Lisa Lima

Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond

The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real‐time polymerase chain reaction (Q‐PCR) for BCR‐ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML).

High-dose cytarabine induction is well tolerated and active in patients with de novo acute myeloid leukemia older than 60 years

High‐dose cytarabine (HiDAC) is safe and very effective in younger patients with acute myeloid leukemia (AML), but it generally is not well tolerated in the elderly.

Prognostic Significance of Leukopenia at the Time of Diagnosis in Acute Myeloid Leukemia

We investigated the clinical significance of leukopenia at the time of diagnosis in a cohort of 225 patients with newly diagnosed acute myeloid leukemia (AML) at a single institution. Leukocyte count was treated as a continuous variable and, using a receiver operating characteristic curve (ROC), a cutoff of 3,600/μL had the best sensitivity and specificity for remission (complete remission [CR]), relapse-free survival [RFS], and overall survival [OS]). In a multivariable model, leukopenia at diagnosis had no effects on CR (hazard ratio [HR] = 2.02; confidence interval [CI], 0.9-4.3; P = .07), RFS (HR = 0.93; CI, 0.5-1.5; P = .8), or OS (HR = 1.05; CI, 0.7-1.5; P = .7). No differential expression of cell surface molecules (CD34, c-Kit, CXCR4, PECAM, VLA2, VLA-, VLA4, VLA5, and FLT3) was observed on simultaneously obtained marrow and blood blasts in the high- vs. low-leukocyte groups. We conclude that leukopenia at diagnosis carries no prognostic significance in AML.

Does pretreatment fluorescence in situ hybridization for BCR-ABL predict imatinib-associated hematologic toxicity in chronic myeloid leukemia?

Imatinib (IM)-associated myelosuppression is rare in gastrointestinal stromal cell tumors (<10%) but common in chronic myeloid leukemia (CML). Selective inhibition of predominantly Philadelphia chromosome (Ph+) driven hematopoiesis may explain myelosuppression in CML. In the absence of clinical methods to quantitate the Ph+/Ph− progenitor ratio, we hypothesized that the pre-IM percentage of BCR–ABL+ cells measured by fluorescence in situ hybridization (FISH) predicts for myelosuppression. FISH analyses performed within 30 days pre-IM 400 mg/day were analyzed in 89 patients with chronic phase CML at three institutions. Patients who developed grade ≥3 cytopenias had a higher percentage of positive FISH (90% vs. 83%; p = 0.02). Cytopenias lasted a median of 16 days, and all patients but one continued IM, achieved complete hematologic and cytogenetic remissions, and did not experience progression, with a follow-up of 61 months. In conclusion, IM-associated cytopenias are associated with a high pre-IM FISH, are reversible, and do not adversely affect outcomes.

Efficacy of dasatinib for the treatment of intractable chronic myeloid leukemia

Dasatinib (DAS) is a well tolerated oral dual SRC inhibitor with remarkable activity against all phases of imatinib-resistant chronic myeloid leukemia (CML). This paper focuses on the activity of DAS in intractable CML, and reviews outcomes of patients enrolled on DAS clinical trials. Safety and tolerability as well as practical tips for management of side-effects, and drug interactions are included.

Use of plasma exchange in pediatric severe sepsis in children's hospitals

ABSTRACT Pediatric severe sepsis (PSS) is an important cause of death in children. Mortality increases in those with sepsis and multiple organ dysfunction syndrome (MODS). Plasma exchange (PE) has been used as an adjuvant therapy in sepsis, with trials demonstrating variable success. This observational retrospective cohort study aimed to characterize patient demographics, PE use, mortality and resource utilization in septic children from 43 childrens hospitals from 2004 to 2012. Of 49,153 PSS cases, 1.8% utilized PE. Utilization increased to 4.8% in those with sepsis and MODS. Comorbidities affected 72–74% of patients. PE patients noted a longer hospitalization than PSS patients (39 vs 17 days). Overall mortality was 14.1% in PSS, increasing to 32.1% in PSS patients receiving PE. Mortality was 22% and 44.4% in PE patients without and with MODS respectively. Mortality decreased over the study period in both PE subgroups. In conclusion, PE utilization in PSS remained stable throughout the study period while PSS mortality decreased over time. Children utilizing PE had a higher associated mortality, but also greater comorbidities and MODS prevalence, likely representing a predilection towards use in more critically ill patients. These data can provide demographic and outcome results to inform future PE trials in sepsis. HIGHLIGHTSUse of plasma exchange (PE) in pediatric severe sepsis remains low, 1.8% of 49,153 patients.Patients with MODS were more likely to receive plasma exchange.Mortality was decreasing over the study period 2004–2012 while the use of PE remained stable.

Safety and efficacy of HiDAC induction in de novo AML patients age 60 and older.

6587 Background: High dose (>1.5 gm/m2) Ara-C (HiDAC) given during induction is effective and well-tolerated in patients with AML <60. We report safety and efficacy of HiDAC in AML patients ≥60. Methods: Retrospective analysis of newly diagnosed de novo AML ≥ 60 who underwent induction with 6 daily doses of cytarabine 2 gm/m2 and 3 daily doses of daunorubicin 45 mg/m2, which was repeated in patients achieving CR. Subsequent consolidations consisted of either 2 additional courses of 6 daily doses of cytarabine 2 gm/m2 or hematopoietic stem cell transplantation (HSCT). Study end points were toxicities, remission, relapse-free (RFS) and overall survival (OS). Kaplan-Meier curves were used to obtain RFS and OS. Results: 59 patients (30 M/29 F) with a median age 68 (range 60-86) received HiDAC induction between July 1996 and February 2005. 4 (7%) had favorable cytogenetics, 36 (61%) intermediate, 15 (25%) unfavorable, and 4 (7%) unknown. Median WBC was 20,000/mcL (700- 279,000/mcL). Overall, 41/59 (69%) achiev...