Treatment in patients with acute myeloid leukemia/high-risk myelodysplastic syndrome with hypomethylating agents: Day-hospital management compared to home care setting.

OBJECTIVES: Aim of the study was to evaluate the role of a Domiciliary Hematologic Care Unit (DHCU) compared to standard DH setting in the active frontline treatment with hypomethylating agents (HMAs) +/- venetoclax of frail patients with acute myelogenous leukemia/high-risk myelodysplastic syndromes (AML/HR-MDS). METHODS: All patients with newly diagnosed AML/HR-MDS unfit for intensive care and treated frontline with HMAs from January 2010 to April 2021 were retrospectively included. RESULTS: Among 112 patients (62 AML/50 HR-MDS), 69 (61.6%) were treated in a standard DH setting and 43 (38.4%) were followed by DHCU, allocated to DH or DHCU by responsible physician. Overall response rate was 29/69 (42.0%) in DH versus 19/43 (44.1%) in DHCU (p = .797). Median response duration was 8.7 months (95%CI 7.0-10.3) in DH versus 13.0 months (95%CI 8.3-17.6) in DHCU (p = .460). Infections were also equally reported. Median overall survival of patients treated in DH was 13.7 months (95%CI 9.9-17.4) compared to 13.0 months (95%CI 6.7-19.3) of patients managed by DHCU (p = .753). CONCLUSIONS: Home care management of HMA is feasible and effective, with results similar to standard DH setting: this approach is thus adequate to offer active therapies in frail patients with AML/HR-MDS considered up to now ineligible.

Cytogenetic and molecular characterization of a recombinant X chromosome in a family with a severe neurologic phenotype and macular degeneration.

BACKGROUND: Duplications of MECP2 gene in males cause a syndrome characterized by distinctive clinical features, including severe to profound mental retardation, infantile hypotonia, mild dysmorphic features, poor speech development, autistic features, seizures, progressive spasticity and recurrent infections. Patients with complex chromosome rearrangements, leading to Xq28 duplication, share most of the clinical features of individuals with tandem duplications, in particular neurologic problems, suggesting a major pathogenetic role of MECP2 overexpression. RESULTS: We performed cytogenetic and molecular cytogenetic studies in a previously described family with affected males showing congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration. Microsatellite, FISH and array-CGH analyses identified a recombinant X chromosome with a deletion of the PAR1 region, encompassing SHOX, replaced by a duplicated segment of the Xq28 terminal portion, including MECP2. CONCLUSIONS: Our report describes the identification of the actual genetic cause underlying a severe syndrome that previous preliminary analyses erroneously associated to a terminal Xp22.33 region. In the present family as well as in previously reported patients with similar rearrangements, the observed neurologic phenotype is ascribable to MECP2 duplication, with an undefined contribution of the other involved genes. Maculopathy, presented by affected males reported here, could be a novel clinical feature associated to Xq28 disomy due to recombinant X chromosomes, but at present the underlying pathogenetic mechanism is unknown and this potential clinical correlation should be confirmed through the collection of additional patients.

A combined analytical approach reveals novel EXT1/2 gene mutations in a large cohort of Italian multiple osteochondromas patients.

Multiple osteochondromas (MO), also known as hereditary multiple exostoses (HME), is one of the most common hereditary musculoskeletal diseases in Caucasians (1/50,000) with wide clinical variability and genetic heterogeneity. Two genes have thus far been identified as causing the disease, namely EXT1 and EXT2. Various methods to detect mutations in the EXT genes have been used. Here a cohort of 100 MO patients belonging to unrelated Italian families have been analyzed by single-strand conformation polymorphism (SSCP) analysis or by denaturing high performance liquid chromatography (DHPLC). However, neither of these techniques can detect deletions or duplications of entire exons. Families that were negative at SSCP/DHPLC analysis underwent two-color multiple ligation-dependent probe amplification (MLPA) analysis. By these complementary techniques mutation detection was significantly improved and 26 novel mutations have been revealed as well as 18 previously described mutations to give a total of 44 different mutations. Thus we can conclude that combining MLPA with DHPLC in point-mutations negative MO families, the detection of mutations in EXT genes can significantly improve the identification of both point-mutations and mid-size rearrangements. More important, we were able to characterize all those patients who were negative at the first PCR-based method screening.

The effects of 99mTc-HMPAO-labelled leucocyte scan on human karyotype.

Technetium-99m hexamethylpropylene amine oxime (HMPAO) white blood cell scan (WBCS) requires separation and labelling of mixed leucocytes, which include particularly radiosensitive cells, lymphocytes. Lymphocytes labelled during the mixed leucocyte labelling procedure could represent a problem for patients owing to the possible induction of chromosomal aberrations. Lymphocytes labelled in mixed leucocyte preparations are probably killed by the high-dose radiation. Nevertheless, it has been reported that some of these lymphocytes can proliferate after in vitro stimulation. If these cells were to reproduce themselves in vivo, onset of, or increase over time in, chromosomal aberrations could occur on peripheral blood lymphocytes. The present study was performed on 21 patients who underwent WBCS for suspected infection/inflammation. Blood samples of these patients were submitted to cytogenetic study, comprising karyotype determination, evaluation of sister chromatid exchanges (SCE) and evaluation of induced chromosomal breakages or rearrangement rate (B/R). This study was performed 2 h before and 7 days and 6 months after the WBCS. The results demonstrated no statistically significant differences between SCE and B/R values before and after WBCS. No cause-effect relationship appeared to exist between WBCS and the onset of chromosomal aberrations in peripheral blood lymphocytes, at least during the first 6 months post WBCS and within the limits of this study's approach. The high-dose radiation administered to lymphocytes was almost certainly sufficient to kill these cells.