Hematopoietic stem cell transplant with HLA-mismatched grafts: impact of donor, source, conditioning, and graft versus host disease prophylaxis

ABSTRACT

Introduction: Allogeneic hematopoietic cell transplantation is frequently used to treat malignant and non-malignant conditions, and many patients lack a human leukocyte antigen (HLA) matched related or unrelated donor. For those patients, available alternative graft sources include HLA mismatched unrelated donors, cord blood, or haplo-identical donors. These graft sources have unique characteristics and associated outcomes requiring graft-specific variations to conditioning regimens, graft-versus-host disease prophylaxis, and post-transplant care.

Areas covered: This manuscript will cover approaches in selecting donors, conditioning regimens, graft versus host disease prophylaxis, post-transplant care, and ongoing clinical trials related to mismatched grafts.

Expert commentary: In the setting, haplo-identical grafts are increasingly popular due to low graft versus host disease (GVHD) risk and control of cellular dose. We recommend young male donors, utilizing bone marrow with post-transplant cyclophosphamide for GVHD prophylaxis. Cord blood transplant is appropriate for young healthy patients, and we recommend 6/8 HLA matched grafts with at least 2.0 × 10⁷/kg total nucleated cell dose. For mismatched unrelated donors we recommend young male donors, utilizing bone marrow with in vivo T-cell conditioning with post-transplant cyclophosphamide, alemtuzumab, or ATG. With these transplants, significant post-transplant surveillance and infectious prophylaxis is key to reducing treatment-related mortality.

KEYWORDS:

• Cord blood
• haplo-identical
• mismatched unrelated donor
• allogeneic stem cell transplant

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 or other relationships to disclose.

Additional information

Funding

This paper was not funded.