Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Abstract

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.

Thiotepa‐based conditioning for allogeneic stem cell transplantation in acute lymphoblastic leukemia—A survey from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…The incidence of acute GvHD grade > II was 26.6%. This is comparable with the rate of acute GvHD we observed in thiotepa prior to allo‐HSCT in AML . Chronic GvHD occurred in 35.9% at 1 year (24.6% with extensive disease).…”

“…One possible explanation is the lower toxicity in our cohort; the NRM at 2 years was 33%, whereas it is reported to be 28–38% after transplantation with a TBI‐based conditioning . We showed an incidence of acute and chronic GvHD comparable to other published regimens, and these results were similar to those from our previous study using thiotepa as a conditioning regimen for allo‐HSCT in patients with AML . Another study, using thiotepa in combination with clofarabine and melphalan for a second allo‐HSCT in acute leukemia (12 of the 18 reported patients where with ALL), could show an acceptable toxicity, even for a second transplantation.…”

“…Those of NRM and relapse were 23.9% (thiotepa) vs. 22.4% (Cy/TBI) and 17.2% (thiotepa) vs. 23.3% (Cy/TBI), respectively. The probabilities of LFS and OS at 2 years were 58.9% (thiotepa) vs. 54.2% (Cy/TBI), and 61.4% (thiotepa) vs. 58% (Cy/TBI), respectively .…”

Killer Cell Immunoglobulin-Like Receptor–Ligand Mismatch in Donor versus Recipient Direction Provides Better Graft-versus-Tumor Effect in Patients with Hematologic Malignancies Undergoing Allogeneic T Cell–Replete Haploidentical Transplantation Followed by Post-Transplant Cyclophosphamide

“…To optimize the antitumor effect of the conditioning regimen, NMAC was progressively replaced by i.v. busulfan-based (6.4 to 12.8 mg/kg) conditioning regimen, mostly in combination with thiotepa (5 to 10 mg/kg) and fludarabine (120 to 160 mg/m 2 ) [11]. Busulfan-based conditioning regimens were classified as reduced-intensity (RIC) or myeloablative (MAC) according to the busulfan dose, as defined by the European Group for Blood and Marrow Transplantation criteria (MAC > 6.4 mg/kg i.v.…”

Thiotepa‐based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched‐pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…and is an appealing option for patients owing to its established safety record and its ability to cross the blood–brain barrier . Thus, thiotepa‐based conditioning is being increasingly used as a preparative regimen prior to allo‐hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) with recent data indicative of overall favorable outcomes in terms of both toxicity and disease control with 3‐year leukemia‐free survival (LFS) and overall survival (OS) rates of 41% and 45%, respectively . Conversely, in ALL we recently published an analysis of 323 patients with ALL and showed that thiotepa‐based conditioning was associated with an acceptable toxicity profile as well as encouraging one year LFS and OS rates (57% and 66%, respectively) .…”