Therapy-related myeloid neoplasms (tMN) develop after exposure to cytotoxic and radiation therapy, and due to their adverse prognosis, it is of paramount interest to identify patients at high risk. The presence of clonal hematopoiesis has been shown to increase the risk of developing tMN. The value of analyzing hematopoietic stem cells harvested at leukapheresis before autologous stem cell transplantation (ASCT) with next-generation sequencing and immunophenotyping represents potentially informative parameters that have yet to be discovered. We performed a nested case-control study to elucidate the association between clonal hematopoiesis, mobilization potential, and aberrant immunophenotype in leukapheresis products with the development of tMN after ASCT. A total of 36 patients with nonmyeloid disease who were diagnosed with tMN after treatment with ASCT were included as case subjects. Case subjects were identified from a cohort of 1130 patients treated with ASCT and matched with 36 control subjects who did not develop tMN after ASCT. Case subjects were significantly poorer mobilizers of CD34+ cells at leukapheresis (P = .016), indicating that these patients possess inferior bone marrow function. Both clonal hematopoiesis (odds ratio, 5.9; 95% confidence interval, 1.8-19.1; P = .003) and aberrant expression of CD7 (odds ratio, 6.6; 95% confidence interval, 1.6-26.2; P = .004) at the time of ASCT were associated with an increased risk of developing tMN after ASCT. In conclusion, clonal hematopoiesis, present at low variant allele frequencies, and aberrant CD7 expression on stem cells in leukapheresis products from patients with nonmyeloid hematologic cancer hold potential for the early identification of patients at high risk of developing tMN after ASCT.

Background This study evaluated myocardial oxygen consumption (MVO 2 ) and myocardial external efficiency (MEE) in patients with cardiac amyloidosis (CA). Furthermore, we compared MEE and MVO 2 in subjects with light chain amyloidosis versus transthyretin (ATTR) amyloidosis. Methods and Results The study population comprised 40 subjects: 25 patients with confirmed CA and 15 control subjects. All subjects underwent an 11 C‐acetate positron emission tomography. Furthermore, the CA patients underwent comprehensive echocardiography and right heart catheterization during a symptom‐limited, semi‐supine exercise test. MEE was calculated from 11 C‐acetate positron emission tomography as the ratio of left ventricular (LV) stroke work and the energy equivalent of MVO 2 . Myocardial work efficiency was calculated as echocardiography‐derived work pressure product divided by three‐dimensional LV mass. CA patients had significantly lower LV‐ejection fraction (54±13% versus 63±4%, P <0.05) and LV‐global longitudinal strain (LVGLS) (12±4% versus 19±2%, P <0.0001) and a more restrictive filling pattern (E/e′‐ratio 18 [12–25] versus 8 [7–9], P <0.0001) than controls. MEE was severely reduced (13±5% versus 22±5%, P <0.0001) whereas total MVO 2 was higher (18±6 mL/min versus 13±3 mL/min, P <0.01) in CA patients than controls. MEE decreased with increasing New York Heart Association symptom burden ( P <0.0001). We found a good relationship between MEE and peak exercise systolic performance (LVGLS: R 2 =0.60, P <0.0001; myocardial work efficiency: R 2 =0.48, P <0.0001; cardiac index: R 2 =0.52, P <0.0001) and between MEE and myocardial blood flow ( R 2 =0.44, P <0.0001). Conclusion Myocardial oxidative metabolism is disturbed in CA patients with increased total MVO 2 and reduced MEE. MEE correlated significantly with echocardiographic derived systolic parameters such as myocardial work efficiency and LVGLS that might be used as surrogate MEE markers.

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Purpose: Autologous stem cell transplantation (SCT) has become standard therapy in high risk stage IV neuroblastoma (NB) patients. Residual NB cells in the bone marrow (BM) shortly before SCT may shape the overall survival. Methods: Thus, we sought to thoroughly investigate minimal residual disease (MRD) in BM prior to SCT using conventional and real time RT-PCR for tyrosine hydroxylase (TH) as well as morphology. To avoid influence of residual NB cells in the stem cell harvest, 17 patients transplanted with MRD negative grafts (n=11 CD34-selected and n=6 unmanipulated) are included in the final analysis, only. Results: 35% of these patients are alive with a median follow up of 8.6 years. In the BM of 9/17 patients residual NB cells could be detected

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