Treosulfan plus fludarabine versus TEAM as conditioning treatment before autologous stem cell transplantation for B-cell Non-Hodgkin lymphoma

Abstract

Conditioning with treosulfan and fludarabine (Treo/Flu) has been proven to be feasible and efficient in several types of malignancies before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Given its favorable reduced toxicity profile, we introduced Treo/Flu as conditioning before autologous HSCT (auto-HSCT) in patients with B-cell Non-Hodgkin lymphoma (NHL). The aim of this study was to evaluate the efficacy and safety of Treo/Flu in comparison to TEAM. Fifty-seven patients with NHL received auto-HSCT after conditioning with either Treo/Flu (n = 22) or TEAM (n = 35). All patients achieved sustained engraftment. PFS, EFS and OS were not significant in both groups. Of note is that patients in the Treo/Flu group were less dependent on thrombocyte transfusions (p = 0.0082), significantly older (in median 11 years, p < 0.0001) and suffered less frequently from infectious complications (p = 0.0105), mucositis and stomatitis (p < 0.0001). This study is the first to present efficacy, feasibility, and safety of conditioning with Treo/Flu preceding auto-HSCT in patients with NHL. Since it demonstrated a lack of significant difference in comparison to TEAM conditioning it might be a valuable alternative especially in elderly patients with B-cell NHL and comorbidities. Further evaluation by prospective clinical trials is warranted.

Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning

“…[37][38][39] BCNU replaced by thiotepa as part of TEAM conditioning regimen has promising activity. [20][21][22] However, an observational study described the BEAM protocol to be superior in terms of clinical outcomes, 40 whereas a recent study shows similar results between BEAM and TEAM. 41 We hypothesize that organ dysfunction might play a crucial role in the outcomes of patients undergoing auto-HSCT and only selected patients might profit from TEAM conditioning before auto-HSCT.…”

“…For this reason, several alternatives to BCNU/carmustine emerged over the years to reduce adverse effects while maintaining the same efficacy 37–39 . BCNU replaced by thiotepa as part of TEAM conditioning regimen has promising activity 20–22 . However, an observational study described the BEAM protocol to be superior in terms of clinical outcomes, 40 whereas a recent study shows similar results between BEAM and TEAM 41 .…”

“…Replacement of BCNU with thiotepa as part of TEAM (thiotepa, etoposide, cytarabine, and melphalan) was initially used in primary central nervous system lymphoma 19 but showed encouraging results in patients with Hodgkin and non-Hodgkin lymphoma as well. [20][21][22] Although impaired lung function has been proven to critically influence the outcomes of patients after conditioning with BEAM, 23 the effect of pulmonary dysfunction has not been systematically studied in patients receiving treatment with TEAM before auto-HSCT. As part of the HCT-CI score, pulmonary function, age, and comorbidities are yet regarded to be important predictive outcome factors for patients undergoing auto-HSCT.…”

“…Several alternative conditioning regimens 17,18 have been considered to improve outcomes of patients after auto‐HSCT. Replacement of BCNU with thiotepa as part of TEAM (thiotepa, etoposide, cytarabine, and melphalan) was initially used in primary central nervous system lymphoma 19 but showed encouraging results in patients with Hodgkin and non‐Hodgkin lymphoma as well 20–22 . Although impaired lung function has been proven to critically influence the outcomes of patients after conditioning with BEAM, 23 the effect of pulmonary dysfunction has not been systematically studied in patients receiving treatment with TEAM before auto‐HSCT.…”

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

“…There is also growing interest in the use of treosulfan as a low-toxicity alternative to busulfan in RIC regimens, and a randomized trial in AML/MDS found that fludarabine-treosulfan (Flu-Treo) was associated with improved NRM and OS compared to Flu-Bu2 ( 88 , 89 ). Preliminary data suggest that Flu-Treo may also be a viable conditioning regimen in NHL ( 90 , 91 ), but confirmation in larger studies is required.…”