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CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60–75 years with newly diagnosed, high-risk/secondary AML received 1–2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25–0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%–61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients. [ABSTRACT FROM AUTHOR]

We investigated the utility of a pediatric-inspired protocol in adults aged 18–40 years with standard-riskBCR-ABLnegative acute lymphoblastic leukemia (ALL). Retrospective outcomes of 25 patients treated with a pediatric protocol between 2008 and 2014 were compared with 22 similarly aged patients treated with an adult protocol between 2003 and 2008. Twenty-five (100%) and 19 (86%) patients achieved complete remission, respectively. At median follow-up of 36.8 months, 3-year event-free survival was increased in patients on the pediatric protocol at 80% versus 45% (p = .019). There was a trend toward improved overall survival at 80% versus 59% (p = .12). Treatment-related toxicity was not increased despite the increased treatment intensity. Patients withBCRand/orABLcopy number variation demonstrated comparatively poorer outcomes in both cohorts. In our experience with this cohort of patients, pediatric-based protocols are safe and effective, justifying their use in younger adults with ALL. [ABSTRACT FROM AUTHOR]

Linifanib, a potent oral inhibitor of fms-like tyrosine kinase 3 (FLT3) and vascular endothelial growth factor receptor tyrosine kinases, has demonstrated promising preclinical single-agent and synergistic anti-leukemic activity in combination with cytarabine. In this phase 1, multicenter, open-label, dose-escalation study, 45 adults with relapsed/refractory acute myeloid leukemia (AML) received linifanib alone in arm A ( n = 29) and linifanib plus intermediate-dose cytarabine in arm B ( n = 16). Median treatment duration was 21 days (range 5-110). Linifanib was well tolerated overall. The most common grade 3/4 events were fatigue (arm A) and febrile neutropenia (arm B). The recommended phase 2 dose was 15 mg (alone), and 10 mg (with cytarabine). Evidence of on-target kinase inhibition in patients with FLT3-mutant and wild-type AML was seen. Decreased phosphorylated FLT3 was seen in 3/3 patients with FLT3-internal tandem duplication (ITD) with peripheral blast reductions and in 8/24 (33%) patients with wild-type, D835 or unknown FLT3 mutation. Eight/29 (28%) patients had decreased phosphorylated extracellular signal-regulated kinase (ERK). [ABSTRACT FROM AUTHOR]

Sudden blast phase (SBP) is a rare event that occurs in an unpredictable fashion amongst patients with chronic myeloid leukemia (CML) who otherwise appear to be responding satisfactorily to imatinib (IM) treatment. We investigated the incidence, clinical characteristics, treatment outcome and long-term follow-up of 213 patients with chronic phase CML treated with IM according to the European LeukemiaNet guidelines. Nine patients, eight of whom received IM as first-line therapy, developed SBP (4.2% of the total). They tended to have low or intermediate risk Sokal scores at diagnosis, a predominance of the lymphoid phenotype and a short interval from 'optimal' response to the development of BP. Five of the nine patients with SBP are alive in complete molecular remission; however, all of them underwent allogeneic hematopoietic stem cell transplant. The cumulative incidence of SBP for the patients who received IM as first-line therapy was 5.9% and the 2-year overall survival of the nine patients who developed SBP was 56%. Despite the improved outcome for patients with SBP receiving tyrosine kinase inhibitors (TKIs) and transplant, many of these patients are not salvaged with these therapies. This illustrates the need to develop predictive models to identify patients early whose response to TKI therapy will not be durable and hopefully prevent the transformation to advanced disease. [ABSTRACT FROM AUTHOR]

Background aims. The ability of hematopoietic progenitor cells-apheresis (HPC-A) that have been stored for many years after cryopreservation to reconstitute hematopoiesis following high-dose chemo/radiotherapy has not been well-documented. Methods. In this retrospective study, eight Canadian centers contributed data from 53 autologous stem cell transplants (ASCT) performed using HPC-A that had undergone long-term storage (>2 years, range 2-7 years) and 120 ASCT using HPC-A stored for <6 months (short-term storage). Results. The doses of nucleated and CD34++ cells per kilogram recipient weight were similar between the short- (mean ± SD, 4.7 ± 4.9 × 108 and 6.8 ± 4.3 × 106, respectively) and long- (4.0 ± 4.9 × 108 and 6.1 ± 3.4 × 106, respectively) term storage groups. The median days to neutrophils (absolute neutrophil count; ANC) >0.5 × 109/L (median 11 days for both short- and long-term storage) and platelets >20 × 109/L (median 12 and 11 for short- and long-term storage, respectively) post-ASCT were not significantly different between the two groups. When ASCT performed with <5 × 106/kg CD34++ cells was compared there was also no difference in ANC or platelet recovery (median 12 days for both after short-term storage, and 12 and 11 days, respectively, after long-term storage). Fourteen HPC-A products stored for >5 years also showed similar count recoveries as the entire long-term storage group (median 11 days for both ANC and platelets). Conclusions. Cryopreserved HPC-A can be stored for at least 5 years with no apparent loss in their ability to support hematopoietic reconstitution after high-dose chemotherapy. [ABSTRACT FROM AUTHOR]

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort. [ABSTRACT FROM AUTHOR]

DT388IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose was >12.5 µg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT388IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT388IL3 antibodies developed in most patients between day 15 and 30. Of 40 evaluable AML patients, 1 had a CR (8 months) and 1 had PR (3 months). Of 5 MDS patients, 1 had a PR (4 months). Because of the prolonged infusion schedule, many patients failed to receive six doses. DT388IL3 produces remissions in patients with relapsed/refractory AML and MDS with minimal toxicities, and alternate schedules of administration are needed to enhance the response rate. [ABSTRACT FROM AUTHOR]

The impact of karyotype on the outcome of patients who undergo autotransplant for acute myeloid leukemia (AML) in second remission (CR2) has not been explored. We evaluated the outcomes of 40 patients who proceeded to autotransplant for AML in CR2 at 2 centers. The median age at autotransplant was 50 years (18?–?64 years) and the median duration of first remission was 15 months (0.8?–?51 months). High-dose therapy was melphalan 140?–?160?mg/m 2 plus etoposide 60?mg/kg with or without total body irradiation (22), a busulfan-based regimen (17), and cyclophosphamide alone (1). Six patients (15%) died of treatment-related causes within the first 100 days. Event-free and overall survival at 3 years were both 38% (95% confidence interval 23?–?53%). At a median follow-up of 76 months (2?–?170) in surviving patients, 13 (32.5%) are alive and disease free. Graft purging did not significantly influence survival outcome (P?=?0.94), although platelet engraftment was significantly delayed (P?=?0.02). The relative risk of an event (relapse or death) for the karyotype risk groups was favorable 1.0; intermediate 4.2 (1.2?–?14.7); adverse 9.9 (1.5?–?63.9); unknown 2.3 (0.6?–?8.8) (P?=?0.028). We conclude that patients with AML in CR2 who undergo autotransplant can have durable remissions and those with a good risk karyotype are the most likely to obtain long-term disease-free survival. [ABSTRACT FROM AUTHOR]

Association between certain surface markers and acute myelogenous leukemia (AML) with t(8;21) has been described. The specificity and the predictive values of these markers have never been assessed. In this study, we aimed, to explore whether a specific pattern could predict for this translocation. Of 405 consecutive AML, 18 (4.4%) had the t(8;21). Patients with this cytogenetic abnormality showed higher frequency of CD34 ( P =0.003), HLA-DR ( P =0.03), Tdt ( P =0.02), CD19 ( P <0.0001), and CD56 ( P <0.0001) and lower CD33 ( P =0.0001). Taken singly, the sensitivity of these markers for AML with t(8;21) ranged between 39 and 100% with CD34 + having the highest and CD33 - having the lowest and the positive predictive values (PPV) ranged between 5 and 21% with CD19 + having the highest and HLA-DR + having the lowest. When combinations of different markers were analyzed by multivariate analysis, the pattern CD34 + /HLA-DR + /MPO + was found to have the highest sensitivity (100%) with a PPV of 14% and the pattern CD34 + /CD19 + /CD56 + had the highest PPV (100%) with a sensitivity of 67%. We conclude that AML with t(8;21) is better identified by a combination of markers than by a single antigen pattern, the absence of CD34 + , HLA-DR + or MPO + would preclude and the expression of the pattern CD34 + /CD19 + /CD56 + is highly predictive and could serve as a screening criteria for the t(8;21). [ABSTRACT FROM AUTHOR]