Current Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphocytic Leukemia: Success, Failure and Future Perspectives—A Single-Center Experience, 2008 to 2016

Abstract

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n = 48), an unrelated matched donor (UMD; n = 56), or a haploidentical donor (n = 20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P = .01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P = .02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.

Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution

“…[10][11][12][13] However, extensive T-cell depletion resulted in delayed immune recovery, and higher risk of relapse and infection. 14,15 Hence, more selective T-cell depletion techniques that effectively remove naïve alloreactive T cells but save potentially beneficial donor T-cell subsets have been studied. 16,17 CD45RA-depletion has been shown to preserve diverse donor memory cell populations that may be effective in providing protection against infections and relapse, with little added risk of severe GVHD.…”

A Comparison of the Clinical Outcomes of Haploidentical Transplantation and Other Graft Sources in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

“…Seventeen of those were retrospective cohort studies 17,18,21,23,25,27,[30][31][32][33][34][35][37][38][39][40]44 , whereas the remaining eleven 19,20,22,24,26,28,29,36,[41][42][43] were prospective cohort studies. Their basic characteristics and quality assessments are summarized in Table 1.…”

“…The comparison of the OS and LFS outcomes of the haplo-SCT and matched donor (either MSD or MUD) groups revealed no statistical differences. Their pooled odds ratios (ORs) were 0.94 (95% CI, 0.79-1.12; P, 0.51; I 2 , 22%; Figure 2A) [18][19][20][21][22][25][26][27][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] ; and 1.05 (95% CI, 0.90-1.22; P, 0.53; I 2 , 0%; Figure 2B) 19,21,22,26,27,[29][30][31][32][33]36,39,41 , respectively. Likewise, the comparison of NRM, CIR, grade II-IV aGVHD, cGVHD, and GRFS outcomes of the 2 groups demonstrated no significant differences.…”

“…The OR of NRM was 1.19 (95% CI, 0.93-1.51; P, 0.17; I 2 , 6%; Figure 3A) 21,22,[29][30][31][32][39][40][41] . The OR of CIR was 0.79 (95% CI, 0.56-1.10; P, 0.16; I 2 , 65%; Figure 3B) 19,21,22,[29][30][31][32][33][34]36,37,[39][40][41][42][43] .The OR of grade II-IV aGVHD was 1.34 (95% CI, 0.91-2.00; P, 0.14; I 2 , 59%; Figure 3C) 21,29,33,39,41 . The OR of cGVHD was 1.18; 95% CI, 0.91-1.55; P, 0.22; I 2 , 49%; Figure 3D) 21,22,27,29,[32][33][34]37,[39][40][41] .…”

Expression of NK Cell Receptor Ligands on Leukemic Cells Is Associated with the Outcome of Childhood Acute Leukemia

“…Natural killer (NK) cell therapies are also offering new opportunities to patients with refractory AML and ALL, either through hematopoietic stem cell transplantation (HSCT) with donors selected to maximize NK-cell alloreactivity [ 8 , 9 ] or through ex vivo activation of patients’ own NK cells or allogeneic NK cells [ 10 , 11 ]. To improve the efficacy of these treatments [ 12 ], advances in the knowledge of the interactions that govern NK cell function are needed, particularly those interactions promoted by molecules expressed on leukemic cells that could define the type and potency of NK cell antitumor response.…”