Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS.

Clonal cytogenetic abnormalities are a major risk factor for relapse after hematopoietic cell transplantation (HCT) for myelodysplastic syndrome (MDS). We determined the impact of the recently established 5-group cytogenetic classification of MDS on outcome after HCT. Results were compared with the impact of the International Prognostic Scoring System (IPSS) 3 cytogenetic risk groups, and the additional effect of a monosomal karyotype was assessed. The study included data on 1007 patients, 1-75 years old (median 45 years), transplanted from related (n = 547) or unrelated (n = 460) donors. Various conditioning regimens were used, and marrow, peripheral blood, or cord blood served as stem cell source. Both IPSS and 5-group cytogenetic risk classifications were significantly associated with post-HCT relapse and mortality, but the 5-group classification discriminated more clearly among the lowest- and highest-risk patients. A monosomal karyotype tended to further increase the rates of relapse and mortality, even after considering the IPSS or 5-group classifications. In addition, the pathologic disease category correlated with both relapse and mortality. Mortality was also impacted by patient age, donor type, conditioning regimen, platelet count, and etiology of MDS. Although mortality declined significantly in recent years, novel strategies are needed to overcome the barrier of high-risk cytogenetics.

Winter body temperature patterns in free-ranging Cape ground squirrel, Xerus inauris: no evidence for torpor.

The body temperature (T(b)) of Cape ground squirrels (Xerus inauris, Sciuridae) living in their natural environment during winter has not yet been investigated. In this study we measured abdominal T(b) of eight free-ranging Cape ground squirrels over 27 consecutive days during the austral winter. Mean daily T(b) was relatively stable at 37.0 ± 0.2°C (range 33.4 to 40.2°C) despite a marked variation in globe temperature (T(g)) (range -7 to 37°C). Lactating females (n = 2) consistently had a significantly higher mean T (b) (0.7°C) than non-lactating females (n = 3) and males. There was a pronounced nychthemeral rhythm with a mean active phase T(b) of 38.1 ± 0.1°C and a mean inactive phase T(b) of 36.3 ± 0.3°C for non-lactating individuals. Mean daily amplitude of T(b) rhythm was 3.8 ± 0.2°C. T(b) during the active phase closely followed T(g) and mean active phase T(b) was significantly correlated with mean active phase T(g) (r(2) = 0.3-0.9; P < 0.01). There was no evidence for daily torpor or pronounced hypothermia during the inactive phase, and mean minimum inactive phase T(b) was 35.7 ± 0.3°C for non-lactating individuals. Several alternatives (including nocturnal huddling, an aseasonal breeding pattern and abundant winter food resources) as to why Cape ground squirrels do not employ nocturnal hypothermia are discussed.

Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

We conducted a study to estimate the maximum tolerated dose (MTD) of (131)I-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of (131)I-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.