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Alisertib, an Aurora kinase A inhibitor, was evaluated in a Phase 1 study in combination with the histone deacetylase inhibitor vorinostat, in patients with relapsed/refractory lymphoid malignancies (N = 34; NCT01567709). Patients received alisertib plus vorinostat in 21-day treatment cycles with escalating doses of alisertib following a continuous or an intermittent schedule. All dose-limiting toxicities (DLTs) were hematologic and there were no study-related deaths. The recommended phase 2 dose (RP2D) of the combination was 20 mg bid of alisertib and 200 mg bid of vorinostat on the intermittent schedule. A 13-patient expansion cohort was treated for a total of 18 patients at the RP2D. There were no DLTs at the RP2D, and toxicities were mainly hematologic. Two patients with DLBCL achieved a durable complete response, and two patients with HL achieved partial response. Alisertib plus vorinostat showed encouraging clinical activity with a manageable safety profile in heavily pretreated patients with advanced disease. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated extramedullary relapse in acute myelogenous leukemia (AML) patients that underwent reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT). Topics explored include the medical history, clinical assessment, and treatment characteristics of AML patients involved in the study, the definition of relapse/progression incidence, and the overall patient survival recorded after alloHCT.

We performed a phase II study of oral vorinostat (200 mg twice daily, days 1-14 of a 21-day cycle), a histone and protein deacetylase inhibitor, to examine efficacy and tolerability in patients with relapsed/refractory Hodgkin lymphoma (HL) with ≤ 5 prior therapies. The primary endpoint was the objective response rate (ORR), with secondary endpoints of progression-free survival (PFS), overall survival (OS), safety and tolerability. A two-stage design was used for patient accrual. Twenty-five eligible patients were accrued in the first stage. Median time on treatment was 3.8 months. The ORR was 4% (one partial response). Median PFS was 4.8 months. The drug was well tolerated. The second stage of accrual was not opened due to few objective responses. Oral vorinostat has limited single-agent activity in relapsed/refractory HL. There was one partial response, while seven other patients had stable disease for > 1 year, including two with stable disease for nearly 3 years, suggesting that further studies in combination with other active agents in this setting may be warranted. [ABSTRACT FROM AUTHOR]

Organ-specific stem cells have been identified in a variety of mammalian tissues. These cells hold great promise for cellular therapy if they can reliably produce functional progeny of specific lineages. A central dogma in development has been that organ-specific stem cells are restricted to making the differentiated cell types of the tissue from which they are isolated. However, a substantial body of evidence exists that stem-cell populations from neural and hematopoietic tissues can generate the other cell types, suggesting that adult organ-specific stem cells may have a broader differentiation potential than originally thought. It remains unclear whether this apparent stem cell plasticity is attributable to transdifferentiation of tissue specific stem cells, the co-existence of multiple stem cells with different potentials, or resident totipotent stem cells in these tissues. Recent evidence, in fact, indicates that there may be a fourth explanation for the "apparent" plasticity of stem cells: cell fusion. Here, the authors critically examine the existing data to assess the extent of phenotypic conversion of bone marrow-tobrain and brain-to-blood and discuss some of the contentious issues surrounding these studies. We conclude that there is strong evidence for a multipotent neurohematopoietic stem-cell population in human and mouse brain, although further characterization of these cells will be required if the goal of engineering tissues for therapeutic applications is to be realized. [ABSTRACT FROM AUTHOR]

AbstractReactive pleocytosis in the CSF has been observed with blinatumomab but has not been well-described. We performed a retrospective study of 88 patients who received intrathecal chemotherapy (IT) while on blinatumomab with CSF analyzed to determine if pleocytosis had an impact efficacy and safety. Blinatumomab was used for relapsed/refractory 62.5%, MRD-positive 31.8%, and consolidation in MRD-negative 5.7%. The incidence of pleocytosis in CSF was 51% and was more frequent after day 15 (55.8% vs. 18.2%, p = 0.025). Pleocytosis did not impact CR, clearance of MRD positivity, PFS and OS rates. Lower incidence of non-CNS extramedullary relapse was seen (3.7% vs. 30.8%, p = 0.011) with pleocytosis in CSF. Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity. [ABSTRACT FROM AUTHOR]

A letter is presented in response to the article "Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist," by H. E. Broxmeyer and colleagues in the 2005 issue.

The article discusses research on the administration of plerixafor to Hodgkin lymphoma (HL) patients. Topics explored include the effectiveness of plerixafor in improving mobilization in non-HL patients that received granulocyte-colony stimulating factor (G-CSF), the demographic background of patients involved in the study, and the favorable response of patients to plerixafor. Details about the peripheral blood CD34+ cells recorded in HL patients that received plerixafor are also presented.