Cord blood transplantation for acute leukemia

ABSTRACT

Introduction

Umbilical cord blood transplantation (UCBT) is a suitable alternative for patients with acute leukemia (AL) in need of an allograft and who lack an HLA-matched donor. Single-institution and registry studies have shown that, in both children and adults with AL, the outcome of UCBT is comparable to that of matched unrelated donor. At the same time, these studies have highlighted some limitations of UCBT, such as increased early mortality and delayed recovery of both hematopoietic and immune compartment, which hamper a more widespread adoption of this approach.

Areas covered

In this review, we will analyze the current results of UCBT in children and adults with AL, including comparisons with other hematopoietic stem cell sources and transplant strategies. We will also discuss important factors to be considered when selecting UCB units, as well as future strategies to further improve the outcome of UCBT recipients.

Expert opinion

The utilization of UCBT for the treatment of AL patients has decreased in recent years. However, recent clinical data suggesting that UCBT might offer better results in patients with minimal residual disease, as well as innovative strategies to facilitate engraftment, reduce transplant-related mortality, and optimize anti-leukemic activity, may pave the way toward a second youth for use of UCB cells.

KEYWORDS:

• Acute leukemia
• adoptive cell therapy
• cell dose
• cord blood expansion and homing
• double cord transplantation
• engraftment
• minimal residual disease
• umbilical cord blood transplantation

Article highlights

• UCBT from either a related or an unrelated donor is a valuable option for patients with hematological malignancies in need of an allograft of hematopoietic progenitors.

• In comparison to BM or PBSC transplantation, advantages of UCBT are represented by lower incidence and severity of GvHD, easier procurement and prompter availability of cord blood cells, and by the possibility of using donors showing HLA disparities with the recipient.

• In children and adults with malignancies, UCBT was shown to translate into outcomes comparable with those of other alternative donor sources, including HLA-matched unrelated donors and HLA-haplotype-mismatched relatives.

• In adult recipients, the use of unrelated double UCB units has extended the applicability of UCBT, overcoming issues related to the cell dose infused; in children, no clear evidence of clinical benefit exists and data suggest that double-unit UCBT entails an increased risk of GvHD.

• There is evidence indicating that UCB may be considered the preferred option in situations at high risk of leukemia relapse, as recently observed in patients with pre-transplant persistent MRD.

• Despite having consistently shown promising results, the utilization of UCBT for treatment of patients with acute leukemia has decreased in recent years, as a result of intrinsic limitations of the approach (delayed engraftment, increased risk of TRM) and the emergence of HLA-haploidentical transplantation platforms.

• Better HLA-matching (at high-resolution level for HLA-A, HLA-B, HLA-C, and HLA-DRB1) and tailored, individualized ATG dosing have been shown to reduce TRM after UCBT.

• Several strategies aimed at expanding the number of UCB progenitors ex-vivo and favoring stem cell homing in-vivo have been developed with encouraging preliminary results. A major challenge for these techniques in the near future will be demonstration of their cost effectiveness.

• Promising UCB-based adoptive immune cell therapies, such as in vitro cultured antigen-specific T cells against virus, UCB-derived regulatory T cells, in vitro expanded NK cells and UCB T- and NK-cells transduced with chimeric antigen receptors, are under investigation in order to ameliorate post-transplantation outcome and/or boost an anti-leukemia effect.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.