1779 Introduction: Tumor Lysis Syndrome (TLS) is an oncologic emergency that leads to a host of metabolic disturbances which can ultimately result in acute renal failure and death. Currently rasburicase, Elitek™, is FDA approved for the treatment of TLS in patients with leukemia, lymphoma, and solid tumor malignancies which have risk factors for TLS. The approved adult dose is 0.2mg/kg/day over 30 minutes for up to 5 days. Chemotherapy should be initiated within 24 hours of rasburicase administration. Since rasburicase's introduction to the market, various studies have examined single dose use (3mg and 6mg) in the adult population, trying to resolve the dilemma of determining a dosing regimen for adults that is as effective as the FDA approved dosing regimen, while minimizing cost. This study was aimed at determining if a single 4.5mg dose of rasburicase would be adequate in reducing uric acid levels (UAL) as compared to the FDA approved conventional weight based approach; it also sought to determine the cost-effectiveness of this approach. Method: This is a retrospective study of the John H. Stroger Jr. Hospital of Cook County (JHS) patients who were administered a single dose of 4.5 mg rasburicase for TLS from 12/2007 to 06/2010. We included patients ≥ 18 years old, with a hematologic malignancy and on chemotherapy or about to start receiving chemotherapy within 24 hours of rasburicase administration. Patients with low risk for TLS or an indication other than prevention and management of TLS were excluded. Result: Demographics: Characteristics: Responders are defined as patients that achieved more than 50% reduction in the UAL at 24 hours, 48 hours or 96 hours or a decrease of UAL to normal levels. Two patients required a second dose to achieve response. The non-responders did not receive any additional doses for unclear reasons. No adverse events were noted. Conclusion: This retrospective study provides evidence that a single 4.5mg dose of rasburicase effectively reduced plasma UAL to within normal limits. In addition, decrease in plasma UAL was observed within 24 hours after administration. No effect on electrolytes and serum creatinine was noted. The cost-effectiveness of a single 4.5mg dose of rasburicase was evaluated based on dose and drug cost. The potential cost saving was substantial when compared with the FDA approved dose. In our opinion, this study validates the use of a single dose of 4.5mg rasburicase in the treatment and prophylaxis of TLS. This dose can be considered as a possible alternative to the FDA approved adult dosing regimen. Disclosures: No relevant conflicts of interest to declare.
Introduction Studies of EBV positive (+) and negative (-) classical Hodgkin lymphoma (cHL) have shown the importance of the immune microenvironment in affecting Reed-Sternberg (hRS) cell survival, proliferation, and biologic behavior. For example, macrophage infiltrates may correlate with inferior disease outcome and survival and proliferation of the hRS cells depends on trophic signals from various inflammatory cells, including CD4+ T cells. The latter finding may explain why HIV-cHL patients (pts) usually present with higher circulating CD4+ T-cell counts (cCD4) compared to HIV-related non-Hodgkin lymphoma. Pathobiologically, HIV-cHL differs from HIV negative cHL (cHL) in that it is nearly always EBV+, has higher numbers of hRS cells, presents with more advanced median stage, exhibits more commonly the mixed cellularity (MC) pattern, and some studies suggest it is more clinically aggressive. To investigate the microenvironment of HIV-cHL and its influence on cHL biology, we assessed the immune cell composition and clinical characteristics of HIV-cHL and compared the findings to those of EBV+ and EBV- cHLs. Methods 31 HIV-cHL and 40 cHL (8 EBV+/32 EBV-) cases were identified and corresponding tissue microarrays (TMAs) created. TMAs were evaluated for EBV (EBER), CD30, and microenvironment-associated antigens: PAX5, CD3, CD4, CD8, CD68, CD163 (% positive), TIA1, FOXP3 (relative number 0-4+); the hRS-macrophage microenvironment was evaluated by assessing the number of hRS where >50% of the circumference of the neoplastic cell was associated with CD68+ cells. Results were compared based on HIV status, EBV status (in HIV negative pts), demographics, cCD4 and histology; each was correlated with overall survival. Analyses were performed using non-parametric Fisher's exact test, Kaplan-Meier method and Cox Proportional Hazards model. Results M:F ratio was 9:1 in the HIV group vs. 1.3:1 in the HIV negative pts (p <0.001). The median cCD4 in the HIV+ pts at HIV-cHL diagnosis was 248 cells/mm3. No differences in age, stage, B symptoms, bulky disease, IPS score, and hRS concentration were found between HIV+ and HIV negative cHLs pts. 7% of cHLs and 33% of HIV-cHLs were classified as MC (p<0.01). 90% of HIV-cHLs were EBV+ compared to 20% of the cHL cases. Statistically significant differences were seen in the number of CD4+ and CD8+ cells between the EBV+ and EBV- cHLs irrespective of HIV status. The only difference among all the immune microenvironment markers observed between EBV+ HIV-cHL and EBV+ cHL cases was that of peri-hRS CD68 cells, which were more abundant in the EBV+ HIV-cHL (Table 1; 51% vs. 30% p<0.005). Similar differences in peri-hRS CD68 staining were observed between the HIV-cHL and all cHL pts. The only deaths in HIV-cHL pts occurred when CD68 was >15% (p<0.05). No statistical differences were noted for OS with respect to cCD4, histologic subtype, race, gender, or HIV status. Conclusions No significant differences were observed between HIV-cHL and cHL pts with respect to stage, B symptoms, bulky disease, IPS score, or overall survival, but there were more MC cases in the HIV-cHL cohort. The microenvironment of HIV-cHL and EBV+ cHL is similar, but different from EBV- cHL with respect to percentages of CD163+, PAX5+, CD4+ and CD8+ cells. The location of CD68+ macrophages was the only discordant result between the EBV+ HIV-cHL and EBV+ cHL cohorts. The differences in location of the CD68+ cells, which may be dependent on HIV status, suggests greater influence of these cells on the biologic behavior of the neoplastic process, correlating with poor survival. However, the similarity in the microenvironments in HIV-cHL and EBV+ cHL with respect to CD4, CD8, and CD163 staining implies an important role for EBV on disease biology, as well. Thus, these data suggest that EBV as well as HIV, play prominent roles in determining the immune response and disease behavior in HIV-cHL, warranting further study Disclosures: No relevant conflicts of interest to declare.
Background: Idiopathic Thrombocytopenic Purpura (ITP) is a common hematological disorder. We sort to characterize the risk profiles and efficacy of rituximab in relapsed or refractory ITP in a largely minority cohort. Methods: 23 patients (pts) with relapsed or refractory ITP treated with Rituximab were identified and studied as a retrospective cohort. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student’s T test, categorical data via Fisher’s exact test and time to progression data was analyzed via Kaplan Meier life table analysis and log rank test. Results: Of the 23 patients, 20 female (87%), 3 male (13%). median age at diagnosis was 45 yr (range 20–66).9 pt were African American (39%), 9 Hispanics (39%), 4 Asian (17.4%), 1 Caucasian(4.3%), 9 (39.6%) had more than one co morbidities, 17 (73.8%) had received 3 or more treatment regimens. All pt received steroids, 18 (78.3%) received IVIg, 13 (56.6%) Anti D immunoglobulin, 5 (21.7%) Vincristine, 3 (13%) Azathioprine, 2(8.7%) Cyclophosamide, 6 (26.1%) underwent a Splenectomy before Rituximab therapy. The median time from diagnosis to rituximab therapy was 15 months (range 1 to 269). Median platelet count before rituximab therapy was 11 (range 3 to 200). Rituximab was administered at the dose of 375mg/m2 IV once a week for 4 weeks. The response rate was 47.8%. Response was defined as Complete response, platelet count of > 100 × 109/L, Partial response >50 × 109/L. 9 pt (39%) achieved complete response, 2 pt (8.7%) achieved partial response. 12 pt (52.2%) did not respond. Median time to response was 13.5 days (range 1–30). There was no statistically significant difference in the response when compared by gender (p=0.64), race (p= 0.398), prior splenectomy (p=0.64), prior anti D immunoglobulin (p=1.0), prior Vincristine (p=1.0), prior cyclophosamide (p=.45), prior azathioprine (p=1.0). Four pt (17.4%) had a serious adverse reaction to rituximab. One pt had diffuse hives after infusion, three pt developed diffuse pancytopenia, two pts had gram negative sepsis and died. The median follow up after rituximab therapy was 18 months (range 1–60). The median time to relapse was 7 months (range of 1 to 59). There was no statistically significant difference in time to relapse among gender (p=0.19), race (p= 0.45), Prior splenectomy (p=0.86), prior Anti D immunoglobulin (p=0.32), prior vincristine (p=0.75). Conclusion: In this primarily minority based cohort the response rate to Rituximab (48% vs. 62%) and duration of response (7 months vs. 10.5 months) was lower than other published data but the rate of serious adverse events (17% vs. 7%) was higher. Rituximab must be used cautiously in this sub group of patients. There is need for a randomized controlled clinical trail to assess the efficacy of Rituximab in this population and further studies are warranted in minority populations.
Introduction: Imatinib (STI571/ Gleevec) is a tyrosine kinase inhibitor that functions by blocking the binding of ATP to the bcr-abl tyrosine kinase, inhibiting its activity and preventing myeloid proliferation, a characteristic of CML. We report our experience with imatinib use in a minority patient population. Methods: Data from 67 patients (pts) with CML treated at Cook County Hospital, Chicago, Illinois over a 4 year period were collected. Demographics, presentation, dosage schedule, tolerability and response were analyzed. Continuous data were analyzed via Student’s T test and categorical data via Fisher’s Exact test. Results: 57 pts with complete data [mean age at diagnosis 42.8 yrs, range 19–72 yrs, 46 (80.7%) males and 11 (19.3%) females] were identified and analyzed as a retrospective cohort. 41 pts (71.9%) were between 30 and 60 yrs of age and 17 pts (29.8%) had ≥ 1 major comorbidity at presentation. 28 (49.1%) were African American (AA), 4 (7%) Asian, 5 (8.8%) Eastern European, 17 (29.8%) Hispanic, and 3 (5.3%) Middle Eastern. 50 pts (87.7%) were in chronic phase, 5 (8.8%) in accelerated phase, 2 (3.5%) in blast phase, 2 (3.5%) had granulocytic sarcomas and 5 pts (8.8%) had second malignancies at presentation. 54 pts (94.7%) were started on 400mg of imatinib. 19 pts (33.3%) had imatinib-related toxicities including skin rash, cytopenias and nausea. 17 pts (29.8%) were non-compliant with imatinib therapy. AA pts were as old as the non-AA pts [44.8 ± 12.6 yrs vs 40.9 ± 13.8 yrs, p 0.27]. Non-AA pts were predominantly male. Following imatinib therapy a hematologic response (HR) was noted in 45.7± 54.6 days (d) in AA vs 31.3 ± 23.9 d in non-AA (p= 0.27), a major cytogenetic response (MCR) in 351 ± 342.6 d in AA pts vs 289±132.7 d in non-AA (p=0.58) and a complete cytogenetic response in 664±265.1 d in AA vs 642±292.5 d in non-AA pts (p=0.87). 11 AA pts failed imatinib therapy vs 8 non-AA pts. These pts were then subjected to imatinib dose escalation (600mg or 800mg) with only 4 pts in the AA group attaining MCR and 1 pt in the non-AA group attaining CCR. 4 AA pts then received Dasatanib and 2 went on to Allogeneic Stem Cell Transplant (ASCT) and 3 pts in the non-AA group received Nillotinib or Dasatanib and 2 went on to ASCT. There were 3 deaths in the AA group vs 1 in the non-AA group. Conclusion: In this primarily minority-based cohort there appears to be no significant difference in the age or gender distribution of the AA or non-AA pts although there appeared to be a male preponderance amongst the non-AA pts. The ethnic background does not appear to affect the time to significant hematologic response, major cytogenetic response or complete cytogenetic response to imatinib therapy in the AA or non-AA pts. Since the number of patients is small, definitive conclusions in either cohort cannot be made. Further investigation in minority patients is warranted.
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