Cherington, Chad

Abstract Abstract 1749 BACKGROUND: We have previously reported that transformation of a myeloproliferative neoplasm (MPN) to acute leukemia or blast phase (MPN-BP) is accompanied by a median survival of 2.6 months (range 0–24.2 months) (Mesa et. al. Blood 2005) despite treatment. Allogeneic stem cell transplantation (ASCT) offers a potential for cure. We reviewed 13 patients with MPN – BP who were candidates for ASCT, and 8 of those patients received ASCT after induction chemotherapy. METHODS: Retrospective analysis of individuals who had a clear antecedent myeloproliferative neoplasm (essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) (either primary (PMF) or post ET/PV)), transformed to MPN-BP, and were candidates for ASCT. Clinical characteristics at each phase of illness, therapy at each phase of illness, and outcome of ASCT were assessed. RESULTS: Patients (MPN details): Thirteen patients (8 male, 5 female, median age at diagnosis of MPN 42 years in those who underwent ASCT and 64 years in those who did not receive ASCT (combined median 53 years, range 26–70)) were identified who met the inclusion criteria, of whom 2 had ET, 4 PV, 2 Post-ET MF, 1 Post-PV MF and 4 PMF. Jak2-V617F mutation was present in 7 of 8 patients tested. Treatments used during the MPN phase included hydroxyurea in 9 (+ busulfan in 1 and + anagrelide in 1), and thalidomide/prednisone in 2 (two patients received no treatment prior to MPN-BP). Patients (MPN-BP details): Transformation of an MPN to blast phase (from diagnosis of MPN) occurred after a median of 11 years in those who underwent ASCT and 8 years in non-ASCT (range 3 months to 30 years). At the time of MPN-BP diagnosis, 9 patients had an abnormal karyotype, 3 with complex karyotypes, 3 with trisomy 8 (sole abnormality), 1 with del(7q), 1 with del(13q). Leukemic induction consisted of standard anthracycline/cytarabine combination therapy (+/− etoposide), except for one patient received a study medication voreloxin. One patient who did not receive ASCT had remission after induction, but later expired from relapse, two expired soon after leukemic transformation, and two were too ill to receive induction. In the ASCT group (N=8), 5 patients achieved complete remission (CR) of their leukemia/return to MPN chronic phase (one of the five patients required a second induction to achieve CR), while 3 patients were considered primary induction failures due to persistence of > 5% blasts in the blood (2) or marrow (1) at the time of pre-transplant response assessment. The median time from diagnosis of MPN-BP to ASCT was 128 days. ASCT Details and Outcomes: Patients (median age of 55 years at time of ASCT; range 44–73) underwent ASCT (all HLA identical, 3 matched unrelated donors, 5 matched sibling donors) with either reduced intensity conditioning (n=6) or fully myeloablative conditioning (n=2). After a median follow-up of 488 days (range 127 – 1206), 6 of 8 patients are alive and free of disease. MPN-BP recurred in two patients at day 69 and 77 post-transplant; both patients eventually died of progressive leukemia, one after a second transplant. Acute GVHD occurred in 3 patients (1 grade III, 2 grade II), and chronic GVHD in 4 (2 mild, 2 moderate). All five patients who achieved CR (marrow and PB blasts < 5%) after induction therapy remain in continuous CR, while 2 of the 3 patients with evidence of persistent leukemia relapsed and died of MPN-BP. No patient died of transplant-related causes and all patients engrafted promptly. CONCLUSION: Rapid induction followed by ASCT can offer a curative path for individuals with MPN-BP. Although limited by small numbers, our data suggest that leukemic clearance (marrow blast percentage < 5%) prior to ASCT is associated with improved outcome. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; SBio: Research Funding; Astra Zeneca: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding.

Abstract Abstract 4743 Background: BMBX procedures are traditionally performed by physicians, NPs, or PAs using a manual method. It is uncommon for nurses to perform these procedures, and even more rare for nurses to perform them using non-traditional techniques, such as the battery-powered system (OnControl, Vidacare, Shavano, TX). In this study, we report our nurse-led BMBX team experience using OnControl to collect diagnostic BMBX samples. Patient care and safety, team satisfaction, and specimen quality were evaluated. Methods: A team of nurses trained to perform BMBX procedures on sedated and non-sedated patients completed 94 procedures using OnControl and established SOPs. All nurses completed a questionnaire aimed at assessing the patient experience during and after the procedure and overall nurse satisfaction with OnControl. Specimen quality was graded by 3 physicians and compared to 25 specimens obtained by the same nursing team using traditional methods. Bone core specimens were graded based on core length and the presence/absence of artifacts. Biopsies had to be >1 cm or >1.5 cm to qualify good or excellent, respectively. Aspirates were similarly evaluated taking into account the presence/absence of spicules on stained smears. Results: Patient Care & Safety: The majority (86.2%) of patients who underwent a BMBX procedure during the study were outpatients, and minimal sedation was used in 94.7%. Most patients (76.6%) had a prior BMBX using the traditional method. In 94 patients evaluated, pre-procedure pain was 0 (0-10 scale) in 72 (76.5%) while 21 (22.3%) reported pain up to 5 just before the procedure (avg=2). The post-procedure pain score in the same patients was 0 in 78 (83%) and up to 4 in six (6%) (avg=1). No patients had post-procedure bleeding or complications requiring medical care. Seventy patients were reached 24 hrs post-procedure: 33 (47%) reported no pain and 37 (53%) reported pain up to 8 (avg=2.5). Nurse BMBX Team Satisfaction: Team members reported 100% satisfaction with the process of inserting the OnControl biopsy needle through soft tissues and acquiring a core biopsy. The nurses reported having satisfactory control of the depth of needle through the cortex and into the medullary space using the needle guide 95% of the time. Team members were satisfied with the ease of obtaining an aspirate 93% of the time. Nearly all (95%) nurses felt improved ergonomics using the battery-powered driver compared to the manual method. The nurses reported that OnControl was easy to use, with 83% of them obtaining a core biopsy on their first attempt. All nurses indicated they would use OnControl over the manual method if given the choice. Specimen Quality: H&E-stained bone core biopsy slides and W-G-stained aspirate smears from 83/94 specimens collected using OnControl were reviewed and graded. All but two (2.4%) of the bone core specimens were adequate for diagnosis. Of adequate samples, 45.8% were excellent, 12% good, and 39.8% fair. Aspiration artifact was seen in 18/83 (21.6%) of cores, and that artifact was the reason for a downgrade to fair quality in 17/18 (94%). Extra aspirate material for research was collected in 7/18 with fair quality bone core biopsies. Similar grading applied to 25 core biopsy samples collected using the manual method revealed 44% of cores to be excellent, 20% good, 32% fair, and 4% poor. The average core length using OnControl and the traditional method was 1.6 cm and 1.7 cm, respectively. Five of 83 (6%) aspirates obtained using OnControl were poor quality due to lack of bone marrow cells. Of the remaining aspirates, 54.2% were excellent, 20.5% good, and 19.2% fair. Factors related to bedside technique caused a downgrade in 10/16 samples graded as fair and 5/17 samples graded as good. Aspirates obtained by the standard method were graded as 52% excellent, 28% good, 12% fair, and 8% poor. Conclusions: Trained nurses can safely and effectively perform BMBX procedures using traditional methods as well as novel techniques such as the OnControl battery-powered driver system. In the hands of experienced individuals, OnControl can consistently yield high-quality BMBX specimens. Aspiration artifact was the most common flaw found in bone cores obtained with OnControl, but it was usually focal and did not hinder interpretation. When artifact associated with technical aspects out of the control of the BMBX operator was excluded, the OnControl needle produced good-excellent aspirate in 87% of patients. Disclosures: No relevant conflicts of interest to declare.

624 Background: The risk of intravenous contrast induced nephropathy (CIN) is not well described in post-nephrectomy or metastatic kidney cancer. Patients with nephrectomies and tumors of the kidney frequently have CKD and often require serial contrast imaging placing them at risk for CIN. Methods: This is a retrospective review of 292 patients metastatic RCC and/or with partial or radical nephrectomies (PN or RN) for kidney tumors at Mayo Clinic Arizona or Florida from 2010 through 2014. Results: We found 207 patients received at least one contrast scan, of whom 99 had metastatic RCC, 104 had local RCC and 4 had oncocytoma. At baseline (pre-nephrectomy) 41% (46/113) and 15% (11/76) of RN and PN respectively had CKD stages 3-5 and with at least 3 months follow up after both nephrectomy and contrast exposure 61% (68/113) and 33% (25/76) RN and PN developed CKD stages 3-5 respectively. The median contrast exposure scans were 4 (range 1-30 scans) with a median follow up of 26 months (range 1-96 months). In all patients with at least one contrast exposure, the median change in creatinine and GFR from baseline was 0.2 mg/dL and 8 ml/min respectively. Excluding those with bilateral nephrectomy there were 8 (8/207 = 4%) CIN events, 6/113 had a radical nephrectomy and 2/76 with 1 partial nephrectomy and 1 aborted nephrectomy (P value 0.37). Of these patients 5 (5/99 = 5%) had metastatic RCC and 3 (3/104 = 3%) local RCC. The median contrast exposure scans for patients with CIN were 8 (range 3-12) and median follow up was 31 months (range 4-47 months). Three patients all with metastatic RCC developed acute kidney injury from CIN requiring dialysis and died of complications in part related to CIN during that hospital stay or soon after. Two other patients developed CKD stage III after CIN events and 3 patients (including the one with a partial nephrectomy) showed no significant change in GFR after CIN. Conclusions: In this retrospective analysis, CIN after nephrectomy or metastatic RCC contributed to acute renal failure with 3 deaths and 2 patients developing CKD stage III. Further analysis is required to determine what risk factors for CIN in this population.

353 Background: One mechanism leading to castrate-resistant prostate cancer (CRPC) is upregulation of CYP17. Abiraterone acetate (AA) inhibits CYP17 and continuous AA administration (CAAA) is one the most common and effective CRPC treatments. Mathematical models can be potentially powerful clinical tools for optimizing treatment strategies and eliminating guess work. Here, we introduce a new model which builds on our previous work (Morken JD, Packer A, Everett RA, Nagy JD, Kuang Y. Mechanisms of resistance to intermittent androgen deprivation therapy identified in prostate cancer patients by novel computational method. Cancer Res 2014;74:2673-83.) and may be capable of predicting how patients will respond to CAAA and intermittent AA administration (IAAA). We are currently proposing a personalized IAAA protocol on the basis of these results. Methods: In this ongoing retrospective study, we use PSA data from patients whom underwent CAAA to validate the accuracy of our model of tumor growth and evolution. The PSA output is driven by dynamics of three cell populations—castration-sensitive (CS), castration-resistant abiraterone-sensitive (CSAS), and castration-sensitive abiraterone-resistant (CSAR) cells. We fit the model output to PSA data to find parameter values which minimize normalized mean squared error (NMSE). Once parameters are obtained, we ran simulations employing various IAAA protocols. Results: The model’s PSA dynamics are highly accurate. NMSE is very low across patients ranging from 0.0001-0.0085. Conclusions: Our results suggest that there exists an IAAA protocol for each patient that, at worst, yields the same time to tumor progression as CAAA, yet improves quality of life and reduces cost. In nearly 20% of patients, IAAA appears to delay tumor progression over CAAA. The model is accurate at predicting how patients will respond to CAAA and IAAA for patients whose PSA is regularly monitored. Near-future work aims to personalize IAAA protocol based on patient pre CRPC PSA dynamics and to identify a protocol which delays progression for most patients.