#AUTOLOGOUS STEM CELL TRANSPLANT TRIAL#

#AUTOLOGOUS STEM CELL TRANSPLANT TRIAL#

All data were evaluated as of 31st May 2020, and all authors had access to primary clinical trial data. Written informed consent was obtained from the subjects for the use of their data in clinical research, and the Institutional Review Board of the University of Freiburg Medical Center approved the study protocol. 22 This study was conducted in accordance with the Declaration of Helsinki. 21 Causes of death were adapted from previously described criteria. Conditioning regimen–related early toxicity by organ system, after auto-HSCT and before discharge, was assessed as previously described. Comorbidities, including the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), 19,20 and early complications after auto-HSCT, defined as complications after auto-HSCT and before discharge, are described in supplemental Table 1. Patient characteristics, as well as lung and cardiac function parameters, are described in Table 1. Clinical data were prospectively collected and retrospectively analyzed each cohort separately. We included all patients undergoing auto-HSCT. We included 629 patients treated with auto-HSCT (334 patients conditioned with BEAM and 295 patients conditioned with high-dose melphalan) at our institution between 1 January 2007 and 31 December 2017. Nevertheless, lung function was identified as a highly relevant factor for patients with myeloma in the Revised Myeloma Comorbidity Index (R-MCI). 14,15 Very few studies have systematically addressed how lung function affects outcomes and complications after auto-HSCT in patients conditioned with BEAM or high-dose melphalan. 12,13 Higher comorbidity indexes and lower performance scores were reported to be associated with worse outcome in patients with multiple myeloma undergoing auto-HSCT. 9-11 It is well tolerated by patients mucositis, infections, and diarrhea are the most common side effects. 7,8 High-dose melphalan is used as conditioning prior to auto-HSCT in patients with multiple myeloma.

5,6 However, it may be associated with major pulmonary toxicity, as a result of the high dose of BCNU, and induce early treatment-related complications. The BEAM protocol (BCNU/carmustine, etoposide, cytarabine, and melphalan) is the most common conditioning regimen that is used to treat patients with Hodgkin or non-Hodgkin lymphoma prior to auto-HSCT. In summary, we identified DLCOcSB ≤ 60% of predicted as an independent risk factor for decreased OS in patients conditioned with BEAM or high-dose melphalan prior to auto-HSCT. More often, patients with DLCOcSB ≤ 60% of predicted experienced nonrelapse mortality, including pulmonary causes of death. Abnormalities in DLCOcSB ≤ 60% of predicted were associated with chemotherapy with lung-toxic substances, mediastinal radiotherapy, KPS ≤ 80%, current/previous smoking, and treatment in the intensive care unit.

Similarly, DLCOcSB ≤ 60% of predicted, HCT-CI score ≥ 4, and age > 60 years were identified in patients treated with high-dose melphalan. In the multivariate analysis, we identified that progressive disease, CO-diffusion capacity corrected for hemoglobin (DLCOcSB) ≤ 60% of predicted, Karnofsky Performance Status (KPS) ≤ 80%, Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score ≥ 4, and age > 70 years were associated with decreased overall survival (OS) in patients treated with BEAM. The median follow-up was 52 months (range, 0.2-152) and 50 months (range, 0.5-149), respectively. This study included 629 patients treated at our institution between 20 334 and 295 were conditioned with BEAM or high-dose melphalan, respectively.

Therefore, we retrospectively analyzed the association of clinical factors and lung and cardiac function with outcome and complications after conditioning with BEAM (BCNU/carmustine, etoposide, cytarabine, melphalan) or high-dose melphalan in patients undergoing auto-HSCT. However, the assessment of organ dysfunction prior to auto-HSCT has not been well studied. The age of patients undergoing auto-HSCT and, therefore, the comorbidities, has increased over the last decades. High-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation (auto-HSCT), is an established therapy for patients with hematological malignancies.

Autologous stem cell transplant