Letendre, Louis

Abstract Background: Overall prognosis in CMML is unfavorable. The only curative option is ASCT, yet the limited data available from the largest reported series, reports 2 year overall (OS) and disease free (DFS) survival of only 21% and 18%, respectively [Kroger et al, BJH 2002, 118: 67]. Data on DLI for CMML are generally restricted to case reports. We retrospectively reviewed our experience of ASCT and DLI for adults with CMML. Patients: Seventeen consecutive patients (11 males) with CMML underwent ASCT from 1992 to 2004. At transplant, median (range) age was 50 years (26–60), duration of disease 7 months (2.5–44), and bone marrow (BM) blast count 6% (1–58%). Prior to transplant, 11 had evolved into acute myeloid leukemia (AML). Of these, 10 received standard induction chemotherapy but only one achieved complete remission (CR); 5 had persistent CMML and 4 refractory AML. Karyotype at transplant was either normal (n=9) or revealed isolated monosomy 7 (n=4), complex (n=1), or single, nonrecurrent abnormalities. ASCT: Conditioning was Cytoxan/Total Body Irradiation in all but one who received a non-myeloablative (NMA) regimen (cladrabine/ATG/thiotepa). Stem cell source was HLA-identical sibling in 14 patients and unrelated in 3 peripheral blood (PB) in 7, BM in 8, or both in 2. Median BM mononuclear cell/kg dose was 2.3 (1.7–4.15) x 108 and PB CD34 cell/kg was 5.12 (0.94–7.29) x 106. Graft versus host disease (GVHD) prophylaxis was cyclosporin alone (n=3), with methotrexate (n=12), or prednisone (n=1) or was tacrolimus/methotrexate (n=1). Post-transplant course: All but one patient who died on day 11 of sepsis engrafted (sustained ANC > 500) at a median of 19.5 days (13–31). CR was documented in 13 (76%) post-ASCT. Acute GVHD was grade II-IV (75%) and III-IV (37.5%) and chronic GVHD was extensive (n=37.5%). Seven (41%) demonstrated relapse or persistent disease at a median of 6 months (3–55.5) and 13 (76%) have died due to disease (n=6) or transplant related mortality (n=7). DLI: Six patients underwent DLI for morphologic (4 recurrent/persistent CMML, 1 early AML with extramedullary disease) or cytogenetic relapse (n=1), at a median of 19.5 days (6–52) post-relapse. Median BM blast count at DLI was 3% (1–22%). The median CD3+ cell dose infused was 30.45 x 107 cells/kg (11.2–45.5), given in a median of 3 infusions (range: 1–3). Four did not respond, but two (one with cytogenetic and one with morphologic relapse) achieved a durable CR of 15 months each, both had extensive CGVHD, from which one died of complications. The other relapsed but failed to respond to a second DLI and died of disease. Survival: For the entire cohort, median DFS and OS were 6 months and 7 months, respectively. At last follow up, 4 remain alive, 3 in continuous CR (18%), at 12, 29 (treated with the NMA regimen) and 116 months, respectively. Of the 3 patients surviving in remission, all had transformed to AML prior to ASCT and only one had achieved CR following induction chemotherapy. Multivariate analysis failed to demonstrate any significant effect of age, duration of disease, BM blast %, karyotype or induction chemotherapy on RFS or OS, likely reflecting the small numbers available for analysis. Conclusion: The current study demonstrates anti-CMML activity of both ASCT and DLI although overall outcome is less than encouraging and unpredictable. Novel approaches are needed.

Abstract This phase 1 clinical trial evaluated the safety and effects of autologous dendritic cells (DC) injected to patients in late chronic or accelerated phase of chronic myelogenous leukemia (CML). Seven patients with a median age of 63 years (range 55–78) entered the trial. Median time from diagnosis to registration was 38 months (range 16–94). Two patients were in the accelerated phase of disease based on the presence of additional bone marrow chromosomal abnormalities, all other patients were in chronic phase. Prior therapies included hydroxyurea and alpha interferon with or without cytosine arabinoside. Four patients were on therapy with imatinib mesylate during the course of the trial, two were treated before imatinib became available and one was previously intolerant of imatinib. CD14+ monocytes were selected from a leukapheresis product by clinical grade immunoadsorption (Miltenyi Biotec). The monocytes were matured to CD83+ and bcr-abl+ DC after 10 days in culture with X-VIVO 15 medium with 1% human AB serum, GM-CSF, IL-4, as the base culture media followed by maturation mediated by TNF-alpha, IL-6 and prostaglandin E2. The first patient entered had a positive mycoplasma reaction by polymerase chain reaction at the time of his first DC injection, the cells were not given and he was withdrawn from the study. The other six patients were treated in two cohorts of three patients and received four injections each of 3x106 DC and 15x106 DC per injection, respectively. CML-DC injections were generally well tolerated and all non-hematologic toxicities were ≤ grade 2. All injections were given intra-nodally into a cervical lymph node except in the first patient where the DCs were injected subcutaneously. We observed no major clinical responses, but the white blood cell counts normalized or were maintained at normal level in four patients during therapy. Three patients experienced a transient reduction in the percentage of bcr-abl+ cells suggesting that the treatment may have affected the cells in a leukemia specific manner. We detected vascular endothelial growth factor (VEGF) in the plasma prior to therapy. In four of five patients, VEGF levels decreased by more than 75 percent during therapy. T cells isolated from patients’ blood and incubated with autologous CML DC before, during and after therapy showed increased proliferation and secretion of interferon gamma during the course of therapy. DCs from three patients were transfected with a recombinant replication-defective adenovirus carrying the gene for IL-2 under a constitutively active promoter. IL-2 secreted by transfected dendritic cells enhanced in vitro T cell proliferation and interferon gamma release and these effects increased with increasing numbers of DC injections. This study demonstrates that CML-DC can be prepared from the blood of patients treated with imatinib mesylate, that they can be administered safely and that progress of therapy is accompanied by an increase in DC-specific T cell reactivity and a decrease in circulating VEGF.

Abstract Background: In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors for achieving remission and for relapse-free survival (RFS). However, in AML parameters of chemosensitivity have been restricted to the assessment of residual bone marrow (BM) blasts during aplasia. We hypothesized that time to peripheral blood (PB) blast clearance would have prognostic relevance with respect to RFS in AML. Methods: From 1994 to 2006 outcomes of 86 adults (47 males; median age 52 y) with previously untreated AML (non- acute promyelocytic leukemia) achieving CR and receiving high-dose cytarabine (HDAC)-based consolidation have been included in this retrospective analysis. The median and range of white blood cell count (WBC), platelet count and PB blast percent were 5.3 × 109/L (0.9–267), 59 ×109/L (5–361) 22.5% (0–97), respectively. A 100 cell manual slide differential count was done in all with PB blasts unless the WBC was less than 0.5 ×109/L. Karyotype was classified as favorable, intermediate and unfavorable in 10, 63 and 12 cases, respectively and failed in one. Induction consisted of idarubicin at 12 mg/m2/ d (n=70) or daunorubicin at 45 mg/m2/d (n=16) on days 1–3 with infusional cytarabine at 100 mg/m2/ d on days 1–7 and repeated in those with persistent BM blasts on day 14 (n=17). The first consolidation was the same as that used to achieve CR. Thereafter, 3 courses of HDAC at 3g/m2 (1.5 g/m2 if ≥ 60 y) q12 h on days 1, 3 and 5 were planned. Results: At the time of analyses, 43% had died, primarily of relapse (97%). Median overall survival (OS) and RFS were 30.2 m (5.5–133) and 14 m (2–131.5), respectively. The median time to PB blast clearance was five days (range: 2–10). For this analysis, only those with PB blasts at initiation of induction (n=73) were included. We defined the day of PB blast clearance as the first day after commencing induction that PB blasts were absent. Separation according to blast clearance on or before day 5 resulted in the most balanced distribution and strongest significant difference between each subgroup of 45 and 28 patients, with significantly different rates of relapse of 33% and 79%, respectively (p<0.0001). We also defined three “blast risk groups” as good, intermediate and poor, according to PB blast clearance on or before day 3, on days 4 or 5, or on day 6 or beyond, respectively. This provided 3 well-balanced groups (good, intermediate and poor) of 16, 30 and 27 patients with significantly different and escalating relapse rates of 12.5%, 47% and 78%, respectively (Fig 1). Univariate analysis of several variables identified PB blast clearance day (p<0.0001), number of inductions to CR (p =0.0043) and cytogenetic risk group (p=0.028) as being significantly associated with RFS. On multivariable analysis, only the first sustained its significance. The results were similar for OS. Conclusion: In adults who achieve CR after induction chemotherapy for non-APL AML, early PB blast clearance predicts superior RFS and OS. Figure Figure

6614 Background: CDKN2A locus on chromosome 9p21 is implicated in altered molecular pathways leading to leukemogenesis as a tumor suppressor by inhibiting the proliferative kinases CDK4/CDK6 and blocking the cell-cycle division during G1/S phase. Deletion of CDKN2A locus is frequently seen in ALL, although prognostic significance remains unclear. Methods: Retrospective chart review at Mayo Clinic between 8/2005-11/2011 was performed on adult B-ALL patients (pts) who underwent fluorescent in situ hybridization (FISH) studies at diagnosis. Survival estimate was calculated using Kaplan-Meier statistics. Event-free survival (EFS) was defined as time between diagnosis and induction failure, relapse, or death, while overall survival (OS) as time between diagnosis and death Results: Out of 27 pts who had FISH studies for CDKN2A, 15 (56%) pts had CDKN2A deletions (8 homozygous/7 hemizygous), while 12 (44%) pts had diploid cytogenetics (none had abnormalities of MLL, bcr/abl fusion or CDKN2A deletion on FISH). There was no significant difference in median age, gender, WBC, hemoglobin, platelet count, LDH or complete remission (CR) rate (p=0.924) between the two groups. CDKN2A-deleted pts had higher circulating blasts (34% vs 16%, p=0.017). Of 13 CDKN2A-deleted pts, chromosome 9p was intact in 9 (69%) pts using routine cytogenetics. In the CDKN2A-deleted group, allogeneic stem cell transplant (ASCT) was performed in 7 (47%) pts at first CR and 1 at second CR. Four of 15 (27%) CDKN2A-deleted pts also had bcr/abl fusion. Five-year EFS was poorer in CDKN2A-deleted pts compared to normal FISH group (22% vs 60%, p=0.042), while 5-year OS was 72% vs 60% (p=0.308), respectively. Excluding the 4 bcr/abl fusion pts, 5-year EFS was still statistically significant (p=0.008). In the CDKN2A deleted group, both 5-yr EFS (80% vs 0%, p=0.006) and OS (100% vs 42%, p=0.016) were significantly superior in pts who received ASCT. Conclusions: CDKN2A deletions predict earlier relapse in pts with B-ALL. Majority of 9p abnormalities were only found by FISH testing and missed by conventional cytogenetics. In CDKN2A deleted pts, ASCT gave overall survival advantage. Further investigation through larger cohorts of pts is needed to validate these findings.

7055 Introduction: Cytogenetic abnormalities have been shown to be the most important determinant of prognosis in patients with acute myeloid leukemia (AML). In AML, trisomy 13 has been placed in the intermediate prognostic category although recent reports associate it with a more dismal outcome. The number of cases reported in the literature are relatively few, we reviewed our experience with trisomy 13 in hematologic malignancies to determine its significance and prognosis. Methods: We conducted a clinicopathological review of cases seen in our institution from January of 1990 to October of 2006. Our cytogenetic records were searched for patients, who had a hematological disorder whose non-stimulated bone marrow karyotype was found to have trisomy 13 as a sole abnormality. In men the absence of the Y chromosome was not regarded as a separate abnormality. Results: A total of 27 patients were identified. The median age was 76 years (range 25–87), 22/27 were male. The number of cases and diseases identified were 15 with AML, 5 with a myelodysplastic syndrome, 4 with an uncategorized myelodysplastic/myeloproliferative disorder, 2 with acute lymphoblastic leukemia and 1 with a chronic myeloproliferative disorder. Of the AML group 7 were M0 according to the FAB classification, 2 patients were identified to have M4 and another two M2. A single case each of M1 and M6 was also identified. In these 15 patients, 9 underwent induction chemotherapy, which consisted of intermediate dose Ara-C in 3 cases, anthracycline plus Ara-C in 5 patients, and daunorubicin, vincristine and prednisone in 1. Another 3 patients were given palliative treatment. For the rest of the subjects the type of treatment was unknown. A CR was obtained in 6 patients, 1 patient underwent a myeloablative stem cell transplant. Death has occurred in 24 patients, the median survival of the entire group was 5.4 months. In the patients with AML the median survival was 4.7 months, of the patients who achieved a CR the median survival was 9.5 months. Conclusions: We describe one of the largest series reported to date of trisomy 13 in hematologic malignancies and found that trisomy 13 is associated with male gender and an older age at presentation, as well as a poor prognosis. In AML its presence is associated with an FAB-M0 phenotype and its occurrence should be regarded as a high-risk feature. No significant financial relationships to disclose.

Background: Therapy-related MDS/AML (t-MDS/AML) is a common and devastating complication of treatment with alkylating agents and topoisomerase II inhibitors, often employed with curative intent, in standard or high-doses, in the treatment of hematological malignancies and solid tumors. Allogeneic HSC transplant is considered the standard treatment for t-MDS/AML but its applicability is limited by the unavailability of donors, comorbidities in the recipient and risk of acute and chronic graft-versus-host disease. Patients carrying diseases commonly treated with high-dose chemotherapy and autologous HSC transplant (such as multiple myeloma and non-Hodgkin lymphoma) who latter develop t-MDS/AML occasionally have stored HSC harvested prior to the diagnosis of the secondary malignancy (hereafter called early-stored HSC). The benefit of using early-stored HSC to support myeloablative therapy for the treatment t-MDS/AML is unknown. Methods: Retrospective, single center analysis of patients with t-MDS/AML receiving myeloablative chemotherapy with or without irradiation supported with early-stored HSC. Results: Six patients received early-stored HSC transplant for treatment of t-MDS/AML between 2000 and 2007. Median age at the time of the transplant was 57 years (range 15–71). Three patients had been primarily diagnosed with follicular lymphoma, 2 with multiple myeloma and 1 with Ewing’s sarcoma. One patient had received prior autologous HSC transplantation. Two patients developed AML, 1 patient CMML, 1 patient RCMD, 1 patient RAEB1 and 1 patient RAEB2. Median time from diagnosis of primary malignancy to HSC harvesting was 26 (2–122) months and from harvesting to development of t-MDS/AML 44 (7–79) months. Conditioning regimen was Cy/TBI in three patients, BuCy in 2 patients and Samarium + Melphalan in one patient. Five patients engrafted neutrophils and 4 patients engrafted platelets 10–34 and 13–126 days after transplant respectively. In 3/6 patients there was disappearance of the pre-transplant chromosomic abnormality (2 patients -7 and 1 patient -7 and t(1;7)). Two patients obtained hematologic CR and two patients obtained CR without full recovery of platelets. One patient died of sepsis 230 days after transplant, one died with refractory disease on day 103 after transplant and one patient is alive with recurrence of t-MDS. Three patients are alive and free of disease 7, 73 and 87 months after transplant. Conclusion: Myeloablative conditioning followed by autologous, early-stored HSC transplant can provide prolonged survival to patients with tMDS/AML not suitable to allogeneic SCT.

Abstract Background L-asparaginase (LASP) depletion of asparagine reduces antithrombin (AT) and fibrinogen and is associated with thromboembolic (TE) and hemorrhagic events (HE). AT replacement in pediatric ALL patients demonstrated safety and potential benefit as thromboprophylaxis in a prospective, randomized trial.(Mitchell et al, 2003) Current consensus supports AT replacement when AT activity is below 60%.(Stock et al, 2011) The incidence of TE and HE in adults receiving AT repletion during LASP or pegylated asparaginase (PEGASP) requires further investigation. Methods This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board. Consecutive adult patients with a confirmed diagnosis of ALL receiving LASP or PEGASP containing chemotherapy regimens between January 2000 and October 2012 were evaluated. Patients with documented thrombophilia and pre-existing TE or HE were excluded. Patients receiving AT concentrate (ATC) compared to those that did not and were evaluated up to 60 days after the last LASP or PEGASP dose for objectively confirmed TE and HE. Results Of the 74 patients screened, 54 (73%) met inclusion criteria. Forty-seven (87%) received ATC and were evaluable. The remaining 7 (13%) did not meet follow up duration and were excluded from further analysis. Twenty-three (49%) patients received LASP, 20 (42%) received PEGASP and 4 (9%) received both. Distribution per treatment protocols was; CALGB 9111 (n=16 (34%), Larson et al, 1998), E2993 (n=12 (25%), Goldstone et al, 2008), C10403 (n=8 (17%), NLM: NCT00558519), CCG 1941 (n=6 (13%), Gaynon et al, 2006) and Augmented HyperCVAD (n=5 (11%), Faderl et al, 2011). A total of 1465 AT activity levels were analyzed, resulting in 378 doses of ATC. Ten patients (21%) experienced a clinical event, with all events occurring during cycle 1 of chemotherapy (table 1). Median time from last LASP or PEGASP dose to TE was 13 days (range 3-56) with a median of 4 days (range 3-13) from last ATC dose to TE. Median AT activity level at time of TE was 56% (range 47-72). Thrombotic events included; line-related deep vein thrombosis (LRDVT, n=7), cerebral venous sinus thrombosis (CVST, n=1) and pulmonary embolism (PE, n=1). One patient with cerebral hemorrhage constituted the only HE. All LRDVT occurred in central venous catheters and management included; line removal (n=3), anticoagulation (n=1), line removal and anticoagulation (n=2) and no intervention (n=1). The single case of PE was managed with anticoagulation. Two patients had a recurrent LRDVT in different locations during subsequent chemotherapy in spite of ongoing ATC supplementation. Conclusions The incidence of TE in adult ALL patients receiving LASP or PEGASP during induction chemotherapy with AT thromboprophylaxis was 19%. LRDVT was the most common TE with a comparable incidence to adult ALL patients not receiving ATC (15%) (Grace et al 2011). There was a small incidence of non-LRDVT (4%) and HE (2%). As induction-phase chemotherapy and placement of central lines are independent risk factors for thrombosis, the cost-effectiveness of AT replacement for prevention of TE during adult ALL treatment requires prospective evaluation. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Tunneled central venous catheters have traditionally been used for administration of chemotherapy (chemo) for acute leukemia treatment. Peripherally inserted central catheters (PICC) are increasingly being used, but there is an increased risk of PICC-associated thrombosis (PAT). There is limited information on management of PAT in this subgroup of patients (pt). Methods In this retrospective cohort study we investigated the primary management of PICC related upper extremity venous thrombosis (TB) in pt with hematologic malignancy undergoing chemo at Mayo Clinic Rochester. Eligible pt were 18 years and older, had documentation of PICC placement at our institution, initiation of chemo within a week of PICC placement, and the TB was objectively documented by compression venous ultrasound (CVU). Superficial venous TB (SVT) was defined as TB of subcutaneous veins (basilic and cephalic) and deep venous TB (DVT) defined as TB of brachial, axillary, subclavian, or innominate superior vena cava and internal jugular veins. We retrospectively stratified initial management (IM) into 1) PICC removal alone (PR), 2) PR and therapeutic anticoagulation (AC), 3) AC alone, and 4) conservative management (CM) consisting of symptomatic care and observation. We also investigated factors influencing IM of PAT. Long term outcomes including incidence of pulmonary embolism (PE), post phlebitic syndrome and recurrence of TB were noted. Results Between 2006 and 2012, 190 pt with AML (n=160), MDS or MDS/MF (n=10), or ALL (n=20) met our study criteria. Overall, 40/190 (21.6%) developed PAT: AML n=38, ALL n=1, MDS/MF n=1. SVT occurred in 16/40 (40%) pt and DVT occurred in 24/40 (60%) pt. IM is shown in Table 1. One pt with SVT received AC for 6 weeks as well as PR. In this pt, IM included AC because of proximity of TB to deep veins. 7 pt had a follow up (f/u) CVU within 3 months demonstrating: TB progression (prog, n=1, IM with PR alone but with prog AC was started); TB stability (stab, n=2, both IM with PR alone) and TB resolution/improvement (R/I, n= 4, 2 IM with PR and 2 IM with CM) In the 5 pt with CM, 2 pt had f/u CVU demonstrating improvement, one pt had charted clinical improvement , and 2 pt had no charted clinical f/u. Of DVT pt on AC (n=14), 5 pt completed at least 2 months of AC. Reasons for early cessation (n=9) of AC included thrombocytopenia (tcp, n=4), hematoma (n=1), hematuria (n=1), subarachnoid hemorrhage (n=1), and unknown (n=1). One pt died 2 days after presence of DVT was noted. Two pt initially treated with PR alone developed a second TB with placement of a new PICC on contralateral arm and AC was subsequently initiated (duration: 3 months (n=1), and 8 days (n=1)). 14 pt with DVT had f/u CVU within 3 months which demonstrated prog (n=2), stab (n= 8), or R/I ( n=4) of TB (Table 2). The 2 pt with TB prog subsequently received longer term AC guided by platelet count. In 5 pt with PICC not initially removed, 3 pt had PR after completion of chemo. (1-4 days), one pt had PR at discharge (27 days from TB), and one pt had PICC in place on discharge. One pt with DVT experienced a PE within one year f/u. This pt had initially completed 3 days of AC which was stopped because of tcp. Conclusion In this cohort of patients with PAT, the most common IM consisted of PR, which appeared to result in a low recurrence rate among pt with SVT. In pt with DVT, the role of AC remains to be defined given the abbreviated course of AC in most pt. Though, the lack of CVU followup in all pt limits conclusions, there appeared to be a low rate of symptomatic prog. Initiation of AC was largely guided by platelet count and degree of occlusive symptoms. Thrombocytopenia was also the most commonly cited reason for discontinuing AC. Close clinical follow up aided by the use of CVU was integral to ensure that PAT did not lead to further adverse events. Disclosures: No relevant conflicts of interest to declare.

Abstract Background L-asparaginase (LASP) therapy in adults is associated with frequent hepatic and metabolic side effects, often resulting in dose adjustments and omissions. Pegylated asparaginase (PEGASP) substituted for LASP improves convenience of administration with comparable efficacy; however, adverse event (AE) management remains challenging. The incidence and management of LASP- and PEGASP-induced metabolic and hepatic complications in adult ALL patients is not well defined. Methods This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board. Consecutive adult patients with a confirmed diagnosis of ALL receiving LASP or PEGASP containing chemotherapy regimens between January 2000 and October 2012 were evaluated. Patients were followed up to 60 days after the last LASP or PEGASP dose for development of biochemical and clinical pancreatitis, hypertriglyceridemia and hepatotoxicity. Hyperglycemia was not analyzed due to confounding variables, such as concomitant corticosteroid administration. AEs were graded as per the National Cancer Institute Common Terminology Criteria (CTCAE) version 4.03. Analysis was performed using Cox proportional hazard models with odds ratios (with 95% confidence intervals) reported to demonstrate the strength of association between group and AE rate. Results Of 74 adult patients, 54 (73%) met inclusion criteria. History of dyslipidemia, diabetes mellitus, cholelithiasis and coronary artery disease was documented at baseline in 13 (24%), 4 (7%), 4 (7%) and 10 (19%) patients, respectively. Twenty eight (52%) patients received LASP, 22 (41%) received PEGASP and 4 (7%) received both. A total of 399 doses including 335 (84%) LASP and 64 (16%) PEGASP were administered. Distribution based on treatment schedules was as follows; CALGB 9111 (n=20 (37%), Larson et al, 1998), E2993 (n=13 (24%), Goldstone et al, 2008), C10403 (n=9 (17%), NLM: NCT00558519), CCG 1941 (n=7 (13%), Gaynon et al, 2006) and Augmented Hyper-CVAD (n=5 (9%), Faderl et al,2011). Six (11%), 20 (37%), and 53 (98%) patients experienced pancreatic, lipid (hypertriglyceridemia) and hepatic adverse events, respectively. In this group, CTCAE grade 3/4 AEs occurred in 0 (0%), 8 (15%), and 28 (52%) patients, respectively. No deaths were directly related to these complications. Patients receiving PEGASP were more likely to experience AE of any CTCAE grade (OR 11.5, 95% CI 4.4-30.3, p < 0.0001), including grade3/4 AEs (OR 27.9, 95% CI 11.4-68.2, p < 0.0001) in comparison to those receiving LASP. All cases of pancreatitis manifested as biochemical elevation in pancreatic enzymes, and were either grade 1 (n=4, 67%) or grade 2 (n=2, 33%). All patients were managed conservatively. Management of hypertriglyceridemia was heterogeneous across all grades and included observation (n=11, 55%), non-pharmacologic interventions (n=1, 5%), medication management (n=4, 20%) and combined strategies (n=4, 20%). The most common practice was a combination of fibrate derivatives (fenofibrate) and fish oil (n= 5). One patient with a peak triglyceride level of 2285 mg/dL was placed on an insulin/dextrose infusion for 4 days. Hepatic toxicity manifested as CTCAE grade 3/4 transaminitis in 13 (24%) patients, hyperbilirubinemia in 4 (7%) patients and both in 11 (20%) patients. Temporal correlation was used to best distinguish confounding variables including possible hepatoxicity from azole antifungals and other drugs. Management of hepatic toxicity included delay in dosing, subsequent LASP or PEGASP dose reduction and laboratory monitoring until resolution. Overall, deviations in LASP or PEGASP administration were documented in 18 (33%) patients due to metabolic or hepatic AEs. Eight (15%) patients required omission of at least 1 dose, 7 (13%) experienced delays of administration and 7 (13%) needed a dose reduction. Conclusion PEGASP administration resulted in significantly higher AE rates in comparison to LASP and this significance was retained when comparing AEs of CTCAE grade 3 and 4. Given the growing trend of using PEGASP combination chemotherapy in adults with ALL, a detailed analysis looking at the increase in side effects, their consequences (delayed tereatment and dose reductions) and the impact of these factors on disease remission and survival is needed. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1476 Background: Monosomal Karyotype (MK) is defined as the presence of two or more autosomal monosomies or one autosomal monosomy and one structural abnormality. MK has been found to be an independent poor prognostic factor in myeloid diseases (Patnaik et al, Leukemia 2011, Haferlach et al, Blood 2012) even in the setting of allogeneic stem cell transplantation (Fang et al, Blood 2011). The prognostic relevance of MK in Acute Lymphoblastic Leukemia (ALL) is unknown. Absolute lymphocyte count (ALC) at diagnosis, on the other hand, has been shown to be prognostic in a variety of lymphoproliferative disorders (Porrata et al, Leukemia 2010). However, the prognosis of ALC at diagnosis in ALL is undetermined Methods: This is a retrospective analysis of the Mayo Clinic leukemia database (1998–2010). The study was approved by the Institutional Review Board. Outcomes analyzed included overall survival (OS), leukemia free survival (LFS) and relapse rate. Clinical characteristics, cytogenetics, therapy and outcomes of patients with Philadelphia negative ALL (Ph-negative ALL) were analyzed. Cytogenetics were classified as follows: standard risk [hyperdiploidy], intermediate risk [Normal, del(11q)-not MLL, del(6q), del(17p), del(9p), del(12p), del(13q), t(14q32), t(10;14), low hyperdiploidy, others], high risk [-7, del(7p), +8, MLL translocations, t(1;19), t(17;19), t(5;14)], and very high [t(4;11), t(8;14), complex (≥5 abnormalities), hypodiploidy, triploidy] (Pullarkat et, Blood 2008). Multivariate analysis was performed using Cox Regression Model. Results: Between 1998 and 2010, a total of 175 consecutive patients with ALL were identified. Of these, 112 (64%) had Ph-negative ALL. The median age was 39.5 (16–88) years and 74 were male (66%). The majority of cases were B-ALL (78 patients, 69%). At presentation, the median hemoglobin was 10 (4.1–18.5) g/dL, platelet count was 61 (3–523) ×10(9)/L, WBC was 7.2 (0.8–377) ×10(9)/L and ALC was 1.9 (0–69.0) ×10(9)/L. The ALC was > 1000 in 75 (71%) patients. Cytogenetics risk categories were as follows: standard risk in 5 (4.4%), intermediate risk in 70 (62.5%), high risk in 8 (7.1%) and very high risk in 29 (25.9%) patients. Twenty-two patients (20.9%) presented with extranodal disease (CNS disease in 13 patients, 11.6%). Six patients (5.4%) had prior exposure to chemotherapy. Treatment involved allogeneic stem cell transplantation (SCT) in 34 (30.4%) patients. The median OS for the whole cohort was 24 (0–206) months and LFS was 18 (0–193) months. Forty four patients (39.3%) relapsed after achieving initial remission with a median time to relapse of 15 (2–73) months In a univariate analysis, low platelet count at diagnosis, poor ECOG performance status (PS), and high or very high risk cytogenetics risk categories were associated with inferior OS. ALC at diagnosis did not impact OS or LFS. On a multivariate analysis, high/very high risk cytogenetics, low platelet counts and poor ECOG PS were independent predictors of inferior outcomes. Nineteen patients (16.9%) had a MK. Of these, 16 (84.2%) fell in the very high risk cytogenetics category regardless of MK status. Three patients (1.6%) presented with extramedullary disease and six (3.2%) underwent SCT. The median OS of these 19 patients was 15 (1–73) months. While MK was associated with inferior LFS and a trend towards worse OS, this was not significant on a multivariate model that included cytogenetic risk categories, thrombocytopenia and the ECOG PS. Conclusions: Our study demonstrates that cytogenetics risk stratification, thrombocytopenia and ECOG performance status are independent prognostic factors in ALL. MK and ALC at diagnosis had no prognostic significance. Disclosures: No relevant conflicts of interest to declare.