Hematopoietic stem cell transplantation for classical inherited bone marrow failure syndromes: an update

ABSTRACT

Introduction

Inherited bone marrow failure syndromes (IBMFS) feature complex molecular pathophysiology resulting in ineffective hematopoiesis and increased risk of progression to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Allogenic hematopoietic stem cell transplantation (HSCT) is the only well-established cure for the hematological manifestations of these diseases.

Areas covered

In recent years, analysis of large series from international databases (mainly from the European Bone Marrow Transplantation [EBMT] database) has improved knowledge about HSCT in IBMFS. This review, following a thorough Medline search of the pertinent published studies, reports the most recent data on HSCT in IBMFS.

Expert opinion

Despite the common features, IBMFS are very different in their manifestations and in the occurrence and management of HSCT complications. Thus, a ‘disease-specific’ HSCT using an optimized conditioning regimen based on the characteristics of the disease is essential for achieving long-term survival. The phenotypical heterogeneity associated with extramedullary abnormalities has to be carefully evaluated before HSCT because transplantation may only correct impaired hematopoiesis. HSCT may be associated with the risk of treatment-related mortality and with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks.

KEYWORDS:

• Inherited bone marrow failure syndromes
• hematopoietic stem cell transplantation
• conditioning regimen
• donor type
• stem cells source

Article highlights

• Allogenic HSCT is the only established curative modality for hematological manifestations (BMF, clonal evolution) of IBMFS.

• Because of the systemic nature of these disorders, HSCT procedures have to be adapted and ‘disease specific’ to decrease early and late toxicities.

• Before HSCT, patients should be evaluated carefully for extrahematologic manifestations and followed by a multidisciplinary team.

• The best donor is an MRD; however, it is important to test the donor for the same genetic defect.

• BM is the preferred source of HSC.

• Whenever possible, irradiation should be avoided owing to the known risk of cancer in these diseases.

• Haploidentical transplantation with in vivo or in vitro TCD is a promising strategy, but it should be still considered experimental in these settings.

• Long-term follow-up is crucial to detect complications related to the disease or HSCT.

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.