It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versushost disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P ¼ 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) 41.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P ¼ 0.48). However, the adjusted hazard of increased creatinine 41.5 normal was significantly higher in the imatinib group (HR ¼ 4.09, P ¼ 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR ¼ 0.86, P ¼ 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR ¼ 0.65, P ¼ 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.

No abstract

In this paper we asked whether the increased production of two proinflammatory cytokines – tumor necrosis factor-α (TNFα) and interleukin-6 (IL6) in the absence of the inflammatory stimulus, a phenomenon frequently occurring in the elderly, may contribute to the decrease of natural killer (NK) cytotoxic activity. NK cell activity is a part of a nonspecific immunity directed against infected and transformed cells. We measured the levels of bioactive TNFα and IL6 during cytotoxic NK reactions and analyzed the effect of neutralizing monoclonal antibodies anti-TNFα and anti-IL6 on the outcome of cytotoxic reaction. Bioactive TNFα was produced in higher amounts during cytotoxic reactions of the elderly with low NK activity in comparison with its production by the elderly with high NK activity. Anti-TNFα decreased already low cytotoxic responses of the elderly while not having an effect on the cytotoxic potential of high responders. More of the bioactive IL6 was released during cytotoxic reactions of the elderly as compared with young people. There was, however, no relation between the height of NK cytotoxic activity and the amount of IL6. Our results suggest that the increased level of TNFα seen in the elderly low NK responders may pose a compensatory mechanism, necessary to keep the highest possible level of NK responses. The increased bioactivity of IL6 during NK reaction of the elderly does not seem to participate in the regulation of the level of NK cytotoxic activity.

Granulocyte-colony stimulating factor (G-CSF), in addition to myeloid and stem cells, mobilizes a large number of lymphoid cells. We examined which lymphoid populations were mobilized in 21 consecutive donors of peripheral blood stem cells (PBSC) and whether the differences in mobilization could affect the incidence of acute and chronic GvHD in respective HLA-identical recipients. G-CSF administration induced significant increases of donor B (CD3-CD19+) lymphocytes and slight increases of T (CD3+) and cytotoxic (CD16+CD56+) NK cells. The number of extrathymic cells (CD3+ cells with NK markers, or CD7+) remained unchanged except for an increase of CD3+CD57+CD8+ cells. Donors of patients without subsequent grade II-IV acute GvHD compared to donors of patients who developed significant acute GvHD were found to have in peripheral blood stable numbers of CD3+CD4+ cells producing IL2, with a concomitant increased number of CD3+CD4low+CD25+ T regulatory cells and decreased NK-mediated cytotoxicity, together with a higher number of suppressive extrathymic CD57+CD3+ cells in the blood and G-PBMC grafts. Increasing numbers of activated T and NK cells in the blood were associated with the development of chronic GvHD. We suggest that differences in steady-state levels and kinetics of G-CSF induced mobilization of donor lymphoid cells may in addition to other well-known factors affect the incidence of GvHD in HLA-identical recipients. However, owing to the small number of donor-recipient pairs studied, our results must be verified in a larger group of patients.