and 365. Full donor chimerism in CD3 lineage was achieved in 54%, 75%, 94% and 100% of pts on days 30, 100, 180 and 365, respectively. Absolute CD4 counts were 228±170, 238±147 307±151, and 341±184 cells/μ l on days 30, 100, 180, and 365, respectively. Acute GVHD (≥ grade 2) occurred in 48% of pts and resulted in five deaths. Overall, 80% of pts achieved CR by day +30 (AML = 94%, Others = 53%, AML without prior allo HSCT = 100%). Cumulative incidence of relapse in AML patients was 38%. The median duration of remission for AML pts was 15.4 months (range 2–34 m). Non-AML pts experienced a higher incidence of relapse/progression (67%, p=0.008) and shorter remissions (8.6 m, range 2–29 m). At a median follow up of 18 months, overall survival for the entire cohort was 42% at 18 months post-transplant (50% for AML, n=31). In conclusion, these data suggest that clofarabine combined with myeloablative doses of busulfan is well tolerated, facilitates engraftment, and has significant anti-tumor activity, particularly in patients with non-remission AML at HSCT. Given that CloBu4 reliably led to remissions that lasted a median of 15.4 months in non-remission AML pts, this regimen may provide a platform for further interventions such as maintenance therapy for this population of pts. [Display omitted] [Display omitted] Disclosures:Mineishi:Genzyme: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding. Off Label Use: Clofarabine use for transplant conditioning regimen. Erba:Genzyme: Consultancy, Honoraria, Research Funding.

Temsirolimus, An mTOR Inhibitor, In Combination with Low-Dose Clofarabine in Older Patients with Advanced Acute Myeloid Leukemia: Results of a Phase 2 GIMEMA Study (AML-1107)

AbstractAbstract 510 Background:Elderly patients with refractory or relapsed AML have a dismal prognosis and new treatments are needed for these patients.The PI3K/AKT signaling pathway is frequently dysregulated in AML and contributes to cell proliferation and survival through activation of the mTOR kinase and its downstream effectors. mTOR inhibition with Sirolimus or its analogs, such as Temsirolimus, has been associated with clinical responses in AML and may enhance the sensitivity of leukemic cells to cytotoxics. Clofarabine is a second-generation nucleoside analog with activity in AML. Based on this, a multicenter, phase 2, open label, two-stage study was conducted to assess the efficacy and safety of Temsirolimus in combination with low-dose Clofarabine as salvage therapy for older pts with AML. Methods:Eligible were pts older than 60 years of age with first relapse or primary refractory AML. Induction consisted of a single course of Clofarabine 20 mg/m2 iv d 1–5 and Temsirolimus 25 mg (flat dose) iv d 1, 8 and 15; a second course was allowed in pts achieving PR. Pts entering CR/CRi receive up to 12 monthly courses of maintenance with Temsirolimus (25 mg iv d 1 and 8 per course). The primary endpoint was complete remission with (CR) or without (CRi) hematopoietic recovery; secondary endpoints were overall survival, disease-free survival and toxicity. Pre and post-therapy bone marrow samples were obtained from a subset of pts to assess biomarkers. Results:Accrual began April 2009 and was completed in June 2010. To date, 52 of 54 enrolled pts are evaluable for response and toxicity (1 too early; 1 died pre-therapy): median age 70 yrs (range 60–78); 58% males; 17 pts with primary refractory AML; 35 pts with AML in first relapse (duration of CR1 < 6 mos 34%, ≥ 6 mos 66%); cytogenetics (MRC criteria): favorable in 4, intermediate in 37, adverse in 6, and unavailable in 5 pts. In all, 11 pts (21%; 95% CI 11–35%) have achieved CR (n=4) or CRi (n=7); 1 achieved PR; 7 (13%) died within 30 days of induction therapy (3 from infection, 3 from disease progression, 1 from cerebrovascular accident); 33 were resistant. CR or CRi was achieved in 9/35 pts (26%) in first relapse, and 2/17 (12%) with primary refractory disease. CR+CRi rates among: age < 70 and ≥ 70, 19% and 25%; first CR duration shorter and longer than 6 mos, 17% and 30%; favorable, intermediate, adverse and unknown cytogenetics, 50%, 22%, 0% and 20%. The median duration of remission for the 11 responders was 3.5 mos; 7 pts have relapsed to date and 4 (2 CR, 2 CRi) are currently maintaining a response at 2+, 4+, 11+ and 12+ mos from remission. With a median follow-up of 5 mos (range 0.3–14), the median overall survival for the entire population was 4.3 mos, and for responders 7.6 mos. Besides myelosuppression, most common grade 3–4 adverse events included infection (48%), febrile neutropenia (35%), transaminase elevation (11%), nausea and vomiting (8%), and fatigue (8%). Median times to recovery of neutrophils to 500/cmm and platelets to 50,000/cmm in responders were 28 and 32 days, respectively. Inhibition of phospho-S6RP, a downstream effector of mTOR, was documented in 12/21 (57%) pts analysed, and correlated with an improved rate of clinical response: 7/12 (58%) responded vs 0/9 pts with no detectable target inhibition. Conclusion:These data indicate that a regimen combining Temsirolimus with low-dose Clofarabine can be safely administered to elderly pts with advanced AML. Encouraging anti-leukemic activity was recorded in this difficult-to-treat patient population, particularly in pts showing evidence of an on-target effect on mTOR signaling. Further investigation of this novel regimen as front-line therapy in older pts with AML considered unsuitable for intensive chemotherapy is planned. Disclosures:Off Label Use: Clinical trial investigating Clofarabine and Temsirolimus in patients with acute myeloid leukemia.

Multiple Extranodal Involvements; Significant Risk Factor of Relapse In Peripheral T-Cell Lymphoma, Not Otherwise Specified

AbstractAbstract 4887 Background:Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) comprises clinically and histopathologically a heterogeneous group of predominantly nodal diseases which do not fit into definition of any other identified subtype of PTCLs. Most of cases are advanced diseases and characterized by aggressive behavior and very poor prognosis. Although several risk factors for response and survival in PTCL-NOS have been reported, little information is available for the incidence and risk factors of relapse after complete response (CR) achievement. Further analyses of the relapse will give valuable information for effective therapeutic strategies for PTCL-NOS. The aim of this study is to evaluate the incidence and risk factors of the relapse in PTCL-NOS patients. Methods:We retrospectively reviewed 107 patients with PTCL-NOS diagnosed by The 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in Hokkaido Hematology Study Group, which includes 30 hematology/oncology or pediatrics departments of 23 institutes, from January 2002 to December 2009. We further investigated the incidence, clinical backgrounds, and risk factors of relapse of the PTCL-NOS patients. Response to treatment was assessed by international workshop to standardize response criteria for non-Hodgkin's lymphomas (Cheson BD et al. J Clin Oncol. 1999). Overall survival (OS) curves were estimated using Kaplan-Meier method and compared by log-rank test. The association between clinical factors and relapse rate was evaluated in univariate analysis by the chi-squared test. Factors independently associated with relapse or OS were identified in multivariate analysis by logistic regression model or Cox proportional hazards model, respectively. Results:The median follow-up of the patients was 24 months (range 1–95). The sample population included 70 males and 37 females with a median age of 67 years (range 9–94). Chemotherapy (ChT) was selected in 90% (96/107) patients as the primary treatment. CHOP-lile regemens were chosen in 91% (86/96) patients as the primary ChT. The estimated 5 year-OS of all the patients was 35%. 48 (52%) patients achieved CR after primary treatment in the evaluable 92 patients, and were futher analyzed. Relapse was occured in 46% (22/48) patients with a median remission duration of 9 months (range 2–51). Multiple or diffuse extranodal relapses were presented in 64% (14/22) patients. Only 5 (24%) paitients achived 2nd CR in the 21 relapsed patients recived salvage ChT. Survaval of patients with relapse was significantly shorter than that without relapse (5 year-estimated OS 32% vs 100%, p<0.0001). Factors of high relapse rates at diagnosis were as follows; central nervous system involvement (100%), extranodal involvement sites>1 (87%), gastrointestinal involvement (80%), bulky disease (67%), bone marrow (BM) involvement (67%), high (H) and high-intermediate (HI) risk groups of International Prognositic Index (IPI) (63%). In addition, relapse rate of the patients showing FDG-uptake by PET after primary treatment was 100%. In univariate analysis, extranodal involvement sites at diagnosis >1 (p=0.022), H and HI risk groups of IPI at diagnosis (p=0.021), FDG-uptake by PET after primary treatment (p=0.043) were identified as risk factors of relapse. Age, clinical stage, B-sympton, perfomance status, BM imvolvement, bulky disease, high LDH level, risk groups of prognositic index for PTCL-U (PIT), and regemen or dose-reduction of primary treatment were not significant indicators for relapse in univariate analysis. In multivariate analysis, extranodal involvement sites at diagnosis >1 was identified as an independent risk factor not only for relapse (relative risk 26.0; 95% CI 1.115–605.9; p=0.043) but also for OS (relative risk 10.8; 95% CI 1.1466–80.13; p=0.02). Conclusions:Almost half of PTCL-NOS patients who achieved CR after primary treatment will relapse and the prognosis is poor. Multiple extranodal involvements at diagnosis will be a predictive factor of relapse and survival. These findings warrant further studies regarding specific treatment approaches for PTCL-NOS patients with multiple extranodal involvements to inhibit the relapse. Disclosures:No relevant conflicts of interest to declare.

Treatment of Feline Gastrointestinal Small-Cell Lymphoma With Chlorambucil and Glucocorticoids

Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease-all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy.

Clinical and genetic predictors of response to narrowband ultraviolet B for the treatment of chronic plaque psoriasis

There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index (P = 0·004), lower baseline Dermatology Life Quality Index (P = 0·047), female sex (P = 0·043), lower body weight (P = 0·008), and a higher number of previous courses of TL-01 (P = 0·005). The only clinical factor influencing remission duration was number of exposures (P = 0·0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration (P = 0·038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele (P = 0·026) and those homozygous for the T allele (P = 0·013). This study highlights the fact that both genetic and clinical parameters are important in determining treatment outcomes in psoriasis.

Bortezomib-based regimen for the treatment of 110 multiple myeloma patients

To analyze the outcomes and adverse effects of bortezomib-based regimen for the treatment of multiple myeloma (MM) patients. A total of 110 MM patients were treated with a bortezomib-based regimen at our hospital from January 2006 to February 2010. The patients over 65 years old received bortezomib-prednisone ± thalidomide (PD±T) regimen or velcade-melphalan-prednisone (VMP) regimen therapy and the patients under 65 years old or resistant to PD±T regimen received bortezomib-doxorubicin-prednisone ± thalidomide (PAD±T) regimen therapy. The outcomes and adverse effects of bortezomib-based regimen were retrospectively evaluated. There were 47 newly-diagnosed MM patients and 63 relapsing/refractory MM patients. The overall remission (OR) rate was 76.4% (84/110) and the OR rate of newly-diagnosed MM patients was statistically higher than that of relapsing/refractory MM patients (83.0% vs 71.4%, P<0.05). The complete remission (CR)+very good partial remission (VGPR) rate in group bortezomib 1.0 mg/m2 was lower than that in group bortezomib 1.3 mg/m2 (newly-diagnosed 53.6% vs 73.7%, relapsing/refractory 28.9% vs 40.0%, both P<0.05). The OR rate of ISS III stage patients was as better as that of ISS I and II stage patients (newly-diagnosed 82.1% vs 83.6%, relapsing/refractory 69.2% vs 72.2%, both P>0.05). Thirteen newly-diagnosed MM patients underwent autologous stem cell transplantation (ASCT) after induced therapy and achieved a VGPR or above. The median follow-up time was 13.0 (6.0-20.0) months. Their conditions were stable except two patients with extramedullary plasmacytoma after ASCT. Thirteen relapsing/refractory MM patients were retreated with a bortezomib-based regimen. The CR rate was 15.4% (2/13), VGPR rate was 23.1% (3/13), partial remission (PR) rate was 23.1% (3/13), OR rate 61.5% (8/13) and the median duration of remission (DOR) was 6.7 (3.0-21.0) months. Six MM patients with extramedullary plasmacytoma were treated with a bortezomib-based regimen and all of them achieved a PR or above. The median DOR was 4.5 (2.0-10.0) months. The main adverse effects were peripheral neuropathy, thrombocytopenia, neutropenia, fatigue, gastrointestinal symptoms, anemia, etc. The bortezomib-based combination regimen is the front-line therapy for newly-diagnosed and relapsing/refractory MM patients.

Predictors of Clinical Remission in Cats with Diabetes Mellitus

Clinical remission is frequent in cats with well-controlled diabetes mellitus, but few studies explored predictors of this phenomenon. Data retrieved from medical records at admission might be valuable to identify likelihood of remission and its duration in diabetic cats. Ninety cats with newly diagnosed diabetes, followed-up until death or remission. Retrospective cohort study. Data were collected from records at admission, including history, signalment, physical examination, haematology, and biochemical profile, and the occurrence and duration of remission, defined as normoglycemia without insulin for ≥4 weeks. Predictors of remission were studied with univariate and multivariate logistic regression. Factors associated with remission duration were analyzed with Kaplan-Meier and Cox proportional hazard models. Forty-five (50%) cats achieved remission, after a median time of 48 days (range: 8-216). By study end, median remission duration was 114 days (range: 30-3,370) in cats that died and 151 days (range: 28-1,180) in alive cats. Remission was more likely with higher age (OR: 1.23, 95% CI: 1.04-1.46; P=.01) and less likely with increased serum cholesterol (OR: 0.36, 95% CI: 0.11-0.87; P=.04). Remission was longer with higher body weight (HR: 0.65, 95% CI: 0.42-0.99; P=.04) and shorter with higher blood glucose (HR: 1.01, 95% CI: 1.00-1.02; P=.02). Age, body weight, cholesterol, and glucose levels are suggested for prediction of remission or its duration in diabetic cats. Older cats developing diabetes may have a better outcome, possibly suggesting a slower disease progression.

CHEMOTHERAPY FOLLOWED BY ABDOMINAL CAVITY IRRADIATION FOR FELINE LYMPHOBLASTIC LYMPHOMA

Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6-week combination chemotherapy protocol followed 2 weeks later by whole-abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, > 266 to > 1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.

Unfavorable prognosis of acute leukemia in infancy

Pretreatment characteristics of 48 infants (under 2 years of age) with leukemia treated over a period of 18 years at a single institution were studied in relation to response to therapy, extramedullary involvement, and survival. In order to provide a basis of comparison, 45 of the infants were each paired with an older (2–9 years of age) leukemic child, who had the same race, and disease type, who was treated within the same period of time and received similar suportive care and chemotherapy, and when possible, was of the same sex. The overall median survival times of infants and their pairmates were 211 days and 445 days, respectively. Initial status of the spleen was the single significant factor in relation to the length of survival. Median survival time for infants with splenomegaly was 186 days compared to a median survival time of 414 days for infants without splenomegaly. The complete response rate was 75% for infants and 80% for the pairmates. Median duration of remission was 84 days for infants and 280 days for their pairmates. Initial peripheral leucocyte count was significantly related to the duration of remission; patients with very high leucocyte counts had the shortest remissions. The duration of remission increased throughout the period covered by this study, however, prognosis relative to pairmates remained poor. Central nervous system leukemia occurred in 44% of infants and 40% of the pairmates; incidence of CNS leukemia was much higher (70%) in infants under one year of age than in infants one year old (37%). Extramedullary leukemia occurred at other sites in 46% of the infants and 31% of the pairmates. The only pretreatment characteristic of prognostic importance for predicting extramedullary involvement was the patient's age at diagnosis.

Initial features and prognosis in 363 children with acute lymphocytic leukemia

The relationship of a variety of initial features and the outcome of therapy was analyzed for 363 children with acute lymphocytic leukemia (ALL). All had entered “total therapy” studies between 1962 and 1971. The standard for comparing outcome of therapy was whether patients with a given feature attained or exceeded the median duration of complete remission, hematologic remission or survival for the group. The results showed that, in general, the more massive or extensive the disease at diagnosis, the poorer the outcome. Factors associated with a significantly poorer prognosis included: initial leukocyte count above 100,000/mm3; spleen enlargement greater than 5 cm; me–diastinal involvement and early CNS involvement. Children over 10 years old at diagnosis and Negro children also had a poor prognosis. From another viewpoint features were examined for patients who attained at least 3 years of continuous complete remission. This confirmed some earlier findings and, in addition, showed that children under 2 years of age at diagnosis or with hepatomegaly over 5 cm were less likely to attain this goal. With the exception of early CNS involvement, however, patients with excellent responses to therapy were found with each factor of poor prognosis. Two major factors were not analyzed because their relationship to prognosis is generally accepted: therapeutic differences and acute nonlymphocytic leukemia.

Voreloxin single-agent treatment of older patients (60 years or older) with previously untreated acute myeloid leukemia: Final results from a phase II study with three schedules.

6525 Background: Voreloxin, an anticancer quinolone derivative that inhibits topoisomerase II, has demonstrated clinical activity in ovarian cancer and acute myeloid leukemia (AML). Final results are reported from this phase II study (n = 113). Methods: Eligible patients had AML (WHO subtype, except APL) considered unlikely to benefit from standard induction therapy, with ≥ 1 adverse risk factor: age ≥ 70, secondary AML, intermediate (I) or unfavorable (U) cytogenetics, or PS = 2. Voreloxin was administered by short (≤ 10 min) IV infusion in 3 dosing schedules: A, weekly (qwk)×3 (days [d] 1, 8, 15) at 72 mg/m2 (n = 29); B, qwk×2 (d 1, 8) at 72 mg/m2 (n = 35); and C, twice weekly (biw)×1 (d 1, 4) at 72 (n = 29; C72) or 90 mg/m2 (n = 20; C90) for up to 4 cycles. Results: Median age was 74 years, most patients were male with an ECOG PS 0 or 1, and cytogenetics were I (46%) or U (42%) per 2010 NCCN guidelines. The overall remission rate (ORR = CR+CRp [complete remission + CR with incomplete platelet recovery]) across all doses and schedules was 34% (range, 25-41%) and 74% of CR were in first cycle. Reinduction resulted in CR(p) for 35% of those reinduced. By schedule, ORR was 41% for A, 29% for B, 38% for C72, and 25% for C90. No dose response was observed between C72 and C90. All-cause mortality rates were lowest in C72 (7% at 30 days, 17% at 60 days) compared with A, B, and C90. Median duration of remission (DR) was 10.7 months (mo) for A (median too early to evaluate [TETE] for B, C72, or C90). Median overall survival (OS) was 8.7 mo (A), 5.8 mo (B), 7.3 mo (C72, preliminary); C90 is TETE. One-year OS was 38% for A and TETE for other schedules. Across all schedules, the most common nonhematologic adverse events grade ≥ 3 were febrile neutropenia (49%) and infections: pneumonia (28%) and sepsis/bacteremia (28%). Overall safety profile was more acceptable for C72 than for A and appeared further improved over B. ORR was 30% for patients ≥ 75 years. Conclusions: Voreloxin induced durable remissions in 3 dosing schedules. Schedules B and C maintained activity and improved tolerability over A. Schedule C72 is appropriate for further development based on ORR, all-cause mortality, and safety profile. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sunesis Pharmaceuticals Sunesis Pharmaceuticals Sunesis Pharmaceuticals

Individual Approach In Treatment Of Advanced Stomach Cancer

Background: To study efficiency of the combined treatment of advanced gastric cancer with inclusion Trastuzumab.Material: We present the intermediate analysis of the use of target therapy with Trastuzumab in patients with a HER2-positive gastric cancer. Up to 01.10.2009y 118 patients have been tested for HER-2 expression, and in 24 gastric cancer patients it is revealed HER2-positive status of tumor. It is lead chemotherapy to all patients by the PLF regimen and Herceptin in doze 6 mg/kg once in 3 weeks (6 cycles). In control group in 26 patients it is lead only chemotherapy by the PLF regimen once in 3 weeks without addition Trastuzumab (6 cycles).Results: At the moment of the analysis of preliminary data, the median remission duration in compared groups has made 8.3 months, and 5.2 months, accordingly.Conclusion: At advanced gastric cancer with high level HER-2 expression Trastuzumab increases frequency of objective effect and the median remission duration.

Phase II Study of Clofarabine Monotherapy in Previously Untreated Older Adults With Acute Myeloid Leukemia and Unfavorable Prognostic Factors

This phase II study assessed clofarabine monotherapy in older adults (>or= 60 years of age) with untreated acute myeloid leukemia (AML) and at least one unfavorable baseline prognostic factor. Clofarabine was administered intravenously for 5 days at 30 mg/m(2)/d during induction and 20 mg/m(2)/d during reinduction/consolidation (six cycles maximum). The primary end point was overall remission rate (ORR; ie, complete remission [CR] plus CR with incomplete platelet recovery [CRp]). In 112 evaluable patients who were treated (median age, 71 years; range, 60 to 88 years), the ORR was 46% (38% CR, 8% CRp). ORR by unfavorable prognostic factor was 39% for patients >or= 70 years of age; 32% for Eastern Cooperative Oncology Group (ECOG) performance status 2; 51% for antecedent hematologic disorder; 54% for intermediate karyotype; 42% for unfavorable karyotype; and 48%, 51%, and 38% for one, two, and three risk factors, respectively. The median disease-free survival was 37 weeks (95% CI, 26 to 56 weeks). Median duration of remission was 56 weeks (95% CI, 33 to not estimable). The estimated median overall survival was 41 weeks (95% CI, 28 to 53 weeks) for all patients, 59 weeks for patients with CR/CRp, and 72 weeks for patients with CR. The 30-day all-cause mortality was 9.8%. The most common non-laboratory drug-related toxicities (>or= 20% patients) were nausea, febrile neutropenia, vomiting, diarrhea, rash, and fatigue. Clofarabine is an active agent with acceptable toxicity in patients age 60 years or older with untreated AML who have at least one unfavorable prognostic factor. ORR did not seem affected by the presence of multiple unfavorable prognostic factors.