Haploidentical stem cell transplantation for the treatment of leukemia: current status

Abstract

Haploidentical stem cell transplantation (haplo-SCT), either with T-cell depletion or T-cell replete, has been a reliable source of stem cells for patients with high-risk leukemia who do not have matched donors because it provides comparable outcomes to human leukocyte antigen-matched sibling donor transplantation, unrelated donor transplantation and umbilical cord blood transplantation. Factors, such as the Hematopoietic Cell Transplantation-Specific Comorbidity Index, associated with transplant outcomes may help us design risk-stratification-directed intervention to improve the prognosis of leukemia patients. Preliminary results of novel protocols, including co-transplant of haploidentical allografts and cord blood, as well as human leukocyte antigen-mismatched stem cell microtransplantation, for leukemia have shown that these approaches are feasible. Several strategies for enhancing the graft-versus-leukemia effects significantly decreased the relapse rate after haplo-SCT. Future direction of research will focus on perfecting available haplo-SCT protocols and determining the optimal time of haplo-SCT for leukemia and ‘fit’ haploidentical transplant candidates.

Keywords::

• graft-versus-leukemia effects
• haploidentical stem cell transplantation
• leukemia
• relapse

Acknowledgement

The authors would like to thank many agencies that provided grant support, including the National Natural Science Foundation of China (Grant No. 30971292), the National High Technology Research and Development Program of China (Program 863) (Grant No. 2013AA020104) and the Clinical Subject’s Key Project of the Ministry of Health and the National Natural Science Foundation of China (Grant No. 30725038). The authors would also like to thank American Journal Experts (www.aje.com) for their assistance in language polishing and correction of errors in grammar, which was paid for by the authors.

Financial & competing interests disclosure

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.

Key issues

• Haploidentical stem cell transplantation (haplo-SCT) with or without in vitro T-cell-depleted has been an alternative source of SCT for patients with leukemia, which offers comparable outcomes to matched sibling donor transplantation, matched unrelated transplantation and umbilical cord blood transplantation.

• The T-cell-replete approach will likely be the predominant approach outside clinical trials worldwide because of practicality and cost.

• Factors associated with haplo-SCT outcomes may help us find patients with poor prognosis, early intervention to these patients could improve transplant outcomes.

• Microtransplantation and co-transplant of haploidentical allografts and cord blood may provide novel ‘haplo-SCT platforms’ for leukemia patients.

• Several strategies, including haploidentical donor lymphocytes, and natural killer cell infusion, have been successfully used to reduce relapse of high-risk leukemia patients after haplo-SCT.

• A specific and sensitive method for monitoring of minimal residual disease should be developed to find fit, compatible candidates after consolidation therapy and to determine the optimal time of administration of haplo-SCT.