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Aims: Fusion proteins of unequal recombination events at the β-globin locus have pathological effect. The haemoglobin (Hb) variants of type Lepore are fusion proteins characterised by β-like globin chains with a δ-globin ( HBD ) N-terminus and a β-globin ( HBB ) C-terminus, whereas reciprocal products of underlying crossover events hold a HBB N-terminus and HBD C-terminus instead. Finally, Hb Parchman contains a β-like globin chain with a central HBB fragment and HBD -derived N-termini and C-termini, whereas reciprocal hybrid proteins are as yet unknown., Methods: The propositus was an 80-year-old Caucasian man, whose HbA1c quantification by HPLC (Variant II turbo) for exclusion of type-2 diabetes revealed an abnormal peak. Haemoglobins were analysed by ion-exchange HPLC (Variant II) and capillary electrophoresis (Sebia Capillarys Flex) and DNA by automatic Sanger sequencing of δ-globin and β-globin genes., Results: Sequencing showed an HBB-HBD-HBB hybrid gene, with HBD -derived central codons 9-31, and HBB -derived UTRs and complementary coding regions. The corresponding new hybrid haemoglobin (Hb Palencia) is represented at ≈40%, similar to HbA., Conclusion: Hb Palencia contains the first globin variant with internal HBD sequences and HBB -derived N-terminal and C-terminal and regulatory sequences. Relative quantity of the new βδβ-type variant suggests transcriptional control by HBB elements and a half-life similar to normal HBB ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Splenic marginal zone lymphoma (SMZL), characterized in the WHO classification of lymphoid tumors, is a rare disorder comprising less than 1% of lymphoid neoplasms; only a few series concerning this entity have been published. Although this type of lymphoma is well defined histologically, its histogenesis remains obscure. Moreover, specific biological markers are still lacking and immunophenotype profile is not specific. These and other reasons, such as the existence of cytogenetic subtypes, have led to some authors to suspect that SMZL constitutes a heterogeneous entity. We have analyzed a series of sixteen SMZL cases from four hospitals in our community, from a clinical, biological and pathological point of view. When compared with those reported in the literature, our findings show three main differences: our patients less frequently showed an intrasinusoidal bone marrow infiltration pattern; the presence of a serum monoclonal component was rarely seen; and CD5-positive SMZL cases appear to be more common than previously thought.

Melphalan-prednisone (MP) has been the gold standard treatment for more than 30 years in elderly multiple myeloma (MM) patients. In order to assess whether the combination of dexamethasone with melphalan (MD) could improve on the efficacy of MP, we have carried out a randomized trial comparing both treatment approaches. A total of 201 patients >/=70 years old were included in the study. The overall response rate was similar after six cycles (MP: 67.9%versus MD: 64.5%) and after 12 cycles (MP: 49.4%versus MD: 46.1%). However, the proportion of complete responses (CR) was higher in the MD arm, particularly after 12 cycles (MD: 22.4%versus MP: 9.1%; P < 0.05). There was no significant difference in event-free survival (MP: 15.9 months versus MD: 23.3 months). The median overall survival in both arms was almost identical (MP: 29.4 months versus MD: 27.2 months; P = 0.63). No significant differences in haematological toxicity were observed, but non-haematological toxicity was significantly higher in the MD arm. According to these results MP remains as the gold standard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents.