Fludarabine and treosulfan compared with other reduced-intensity conditioning regimens for allogeneic stem cell transplantation in patients with lymphoid malignancies

Yerushalmi, Ronit; Shem‐Tov, Noga; Danylesko, Ivetta; Avigdor, Abraham; Nagler, Arnon; Shimoni, Avichai

doi:10.1038/bmt.2015.174

Cited by 20 publications

(35 citation statements)

References 46 publications

(84 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This regimen was associated with a relatively low NRM in a relatively high‐risk older population with mostly advanced AML and MDS. As previously reported treosulfan is associated with a low‐risk for acute GVHD and organ toxicity . NRM was higher in patients with advanced leukemia and mismatched transplant.…”

Section: Discussionsupporting

confidence: 74%

“…As previously reported treosulfan is associated with a low-risk for acute GVHD and organ toxicity. 3,[8][9][10][11][12][13][14][15][16][17] NRM was higher in patients with advanced leukemia and mismatched transplant. However, interestingly, NRM was not significantly associated with patient age or comorbidities, suggesting it is relatively safe in these patient groups.…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning

et al. 2017

View full text Add to dashboard Cite

Reduced-toxicity conditioning with fludarabine and treosulfan is a dose-intensive regimen with enhanced anti-leukemia effect and acceptable toxicity in AML/MDS. HLA-C regulates natural-killer (NK) cell function by inhibiting Killer immunoglobulin-like receptors (KIR) and is divided into C1 and C2 epitopes. The missing-ligand theory suggests that missing recipient KIR ligands drives NK-alloreactivity after SCT, in the absence of HLA-mismatch by activating unlicensed donor NK cells. We analyzed SCT outcomes in 203 patients with AML/MDS, median age 58 years, given SCT from matched-siblings (n = 97) or matched-unrelated donors (n = 106), using two treosulfan doses (total 36 or 42 g/m ). 34% expressed one HLA-C group 1 allele (C1C1), 19% one HLA-C group 2 allele (C2C2), and 48% both KIR ligands (C1C2). Median follow-up was 48 months. 5-year relapse, nonrelapse mortality (NRM) and leukemia-free survival (LFS) rates were 38%, 27%, and 36%, respectively. Relapse rates were 43%, 45%, and 26% in patients expressing C1C1, C1C2, and C2C2 ligands, respectively (P = .03). Multivariate-analysis identified chemo-refractory disease (HR 3.1, P = .003), poor cytogenetics (HR 1.7, P = .08), female donor to male recipient (HR 0.4, P = .01) and C2C2 ligands (HR 0.4, P = .04) as independent factors predicting relapse. HLA-C ligands were not associated with GVHD or NRM. LFS was 33%, 30%, and 46%, respectively (P = .07). Chemorefractory disease (HR 3.1, P = .0004) and C2C2 group ligand (HR 0.6, P = .06) independently predicted LFS. Treosulfan dose did not predict any SCT outcome. In conclusion, missing HLA-C group 1 ligand is associated with reduced relapse risk, similar NRM and improved LFS, after HLA-matched SCT with treosulfan conditioning in AML/MDS.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 93%

Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The literature is, however, deficient in comparisons between fludarabine‐treosulfan (RTC) and other regimens. In a retrospective analysis, our group has previously reported low rates of mucositis (oral and gastrointestinal combined) in lymphoma patients conditioned with fludarabine‐treosulfan compared with other RIC regimens . We now extend the analysis to a new set of patients with a variety of diagnoses, in whom mucositis was documented prospectively, with a focus on oral mucositis.…”

Section: Discussionmentioning

confidence: 98%

“…In a retrospective analysis, our group has previously reported low rates of mucositis (oral and gastrointestinal combined) in lymphoma patients conditioned with fludarabine-treosulfan compared with other RIC regimens. 28 We now extend the analysis to a new set of patients with a variety of diagnoses, in whom mucositis was documented prospectively, with a focus on oral mucositis. Our findings indicate that rates of OM with RTC are low in comparison with myeloablative regimens.…”

Section: Discussionmentioning

confidence: 99%

Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

Shouval

Kouniavski

Fein

et al. 2019

European J of Haematology

View full text Add to dashboard Cite

Background Oral mucositis (OM) is a common toxicity of stem cell transplantation (SCT). We sought to evaluate OM burden, risk factors, and implications in a cohort of allogeneic‐SCT recipients. Methods This was a single‐center study including 115 adult allogeneic‐SCT transplanted between 2016 and 2018 for various hematological conditions. Conditioning intensity was categorized as myeloablative (MAC, 39%), reduced intensity (34%), or reduced toxicity (RTC, 27%) in patients conditioned with fludarabine‐treosulfan. OM was prospectively graded using the Common Terminology Criteria for Adverse Events (v.4.0) system. Results Moderate‐to‐severe OM (grade 2‐4) was experienced by 60% of patients. In a univariate analysis, younger age (P = .023), lower body mass index (P = .01), recent smoking (P = .08), recent antibiotics exposure (P = .018), MAC (P < .001), and methotrexate (P = .009) were associated with moderate‐to‐severe OM. In a multivariable logistic regression model, conditioning and graft‐versus‐host disease prophylaxis remained significant. OM risk was lowest with RTC (RTC vs MAC: odd ratio [OR] 0.05, P < .001), and recent antibiotic exposure trended toward increased risk (OR 1.88, P = .168). OM was associated with longer hospitalization, delayed neutrophil engraftment, and gastrointestinal‐related infections. Conclusion Oral mucositis remains a leading SCT complication. Treosulfan‐based conditioning has low mucosal toxicity and is appealing given previous reports on its high efficacy.

show abstract

“…Seven studies [13][14][15][16][17][18][19] comprising a total 1955 patients with various hematologic malignancies met the criteria for inclusion in the meta-analysis after the screening process (Supplementary Figure 1). Study descriptions and patient characteristics are elaborated in Table 1.…”

Section: Patient and Study Characteristicsmentioning

confidence: 99%

Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis

Jain

Alahdab

Firwana

et al. 2019

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

A B S T R A C T Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We present a systematic review and meta-analysis of studies comparing these 2 RIC regimens. We searched electronic databases from inception through November 1, 2017 for literature searches to identify relevant studies. A DerSimonian random effects model was used to measure efficacy outcomes; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported. Seven studies, including a total of 1955 patients, met criteria for inclusion, of which 6 were included in the overall pooled analysis because of repetition of some patients in 2 studies. Three studies were included in the subgroup analysis of acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) and 2 in the subgroup analysis of lymphoid malignancies. Overall survival (OS) and progression-free survival were not statistically significantly different between the 2 RIC regimens in analysis of all studies. However, OS was better with FM in subgroup analysis of AML/MDS studies (HR, .83; 95% CI, .73 to .95). Nonrelapse mortality was lower with FB (HR, .64; 95% CI, .46 to .89), whereas relapse was lower with FM (HR, 1.52; 95% CI, 1.13 to 2.06) in the analysis of all studies. This meta-analysis shows that FB and FM are associated with a similar OS in patients undergoing HCT. Relapse rates are lower with FM but at the cost of higher nonrelapse mortality.

show abstract

Fludarabine and treosulfan compared with other reduced-intensity conditioning regimens for allogeneic stem cell transplantation in patients with lymphoid malignancies

Cited by 20 publications

References 46 publications

Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning

Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning

Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About