Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis

Abstract

SUMMARY Background Umbilical cord blood (UCB) is increasingly considered as an alternative to peripheral blood progenitor cells (PBPC) or bone marrow (BM), especially when a HLA-matched adult unrelated donor is not available. Methods In order to establish the appropriateness of current graft selection practices, we retrospectively compared leukemia-free survival and other outcomes for each graft source in patients aged >16 years transplanted for acute leukemia using Cox regression. Data were available on 1525 patients transplanted between 2002 and 2006 using UCB (n=165), PBPC (n=888) and BM (n=472). UCB units were matched at HLA-A and B at antigen level and DRB1 at allele level (n=10) or mismatched at one (n=40) or two antigens (n=115). PBPC and BM grafts from unrelated adult donors were matched for allele-level HLA-A, B, C and DRB1 (n=632; n=332) or mismatched at one locus (n=256; n=140). Findings Leukemia-free survival after UCB transplantation was comparable to that observed after 8/8 and 7/8 allele-matched PBPC or BM transplantation. Transplant-related mortality, however, was higher after UCB transplantation compared to 8/8 allele-matched PBPC (HR 1.62, p<0.01) or BM (HR 1.69, p<0.01). Grades 2–4 acute and chronic graft-versus-host disease were lower in UCB recipients compared to allele-matched PBPC (HR 0.57, p<0.01 and HR 0.38, p<0.01, respectively), while chronic and not acute graft-versus-host disease was lower after UCB compared to allele-matched BM transplantation (HR 0.63, p=0.01). Interpretation Together, these data support the use of UCB for adults with acute leukemia when an HLA-matched unrelated adult donor is lacking and when transplant is urgently needed.

Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels

“…41 However, despite improved outcome of allo-HCT, GvHD grade 2 --4 remains a major factor causing high treatmentrelated mortality. 42 In contrast to the tradition of interfering with lymphocyte function by immunosuppressive drugs recent evidence support the concept that DCs are attractive targets for pharmacological interventions as they are key regulators of GvHD. 43 We therefore hypothesized that agents that target both Tc activation and allostimulatory functions of DCs may have a strong therapeutic potential in GvHD.…”

Umbilical cord blood banking: an update

“…Cord blood is considered a treatment option in pediatric and adult patients with hematologic malignancies and disorders (leukemia, thalassemia, sickle cell disease, etc. ), bone marrow failures, inherited metabolic disorders, immunological defects and other genetic diseases [1][2][3][4][5][6][7][8][9][10][11][12]. Double umbilical cord blood grafts, that use cord blood units from two donors, mitigate cell dose limitations for larger children and adults with malignant disorders [12][13][14].…”

“…The results, to date, are encouraging and appear at least comparable to bone marrow or peripheral blood progenitor cells as the donor source for transplants [12,13]. Later, Rubenstein and others were the first to establish an unrelated cord blood bank from voluntary donors and then used the blood units from the bank for unrelated cord blood transplantation [19][20][21].…”

“…There are now two international registries: NETCORD, which lists cord blood units only and Bone Marrow Donors Worldwide which lists both bone marrow and cord blood donors [22]. EuroCord and the Center for International Blood and Marrow Transplant Research (CIBMTR) provide extensive analytical expertise in evaluating efficacy and outcomes [4,10,12].…”

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

“…There is considerable evidence that CB is a promising option for patients who lack a human leukocyte antigen (HLA)‐matched related or unrelated donor 1. Several studies comparing results of CBT and either bone marrow or peripheral blood stem cell transplantation showed similar results regarding OS and leukemia‐free survival, despite slower hematopoietic recovery and higher incidence of GF for CB transplant recipients 2, 3…”