Трансплантация пуповинной крови взрослым: результаты и перспективы трансплантации пуповинной крови

Cornetta K., Laughlin M., Carter S., Wall D., Weinthal J., Delaney C., Wagner J., Sweetman R., McCarthy P., Chao N.
Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 W. Walnut St., Indianapolis, IN 46202, USA. kcornett@iupui.edu

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.