Results of a prospective, monocentric study on the search of an unrelated donor for patients with high-risk acute lymphoblastic leukaemia

Allogeneic stem cell transplantation (HSCT) is potentially curative for patients (pts) with high risk acute lymphoblastic leukemia (HRALL), and the search of an unrelated donor is a common strategy for pts lacking a family donor. To assess the effect of the search on the outcome of pts with HRALL, we analyzed prospectively 136 pts, median age 11 yrs (1-59), on search of an unrelated donor through the BMDWW Registry and Cord Blood (CB) Banks, between 1995 and 2008. At the start of the search, 37 pts were in ICR, 70 in IICR, 3 in >IICR, 26 in relapse. The cumulative incidence (CI) of finding a donor (CB or volunteer donor, VD) was 62% and 72% at 3 and 6 months, respectively; after this time no increase in the CI of finding a donor was observed. The median time from the start of the search to find a donor was 1.5 months for CB and 3.5 months for VD. Fifty-one % of the 110 patients who entered into the study in CR showed a relapse at a median of 4 and 2 months from the start of the search for pts in I-II CR and >II CR, respectively. Of the 101 pts with a donor, 61% underwent a transplant: 25% in a more advanced phase compared to the start of the search; 35% of pts who started the search in relapse obtained a CR and underwent an HSCT. Therefore, 44% of pts failed to undergo a transplant because of lost eligibility due to disease progression. The 10-year probability of OS was 22.5%. Disease progression was the major cause of death. In univariate analysis, relapse vs no relapse during the search (HR:4.1; CI%95:2.75-6.12) and transplant vs no transplant (HR:0.62;CI%95:0.4-0.98) significantly affected OS. For pts who underwent an HSCT, disease phase at transplant was the most important factor affecting OS. In conclusion, by decreasing the length of the search (waiting for more than 3 months increases the probability of finding a donor of just 10%, while half of the pts relapse) the risk of relapse can be reduced, increasing the possibility of performing a transplant. To address the search at the same time for both VD and CB allows to increase the availability of stem cells for a transplant to be carried out prior to the median time of relapse, if the monitoring of the disease, during the search, shows an increased risk of disease recurrence. During the search of a donor for pts with HRALL, the major strategic factor must be considering "the time" of the transplant, more than the type of the transplant;according to this strategy, haploidentical transplant need to be