Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia

Abstract

Summary:Acute lymphocytic leukemia (ALL) is a common indication for hematopoietic stem cell transplantation (HSCT) in children. Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased GVHD potential. Publications describing outcomes of children with leukemia who underwent UCB transplants have compared them to those having received unrelated donor marrow transplants. Results are similar. We compared our outcomes using UCB vs allogeneic-related hematopoietic stem cells in pediatric ALL patients since 1992. A total of 49 patients were analyzed. All patients were either in CR1 with high-risk features (n ¼ 21) or in CR2 (n ¼ 28) with initial remission less than 36 months. Patients received myeloablation with fractionated total body irradiation, cyclophosphamide, and etoposide and GVHD prophylaxis with cyclosporine and methotrexate. Antithymocyte globulin was added for UCB recipients to address the HLA differences. In all, 23 patients underwent allogeneic -related HSCT and 26 underwent UCB transplantation. Other than increased time to engraftment for UCB recipients, results are equivalent. The 3-year overall survival is 64% and 3-year event-free survival is 60% for both groups. Rates of GVHD and transplant-related mortality are also equivalent. UCB is a reasonable option for children with ALL who are referred for HSCT. Although the majority of children with acute lymphocytic leukemia (ALL) enjoy excellent outcomes with conventional multiagent chemotherapy, the outlook for those patients who develop recurrent disease, particularly within the first 2 years of therapy, is far less favorable. Patients who relapse within 24 months of diagnosis and are treated with chemotherapy alone have less than 20% survival. 1,2 Hematopoietic stem cell transplantation (HSCT) has been commonly employed for patients with relapse or high-risk features. 3,4 While most children with recurrent or high-risk ALL can achieve a remission with intensified therapy, the most appropriate management strategy to employ once remission has been achieved remains controversial. Some transplant centers base that decision on whether a matched related donor is available.For patients with relapse, HSCT with HLA-matched related donors during the second complete remission (CR2) has provided leukemia-free survival (LFS) rates in the range of 40-50% at 2-5 years. 3,4 There exists controversy with regard to what length of time defines a late relapse after which point an HSCT may have no advantage over chemotherapy. In analyzing 287 patients with ALL in CR2, Uderzo reported no advantage of matched-sibling HSCT over chemotherapy for patients who relapsed more than 30 months from diagnosis. 5 With unrelated cord blood transplantation (UCBT) for ALL and AML, a relapse on therapy prior to transplant confers a worse LFS (22% on therapy vs 48% off therapy). 6 UCB can be an attractive alternative stem cell source for a variety of reasons. Cells are rapidly available, HLAmatching can be considerably...

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group

“…However, the incidence of relapse after UCBT is similar to that in recipients of unmanipulated BM. 20,22,35 In fact, Eapen et al 20 report lower relapse rates after two-antigen HLA-mismatched cord blood transplants. In our series, we found the 5-year relapse rates for ALL and AML to be 33 and 22% respectively, which are comparable to these previous studies.…”

“…However, in the unrelated setting, most comparative studies fail to demonstrate a statistical difference between UCB and BM. 2,16,21,22,35 Only seven patients in our study cohort developed chronic GVHD. However, as with other studies, our follow-up may be too short to draw any definite conclusions.…”

“…2,6,16,21,28,29,35 There appears to a significantly lower risk of chronic GVHD in recipients of HLA-identical sibling UCB. However, in the unrelated setting, most comparative studies fail to demonstrate a statistical difference between UCB and BM.…”

Future of cord blood for oncology uses

“…[2][3][4][5][6][7][8][9][10][11] Studies comparing UCB with adult donor HSCs show that outcomes are similar, suggesting an important role for UCB as a source of stem cells in this patient population. 8,9,[12][13][14] In children, where UCB units with cell doses of 2.0 Â 10 7 /kg at cryopreservation are frequently found, engraftment has been consistently above 90% despite the number of nucleated or CD34 þ cells being about 1 log lower than in adult donor grafts. 15 The incidence of acute GVHD after UCB transplantation is low compared with that of adult HSC grafts, despite the consideration that most UCB grafts are mismatched.…”

“…15 The incidence of acute GVHD after UCB transplantation is low compared with that of adult HSC grafts, despite the consideration that most UCB grafts are mismatched. 8,9,[12][13][14]16 The reduced incidence of GVHD has been attributed to the naivete´of the neonatal immune system. This apparently reduced alloreactivity, however, does not compromise long-term risks of relapse.…”