Optimizing outcomes for haploidentical hematopoietic stem cell transplantation in severe aplastic anemia with intensive GVHD prophylaxis: a review of current findings

ABSTRACT

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has resulted in increased levels of disease-free survival in severe aplastic anemia (SAA). Haploidentical transplantation (haplo-SCT) was previously not recommended due to unacceptable incidences of graft-versus-host disease (GvHD) and graft failures. With the advent of intensive GvHD prophylaxis strategies, the outcomes obtained with haplo-SCT for SAA have gradually improved.

Areas covered: A comprehensive search considered PubMed reported articles before 1 February 2021, presented abstracts, and clinical trials pertaining to haplo-HSCT for SAA. This manuscript covers modern approaches with intensive GvHD prophylaxis in haplo-SCT for SAA. The representative methods consist of granulocyte colony stimulating factor (G-CSF) plus ATG-based and posttransplantation cyclophosphamide (PT-Cy)-based protocols.

Expert opinion: Currently, haplo-SCT has become a feasible option for treating SAA. The G-CSF/ATG-based protocol included the largest sample size and reported comparable survival rates with identical siblings. The PT-Cy protocol resulted in a relatively lower incidence of GvHD and seemingly poorer but continuously improved engraftment with augmented conditioning. The optimized outcomes are constantly updated with the modification of the conditioning regimen, donor selection, graft source and GvHD prophylaxis. In the future, we should pay more attention to quality of life in addition to survival, and personalized haplo-SCT may improve outcomes.

KEYWORDS:

• Haploidentical
• transplantation
• optimizing outcome
• aplastic anemia
• intensive gvhd prophylaxis

Article highlights

• The outcomes of haplo-SCT for SAA have dramatically improved in the recent years.

• The G-CSF and ATG-based haplo-SCT for SAA can achieve survival results comparable to those of MRD-SCT in both salvage and upfront cohorts.

• In PT-Cy based protocol, an augmented conditioning might be beneficial to improve engraftment outcomes.

• The social status and quality of life should be considered for long-term survivors for SAA.

• To explore optimal and personalized conditioning regimen, graft source, haploidentical donor and GvHD prophylaxis is the direction in future clinical trials.

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 disclosure

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

Additional information

Funding

This paper was partly funded by Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001), The Key Program of National Natural Science Foundation of China (81930004) and The National Key Research and Development Program of China (2017YFA0104500).