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An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), prednisone (100 mg days 3-7) and vincristine (1·4 mg/m2) (O- CHOP), as frontline treatment for follicular lymphoma ( FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg ( n = 29) or 1000 mg ( n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high-risk Follicular Lymphoma International Prognostic Index ( FLIPI) scores in the 500- and 1000-mg dose groups, respectively. Overall response rate was 90% for the 500-mg group and 100% for the 1000-mg group. 62% of patients achieved complete response ( CR)/unconfirmed CR ( CRu). 76% of patients with FLIPI score 3-5 attained CR/ CRu. Longer follow-up time is needed for analysis of survival end points. The most common Common Terminology Criteria grade 3-4 investigator-reported adverse events were leucopenia (29%) and neutropenia (22%). No deaths have been reported. O- CHOP was safe and efficacious in patients with previously untreated FL, including high-risk FLIPI groups. This trial was registered at ( NCT00494780). [ABSTRACT FROM AUTHOR]

The treatment of chronic lymphocytic leukaemia ( CLL) has been improved by introduction of monoclonal antibodies (m Abs) that exert their effect through secondary effector mechanisms. CLL cells are characterized by expression of CD5 and CD23 along with CD19 and CD20, hence anti- CD5 Abs that engage secondary effector functions represent an attractive opportunity for CLL treatment. Here, a repertoire of m Abs against human CD5 was generated and tested for ability to induce complement-dependent cytotoxicity ( CDC) and antibody-dependent cell-mediated cytotoxicity ( ADCC) both as single m Abs and combinations of two m Abs against non-overlapping epitopes on human CD5. The results demonstrated that combinations of two m Abs significantly increased the level of CDC compared to the single m Abs, while no enhancement of ADCC was seen with anti- CD5 m Ab combinations. High levels of CDC and ADCC correlated with low levels of Ab-induced CD5 internalization and degradation. Importantly, an anti- CD5 m Ab combination enhanced CDC of CLL cells when combined with the anti- CD20 m Abs rituximab and ofatumumab as well as with the anti- CD52 m Ab alemtuzumab. These results suggest that an anti- CD5 m Ab combination inducing CDC and ADCC may be effective alone, in combination with m Abs against other targets or combined with chemotherapy for CLL and other CD5-expressing haematological or lymphoid malignancies. [ABSTRACT FROM AUTHOR]

Abstract: During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients by treatment with chemotherapy and/or irradiation (t-AML). Cytogenetic analysis was carried out in 93%, of which 61% had clonal chromosome aberrations. MDS-AML correlated to a normal karyotype (P < 0.001). t-AML correlated to abnormal clones with numerical and structural aberrations (P = 0.03), five or more unrelated aberrations (P = 0.03), marker chromosomes (P = 0.006), abnormal mitoses only (P = 0.01), female sex (P < 0.001), and −7 (P = 0.006). Centromeric breakage correlated to a complex karyotype (P = 0.01). The frequencies of aberrations in s-AML patients were compared with an age-matched group of de novo AML patients diagnosed in the same area and period. In this comparison, s-AML only correlated to −7 (P = 0.02). In 42 patients, we found that MDS patients with an abnormal karyotype were more likely to show cytogenetic evolution during progression to AML than MDS patients with a normal karyotype (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities. [ABSTRACT FROM AUTHOR]

The purpose of this phase 1–2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumumab concentration profiles were fitted well by a two-compartment model with different elimination rate constant at first infusion compared to the remaining infusions in line with the observed rapid and sustained B-cell depletion. Exposure to ofatumumab was linked to clinical outcomes: high exposure was associated with higher probability of overall clinical response and longer progression-free survival. This association still remained statistically significant even when adjusting for relevant baseline covariates including tumour burden. The trial was registered at (NCT00093314). [ABSTRACT FROM AUTHOR]

During a 10-year period (1992–2001) in the region of Southern Denmark, 337 patients aged 15 years or older (range 16–93 years, median 67 years) were diagnosed with acute myeloid leukaemia (AML). Cytogenetic analysis was carried out in 90%, of whom 53% had clonal chromosome aberrations. Some 24% and 31% had only numerical or structural abnormalities respectively. The remaining patients showed both types of abnormalities. Ploidy levels in decreasing order were: pseudodiploidy, 41%; hyperdiploidy, 32%; and hypodiploidy, 27%. Pseudodiploidy characterizes type M3 (70%) and hypodiploidy M6 (56%). Recurrent cytogenetic abnormalities – t(8;21), t(15;17) and inv(16) – were found in 3·3%, 3·3% and 2·0% of all patients respectively. Prognostically intermediate and adverse aberrations were found in 39% and 44%, respectively, of those with an abnormal karyotype. Rare recurrent aberrations were found in two patients in this material. A previously described non-recurrent abnormality was found to be recurrent in one patient [der(20)t(11;20)(q13.2;p13)]. New, previously undescribed abnormalities were found in 41 patients. Statistically significant correlations were found between t(15;17) and young age ( P < 0·001), inv(16) and young age ( P < 0·006), −17 and M6 ( P = 0·007), and M6 and complex karyotype with five or more unrelated aberrations ( P = 0·004). We conclude that this truely population-based cytogenetic study of adult AML showed distributions of chromosome abnormalities that differ from those described so far. [ABSTRACT FROM AUTHOR]