Abstract
BackgroundThiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established.MethodsThis was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics.ResultsSUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002).ConclusionsOur results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.
Highlights
Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT)
In patients receiving TBF-myeloablative conditioning (MAC), survival with non-T cell depleted (NTD)-haploidentical transplantation (Haplo) may be better compared to SUCBT due to decreased Non-relapse mortality (NRM)
UCBT and Haplo are considered a valid option for patients with acute leukemia lacking a human leukocyte antigen (HLA) matched sibling or unrelated donor, or when transplantation cannot be delayed [2,3,4,5,6]
Summary
This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Study design and definition We retrospectively analyzed patients aged ≥18 years diagnosed with de novo AML, who received a first HSCT either from an NTD haploidentical-related donor (recipient-donor number of mismatches ≥ 2) (n = 186) or an unmanipulated single cord blood unit (n = 147). For patients receiving Haplo, peripheral blood or bone marrow was used as a stem cell source, without ex vivo T cell depletion. All patients were given a myeloablative reduced toxicity conditioning regimen consisting of thiotepa, IV busulfan, and fludarabine. TBF-MAC was defined as a regimen containing a total dose of IV busulfan ≥ 9.6 mg/kg [33]. Cytogenetic risk groups were defined according to the Medical Research Council (MRC) classification system [34]
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