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Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT
Forcade, E., Chevret, S., Finke, J., Ehninger, G., Ayuk, F., Beelen, D., Koster, L., Ganser, A., Volin, L., Sengeloev, H., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
While in vivo T-cell depletion (TCD) is widely used, its benefit in patients with MDS still remains a matter of debate. This study evaluates the impact of TCD on outcomes, and compares ATG and alemtuzumab, in patients with MDS. 1284 patients from the EBMT registry were included in this study with 470 patients in the no-TCD group and 814 in the TCD group (alemtuzumab N = 168; ATG N = 646). At 6 months, aGVHD III-IV cumulative incidences (CI) for no-TCD, ATG or alemtuzumab groups were 13% vs 14% vs 11% (ns), respectively. At 5 years, CI of chronic GVHD were 64% vs 52% vs 51% (p < 0.00017); and CI of relapse was 23% vs 25% vs 39% (p < 0.0001) for no TCD, ATG and alemtuzumab respectively; OS was 47% vs 46% vs 34% (p = 0.009) respectively; and GRFS was 21% vs 28% and 20% (p = 0.045) respectively. In multivariable analysis, ATG improved GRFS, and alemtuzumab decreased OS. Both ATG and alemtuzumab decreased risk of chronic GVHD, but the increased risk of relapse with alemtuzumab is associated with a poor GRFS and suggest to not use alemtuzumab in the setting of allo-SCT for high risk disease.
PICO Summary
Population
Patients with myelodysplastic syndromes undergoing allogeneic transplant and reported to the EBMT registry (n=1284)
Intervention
In vivo T-cell depletion (TCD, n=814: receiving alemtuzumab n=168 or ATG n=646)
Comparison
No in vivo T-cell depletion (No-TCD, n=470).
Outcome
At 6 months, aGVHD III-IV cumulative incidences (CI) for no-TCD, ATG or alemtuzumab groups were 13% vs 14% vs 11% (ns), respectively. At 5 years, CI of chronic GVHD were 64% vs 52% vs 51%; and CI of relapse was 23% vs 25% vs 39% for no TCD, ATG and alemtuzumab respectively; OS was 47% vs 46% vs 34% respectively; and GRFS was 21% vs 28% and 20% respectively. In multivariable analysis, ATG improved GRFS, and alemtuzumab decreased OS. Both ATG and alemtuzumab decreased risk of chronic GVHD, but the increased risk of relapse with alemtuzumab is associated with a poor GRFS
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Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced-intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT
Shimoni, A., Robin, M., Iacobelli, S., Beelen, D., Mufti, G. J., Ciceri, F., Bethge, W., Volin, L., Blaise, D., Ganser, A., et al
British journal of haematology. 2021
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Editor's Choice
Abstract
Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reduced-intensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile. We investigated post-transplant outcomes in 1722 MDS patients following allo-HCT with FT (n = 367), RIC (n = 687) or MAC (n = 668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively (P < 0·001) but other disease characteristics were similar. The median follow-up was 64 months (1-171). Five-year relapse rates were 25% (21-30), 38% (34-42) and 25% (22-29), after FT, RIC and MAC, respectively, (P < 0·001). NRM was 30% (25-35), 27% (23-30) and 34% (31-38, P = 0·008), respectively. Five-year OS was 50% (44-55), 43% (38-47), and 43% (39-47), respectively (P = 0·03). In multivariate analysis, FT was associated with a lower risk of relapse (HR 0·55, P < 0·001) and better OS (HR 0·72, P = 0·01). MAC was associated with higher NRM (HR 1·44, P = 0·001). In conclusion, FT is associated with similar low relapse rates as MAC and similar low NRM as RIC, resulting in improved OS. FT may be the preferred regimen for allo-HCT in MDS.
PICO Summary
Population
Patients reported to the EBMT registry with a diagnosis of myelodysplastic syndrome, receiving allogeneic transplant (n=1722)
Intervention
Fludarabine/treosulfan based conditioning (FT, n=367)
Comparison
Other reduced intensity conditioning regimens (RIC, n=687) or myeloablative conditioning (MAC, n=668)
Outcome
FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively but other disease characteristics were similar. The median follow-up was 64 months (1-171). Five-year relapse rates were 25% (21-30), 38% (34-42) and 25% (22-29), after FT, RIC and MAC, respectively. NRM was 30% (25-35), 27% (23-30) and 34% (31-38), respectively. Five-year OS was 50% (44-55), 43% (38-47), and 43% (39-47), respectively. In multivariate analysis, FT was associated with a lower risk of relapse (HR 0·55) and better OS (HR 0·72). MAC was associated with higher NRM (HR 1·44).
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Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT
Poire, X., Labopin, M., Polge, E., Forcade, E., Ganser, A., Volin, L., Michallet, M., Blaise, D., Yakoub-Agha, I., Maertens, J., et al
Haematologica. 2019
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Editor's Choice
Abstract
Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia is a common high-risk feature referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with acute myeloid leukemia harboring -5/5q- having their first allogeneic transplantation between 2000 and 2015. Five hundred and one patients with -5/5q- have been analyzed. Three hundred thirty-eight patients (67%) were in first remission and 142 (28%) had an active disease at time of allogeneic transplantation. The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. We identified 4 different cytogenetic groups according to additional abnormalities with prognostic impact: -5/5q- without complex karyotype, monosomal karyotype or abn(17p), -5/5q- within a complex karyotype, -5/5q- within a monosomal karyotype and the combination of -5/5q- with abn(17p). In multivariate analysis, factors associated with worse overall survival and leukemia-free survival across the 4 groups were active disease, age, monosomal karyotype and abn(17p). The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.
PICO Summary
Population
Adult patients with acute myeloid leukemia harboring deletion 5q or monosomy 5 (-5/5q-) (n=501)
Intervention
First allogeneic transplantation between 2000 and 2015
Comparison
None
Outcome
The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.
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EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL)
Wiktor-Jedrzejczak, W., Drozd-Sokolowska, J., Eikema, D. J., Hoek, J., Potter, M., Wulf, G., Sellner, L., Ljungman, P., Chevallier, P., Volin, L., et al
Bone marrow transplantation. 2019
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Editor's Choice
Abstract
Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.
PICO Summary
Population
Allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL.
Intervention
Observational study
Comparison
None
Outcome
With a median follow-up of 50 months, the 4-year non-relapse mortality was 32%, relapse incidence 38%, progression-free (PFS) 30% and overall survival 42%. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM.