Duration of Unrelated Donor Search for Hematopoietic Stem Cell Transplantation
Authors: Schetelig Johannes , Lehnert Christina , Klesse Christian , Füssel Monika , Pingel Julia , Schmidt Alexander H. , Ehninger Gerhard 
Published: October 2019

Abstract
Abstract 2046

Objective:
Donor search is a major challenge once the indication for allogeneic hematopoietic stem cell transplantation (HCT) has been established. For those patients who lack an HLA-identical sibling, unrelated donor search (UDS) needs to be initiated. Only if UDS is not successful, alternative stem cell sources like cord blood (CB) or alternative concepts like haploidentical HCT have to be considered. Since UDS is a time consuming process it is important to assess the probability to find a matched unrelated donor (UD) during prolonged UDS. Yet, very few data on the required times and the success rates of unrelated donor searches are available. Furthermore, information on the probability to find a donor within short time is crucial in the context of early allogeneic transplantation including HCT in aplasia after induction chemotherapy in AML or for the interpretation and planning of clinical trials employing donor versus no donor comparisons. Therefore, we have retrospectively analyzed the duration of UDS for a large cohort of patients.

Methods:
All unrelated donor searches of one large search unit, which were initiated between January 2004 and July 2010 were analyzed retrospectively. Throughout that period blood from all donor-recipient pairs has been typed for HLA-A, -B, -C, -DRB1 and –DQB1 at the allele level (4 digits). A full match was defined by HLA-identity for HLA-A, -B, -C and DRB1 (8/8), while a partial match was defined as a single mismatch in the HLA-A, -B, -C or DRB1 locus without additional DQB1 mismatch (9/10). The duration of UDS was calculated from the date of data entry to the date of receipt of confirmatory typing (CT) of the first 8/8 HLA-matched donor or the first 9/10 HLA-matched donor. When given as reasons for the termination of the search, poor clinical condition or death of a patient were considered as competing events. Unsuccessful searches were censored at the day of the receipt of the last typing request or when UDS was stopped for other reasons. Cumulative incidences of successful UDS were calculated with competing event statistics. Approximative 95% confidence intervals are provided for point estimates.

Results:
In the respective time period 852 UDS comprising 8477 donor requests were performed. In the Caucasian population, an HLA compatible UD (8/8) has been found for 29% (95% CI, 26% to 32%) of the patients within two weeks, 54% (95% CI, 51% to 58%) of patients within 4 weeks, and 61% (95% CI, 57% to 64%) of patients within 6 weeks (Figure 1). In high risk diseases and high urgent indications for allogeneic transplantation one antigen or allele mismatch may be acceptable. Therefore, we calculated the probabilities to find an HLA matched UD (8/8) or a partially matched UD (9/10) within defined times. The resulting probabilities of finding an acceptable donor who met these criteria for Caucasian patients were 35% (95% CI, 32% to 39%), 66% (95% CI, 63% to 70%) and 75% (95% CI, 72% to 78%) at two, four, and six weeks respectively. After six weeks of UDS the probability of finding a donor declined. Between the six week landmark and the 12 week landmark 8/8 HLA matched unrelated donors have been identified only for additional 4% of the patients. Extending UDS up to one year resulted in additional 3% HLA matched donors (8/8). The incidence of the competing events (death or deteriorated condition of the patient) was 10% (95% CI, 6.6% to 13.8%) at one year when the aim was to find an 8/8 HLA matched UD. Eight UDS (1%) were started for non-Caucasian patients. Only for one of the eight non-Caucasian patients an HLA-compatible donor (8/8) was found.

Conclusions:
For Caucasian patients HLA compatible UDs (8/8) can be identified in our population for 61% of the patients within six weeks. If donors with one mismatch (9/10) are accepted the probability increases to 75% at that time. Beyond that landmark, the probability of finding donors for the remaining patients declines steeply and alternatives like haploidentical or cord blood transplantation should be considered. Since an HLA matched donor can be identified for 29% of the patients within two weeks, UDS is a valid option even for very high urgent searches like in the context of allogeneic HCT in aplasia. Unrelated donor searches for patients with non-Caucasian ancestry are much less successful. Further analyses are planned in order to define the probability to find a donor related to the haplotype frequency of the patient.

Disclosures:
Off Label Use: pentostatin is not licensed for use in acute GvHD.