Treosulfan-fludarabine-thiotepa conditioning before allogeneic haemopoietic stem cell transplantation for patients with advanced lympho-proliferative disease. A single centre study

Abstract

In recent years, with the aim of reducing transplant-related mortality, new conditioning regimens have been explored in patients not eligible for conventional haemopoietic stem cell transplantation. In this setting, we investigated safety and feasibility of the treosulfan-fludarabine-thiotepa combination prior to allogeneic haemopoietic stem cell transplantation in patients with advanced lympho-proliferative diseases and at high transplant risk. Twenty-seven consecutive patients, median age 43 years (range 19-60), entered this study. All of them were affected by lympho-proliferative disease in advanced phase and have been heavily pre-treated. The median haemopoietic stem cell transplant co-morbidity index was 1 (range 0-3). Twenty-five patients had regular engraftment, while the remaining two patients were not evaluable for early deaths. Non-haematological toxicity was limited. No patient developed veno-occlusive disease. The estimated probability of overall survival and progression-free survival with a median follow-up of 40 months was 52% (95% confidence interval 33-73) and 50% (95% confidence interval 30-70) respectively. Six patients have relapsed; all of them were not in remission before transplantation. The treosulfan-fludarabine-thiotepa combination is a reduced toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional myeloablative transplant regimens. Longer follow-up and prospective randomized studies are necessary to evaluate this regimen.

Outcome of treosulfan‐based reduced‐toxicity conditioning regimens for HSCT in high‐risk patients with primary immune deficiencies

“…Liver toxicity, especially SOS, pulmonary hypertension, interstitial pneumonitis, skin toxicity, mucositis, and seizures were lower compared with traditional combinations of busulfan and Cy. Also, low GvHD rates were observed in previous studies . Treosulfan has increasingly been used for pediatric patients undergoing HSCT for both malignant and non‐malignant diseases …”

“…Moreover, it is responsible for long‐term pulmonary toxicities such as pulmonary fibrosis and interstitial pneumonitis. Conditioning regimens with reduced toxicity have become an inevitable strategy for patients with PID, particularly those with pretransplant infections and organ damage due to inflammatory burden …”

“…Conditioning regimens with reduced toxicity have become an inevitable strategy for patients with PID, particularly those with pretransplant infections and organ damage due to inflammatory burden. [1][2][3][4] Treosulfan is a prodrug of an alkylating agent structurally related to busulfan and has similar myelosuppressive and immunosuppressive properties. Having a different mode of alkylation and not being activated by liver enzymes, the potential of treosulfan for causing liver toxicity as well as other tissue damage is reduced.…”

“…Also, low GvHD rates were observed in previous studies. 2,3,[8][9][10][11][12] Treosulfan has increasingly been used for pediatric patients undergoing HSCT for both malignant and non-malignant diseases. [8][9][10]12 The purpose of this single-center retrospective study was to analyze the outcome of treosulfan-based conditioning regimens before HSCT for patients with PID.…”

Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sézary Syndrome

“…These regimens can have significant immediate toxicity that can contribute to significant regimen-related morbidity and mortality in the immediate posttransplant period. 16,17 Nonrelapse mortality (NRM) of 22% was reported in a cohort of 60 patients with advanced CTCL (clinical stage IIB-IVB) treated with allogeneic stem cell transplant. In multivariate analysis, MAC was associated with a higher NRM (hazard ratio, 4.5; P 5 .1) 18 RIC or nonmyeloablative transplants are less cytotoxic and mostly immunosuppressive, resulting in decreased immediate transplant-related toxicity and allowing older and more frail patients to undergo transplant.…”