Stem cell transplant for the treatment of myelofibrosis

ABSTRACT

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the cornerstone of curative approach to myelofibrosis (MF), although it is burdened by not negligible toxicity and mortality.

Areas covered: In this review, authors discuss the status-of-the-art of HSCT in MF, emphasizing the current limits and the areas for improvement. We interrogated public databases for papers published in the last 30 years.

Expert opinion: The therapeutic landscape of MF has been revolutionized after the approval of JAK inhibitor ruxolitinib, which showed impressive efficacy in reducing splenomegaly and ameliorating symptoms and quality of life. Unfortunately, the disease-modifying activity of ruxolitinib is modest, with most patients ultimately dying due to disease progression. Identification of potential candidates to HSCT is critical in order to balance risks and expected benefits, and should rely on risk scores specifically developed to such purpose. The use of ruxolitinib as bridge to HSCT might increase the proportion of patients ultimately able to undergo the procedure and possibly improve their outcome, and represents an important area of research. Since MF is a disease of middle age, further improvements should aim to reduce toxicity of the HSCT procedure and expand the use of alternative, particularly haploidentical, donors.

KEYWORDS:

• Myelofibrosis
• stem cell transplant
• prognosis
• mutation
• risk scores
• ruxolitinib
• splenectomy

Article highlights

• Allogeneic HSCT currently remains the only curative options for patients with MF.

• Use of JAK1/JAK2 inhibitors resulted in remarkable improvements for the management of patients with MF, and might be useful as bridge to transplantation.

• Selection of recipients of Allo-HSCT is facilitated by the availability of clinical and integrated prognostic risk models.

• Fully myeloablative and RIC regimens were both explored successfully for transplantation in MF

• The role of new transplant schemes, alternative donors, and immunotherapy intervention have to explored in future clinical trials.

Declaration of interest

AM Vannucchi is on the advisory board for Novartis, Celgene, AbbVie, Incyte, Italfarmaco, CTI; and a speaker for Novartis, Celgene, CTI. P Guglielmelli is on the advisory board and a speaker for Novartis. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper was funded by Associazione Italiana per la Ricerca sul Cancro.