Low-dose melphalan in elderly patients with relapsed or refractory acute myeloid leukemia: A well-tolerated and effective treatment after hypomethylating-agent failure.

Relapsed or refractory (R/R) disease remains challenging in acute myeloid leukemia (AML), especially in elderly patients not considered eligible for intensive treatment options. We retrospectively evaluated the safety and efficacy of low-dose melphalan (LD-Mel) in a multicenter analysis in patients over 65 years with R/R AML, who previously had received ≥1 non-curative treatment line. The study included 31 patients (median age 77 years) with 1-4 previous treatment lines. Three patients (9.7%) achieved a complete remission. Two patients (6.5%) achieved a partial remission, nine patients (29.0%) had disease stabilization with reduction of peripheral or bone marrow blast burden, resulting in an overall response rate of 16.1% and 45.2% achieved clinical benefit. Responders showed a significantly longer median overall survival than non-responders (16.3 vs. 2.3 months, p < 0.001). Multivariate analysis identified complex karyotype as the only risk factor associated with inferior survival (p < 0.001), whereas prior treatment with hypomethylating agents (HMAs) in 25 of 31 patients was associated with superior OS, regardless of prior response to HMAs (p = 0.03). LD-Mel was well tolerated, with mild myelosuppressive side effects. Conclusively, LD-Mel is an effective treatment option in elderly patients with R/R AML, particularly after HMA therapy and in the absence of a complex karyotype.

Qualitative and Quantitative Analysis of Primary Neocortical Areas in Selected Mammals.

The present study focuses on the relationship between neocortical structures and functional aspects in three selected mammalian species. Our aim was to compare cortical layering and neuron density in the projection areas (somatomotor, M1; somatosensory, S1; auditory, A1; and visual, V1; each in a wider sense). Morphological and design-based stereological analysis was performed in the wild boar (Sus scrofa scrofa) as a representative terrestrial hoofed animal (artiodactyl) and the common dolphin (Delphinus delphis) as a highly derived related aquatic mammal (cetartiodactyl). For comparison, we included the human (Homo sapiens) as a well-documented anthropoid primate. In the cortex of many mammals, layer IV (inner granular layer) is the main target of specific thalamocortical inputs while layers III and V are the main origins of neocortical projections. Because the fourth layer is indistinct or mostly lacking in the primary neocortex of the wild boar and dolphins, respectively, we analyzed the adjacent layers III and V in these animals. In the human, all the three layers were investigated separately. The stereological data show comparatively low neuron densities in all areas of the wild boar and high cell counts in the human (as expected), particularly in the primary visual cortex. The common dolphin, in general, holds an intermediate position in terms of neuron density but exhibits higher values than the human in a few layers. With respect to the situation in the wild boar, stereological neuron counts in the dolphin are consistently higher, with a maximum in layer III of the visual cortex. The extended auditory neocortical field in dolphins and the hypertrophic auditory pathway indicate secondary neurobiological adaptations to their aquatic habitat during evolution. The wild boar, however, an omnivorous quadruped terrestrial mammal, shows striking specializations as to the sensorimotor neurobiology of the snout region.