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
• Názvy látek
• cyklofosfamid * MeSH

Choice of calcineurin inhibitor may impact the outcome of patients undergoing T-cell replete hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PT-Cy) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD). We retrospectively analyzed 2427 patients with acute myeloid leukemia (AML) in first remission transplanted from a haploidentical (n = 1844) or unrelated donor (UD, n = 583) using cyclosporine A (CSA, 63%) or tacrolimus (TAC, 37%) and PT-Cy/MMF. In univariate analysis, CSA and TAC groups did not differ in 2-year leukemia-free or overall survival, cumulative incidence (CI) of relapse or non-relapse mortality. CI of severe grade III-IV acute GVHD was lower with TAC (6.6% vs. 9.1%, p = 0.02), without difference in grade II-IV acute GVHD or grade III-IV acute GVHD/severe chronic GVHD, relapse-free survival (GRFS). In multivariate analysis, TAC was associated with a lower risk of severe grade III-IV acute GVHD solely with haploidentical donors (HR 0.64 [95% CI, 0.42-0.98], p = 0.04), but not UD (HR 0.49 [95% CI, 0.2-1.21], p = 0.12). There was no significant difference for chronic GVHD. In conclusion, PT-Cy/MMF-based GVHD prophylaxis resulted in favorable OS and GRFS, irrespective of the CNI added. In haploidentical HCT, TAC seemed to prevent severe acute GVHD more effectively than CSA without impact on other outcome parameters.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   MeSH
• cyklosporin * terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli * prevence a kontrola   mortalita   etiologie   MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• senioři MeSH
• takrolimus * terapeutické užití   MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH
• Názvy látek
• cyklofosfamid * MeSH
• cyklosporin * MeSH
• imunosupresiva MeSH
• takrolimus * MeSH

Poor-risk (PR) cytogenetic/molecular abnormalities generally direct pediatric patients with acute myeloid leukemia (AML) to allogeneic hematopoietic stem cell transplant (HSCT). We assessed the predictive value of cytogenetic risk classification at diagnosis with respect to post-HSCT outcomes in pediatric patients. Patients younger than 18 years at the time of their first allogeneic HSCT for AML in CR1 between 2005 and 2022 who were reported to the European Society for Blood and Marrow Transplantation registry were subgrouped into four categories. Of the 845 pediatric patients included in this study, 36% had an 11q23 abnormality, 24% had monosomy 7/del7q or monosomy 5/del5q, 24% had a complex or monosomal karyotype, and 16% had other PR cytogenetic abnormalities. In a multivariable model, 11q23 (hazard ratio [HR] = 0.66, P = 0.03) and other PR cytogenetic abnormalities (HR = 0.55, P = 0.02) were associated with significantly better overall survival when compared with monosomy 7/del7q or monosomy 5/del5q. Patients with other PR cytogenetic abnormalities had a lower risk of disease relapse after HSCT (HR = 0.49, P = 0.01) and, hence, better leukemia-free survival (HR = 0.55, P = 0.01). Therefore, we conclude that PR cytogenetic abnormalities at diagnosis predict overall survival after HSCT for AML in pediatric patients.

• MeSH
• akutní myeloidní leukemie * genetika   terapie   diagnóza   MeSH
• chromozomální aberace MeSH
• chromozomální delece MeSH
• dítě MeSH
• homologní transplantace MeSH
• lidé MeSH
• lidské chromozomy, pár 7 MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2-3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2-3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2-3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2-4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2-3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.

• Publikační typ
• časopisecké články MeSH

HLA-matching largely contributes to unrelated donor hematopoietic cell transplantation (UD-HCT) success but, due to the selective deletion of alloreactive T-cells, post-transplantation cyclophosphamide (PTCy) could modulate its negative impact on outcomes. We retrospectively compared acute leukemia patients receiving 10/10 or 9/10 HLA allele-matched UD-HCT with PTCy-GvHD prophylaxis between 2010 and 2017, reported to EBMT registry. The 100-day incidence of grade ≥2 and grade ≥3 aGvHD were comparable for 10/10 and 9/10 UD (28% versus 28%, p = 0.8 and 10% versus 8%, p = 0.5, respectively). The 2-year cGvHD and extensive cGvHD were similar between 10/10 and 9/10 UD (35% versus 44%, p = 0.2 and 21% versus 20%, p = 0.6, respectively). The 2-year nonrelapse mortality was 20% after 10/10 and 16% after 9/10 UD-HCT (p = 0.1). Relapse incidence at 2-year was 24% for 10/10 and 28% for 9/10 UD-HCT (p = 0.4). Leukemia-free survival at 2-year was the same for 10/10 and 9/10 UD (56 and 56%, p = 0.6, respectively), with comparable overall survival (62 and 59%, p = 0.9, respectively). Multivariate analysis showed no effect of HLA-matching on outcomes. An advanced disease status and patient disability remained the most important factors portending a worse survival. PTCy could alleviate the detrimental effect of HLA-allele mismatching in UD-HCT, potentially expanding the donor pool for acute leukemia patients.

• MeSH
• akutní lymfatická leukemie mortalita   patologie   terapie   MeSH
• akutní myeloidní leukemie mortalita   patologie   terapie   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dospělí MeSH
• homologní transplantace MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru mortalita   patologie   terapie   MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• nemoc štěpu proti hostiteli farmakoterapie   etiologie   mortalita   patologie   MeSH
• nepříbuzný dárce * MeSH
• příprava pacienta k transplantaci MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   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
• Názvy látek
• cyklofosfamid MeSH
• imunosupresiva MeSH

IMPORTANCE: Use of haploidentical (HAPLO) stem cell transplantation with posttransplant cyclophosphamide is rapidly increasing in adults with hematologic cancers. However, its specific role compared with other transplant strategies has yet to be identified. OBJECTIVE: To synthesize the existing evidence regarding outcomes of stem cell transplantations comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from matched related donors (MRDs), matched unrelated donors (MUDs), or mismatched unrelated donors (MMUDs). DATA SOURCES: PubMed, Cochrane Library, ClinicalTrials.gov, and meeting abstracts were searched for the key words haploidentical and cyclophosphamide from inception through March 1, 2019. STUDY SELECTION: Studies comparing HAPLO stem cell transplantation and posttransplant cyclophosphamide therapy with transplantations from other donors in adults with hematologic cancers were eligible for meta-analysis. DATA EXTRACTION AND SYNTHESIS: Pooled odds ratios (ORs) and 95% CIs were calculated using a random-effects model. MAIN OUTCOMES AND MEASURES: Main outcomes were all-cause mortality, nonrelapse mortality, and relapse. RESULTS: A total of 30 studies including 22 974 participants were analyzed. HAPLO stem cell transplantation with posttransplant cyclophosphamide therapy was associated with increased all-cause mortality compared with MRDs (OR, 1.17; 95% CI, 1.05-1.30), similar all-cause mortality compared with MUDs (OR, 1.06; 95% CI, 0.96-1.18), and reduced all-cause mortality compared with MMUDs (OR, 0.75; 95% CI, 0.61-0.92). Regarding nonrelapse mortality, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with worse outcomes compared with MRDs (OR, 1.20; 95% CI, 1.04-1.40) but better outcomes compared with MUDs (OR, 0.75; 95% CI, 0.61-0.92) and MMUDs (OR, 0.51; 95% CI, 0.25-1.02). In terms of relapse, HAPLO stem cell transplantation with posttransplant cyclophosphamide was associated with similar outcome compared with MRDs (OR, 1.01; 95% CI, 0.86-1.17) and MMUDs (OR, 1.06; 95% CI, 0.77-1.47) but showed increased relapse compared with MUDs (OR, 1.20; 95% CI, 1.03-1.40). CONCLUSIONS AND RELEVANCE: Results of this meta-analysis suggest that MRDs, if available, remain the optimal donors regarding mortality and HAPLO stem cell transplantation with posttransplant cyclophosphamide may be preferred over MMUDs. Prospective comparisons with MUDs are needed.

• MeSH
• cyklofosfamid terapeutické užití   MeSH
• dospělí MeSH
• haploidentická transplantace MeSH
• hematologické nádory terapie   MeSH
• lidé MeSH
• nepříbuzný dárce MeSH
• přežití bez známek nemoci MeSH
• transplantace hematopoetických kmenových buněk metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• srovnávací studie MeSH
• systematický přehled MeSH
• Názvy látek
• cyklofosfamid MeSH

BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. METHODS: We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. RESULTS: HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II-IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. CONCLUSIONS: Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.

• Klíčová slova
• Acute leukemia, Allogeneic stem cell transplantation, Anti-leukemic effect, HLA matching, Older patients, Toxicity, Unrelated donor,
• MeSH
• akutní myeloidní leukemie komplikace   mortalita   terapie   MeSH
• analýza přežití MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli etiologie   imunologie   MeSH
• nepříbuzný dárce * MeSH
• přežívání štěpu MeSH
• příprava pacienta k transplantaci metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• testování histokompatibility * MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH