T-cell-depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT).

T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor. To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117]). The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft-versus-host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2-year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced-intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2-year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia-free survival and GvHD-free/relapse-free survival (GRFS) improved over time: the leukemia-free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia-free survival and GRFS improved among patients who received a RIC regimen. The outcome of patients with acute leukemia who underwent T-cell-depleted haplo has improved over time. Cancer 2018;124:2142-50. © 2018 American Cancer Society.

Sestili S ，Labopin M ，Ruggeri A ，Velardi A ，Ciceri F ，Maertens J ，Kanz L ，Aversa F ，Lewalle P ，Bunjes D ，Mohty M ，Nagler A ... -  《-》

Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplanta

Nagler A ，Labopin M ，Houhou M ，Aljurf M ，Mousavi A ，Hamladji RM ，Al Zahrani M ，Bondarenko S ，Arat M ，Angelucci E ，Koc Y ，Gülbas Z ，Sica S ，Bourhis JH ，Canaani J ，Brissot E ，Giebel S ，Mohty M ... -  《Journal of Hematology & Oncology》

Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood a

In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs. In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics. Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10-4 ) but lower leukemia-free survival (HR, 1.7; P = .04). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40; P = .004), better leukemia-free survival (HR, 0.46; P = .003), better overall survival (HR, 0.43; P = .003), and better GRFS (HR, 0.54; P = .006). In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice.

Gorin NC ，Labopin M ，Blaise D ，de Groot M ，Socié G ，Bourhis JH ，Ciceri F ，Polge E ，Nagler A ，Mohty M ... -  《-》

Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.

Rashidi A ，Hamadani M ，Zhang MJ ，Wang HL ，Abdel-Azim H ，Aljurf M ，Assal A ，Bajel A ，Bashey A ，Battiwalla M ，Beitinjaneh AM ，Bejanyan N ，Bhatt VR ，Bolaños-Meade J ，Byrne M ，Cahn JY ，Cairo M ，Ciurea S ，Copelan E ，Cutler C ，Daly A ，Diaz MA ，Farhadfar N ，Gale RP ，Ganguly S ，Grunwald MR ，Hahn T ，Hashmi S ，Hildebrandt GC ，Holland HK ，Hossain N ，Kanakry CG ，Kharfan-Dabaja MA ，Khera N ，Koc Y ，Lazarus HM ，Lee JW ，Maertens J ，Martino R ，McGuirk J ，Munker R ，Murthy HS ，Nakamura R ，Nathan S ，Nishihori T ，Palmisiano N ，Patel S ，Pidala J ，Olin R ，Olsson RF ，Oran B ，Ringden O ，Rizzieri D ，Rowe J ，Savoie ML ，Schultz KR ，Seo S ，Shaffer BC ，Singh A ，Solh M ，Stockerl-Goldstein K ，Verdonck LF ，Wagner J ，Waller EK ，De Lima M ，Sandmaier BM ，Litzow M ，Weisdorf D ，Romee R ，Saber W ... -  《-》

Immune Modulation Properties of Zoledronic Acid on TcRγδ T-Lymphocytes After TcRαβ/CD19-Depleted Haploidentical Stem Cell Transplantation: An analysis on 46 Pediatric Patients Affected by Acute Leukemia.

TcRαβ/CD19-cell depleted HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a promising new platform for children affected by acute leukemia in need of an allograft and lacking a matched donor, disease recurrence being the main cause of treatment failure. The use of zoledronic acid to enhance TcRγδ+ lymphocyte function after TcRαβ/CD19-cell depleted haplo-HSCT was tested in an open-label, feasibility, proof-of-principle study. Forty-six children affected by high-risk acute leukemia underwent haplo-HSCT after removal of TcRαβ+ and CD19+ B lymphocytes. No post-transplant pharmacological graft-versus-host disease (GvHD) prophylaxis was given. Zoledronic acid was administered monthly at a dose of 0.05 mg/kg/dose (maximum dose 4 mg), starting from day +20 after transplantation. A total of 139 infusions were administered, with a mean of 3 infusions per patient. No severe adverse event was observed. Common side effects were represented by asymptomatic hypocalcemia and acute phase reactions (including fever, chills, malaise, and/or arthralgia) within 24-48 h from zoledronic acid infusion. The cumulative incidence of acute and chronic GvHD was 17.3% (all grade I-II) and 4.8% (all limited), respectively. Patients given 3 or more infusions of zoledronic acid had a lower incidence of both acute GvHD (8.8 vs. 41.6%, p = 0.015) and chronic GvHD (0 vs. 22.2%, p = 0.006). Transplant-related mortality (TRM) and relapse incidence at 3 years were 4.3 and 30.4%, respectively. Patients receiving repeated infusions of zoledronic acid had a lower TRM as compared to those receiving 1 or 2 administration of the drug (0 vs. 16.7%, p = 0.01). Five-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 67.2 and 65.2%, respectively, with a trend toward a better OS for patients receiving 3 or more infusions (73.1 vs. 50.0%, p = 0.05). The probability of GvHD/relapse-free survival was significantly worse in patients receiving 1-2 infusions of zoledonic acid than in those given ≥3 infusions (33.3 vs. 70.6%, respectively, p = 0.006). Multivariable analysis showed an independent positive effect on outcome given by repeated infusions of zoledronic acid (HR 0.27, p = 0.03). These data indicate that the use of zoledronic acid after TcRαβ/CD19-cell depleted haploHSCT is safe and may result in a lower incidence of acute GvHD, chronic GvHD, and TRM.

Merli P ，Algeri M ，Galaverna F ，Milano GM ，Bertaina V ，Biagini S ，Girolami E ，Palumbo G ，Sinibaldi M ，Becilli M ，Leone G ，Boccieri E ，Grapulin L ，Gaspari S ，Airoldi I ，Strocchio L ，Pagliara D ，Locatelli F ... -  《Frontiers in Immunology》