Utilization of Total Body Irradiation Is Not Necessary for Unrelated Donor Umbilical Cord Blood Transplants: a Single-Center Experience

Background: Umbilical cord blood (UCB) is rich in primitive hematopoietic stem cells (HSC) and progenitor cells that can reconstitute the hematopoietic system in recipients under proper conditioning. Initially umbilical cord blood transplantation was limited to children because of the low cell dose requirement. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders in the pediatric setting. To overcome the disadvantage of low cell dose in a single unit of UCB, the double-units umbilical cord blood transplantation (dCBT) strategy was introduced to adult patients with various hematological malignant diseases who had no suitable related or unrelated stem cell donor. Over the last decade, this dCBT strategy has been validated in several elegant adult HSC transplantation studies. Because of its loose HLA-matching requirement and abundant UCB resource available, UCB transplantation (UCBT) has emerged as an effective alternative therapy for both pediatric and adult HSC transplantations. However, the optimal conditioning regimens prior to UCBT remains unclear in regards to engraftment, treatment related mortality (TRM), graft-versus-host-disease (GVHD), and prevention of disease relapse. Further more, most published UCBT conditioning regimens have utilized total body irradiation (TBI), but there is no stringent study to evaluate the efficacy of this treatment in regards to UCBT outcome.

Method: This is a retrospective study to analyze the outcomes of 47 patients with various hematological diseases receiving UCBT at Pennsylvania State University Hershey Cancer Institute in last 13 years. In this study, individual patient was characterized by his/her gender, age and weight at the time of receiving UCBT, disease status, the HLA compatibilities among UCB units and recipient, the conditioning regimens prior to UCBT, the ABO and gender compatibilities among UCB units and recipient, time to engraftment and chimerism status post UCBT, the incidence and severity of GVHD (acute and chronic), and the incidence of systemic infection. The rates for TRM, event free survival (EFS), and overall survival (OS) were calculated and compared among patients who received different conditioning regimens that contained TBI and those that did not.

Result: This study analyzed 47 patients with an age range from 0.5 years old to 65.4 years old (mean: 14.3) at the time of UCBT. The lengths of individual patient follow up ranged from 0.9 years to 12.8 years (mean: 6.8 years). The long term OS rate was 55.3%, which was comparable to progress-free survival rate. Twenty-six patients were male (55%) and 21 patients were female (45%). Days to neutrophil engraftment (absolute neutrophil count ≥500/dl) post UCBT ranged from 10 days to 38 days (mean: 21.8 days). Nine patients (19%) developed severe acute GVHD (≥degree 3) and 8 patients (8%) had severe chronic GVHD. Twenty eight patients (58%) had a systemic infection, of which 5 patients (11%) had systemic CMV infection. Thirty eight patients underwent a busulfan and cyclophosphamide (Bu/Cy) combination as conditioning regimen, 9 patients used fludarabine and cyclophosphamide (Flu/Cy) combination as conditioning regimen. Thirty four patients didn’t utilize TBI as part of conditioning regimens and 13 patients utilized TBI. The long term OS rate of patients not receiving TBI was 55.9% (19/34) and the long term OS rate of patients receiving TBI was 53.8% (7/13). The TRM rate of patients not receiving TBI was 32.4% (11/34) and receiving TBI was 38.5% (5/13).

Conclusion:

1. UCBT has a comparable outcome to HSC transplantation from suitable related or unrelated blood or bone marrow donors in regards to TRM, EFS, and OS.

1. The conditioning regimens not utilizing TBI are not inferior to the conditioning regimens utilizing TBI for unrelated donor UCBT.