Comparison of Haploidentical Bone Marrow versus Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation with Posttransplant Cyclophosphamide in Patients with Acute Leukemia.

Posttransplant cyclophosphamide (PTCy) is increasingly being utilized as a principle GvHD prophylaxis strategy in allogeneic hematopoietic cell transplantation (allo-HCT). A haploidentical (haplo) or matched unrelated donor (UD) is a valid option in the absence of a matched related donor. We compared the outcomes of patients with acute leukemia who underwent haplo bone marrow (haplo-BM, N = 401) versus UD mobilized peripheral blood stem cells (UD-PB, N = 192) transplantation in the setting of PTCy. The median follow-up duration was 36 months in the haplo-BM group and 16.6 months in the UD-PB group, respectively (P < 0.01). Myeloablative conditioning was used in 64.6% and 42.7% of haplo-BM and UD-PB patients, respectively (P < 0.01). Cumulative incidence of neutrophil engraftment at day 30 was 87% in haplo-BM versus 94% in UD-PB, respectively (P = 0.21). In the multivariate analysis, the risk of grade 2-4 acute GvHD (HR = 0.53, P = 0.01) and chronic GvHD (HR = 0.50, P = 0.02) was significantly lower in the haplo-BM group compared with the UD-PB group. There was no significant difference between the study groups with respect to relapse incidence, nonrelapse mortality, leukemia-fee survival, overall survival, or GvHD-free and relapse-free survival. The use of a haplo donor with a BM graft resulted in a lower incidence of GvHD compared with a UD-PB stem cell graft in the setting of PTCy for patients with acute leukemia. However, differences in GvHD did not translate into a difference in survival outcomes. Based upon these data, UD-PB or haplo-BM should be considered equally acceptable sources for allo-HCT.

Nagler A ，Labopin M ，Dholaria B ，Angelucci E ，Afanasyev B ，Cornelissen JJ ，Sica S ，Meijer E ，Ciceri F ，Van Gorkom G ，Kröger N ，Martin H ，Pioltelli P ，Risitano A ，Canaani J ，Savani BN ，Sanz J ，Mohty M ... -  《-》

Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia.

Nagler A ，Dholaria B ，Labopin M ，Savani BN ，Angelucci E ，Koc Y ，Arat M ，Pioltelli P ，Sica S ，Gülbas Z ，Tischer J ，Bernasconi P ，Pavlu J ，Socié G ，Blaise D ，Rigacci L ，Martino M ，Diez-Martin JL ，Perić Z ，Giebel S ，Mohty M ... -  《-》

Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission.

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.

Lee KH ，Lee JH ，Lee JH ，Kim DY ，Park HS ，Choi EJ ，Ko SH ，Seol M ，Lee YS ，Kang YA ，Jeon M ，Baek S ，Kang YL ，Kim SH ，Yun SC ，Kim H ，Jo JC ，Choi Y ，Joo YD ，Lim SN ... -  《-》

Impact of Thymoglobulin by Stem Cell Source (Peripheral Blood Stem Cell or Bone Marrow) After Myeloablative Stem Cell Transplantation From HLA 10/10-Matched Unrelated Donors: A Report From the Société Française de Greffe de Moelle et de Thérapie Cellulair

Ravinet A ，Cabrespine A ，Socié G ，Milpied N ，Yakoub Agha I ，Nguyen S ，Michallet M ，Menard AL ，Maillard N ，Mohty M ，Suarez F ，Huynh A ，Marchand T ，Deteix C ，Cassuto JP ，Maury S ，Chevallier P ，Reman O ，Peffault de Latour R ，Bay JO ... -  《-》

Comparative Outcomes after Haploidentical or Unrelated Donor Bone Marrow or Blood Stem Cell Transplantation in Adult Patients with Hematological Malignancies.

Most patients eligible for allogeneic hematopoietic stem cell transplantation will require identification of an alternate (unrelated or mismatched related) donor. We explored the transplantation outcomes for a sequential series of 54 patients undergoing haploidentical donor transplantation (HAPLO) compared to those from a control group of patients receiving cells from matched or mismatched unrelated donors (URD) selected by diagnosis and stem cell source. Patients undergoing HAPLO transplantations received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (Cy). Day 15 neutrophil recovery was lower after HAPLO than in URD recipients (43% versus 77%, P < .001), as was day 30 platelet recovery (67% versus 84%, P = .043). HAPLO patients receiving bone marrow achieved neutrophil engraftment at a median of 17 days and platelet engraftment at a median of 29 days, compared with 16 days and 24 days, respectively, for recipients of peripheral blood stem cells. The incidence of graft failure was similar for both HAPLO and URD recipients (P = .42). HAPLO recipients were more likely to reach donor CD3 chimerism >95% by day 28 after transplantation (88% versus 62%, P = .003). The cumulative incidence of grades II to IV acute GVHD (aGVHD) at 6 months after transplantation did not differ for these 2 groups (63% for HAPLO and 53% for URD recipients; P = .269), nor did the cumulative incidence of severe grade III/IV aGVHD (13% for HAPLO and 8% for URD recipients; P = .44). The cumulative incidence of moderate or severe chronic GVHD at 2 years did not differ, with probabilities of 24% for HAPLO and 18% for URD recipients (P = .43). The cumulative incidence of cytomegalovirus reactivation by day 100 after transplantation did not differ (45% for HAPLO and 46% for URD recipients; P = .96). The HAPLO recipients experienced a lower incidence of Epstein-Barr virus reactivation by day 100 (6% versus 32%, P < .001) but a higher incidence of Human Herpesvirus-6 reactivation (35% versus 10%, P = .001). Relapse risk, regimen-related mortality, progression-free survival, and overall survival probabilities did not differ between these 2 groups. These data support the use of HAPLO transplantation with post-transplantation Cy as an alternate transplantation technique for patients lacking HLA-matched sibling donors. Transplantation of peripheral blood stem cells does not appear to enhance the speed of neutrophil recovery. The different patterns of viral reactivation require additional studies to explain.

Baker M ，Wang H ，Rowley SD ，Cai L ，Pecora AL ，Skarbnik A ，Vesole DH ，Adler-Brecher B ，Kim D ，Donato ML ... -  《-》