Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions

Abstract

We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34 ؉ stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P ‫؍‬ .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800. (Blood. 2011;118(24):6438-6445)

Early peripheral blood and T-cell chimerism dynamics after umbilical cord blood transplantation supported with haploidentical cells

“…2,4 Single CB transplantation supported by mobilized and selected CD34 þ cells from a HLA-mismatched third party donor (TPD), known as dual or haplo-cord SCT, has shown to reduce the period of post-transplant neutropenia and related early morbidity and mortality associated with single CB transplantation. [5][6][7][8] This strategy offers a rapid neutrophil recovery at the expense firstly of TPD cells with subsequent replacement and long-term engraftment of CB cells.…”

“…2,4 Single CB transplantation supported by mobilized and selected CD34 þ cells from a HLA-mismatched third party donor (TPD), known as dual or haplo-cord SCT, has shown to reduce the period of post-transplant neutropenia and related early morbidity and mortality associated with single CB transplantation. [5][6][7][8] This strategy offers a rapid neutrophil recovery at the expense firstly of TPD cells with subsequent replacement and long-term engraftment of CB cells.Graft failure and graft rejection are major complications after allogeneic SCT, with a frequency as high as 23% using CB transplants. 9-11 Outcome of patients who develop graft failure without a second transplantation is dismal with survival rates lower than 10%; 12 however, survival rates improve significantly to 30-60% after salvage transplantation using reduced intensity conditioning regimens.…”

In Vivo DPP-4 Inhibition to Enhance Engraftment of Single-Unit Cord Blood Transplants in Adults with Hematological Malignancies

“…Delayed engraftment, however, remains a significant limitation due to low cell doses in UCB units. Strategies to overcome this limitation include use of multiple cord blood units [2,3], ex vivo expansion of UCB stem cells [4], and co-infusion of third party haploidentical CD34 + cells [5,6], but technical obstacles, complexity of procedures, and/or economic considerations may limit their widespread use.…”

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

“…A number of strategies have been proposed to reduce the risk of graft failure after UCBT, including the use of multiple units, 27 intrabone infusion of the UCB unit, 28 co-infusion of purified stem cells from a haploidentical family donor, 29,30 administration of molecules facilitating stem cell homing, 31 and the co-infusion of ex-vivo expanded progenitor cells 32,33 or mesenchymal stromal cells. All the above strategies were reported to give promising results, but so far no definitive conclusion can be drawn on their long-term outcome or reproducibility.…”