Functional Dominance of CHIP-Mutated Hematopoietic Stem Cells in Patients Undergoing Autologous Transplantation.

Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high incidence of CHIP (22%) after ASCT with a high mean variant allele frequency (VAF) of 10.7%. Most mutations were already present in the graft, albeit at lower VAFs, demonstrating a selective reconstitution advantage of mutated HSCs after ASCT. However, patients with CHIP mutations in DNA-damage response genes showed delayed neutrophil reconstitution. Thus, CHIP-mutated stem and progenitor cells largely gain on clone size upon ASCT-related blood reconstitution, leading to an increased future risk of CHIP-associated complications.

Sonographic signs of neutropenic enterocolitis.

AIM: To investigate the sonographic features at time of diagnosis and follow-up in patients with neutropenic enterocolitis. METHODS: The sonographic findings in 14 patients with neutropenic enterocolitis were described and evaluated regarding symptoms and clinical outcome. RESULTS: In all patients with neutropenic enterocolitis, the ileocoecal region was involved with wall thickening >10 mm. A transmural inflammatory pattern, hypervascularity of the thickened bowel wall and free abdominal fluid were the common findings. The sonographically revealed thickness of the bowel wall was associated with lethal outcome (P<0.03). In the 11 surviving patients,the improvement of clinical symptoms was accompanied by progressive reduction of intestinal wall thickness. CONCLUSION: High-end sonography of the bowel is a helpful tool for diagnosis,assessment of prognosis and follow-up of patients with neutropenic enterocolitis.The ultrasonographically revealed bowel thickness reflects the severity and the course of the disease, and seems to be predictive for the clinical outcome.

Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia.

Patients with haematological malignancies and prolonged periods of neutropenia after chemotherapy are at high risk for severe bacterial and fungal infections. Those infections have long time been considered as a contraindication for subsequent haematopoietic stem cell transplantation (HCT). We conducted a prospective, non-randomized study of granulocyte transfusions (GTX) to control acute life-threatening infections (44 episodes) and to prevent recurrence of severe fungal infections during HCT or intensive chemotherapy (23 episodes). GTX achieved control in 82% (36/44) of acute life-threatening infections. No single reactivation of a previous infection occurred under prophylactic GTX (0/23). Median survival was 170 days in the interventional group and 185 days in the prophylactic group; death in both patient groups was mainly due to underlying progressive malignant disease. We conclude that under GTX, the infection-related mortality even in high-risk patients is low. Due to a secondary prophylaxis with GTX, haematopoietic allografts can be safely given to patients with previous fungal infections.