No abstract

Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS.

9085 Background: Capecitabine is an oral fluoropyrimidine that is used to treat various malignancies. Hand and Foot Syndrome (HFS) is a dose limiting toxicity of capecitabine and can limit the use of this agent in some patients. Some investigators have observed that pyridoxine (vitamin B6) can ameliorate HFS caused by capecitabine. We designed a prospective trial to determine if pyridoxine can prevent HFS in patients receiving capecitabine. Methods: In our double-blind, placebo controlled trial, we randomly assigned eligible patients treated with capecitabine to receive either daily pyridoxine 100 mg or placebo along with their capecitabine-containing chemotherapy regimen. Patients were observed during the first four cycles of capecitabine treatment. The primary end point was the incidence and grade of HFS that occurred in both arms. Results: Between 2008 and 2011, 77 patients were randomly assigned to receive either pyridoxine (n=38) or placebo (n=39). Both arms were matched in baseline characteristics. The median age was 53.5 years. The ethnic composition of the study population was African American 53%, Caucasian 22%, Hispanic 18%, and Asian 7%. The daily doses of capecitabine were: 2000 mg/m2 (69 pts), 1650 mg/m2 (5 pts), 1400 mg/m2 (2 pts) and 1000 mg/m2 (1 pt). Dosages of capecitabine were equally matched between the two arms of the study. HFS occurred after a median of 2 chemotherapy cycles in both groups. HFS developed in 10/38 (26%) patients in the pyridoxine group and in 8/39 (20%) patients in the placebo group (p=0.547). Therefore, the risk of HFS was 6 percentage points higher in pyridoxine group (95% CI for difference: -13 percentage points to +25 percentage points). Given our study results, we can be confident of excluding a true benefit from pyridoxine larger than 13 percentage points. No difference in HFS grades was observed. Conclusions: Prophylactic pyridoxine (vitamin B6), given concomitantly with capecitabine-containing chemotherapy, was not effective for the prevention of HFS. [Table: see text]

2807 Background: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) are the most common non-HIV-defining and HIV-defining malignancies, respectively1. Patients (pts) treated for lymphoma concomitantly with highly active retroviral therapy (HAART) have much better response rates and overall survival2. However, few studies have assessed the impact of HAART on the adverse events of chemotherapy. The Stanford V regimen for HL has a 48 % increase in neurotoxicity and neutropenia when taken concomitantly with HAART compared to non-HIV patients3. Case reports exist associating gastrointestinal and neurotoxicity with vinblastine (less so vincristine) and ritonavir-based HIV therapy. Unfortunately, the frequency of this association has yet to be shown. We retrospectively analyzed pts at our institution with lymphomas and HIV and the relationship between HAART and chemotherapy adverse events (AE) in an attempt to minimize future chemotherapy-related complications. Methods: We retrospectively identified HIV infected patients treated for lymphoma (2002-2008) at Stroger Hospital of Cook County by computer database search using ICD9 and pharmacy codes and then confirmed by medical record review. The adverse events during chemotherapy were assessed by chart review and graded per the NCI Common Terminology Criteria for Adverse Events. Those pts where HAART or chemotherapy regimen could not be confirmed were excluded from the study. Patient, disease, and the HIV characteristics were assessed. Statistics: A non-parametric Fisher's exact test was used to examine the difference in proportion of patients that developed an adverse event in the pts with a particular HAART medication and the ones without. Results: Twenty-five HIV infected pts with HL and 46 pts with NHL were identified. Identification of HAART administered during chemotherapy was found in 23/25 (92%) pts with HL and 22/46 (48%) pts with NHL. Patients diagnosed with HL were 87% male with a median age of 43. Mixed cellularity (26%) and nodular sclerosis (26%) pathologies were the most common with 60% (14/23 pts) presenting as stage III/IV disease. The median CD4 count at diagnosis was 174 cell/ml with a range of 26–341. The most common HAART regimen was efavirenz/emtricitabine/tenofovir (17%), though ritonavir-based regimens accounted for 48% of all HIV treatments. Twenty-six percent (6/23 pts) had neurotoxicity (13% G3, 4% G2, 8% G1) and among those with any neurotoxicity,100% were taking ritonavir. Each of the 3 pts with G3 neurotoxicity, and the patient with G3 constipation experienced their AE after just 1 to 2 doses of vinblastine (before cycle #2). Each pt with G3 neurotoxicity, vinblastine was held with only slight improvement in symptoms. A statistically significant difference in the proportion of patients that developed neurotoxic effects after initiation of vinblastine was observed in the ritonavir vs. non-ritonavir based HAART therapy groups (55% vs. 0%, p<0.01). The most common non-hematological side effects were nausea and vomiting (29%) and neuropathy (28%; 13% G3 and 25%G1 and 2). Twenty-nine percent of the pts had G4 neutropenia. Two deaths occurred during induction therapy secondary to CMV pneumonia and cryptococcal infection. In contrast, no correlation was found between any HAART and AE in any vincristine-based chemotherapy regimen used to treat NHL. The most common diagnosis was diffuse large B cell lymphoma (63%). All 22 pts received CHOPR (63%), HYPERCVAD (27%), or CHOP (9%). Thirty-two percent (7/22 pts) were placed on a ritonavir based HAART, but no G3/4 neurotoxicity were observed. No G4 complications were seen aside from neutropenia (18%). Conclusions: Ritonavir-based HIV therapy in conjunction with ABVD (vinblastine based) in the treatment of HL was both temporally and statistically associated with serious, sometimes irreversible neurologic toxicity after just one dose of vinblastine. This same relationship was not seen in vincristine-based therapies for NHL. These data suggest that the CYP3A4 enzyme inhibition caused by ritonavir leads to severe vinblastine-associated adverse events and clinicians should consider non-ritonavir based HIV therapy during ABVD treatment for HL. Disclosures: No relevant conflicts of interest to declare.

4340 Introduction: The routine blood type and screen involves screening for unexpected antibodies, in addition to checking the ABO group and RH type. Most of these antibodies are IgM type, also known as nuisance antibodies. They are thought not to have much clinical significance. A positive antibody screen can sometimes be associated with inconclusive antibody identification. An inconclusive antibody screen is defined as test reactive for gel screen (which is a two cell screen) and no defined pattern on antibody identification panel. American Association of Blood Banking states that if an antibody screen is positive, an attempt should be made to identify the antibody and cross match for the same along with ABO and RH. If the antibody screen is negative, they recommend only ABO/RH compatibility testing to be done before transfusion. However, there is great paucity of literature regarding the scenario where the antibody screen is positive but the antibody identification (ABID) is inconclusive, to see if this has any clinical implications. This study was undertaken to review the clinical implications of a positive antibody screen with inconclusive ABID. Methods: All patients who had an antibody screen performed and the antibody identification was inconclusive during Jan 1st 2005 to Dec 31st 2010, were identified from the blood bank database of our hospital. The charts were then retrospectively screened for clinical diagnosis, antibody screen and ABID, repeat screen, blood transfusions given, if any, and occurrence of transfusion reactions. The patients were also studied for rise in hemoglobin per unit of red cell (excluding patients with active blood loss or hemolysis). Patients in the screened group who had a positive antibody identified in previous screening were excluded from the study group. The control group was composed of patients with a definite positive antibody screen with an identifiable antibody during the same period. In our institution, the patients who have a positive antibody screen get a cross match by gel technology. We use Reagent Red Blood Cells 0.8% Selectogen (Ortho clinical Diagnostics) for two-cell screen and Reagent Red Blood Cells 0.8% Resolve panel A Antigram Antigen Profile (Ortho Clinical Diagnostics) for detection and defining pattern of antibodies. Results: A total of 149 patients were identified from the blood bank database, which were included in study group. 150 controls were selected as well who had identified antibodies. Subsequently 69 (46.3%) patients from the study group had a repeat antibody screen done at a later date and out of that, 16 (23.2%) patients had a definite antibody identified and in 33 (48%) patients the repeat antibody screen was negative. In 26% the repeat screen was also inconclusive. 38 patients received transfusions in the study group and 37 in the control group. The average rise in hemoglobin per unit of red blood cell was 1.1 g/dL in the study group and same 1.1 g/dL in the control group. One patient in the study group had a transfusion reaction compared to no transfusion reactions in the control group. The transfusion reaction in was in the form of delayed hemolytic reaction in this patient who was subsequently identified to have “Jka” antibody at a later date. This would equate to 0.7% of all patients with inconclusive screen and 6% of patients who would have an antibody identified on subsequent testing. There was no mortality related to blood transfusion in either group. Conclusion: Patients who have an inconclusive ABID on antibody screen are usually ignored as having not much clinical significance. Our study indicates that although transfusion appears relatively safe in such patients, they can rarely have transfusion reactions, likely due to yet unidentified antibodies. Although 48% of patients retested will have a negative antibody screen, about a quarter of patients will have an antibody identified on subsequent testing. Hence, all patients with inconclusive ABID screen should be tested again, to identify if an antibody is present, in order to avoid any untoward reactions. Disclosures: No relevant conflicts of interest to declare.