Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.

The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.

Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of Akkermansia muciniphila, a species of mucin-degrading bacteria (P = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded A. muciniphila and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Antibiotic treatment to eradicate A. muciniphila before caloric restriction preserved colonic mucus, whereas A. muciniphila reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting A. muciniphila or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.

Fluorescence in Situ Hybridization (FISH) Utility for Risk Score Assessment in Patients With MDS With Normal Metaphase Karyotype.

BACKGROUND: Cytogenetic profile is an essential parameter in myelodysplastic syndromes (MDS) risk stratification by both International Prognostic Symptom Score (IPSS) and Revised (R)-IPSS. Almost one-half of patients with MDS have normal cytogenetics by metaphase karyotype. Here we report the yield of MDS fluorescence in situ hybridization (FISH) panel detecting cytogenetic abnormalities in these patients and its impact on risk stratification. PATIENTS AND METHODS: Among patients with normal metaphase karyotype, we assessed those patients who had cytogenetic abnormalities detected by an MDS FISH panel, which included probes for del (5), del (7), del (20), trisomy 8, and del (17p). Risk stratification was calculated by both IPSS and R-IPSS. RESULTS: Of 1600 patients with MDS with normal metaphase karyotype, 53 (3%) patients had cytogenetic abnormality detected by MDS FISH panel. Integrating the MDS FISH panel cytogenetics (IPSS + FISH restaging) resulted in upstaging the score, where 53% of low-risk IPSS were upstaged to intermediate (int)-1, 56% of int-1 were upstaged to int-2, and 78% of int-2 were upstaged to high risk. Based on the R-IPSS, 61% of very low-risk patients, all low-risk patients, 92% of intermediate-risk patients, and 50% of high-risk patients with FISH abnormalities were upstaged, respectively. CONCLUSION: The yield of MDS FISH panel detecting cytogenetic abnormalities in patients with normal karyotype by G-banding is low and may not warrant ordering the panel in all patients. Among the 3% of patients with normal karyotype who had cytogenetic abnormality detected by FISH, the risk score assignment by IPSS and R-IPSS was upstaged.

Congenital dysfibrinogenaemia presented with preterm premature rupture of the membranes and vaginal bleeding.

A 26-year-old woman was found to have congenital dysfibrinogenaemia after presenting to our hospital with premature rupture of the membranes and vaginal bleeding. Given the absence of clear guidelines for the management of pregnancy complicated by dysfibrinogenaemia, we followed expert consensus that exists among published works, with some modifications. This case was managed by a multidisciplinary team of obstetrics-gynaecology, haematology and paediatric haematology. Here we review how the patient presented, the investigations that led to the diagnosis and the treatment options.