Immunosuppressive therapy for transplant-ineligible aplastic anemia patients

Abstract

Aplastic anemia is a rare life-threatening bone marrow failure that is characterized by bicytopenia or pancytopenia in the peripheral blood and a hypoplastic or aplastic bone marrow. The patients are at risk of infection and hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of anemia. The main treatment approaches are allogeneic stem cell transplantation and immunosuppression. Here, we review current standard immunosuppression and the attempts that have been made in the past two decades to improve results: review of recent developments also reveals that sometimes not only the advent of new drugs, good ideas and well-designed clinical trials decide the progress in the field but also marketing considerations of pharmaceutical companies. Aplastic anemia experts unfortunately had to face the situation that efficient drugs were withdrawn simply for marketing considerations. We will discuss the current options and challenges in first-line treatment and management of relapsing and refractory patients with an emphasis on adult patients. Some promising new approaches are currently under investigation in prospective, randomized trials.

Keywords:

• acquired aplastic anemia
• alemtuzumab
• androgens
• antithymocyte globulin
• cyclosporine A
• eltrombopag
• granulocyte colony-stimulating factor
• high-dose cyclophosphamide
• immunosuppressive treatment

Financial & competing interests disclosure

H Schrezenmeier and B Hoechsmann received research grants from Genzyme, now Sanofi Aventis, and GlaxoSmithKline for research projects. H Schrezenmeier received honoraria for presentations in Genzyme-sponsored symposia. 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.

Key issues

• Careful diagnostic work up is necessary, in particular to rule out congenital aplastic anemia and hypoplastic myelodysplastic syndrome.

• The patients should be referred to an expert center immediately.

• An overall treatment plan should be issued and definitive treatment should start early.

• Horse antithymocyte globulin (ATG) + cyclosporine A is still the standard immunosuppressive regimen.

• Addition of G-CSF to horse ATG and cyclosporine A does not improve trilineage response rate and overall survival.

• A combination of horse ATG + cyclosporine A ± eltrombopag is currently being investigated in ongoing randomized clinical trials for first-line treatment.

• Treatment of refractory patients, in particular, remains a challenge.

• Options for non-transplant second-line treatment include repeat cycle of ATG, alemtuzumab, eltrombopag, high-dose cyclophosphamide or androgens.

• Both outcome after immunosuppression and stem cell transplantation have improved over the past two decades. The criteria for allocation to the various treatment schedules need regular update to reflect new developments.

• Eligible patients should be entered for clinical trials.

Notes