Strategies of the donor search for children with second CR ALL lacking a matched sibling donor

Abstract

During the last 10 years, the number of alternative Haematopoietic stem cell transplantations (HSCTs) performed on children in Europe has increased significantly and has reached 61% of the allografts. In this paper, we provide practical guidelines to help define an algorithm for the treatment of children relapsing during or after first-line chemotherapy for ALL and lacking a matched sibling donor. A simultaneous search for an unrelated donor and for a cord blood unit should be started. This study focuses mainly on the effects of some factors on survival in an effort to highlight the influence that these factors have on our choices. Matching the patient for HLA-A, -B, -C and -DRB1 alleles remains the top priority: a single HLA class I or II allele mismatch has no influence on survival, while multiple mismatching for more than one class I allele and simultaneous disparities in class I and II alleles increase mortality. The impact of additional mismatches for HLA-DQ and -DP loci on survival is still controversial. Young donor age is the most important factor that has a significant effect on better survival from among several other factors, including CMV sero-status, gender and ABO. An 18-to 30-year-old, 8/8 allele-matched donor (excluding allele matching at DQB1) or for many teams 10/10 allele-matched donor; or a 4 out of 6 (considering Ag HLA-A, -B and allelic typing of DRB1) CB unit containing more than 3.0 Â 10 7 nuclear cells is considered by most institutions. The choice should be made on the basis of urgency. If a donor or a CB unit is not found within an appropriate time frame, generally less than 3 months after obtention of remission, haploidentical HSCT should be offered. Some institutions consider haploidentical HSCT the second therapeutic option when a matched donor is not available.

Transplant‐related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25‐year retrospective review

“…Units subjected to external audit have improved post-HSCT outcomes [46]. We expected to see improvement in MUD outcomes, due to introduction of high-resolution typing [3,14,28,47], but small numbers may have limited analysis.…”

“…Allogeneic HSCT indications are evolving [9,10], as survival with chemotherapy-only treatment improves [3,4,9,11].Donor sources for HSCT have changed over the last 25 years. A matched sibling donor (MSD) was historically preferred over unrelated donors, due to perceived transplant-related mortality (TRM) risk [12][13][14]. Limited MSD availability has prompted use of alternate donors, including family-related donors (FRD), matched unrelated donors (MUD), and matched unrelated cord blood transplants (UCT).…”

“…UCT is increasingly used, due to factors including wider range of compatible donors and ease of availability [15]. In childhood ALL, alternate donor HSCTs comprise 61% of allografts (1999)(2000)(2001)(2002) [14] whereas prior to 1996, MSD accounted for 70% of HSCT [14]. UCT now accounts for one-third of HSCT for acute leukemia [16].With the advent of alternate donor HSCT, TRM risk has increased [17].…”

High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia

“…21,30 If a matched sibling donor is not available and the disease carries a sufficiently poor prognosis, then the order of alternative donor selection for most institutions and cooperative group studies is an unrelated adult donor or a cord blood unit, followed by an HLA-haploidentical family donor. 31 There have been significant advances in alternative donor HCT using unrelated adult, [32][33][34] cord blood, 35 and haploidentical graft. 36 However, even 8 of 8 allelic matched unrelated donor HCT was associated with a 2-to 4-fold higher risk of GVHD and mortality compared with sibling-donor transplantations.…”

Impact of Donor Characteristics in Survival and Graft-Versus-Host Disease Following Pediatric Hematopoietic Stem Cell Transplant

“…In that era, the probability of develop ing CMV disease after allogeneic transplant was 5% with seronegative recipient and seropositive donor; 14% with seropositive recipient and seronegative donor; and 12% with seropositive donor and recipient [51,55]. Advances including the use of CMV-negative blood, PCR and antigen-based screening m ethods and the use of pre-emptive and prophylactic antiviral therapy, has reduced the incidence of CMV disease to 1-2% [56,57].…”