The majority of patients with chronic myeloid leukemia in chronic phase gain substantial benefit from imatinib but some fail to respond or lose their initial response. In 2006, the European LeukemiaNet published recommendations designed to help identify patients responding poorly to imatinib. Patients were evaluated at 3, 6, 12, and 18 months and some were classified as "failure" or "suboptimal responders." We analyzed outcomes for 224 patients with chronic myeloid leukemia in chronic phase treated in a single institution to validate these recommendations. Patients were followed for a median of 46.1 months. At each time point, patients classified as "failure" showed significantly worse survival, progression-free survival, and cytogenetic response than other patients; for example, based on the assessment at 12 months, the 5-year survival was 87.1% versus 95.1% (P ‫؍‬ .02), progression-free survival 76.% versus 90% (P ‫؍‬ .002), and complete cytogenetic response rate 26.7% versus 94.1% (P < .001). Similarly, the criteria for "suboptimal response" at 6 and 12 months identified patients destined to fare badly, although criteria at 18 months were less useful. The predictive value of some other individual criteria varied. In general, the LeukemiaNet criteria have useful predictive value, but a case could now be made for combining the categories "failure" and "suboptimal response." (Blood. 2008;112:4437-4444)

Summary Twenty‐two patients with acute myeloid leukaemia were recruited into a phase I/II clinical trial investigating the vaccination of patients in complete remission (CR) with autologous dendritic‐like leukaemia cells (DLLC). At trial entry, leukaemia cells were harvested and tested for their ability to undergo cytokine‐induced dendritic cell differentiation. Patients were then treated with intensive chemotherapy. Five patients achieved both CR and had leukaemia cells that successfully underwent differentiation and therefore proceeded to vaccination. Four escalating doses of DLLC were administered weekly by subcutaneous injection. Vaccination was generally well tolerated although one patient developed extensive eczema and an increased antinuclear factor titre possibly indicating induction of autoimmunity. Development of anti‐leukaemic T‐cell responses was assessed by enzyme‐linked immunospot analysis of gamma‐interferon secreting T lymphocytes and by human leucocyte antigen tetramer analysis for WT1‐specific T cells. Increases in anti‐leukaemic T‐cell responses were demonstrated in four patients, but only two of the five remained in remission more than 12 months postvaccination. The study has demonstrated that generation of DLLC is feasible in only a subgroup of patients and is currently neither broadly applicable or clinically effective.

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SummaryWe assessed the potential of tumour cell/dendritic cell fusion hybrids to generate in vitro anti-leukaemic T-cell responses following co-culture with autologous remission lymphocytes in six patients with acute myeloid leukaemia (AML). Comparison was made to anti-leukaemic responses induced by mature dendritic cells (mDC) co-cultured with autologous, irradiated myeloid blasts. Fusion hybrids induced anti-leukaemic T-cell immune responses in three of six patients. Tumour-pulsed mDC induced T-cellular responses in two other patients. Only one of six patients remission lymphocytes failed to develop leukaemia-directed immune responses following stimulation with either construct. Anti-proliferative properties of fusion hybrids against allogeneic lymphocytes were observed in mixed lymphocyte-leukaemia reactions and were found not to be specific to the cell fusion partners and did not prevent the ability of AML-mDC heterokaryons to induce autologous anti-leukaemic cytotoxicity. We conclude that tumour cell/dendritic cell fusion hybrids hold promise as a cellular vaccine for AML.