Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donors

Abstract

SummaryWe developed the strategy of umbilical cord blood transplants (UCBT) with co-infusion of a limited number of highly purified mobilized haematopoietic stem cells (MHSC) from a human leucocyte antigen (HLA) unrestricted third party donor (TPD). Short post-transplant periods of neutropenia were usually observed in adults with haematological neoplasms receiving UCBT with a relatively low cell content and 0-3 HLA mismatches after myeloablative conditioning. This resulted from an early and initially predominant engraftment of the TPD-MHSC. After a variable period of double complete TPD + UCB chimerism, final full UCB chimerism was achieved (cumulative incidence >90%) within 100 d. Early recovery of the circulating neutrophils resulting from the 'bridge transplant' of the TPD-MHSC reduced the incidence of serious neutropenia-related infections, also facilitating the use of drugs with myelosuppressive side effects to combat other infections. The observed incidence of graft-versus-host disease and relapses was low, with overall and disease-free survival curves comparable to those of HLA identical sibling transplants. Post-transplant recovery of natural killer cells occurred soon after the transplant and B cells recovered around 6 months, but T-cell recovery took more than 1 year. Available data show that T cell recovery derives from UCB-HSC through thymic differentiation and that cytomegalovirus (CMV)-specific lymphocytes develop following CMV reactivations.

Haploidentical, unmanipulated, G-CSF–primed bone marrow transplantation for patients with high-risk hematologic malignancies

“…6 The results of UCB transplantation in children and adults are well established [7][8][9][10] and comparable with those reported for MUD transplantations. 11,12 However, the low number of hematopoietic stem cells contained in a single UCB unit limits its use for transplantation and, despite several alternative strategies that are currently being explored, [13][14][15][16] it remains the main obstacle for successful UCB transplantation, particularly in adults. Considering that virtually all patients have at least 1 HLA-haploidentical family member, when neither matched sibling donor nor MUD nor UCB are available, transplantation from a haploidentical family donor represents a valid alternative for patients with high-risk hematologic malignancies.…”

An overview of the progress on double umbilical cord blood transplantation

“…Within the context of dual transplant, the co-infusion of unrelated umbilical cord blood with mobilized hematopoietic stem cells (HSCs), whether or not these are T-cell depleted, from thirdparty donors has been used in clinical practice. 19 Compared to single UCBT, this approach is accompanied by shorter periods of neutropenia due to early engraftment of the mobilized hematopoietic stem cells, and therefore a lower incidence of graft-versus-host disease. Studies involving in vitro expansion of a fraction of the umbilical cord blood with cytokines and subsequent co-infusion of the expanded and non-expanded Manuscript received on December 9, 2010.…”

Early engraftment and full-donor chimerism after single-cord blood plus third-party donor dual transplantation in patients with high-risk acute leukemia

“…Ferná ndez et al 3 and Kwon et al 7 have shown similar outcomes when comparing the UCB-TPD dual strategy to myeloablative allogeneic transplantation from HLA-matched related and unrelated donors, respectively. Liu et al have successfully applied this strategy to a somewhat older cohort of patients using a reduced intensity conditioning regimen, which despite good early outcomes, led to prolonged mixed chimerism and persistent recipient hematopoiesis that may raise potential concerns regarding the risk of disease relapse at a longer follow-up than their reported 11 months.…”

“…2 A dual transplant strategy combining UCB plus third-party donor (TPD) HC (UCB-TPD) pioneered at Hospital Puerta de Hierro in Madrid has been shown to improve early outcomes after UCB transplantation by hastening hematopoietic recovery. 3 Here, we present an independent series of 13 consecutive high-risk myelodysplastic syndrome (MDS)/AML and ALL patients, median age 45 years (20-64) and weight 71 Kg (56-104), who received a myeloablative UCB-TPD dual transplant in our center from February 2009 to January 2013. Patients lacked a matched related or unrelated donor, were in advanced stage and heavily pretreated: seven refractory to X1 line of chemotherapy, three relapsed after a previous HC transplant, and two had active AML (9 and 22% blasts) prior to UCB-TPD transplant (Table 1).…”