Blood Cancer Network Ireland (BCNI) and National Cancer Registry Ireland (NCRI) collaboration: challenges and utility of an Enhanced Blood Cancer Outcomes Registry (EBCOR) pilot.

Background: The Blood Cancer Network Ireland and National Cancer Registry Ireland worked to create an Enhanced Blood Cancer Outcomes Registry (EBCOR). Enhanced data in acute myeloid leukaemia (AML) included an extensive data dictionary, bespoke software and longitudinal follow-up.

Aims: To demonstrate the utility of the database, we applied the data to examine a clinically relevant question: Charlson comorbidity index (CCI) usefulness in predicting AML patients' survival.

A novel aryl-guanidinium derivative, VP79s, targets the signal transducer and activator of transcription 3 signaling pathway, downregulates myeloid cell leukaemia-1 and exhibits preclinical activity against multiple myeloma.

Aims: We have recently described a novel guanidinium-based compound, VP79s, which induces cytotoxicity in various cancer cell lines. Here, we aim to investigate the activity of VP79s and associated mechanisms of action in multiple myeloma (MM) cells in vitro and ex vivo.

Main Methods: The effects of VP79s on cell viability and induction of apoptosis was examined in a panel of drug-sensitive and drug-resistant MM cell lines, as well as ex vivo patient samples and normal donor lymphocytes and platelets.

Melphalan 140 mg/m or 200 mg/m for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party.

Melphalan at a dose of 200 mg/m is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m and melphalan 140 mg/m are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m (n=245) and melphalan 200 mg/m (n=1719) groups.

Retinoic acid induction of CD1d expression primes chronic lymphocytic leukemia B cells for killing by CD8 invariant natural killer T cells.

Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL).

BRAF V600E-Negative Hairy Cell Leukaemia.

Since the initial report of the BRAF V600E mutation in hairy cell leukemia, numerous investigators have demonstrated the presence of this activating mutation in nearly all cases of this disease. A case of hairy cell leukemia is documented with a classical clinical, morphological, immunophenotypic, and cytochemical profile in which the BRAF V600E was not detected. The diagnostic and therapeutic implications are discussed.

The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells.

Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells.

Incidence of the BRAF V600E mutation in chronic lymphocytic leukaemia and prolymphocytic leukaemia.

The spectrum of underlying molecular abnormalities of clinically and biologically heterogeneous chronic lymphocytic leukaemia (CLL) and prolymphocytic leukaemia (PLL) has yet to be identified. While whole genome sequencing has identified several genes implicated in the pathogenesis and progression of CLL, the molecular lesions in a substantial proportion of patients remain to be elucidated. The incidence of the BRAF V600E mutation, widely implicated in solid tumours and other B-cell malignancies, was sought in a cohort of patients with CLL and related disorders.

T-lymphoblastic leukemia/lymphoma: a single center retrospective study of outcome.

T-lymphoblastic leukemia/lymphoma (LBL and ALL) is a rare lymphoid malignancy typically presenting in adolescent and young adult males. Patients are traditionally treated with ALL-type protocols, with no consensus on the role of maintenance therapy, or allogeneic or autologous transplant. Outcome results are thus difficult to interpret.

The novel tubulin-targeting agent pyrrolo-1,5-benzoxazepine-15 induces apoptosis in poor prognostic subgroups of chronic lymphocytic leukemia.

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL.

Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma.

Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls).

CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) follows a variable clinical course which is difficult to predict at diagnosis. We assessed somatic mutation (SHM) status, CD38 and ZAP-70 expression in 87 patients (49 male, 38 female) with stage A CLL and known cytogenetic profile to compare their role in predicting disease progression, which was assessed by the treatment free interval (TFI) from diagnosis. Sixty (69%) patients were SHM+, 24 (28%) were CD38+ and ten (12%) were ZAP-70+.

The value of autofluorescence as a diagnostic feature of acute promyelocytic leukemia.

Autofluorescence is an immunophenotypic characteristic of leukemic blasts in acute promyelocytic leukemia (APL). We examined the fluorescent intensity of isotype controls in 25 cases of APML and 25 controls with acute myeloid leukemia. The fluorescence of the FITC- and PE-conjugated controls was consistently higher in APML.