Umbilical cord blood transplantation in adults: Results of the prospective cord blood transplantation (COBLT)

Abstract

The Cord Blood Transplantation study group conducted a prospective study of unrelated cord blood transplantation (CBT) to better define the role of this stem cell source for subjects requiring unrelated allogeneic transplantation. We report on 1 stratum of the study designated for adult subjects. The primary end point of the study was survival at 180 days. Secondary end points included engraftment, graft-versus-host disease, relapse, and long-term survival. Eligibility criteria for malignant and nonmalignant diseases were specified. Subjects with active central nervous system disease, Karnofsky performance status <70%, grade 3 or 4 or primary myelofibrosis, or suitable related donors were excluded. Enrollment required a single cord blood unit containing >10(7) nucleated cells per kilogram of recipient weight and matched at > or =4 HLA-A and -B (low or intermediate resolution) and -DRB1 (high resolution) types. Thirty-four subjects were entered, with a median age of 34.5 years (range, 18.2-55 years). Most subjects (n = 23) had a 4 of 6 match, 10 subjects had a 5 of 6 match, and 1 subject had a 6 of 6 match. Diagnoses at transplantation included acute myelogenous leukemia (n = 19), acute lymphoblastic leukemia (n = 9), chronic myelogenous leukemia (n = 3), myelodysplastic syndrome (n = 1), paroxysmal nocturnal hemoglobinuria (PNH) (n = 1), and non-Hodgkin lymphoma (n = 1); 94% were classified as poor risk according to National Marrow Donor Program criteria. Subjects received total body irradiation/cyclophosphamide (n = 27) or busulfan/melphalan (n = 7) conditioning regimens. Four subjects died before CBT and are described here but are not included in the main analysis. The cumulative incidence rates and median times to neutrophil (500/microL) and platelet (>20,000/microL) engraftment were 0.66 by day 42 (median, 31 days) and 0.35 by day 180 (median, 117 days). The cumulative incidence rate for grade II-IV GVHD was 0.34 by day 100. For the primary end point, survival at 180 days, Kaplan-Meier survival estimates were 0.30 (95% confidence interval, 0.14-0.46) by day 180 after transplantation. To date there are 2 survivors, and both are >36 months from enrollment. A retrospective analysis was performed by using high-resolution HLA-A and -B typing, which revealed that approximately one third of subjects had 1 or more additional HLA mismatches compared with results of low- or intermediate-resolution HLA typing. The findings of high treatment-related mortality and slow engraftment kinetics indicate that CBT should continue to be performed in specialized centers with a research focus on cord blood cells.

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group

“…UCB is enriched with haematopoietic progenitor cells and contains sufficient numbers of HSCs to reconstitute most paediatric patients. 1,2,4,6,8,9,17,19,[26][27][28][29][30][31][32][33] Most studies have shown that the nucleated cell dose is of paramount importance for haematopoietic recovery, 2,4,6,14,16,17 Wagner et al 10 have also shown the CD34 cell dose as being a significant variable not only for haematopoietic recovery but also for survival. The importance of CD34 cell dose has been replicated in other studies.…”

“…2,10,11,21,23,34,36 TRM in adult recipients of UCB after a myeloablative regimen has been reported to be as high as 60%. 7,10,14,17,19,[30][31][32][33] Comparing UCBT to BMT, Rocha et al 22 compared the outcomes of 541 children transplanted for the treatment of acute leukaemia receiving a UCBT (n ¼ 99), unmanipulated BMT (n ¼ 262), or T-cell-depleted BMT (n ¼ 180). UCB recipients were observed to have a higher TRM within the early period after transplantation.…”

Umbilical cord blood transplantation: Basic biology and clinical challenges to immune reconstitution

“…Long et al [17] noted that infection was the primary cause of death in their study of 57 adults with high-risk disease who were transplanted with unrelated UCB. A large multicenter prospective study of UCB transplantation in adults found that in 34 patients 90% experienced infections; two thirds of those studied reported at least 3 infections during the first 6 months post-transplant [19]. These authors suggested that the delay in immune reconstitution in UCB transplant patients versus BMT recipients could play a major role in their increased susceptibility to infection.…”

Selection of cord blood unit(s) for transplantation

“…[5][6][7][8] Early experience in adult CB transplantation (CBT) was hampered by poor engraftment and immune recovery. [9][10][11] Recent experience with better risk patients, double CB unit transplants and submyeloablative preparative regimens have been more encouraging. [12][13][14] There are several important differences between BM or G-CSF-mobilized PBPC and CB when selecting donors/ products for transplantation.…”