Key Points KIT exon 17 mutation is a poor prognostic factor in AML patients with RUNX1-RUNX1T1, but not in those with CBFB-MYH11. NRAS mutation is a poor prognostic factor in AML patients with CBFB-MYH11.

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Knowing the impact of chronic graft-versus-host disease (GVHD) on quality of life (QoL) after allogeneic hematopoietic stem cell transplantation (allo-HCT) by GVHD type and severity is critical for providing care to transplant survivors. We conducted a cross-sectional questionnaire study to examine the relationship between patient-reported QoL as measured by the Medical Outcomes Study 36-Item Short-Form Health Survey, Functional Assessment of Cancer Therapy-Bone Marrow Transplant, and visual analogue scale (VAS) and chronic GVHD defined by the National Institutes of Health (NIH) criteria. Recipients of allo-HCT for hematologic disease between 1995 and 2009 aged ≥ 16 years at transplant and ≥20 years at the time of the survey who were relapse-free were eligible. A total of 1140 pairs of patient and physician questionnaires were included in the analysis. By NIH global severity score, QoL scores in all aspects were significantly lower in patients with higher global and organ-specific severity grades, independent of background variables. Compared with patients without GVHD symptoms, those with mild symptoms had impaired physical and general QoL according to global severity score and organ-specific scores except for the genital tract. Mild symptoms in the lungs, gastrointestinal tract, and joints and fascia were associated with clinically meaningful deterioration of physical QoL. VAS scores provided by physicians were generally higher than those provided by patients. Differences between scores reported by patients and physicians were larger for patients with no or mild GVHD symptoms. Our findings based on more than 1000 long-term survivors after HCT enabled us to identify a target of care, informing survivorship care protocols to improve post-transplantation QoL.

Recent studies have suggested that one of the polycomb group genes, BMI-1, has an important role in the maintenance of normal and leukemic stem cells by repressing the INK4a/ARF locus. Here, we quantitatively examined BMI-1 expression level in samples from patients with acute myeloid leukemia (AML) and other hematologic malignancies. Moderate to high BMI-1 expression was detected in AML patients, and the BMI-1 expression levels in AML samples were significantly higher than in normal bone marrow controls (P = .0011). Specimens of French-American-British classification subtype M0 showed higher relative expression of the BMI-1 transcript (median, 390.2 3 10(-3)) than the other subtypes (median, 139.0 3 10(-3)) (P < .0001). Leukemia other than AML showed low to moderate expression. INK4a-ARF transcript expression tended to be inverse proportion to that of BMI-1. In an M0 patient with a high BMI-1 transcript level, the INK4a-ARF transcript level fell promptly and maintained a low value after the patient achieved complete remission. These results indicated that a subgroup of M0 patients has a high expression level of polycomb group gene BMI-1, which may contribute to leukemogenesis.

Post transplant immune disorders are problematic in cord blood transplantation (CBT) for adult patients, and optimal prophylaxis has not been established. We investigated whether intensive graft-versus-host disease (GVHD) prophylaxis using short-term methotrexate (MTX) has a prognostic impact on CBT. Post-CBT immune reactions were classified according to time course as pre-engraftment immune reaction (PIR), engraftment syndrome (ES) or acute GVHD. Between March 2001 and November 2005, a total of 77 patients underwent CBT at eight transplantation centers. Median age was 48 years (range, 18-69 years). Preparative regimens comprised myeloablative (n ¼ 31) or reduced-intensity (n ¼ 46). Acute GVHD prophylaxis included cyclosporine alone (n ¼ 23), tacrolimus alone (n ¼ 12), cyclosporine plus MTX (n ¼ 17), tacrolimus plus short-term MTX (n ¼ 23) or cyclosporine plus methylprednisolone (n ¼ 2). Cumulative incidences of PIR, ES and grade II-IV GVHD were 36, 12 and 23%, respectively. Short-term MTX exerted significant favorable effects on post-CBT immune reactions (hazard ratio, 0.55; 95% confidence interval (95% CI), 0.31-0.98; P ¼ 0.04) in multivariate analysis. Overall survival rates for patients with and without short-term MTX at day 180 were 59% (95% CI, 42-73%) and 16% (95% CI, 6.6-30%) (P ¼ 0.0001), respectively. Shortterm MTX could offer one optimal regimen to reduce immune reactions and improve outcomes in CBT.