Dendritic cells in bone marrow at diagnosis and after chemotherapy in adult patients with acute myeloid leukaemia.

Dendritic cells (DCs) develop in the bone marrow from haematopoietic progenitor cells. Two subsets, plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), have been identified. Little is known regarding DC levels in bone marrow of patients with acute myeloid leukaemia (AML) before and after chemotherapy. We investigated relative pDC and mDC levels in bone marrow from 37 hospital controls and 60 patients with AML [at diagnosis, complete remission (CR) and follow-up] using four-colour flow cytometry. The pDC immunophenotype was characterized as lin-/HLA-DR+/CD123 +  and mDC as lin-/HLA-DR+/CD11c+. In 69% of patients with AML, no DCs were detected at diagnosis. At CR, mDC levels were the same in patients with AML and hospital controls while pDC levels were slightly lower. There was no association between minimal residual disease or survival rates and DC levels. Patients with low mDC levels at CR were more likely to suffer from complicated infections, although the difference was not statistically significant. Altogether, there was a profound decrease in DC levels in patients with AML at diagnosis. DC levels increased at CR and were higher than in hospital controls after post-remission therapy, suggesting that DCs recover after repeated chemotherapy. There may be an association between mDC levels and infectious complications.

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial.

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of 4 units over 8 weeks were included. Aza 75 mg m(-2) d(-1), 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations.