The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML.

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Minor histocompatibility antigens (mHags) play an important role in both graft-versustumor effects and graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. We applied biochemical techniques and mass spectrometry to identify the peptide recognized by a dominant tumor-reactive donor T-cell reactivity isolated from a patient with relapsed multiple myeloma who underwent transplantation and entered complete remission after donor lymphocyte infu- IntroductionAllogeneic stem cell transplantation (SCT) is a curative treatment in patients with hematologic cancers. In addition to the antitumor effects of chemotherapy, antibody treatment and/or irradiation administered as the conditioning regimen prior to transplantation, an allogeneic graft-versus-tumor (GVT) immunoreactivity significantly contributes to the curative potential of this therapy. [1][2][3][4][5] This GVT reactivity following HLA-matched SCT has been demonstrated to be mediated primarily by T cells from the donor. All reactive T cells from donor origin may not only mediate the beneficial GVT effect but are also responsible for the development of graft-versus-host disease (GVHD), which is the major detrimental complication after allogeneic SCT. 6,7 T-cell depletion of the stem cell graft removes both GVHD and GVT effect. [8][9][10] The antitumor reactivity can be reintroduced in case of persistent or relapsed hematologic malignancies after transplantation by donor lymphocyte infusion (DLI). [11][12][13][14][15] Whereas profound antitumor effects are frequently associated with GVHD in patients responding to DLI, postponed administration of DLI has been associated with a decreased risk of severe GVHD, and clinical observations indicate that more subtle antitumor reactivities can also be observed in the absence of GVHD. [16][17][18] The main targets of both GVHD and GVT reactivity after HLA-matched allogeneic SCT are minor histocompatibility antigens (mHags). [19][20][21] mHags are peptides differentially expressed by donor and recipient that can be recognized in the context of self-HLA molecules. mHags may arise from differential processing of peptides due to polymorphisms in the gene encoding the protein or by direct polymorphisms in the peptide sequence that is presented in the HLA molecules. 22,23 The clinical manifestation of immune responses against mHags is likely to be determined by the specific tissue expression of the proteins encoding these antigens. Whereas mHags constitutively expressed in many tissues are likely to be targets for combined alloreactive GVHD and GVT responses, T-cell responses directed against antigens that are restricted to the hematopoietic cell lineages including the malignant T cells of hematopoietic origin are likely to mediate a GVT reactivity without severe GVHD. 21,[24][25][26][27][28][29][30][31] However, antigens with variable expression in tissues may also be targets for relatively specific GVT responses because these proteins may not be expressed or recognized on normal tissues under steady state c...

PurposeTo describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients.MethodsHRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment (“watch and wait”), chlorambucil treatment only, and patients with other treatment(s).ResultsHRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy.ConclusionsCLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s11136-015-1039-y) contains supplementary material, which is available to authorized users.