The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity. We compared the reduced intensity conditioning FM140 (fludarabine, 150 mg/m2; melphalan 140 mg/m2) with FBM110 (fludarabine 150 mg/m2; BCNU, also known as carmustine, 300-400 mg/m2; and melphalan 110 mg/m2). From the European Bone Marrow Transplantation (EBMT) Acute Leukemia Working Party registry, we identified 293 adult patients (FM140, n = 118 and FBM110, n = 175) with AML with relapsed/refractory disease prior to allo-HCT. There were some differences such as age (FM140 = 59.5 years vs. FBM110 = 65.1 years, p < 0.001) and graft-versus-host disease (GvHD) prophylaxis based on in vivo T-cell depletion (TCD, FM140 = 39% vs. FBM110 = 75%, p < 0.001). No differences were observed between FM140- and FBM110-treated patients regarding overall survival (OS) (2-year OS: 39.3% vs. 45.7%, p = 0.58), progression-free survival (PFS) (2-year PFS: 36.1% vs. 37.3%, p = 0.69), non-relapse mortality (NRM) (2-year NRM: 15.3% vs. 25.7%, p = 0.10) and relapse incidence (RI) (2-year RI: 48.6% vs. 37.0%, p = 0.7). In conclusion, despite differences in age and GvHD prophylaxis, AML patients with active disease undergoing allo-HCT after FBM110 conditioning showed similar outcomes compared to FM140.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• dospělí MeSH
• homologní transplantace metody   MeSH
• karmustin terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melfalan * terapeutické užití   aplikace a dávkování   MeSH
• příprava pacienta k transplantaci metody   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• recidiva MeSH
• registrace * MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• vidarabin * analogy a deriváty   terapeutické užití   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.

• MeSH
• akutní myeloidní leukemie * terapie   MeSH
• cyklofosfamid * terapeutické užití   MeSH
• dospělí MeSH
• HLA antigeny imunologie   MeSH
• homologní transplantace MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli * etiologie   prevence a kontrola   MeSH
• reakce štěpu proti leukémii * MeSH
• senioři MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The role of autologous hematopoietic stem cell transplantation (AHSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL) remains controversial. The aim of this retrospective study was to analyze results of AHSCT and to identify prognostic factors. METHODS: Overall, 700 patients transplanted in first complete remission between the years 1999-2020 were included. Median patient age was 31.9 years (68% male). B-cell precursor ALL (BCP-ALL) and T-cell precursor ALL (TCP-ALL) was diagnosed in 35% and 65%, respectively. Among 190 patients with available data, negative minimal residual disease (MRD) status was reported in 167 (88%) cases. RESULTS: The probabilities of overall survival (OS) and leukemia-free survival (LFS) at 2 years were 67% and 56%; relapse incidence (RI) and non-relapse mortality (NRM) were 39% and 5%, respectively. TCP-ALL was associated with lower RI (41% vs. 56%, p=0.001), higher LFS (52% vs. 38%, p=0.002) and OS (58% vs 45%, p=0.001) at 5 years when compared to BCP-ALL. In the multivariate analysis, TCP-ALL and longer interval from diagnosis do AHSCT were associated with reduced risk of relapse (HR 0.7, p=0.006 and HR=0.95, p=0.018), better LFS (HR=0.76, p=0.02 and HR=0.95, p=0.01) and OS (HR=0.75, p=0.024 and HR=0.94, p=0.013, respectively). Increasing patient age was associated with higher NRM (HR=1.49, p<0.0001), worse LFS (HR=1.1, p=0.01) and OS (HR=1.17, p=0.0001). CONCLUSIONS: Autologous hematopoietic stem cell transplantation is relatively safe option of late treatment intensification in adults with Ph- ALL. It may be a valuable option especially in patients with TCP-ALL, however it should be proved in prospective clinical trials.

• MeSH
• akutní lymfatická leukemie * terapie   mortalita   MeSH
• autologní transplantace MeSH
• dospělí MeSH
• filadelfský chromozom MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• reziduální nádor MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.

• MeSH
• akutní myeloidní leukemie * terapie   genetika   mortalita   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   farmakologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• příprava pacienta k transplantaci * metody   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Post-transplant cyclophosphamide (PTCY) is increasingly used as effective graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic-cell transplantation (allo-HCT). However, PTCY is associated with toxicities. Whether patients with specific comorbidities are more vulnerable to cyclophosphamide-induced toxicity is unclear. We retrospectively evaluated the impact of individual organ dysfunctions for non-relapse mortality (NRM) risk and overall survival (OS) among 5888 adults who underwent PTCY-based allo-HCT for acute myeloid leukemia between 2010 and 2023. In multivariable analyses 5 of the comorbidities (renal, moderate/severe hepatic, cardiac including arrhythmia/valvular disease, severe pulmonary, infection) were independently associated with adverse NRM and OS without influencing relapse rate. A simplified model using the absence (n = 4390), presence of 1 (n = 1229) or presence of 2 or 3 (n = 269) of the comorbidities which were determined individually to contribute to NRM stratified patients into 3 NRM risk (16.2% vs. 21.6% vs. 36%, retrospectively) and OS categories (64% vs. 56% vs. 36.4%, retrospectively). In Cox model, recipients with 2 or 3 comorbidities had an increased hazard ratio for NRM of 2.38 (95% confidence interval [CI], 1.89-3) and for OS of 1.96 (95% CI 1.64-2.33). Whether patients with concomitant diagnoses, as determined here, may benefit from a reduced PTCY dose remains to be evaluated in prospective clinical trials.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   škodlivé účinky   farmakologie   aplikace a dávkování   MeSH
• dospělí MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli prevence a kontrola   mortalita   MeSH
• příjemce transplantátu MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli * prevence a kontrola   etiologie   mortalita   MeSH
• nepříbuzný dárce * MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk MeSH
• transplantace kmenových buněk z pupečníkové krve * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

We assessed outcomes of allogeneic transplantation (HSCT) in favorable risk AML in CR1 over 3 time periods. 1850 patients were included, 2005 to 2009- 222, 2010 to 2014 -392, and 2015 to 2021-1236; 526 with t (8:21), 625 with inv (16), and 699 with NPM1mutFLT3WT. Patients transplanted in 2015-2021 were older (p < 0.0001) with more patients ≥60 years of age (p < 0.0001). The most frequent diagnosis in 2015-2021 was NPM1mutFLT3WT vs. t (8:21) in the 2 earlier periods, (p < 0001). Haploidentical transplants (Haplo) increased from 5.9% to 14.5% (p < 0.0001). Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 vs. the other 2 periods (p < 0.0001). On multivariate analysis, incidence of total chronic GVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005-2009, hazard ratio (HR) = 0.74 (95% CI 0.56-0.99, p = 0.046) and GVHD-free, relapse-free survival (GRFS) improved for patients transplanted from 2010-2014 vs. those transplanted in 2005-2009, HR = 0.74 (95% CI 0.56-0.98, p = 0.037). Other HSCT outcomes did not differ with no improvement ≥2015. LFS, OS, and GRFS were inferior in patients with t (8:21) with HR = 1.32 (95% CI 1.03-1.68, p = 0.026), HR = 1.38 (95% CI 1.04-1.83, p = 0.027) and HR = 01.25 (95% CI 1.02-1.53, p = 0.035), respectively. In conclusion, this retrospective analysis of HSCT in patients with favorable risk AML, transplanted over 16 years showed an increased number of transplants in patients ≥60 years, from Haplo donors with PTCy. Most importantly, 3-year GRFS improved ≥2010 and total chronic GVHD reduced ≥2015, with no significant change in other HSCT outcomes.

• MeSH
• akutní myeloidní leukemie * terapie   MeSH
• alografty MeSH
• dospělí MeSH
• homologní transplantace metody   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli prevence a kontrola   etiologie   MeSH
• nukleofosmin MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison). Acute graft-versus-host disease (aGVHD) grades II-IV were significantly lower in the yHaplo vs. oMMUD group (HR = 0.62, p = 0.007). There were no significant differences in chronic GVHD, non-relapse mortality (NRM), relapse incidence, leukemia-free survival, overall survival, and GVHD-free and relapse-free survival. As for the second comparison, more patients in the oHaplo group had de novo AML, 86.6% vs. 81.9% in the yMMUD group (p = 0.044), while myeloablative conditioning was used more frequently in the yMMUD group, 53.3% vs. 46.8% in the oHaplo group (p = 0.049). aGVHD grades II-IV and NRM were significantly lower in the yMMUD vs. oHaplo group (HR = 0.69, p = 0.013 and HR = 0.60, p = 0.022). All other transplant outcomes did not differ. In conclusion, HSCT from young alternative donors (<35 years) results in a lower incidence of grades II-IV aGVHD. In addition, NRM is lower in HSCT from yMMUD compared to HSCT from oHaplo.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• haploidentická transplantace metody   MeSH
• homologní transplantace metody   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli MeSH
• nepříbuzný dárce * MeSH
• přežití bez známek nemoci MeSH
• příprava pacienta k transplantaci metody   MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

We compared the outcomes of haploidentical stem cell transplantation (haplo-HSCT) with posttransplant cyclophosphamide (PTCy) in 719 patients with primary refractory (PR) or first relapse (Rel) secondary acute myeloid leukemia (sAML; n = 129) vs those with de novo AML (n = 590), who received HSCT between 2010 and 2022. A higher percentage of patients with sAML vs de novo AML had PR disease (73.6% vs 58.6%; P = .002). In 81.4% of patients with sAML , the antecedent hematological disorder was myelodysplastic syndrome. Engraftment was 83.5% vs 88.4% in sAML and de novo AML, respectively (P = .13). In multivariate analysis, haplo-HSCT outcomes did not differ significantly between the groups: nonrelapse mortality hazard ratio (HR), 1.38 (95% confidence interval [CI], 0.96-1.98; P = .083), relapse incidence HR, 0.68 (95% CI, 0.4.7.-1.00; P = .051). The HRs for leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, and GVHD and relapse-free survival were 0.99 (95% CI, 0.76-1.28; P = .94), 0.99 (95% CI, 0.77-1.29; P = .97), and 0.99 (95% CI, 0.77-1.27; P = .94), respectively. We conclude that outcomes of haplo-HSCT with PTCy are not different for PR/Rel sAML in comparison with PR/Rel de novo AML, a finding of major clinical importance.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• dítě MeSH
• dospělí MeSH
• haploidentická transplantace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli etiologie   MeSH
• recidiva MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

An increasing number of older patients with acute myeloid leukemia (AML) are offered an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Normally, older patients have older matched related donors (MRD). Matched unrelated donors (MUD) are an important alternative, but it remains unclear whether a younger MUD is associated with better outcomes, especially in the context of post-transplant cyclophosphamide (PTCy). We compared outcomes of patients older than 50 years with AML in first complete remission (CR1) and receiving a first HSCT from a 10/10 MUD aged younger than 40 years to those receiving a graft from a MRD aged older than 50 years, using PTCy and with well-known transplant conditioning intensity (TCI) score. A total of 345 consecutive patients were included and classified according to TCI score as low, intermediate, or high. On multivariable analysis in the TCI-intermediate/high group, MUD was associated with better graft-versus-host disease-free, relapse-free survival, lower non-relapse mortality and lower relapse incidence. For patients receiving a TCI-low regimen, outcomes are independent on the type of donor. In patients with AML in CR1, older than 50 years and receiving a TCI-intermediate/high conditioning regimen using PTCy, a MUD younger than 40 years is preferable over a MRD older than 50 years.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   farmakoterapie   patologie   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• homologní transplantace MeSH
• indukce remise * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli etiologie   MeSH
• nepříbuzný dárce MeSH
• příprava pacienta k transplantaci * metody   MeSH
• prognóza MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH