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

Abstract

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.

A STAT6 Inhibitor AS1517499 Reduces Preventive Effects of Apoptotic Cell Instillation on Bleomycin-Induced Lung Fibrosis by Suppressing PPARγ

“…12/15-LO is involved in IL-4-dependent enhancement of PPARγ expression and activation via production of PPARγ ligands, such as 15-hydroxyeicosatetraenoic (HETE) and lipoxin-A4 [33, 34]. Thus, we examined whether 12/15-LO also participates in enhancing PPARγ expression and functional activation by apoptotic cell instillation after BLM treatment using PD146176, a specific inhibitor of 12/15-LO.…”

Low incidence of HHV‐6 reactivation in haploidentical hematopoietic stem cell transplantation with corticosteroid as graft‐vs‐host disease prophylaxis compared with cord blood transplantation

“…In this study, we demonstrated for the first time the low incidence of HHV‐6 reactivation in our haplo‐SCT patients, which suggests that HLA‐mismatched/haplo‐SCT patients are not always vulnerable to HHV‐6 reactivation. Compared with our haplo‐SCT studies using corticosteroids as GVHD prophylaxis, recent haplo‐SCT studies using post‐transplant cyclophosphamide infusion reported a higher incidence of HHV‐6 reactivation (35%‐78%) . This discrepancy suggests that the incidence of HHV‐6 reactivation potentially varies according to GVHD prophylaxis or conditioning regimens, or both.…”

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“…Van Besien K et al [10] in their study of Haploidentical (haplo)-cord transplantation combined infusion of an umbilical cord blood (UCB) unit with CD34-selected cells usually from human leukocyte antigen (HLA) mismatched donors and suggested that initial rapid count recovery from the haplo-hematopoietic progenitors, is gradually replaced by durable engraftment from UCB progenitors thus benefitting overall outcomes [5] Hence haploidentical SCT can also be used as a bridge to improving outcomes in patients undergoing UCB SCT thus achieving the best of both the worlds.…”