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Acute myeloid leukemia with mutated nucleophosmin (NPMc+ AML) forms a distinct AML subgroup with better prognosis which can potentially be associated with immune response against the mutated nucleophosmin (NPM). As the T-cell-mediated immunity involves antigen presentation on HLA class I molecules, we hypothesized that individuals with suitable HLA type could be less prone to develop NPMc+ AML. We compared HLA class I distribution in NPMc+ AML patient cohort (398 patients from 5 centers) with the HLA allele frequencies of the healthy population and found HLA-A*02, B*07, B*40 and C*07 underrepresented in the NPMc+ AML group. Presence of B*07 or C*07:01 antigen was associated with better survival in patients without concomitant FLT3 internal tandem duplication. Candidate NPM-derived immunopeptides were found for B*40 and B*07 using prediction software tools. Our findings suggest that a T-cell-mediated immune response could actually explain better prognosis of NPMc+ patients and provide a rationale for attempts to explore the importance of immunosuppressive mechanisms in this AML subgroup. [ABSTRACT FROM AUTHOR]

The article describes a novel strategy to generate high-avidity, Wilms' tumor antigen 1 (WT1)126 peptide-reactive CD8+ T cell clones with acute myeloid leukemia (AML)-directed cytotoxicity. Results of the study suggested that streptamer technology is an effective novel to generate high-avidity, WT1-reactive CD8+ T cell clones with anti-leukemic activity.

The role of allogeneic stem cell transplantation ( HSCT) as compared to chemotherapy in acute myeloid leukaemia ( AML) patients with abnormalities of chromosome 17p [abnl(17p)] has not yet been defined. Therefore, we analysed 3530 AML patients treated in three randomized, prospective, controlled clinical trials and compared post-remission therapies using a multivariate Cox regression analysis to determine whether allogeneic HSCT is superior than chemotherapy in overcoming the detrimental impact of patients with abnl(17p) AML. One hundred and forty-three patients (4%) were identified with abnl(17p) AML. All patients had received intensive induction chemotherapy. Forty-seven patients with a median age of 54 years (18-69 years) proceeded to allogeneic HSCT in first or second remission. The 3-year overall survival ( OS) rate for the entire cohort of patients was 4% [95% confidence interval ( CI), 1-7%]. OS and event-free survival at 3 years, calculated from the day of HSCT, was 11% (95% CI, 2-20%) and 6% (95% CI, 0-13%), respectively. Multivariate Cox regression analysis showed no benefit of allogeneic HSCT compared to chemotherapy (Hazard Ratio 0·97, 95% CI 0·56-1·67, P = 0·9). In conclusion, allogeneic HSCT does not improve survival in patients with abnl(17p) AML as compared to other adverse cytogenetic risk abnormalities. [ABSTRACT FROM AUTHOR]

The addition of radioimmunotherapy to conventional and reduced-intensity conditioning has been shown to be feasible and effective. Within an ongoing prospective phase II trial, 22 patients with advanced myeloid malignancies and a median age of 65 years (range 54–76) received anti-CD66 Rhenium radioimmunotherapy followed by fludarabine (150 mg/m2), busulfan (8 mg/kg) and alemtuzumab (75 mg) before allogeneic haematopoietic stem cell transplantation from matched sibling ( n = 7) and unrelated donors ( n = 15). The extramedullary toxicity in the first 100 d post-transplantation was limited and all patients engrafted with complete donor chimaerism. The incidence of non-relapse mortality at day 100 and after 2 years was 4·5% and 23%, respectively. The probability of overall survival at 2 years was 40%. A comparison with a younger historical cohort (median age 57 years) having received the same dose of fludarabine and busulfan but neither radioimmunotherapy nor alemtuzumab showed no difference in outcome. Although the use of alemtuzumab reduced the incidence of acute graft- versus-host-disease, it was associated with a relapse incidence of 40% despite the incorporation of radioimmmunotherapy. In summary, we confirmed the feasibility of combined radioimmunotherapy and reduced-intensity conditioning in elderly patients. Further optimisation, probably involving less T cell depletion, is necessary before a randomized comparison with standard conditioning can be planned. [ABSTRACT FROM AUTHOR]

Abstract: It is hypothesised that an effective graft-vs.-leukaemia reaction contributes substantially to the therapeutic effect of reduced intensity conditioning stem cell transplantation in chronic myeloid leukaemia. However, kinetic data on eradication of leukaemia cells and stem cell engraftement which could support this assumption are lacking . Thus, we investigated bcr/abl fusion transcripts and haematopoietic chimerism in 14 patients undergoing such a transplantation protocol. Ten of them obtained a complete molecular remission, and two patients achieved haematologic remissions but remained bcr/abl positive. Weekly determinations of bcr/abl transcript numbers by qualitative and quantitative polymerase chain reaction and donor chimerism revealed that 10 responders cleared bcr/abl positive cells from the peripheral blood within a median of 9 wk (range 3–22 wk). The close relation (P = 0.0075) between the firstoccurrence of graft-vs.-host disease and the complete clearance ofbcr/abl positive blood cells argues in favour of an effective graft-vs.-leukaemia reaction. [ABSTRACT FROM AUTHOR]