The case for upfront HLA-matched unrelated donor HCT as a curative option for adult acquired severe aplastic anemia: Upfront MUD HCT for adult severe aplastic anemia

Improved success of HLA HLA: See human leukocyte antigen. -matched unrelated donor unrelated donor: A donor that is not a sibling or other familial relation of the patient (recipient). (MUD) hematopoietic stem cell transplantation (HCT) for severe aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… (SAA) over recent decades has impacted progressively on the indications and timing of this treatment modality. In the absence of a matched sibling donor (MSD), historically MUD HCT was reserved as an option after failure to respond to at least two courses of immunosuppressive therapy immunosuppressive therapy: Immunosuppressive drug therapy lowers your body's immune response. This prevents your immune system from attacking your bone marrow, allowing bone marrow stem cells to grow, which raises blood counts. For older patients with acquired aplastic anemia, immunosuppressive drug therapy is the… (IST) in adults with SAA, but with improved outcomes over time, it is now considered following response failure to one course of IST. Recent national and international studies and guidelines now recommend upfront MUD HCT as an option for children where a MUD is readily available, since outcomes are similar to MSD HCT. Fludarabine Fludarabine: The U.S. Food and Drug Administration (FDA) approved fludarabine for treating chronic lymphocytic leukemia (CCL). Researchers are studying fludarabine in combination with other medicines for treating bone marrow failure. -based conditioning and the use of in vivo T-cell depletion with ATG or alemtuzumab alemtuzumab: Alemtuzumab is a drug used in the treatment of chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma (CTCL) and T-cell lymphoma under the trade names Campath, MabCampath and Campath-1H, and in the treatment of multiple sclerosis as Lemtrada. It is also used in some conditioning regimens for… have reported overall survival (OS) of > 85% in adult patients undergoing MUD HCT. However, in recent times, the use of eltrombopag eltrombopag: What are the possible side effects of eltrombopag (Promacta)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using eltrombopag and call your doctor at once if you have: … in SAA has transformed the treatment landscape and there is currently much interest in its use with IST as upfront treatment, demonstrating high response rate in an early phase study. The risks of HCT, especially graft versus host disease (GVHD), need to be carefully balanced against the concerns of IST, namely relapse and later clonal evolution to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). In the absence of a current prospective randomized trial comparing these two approaches, in this review we examine the evidence for consideration of early MUD HCT in adults with SAA who would have been considered for MSD HCT but who lack a MSD, and where a MUD is readily available, and especially using an irradiation-free conditioning regimen, with a low risk of GVHD, as another treatment option. Such an option may be offered to patients to provide them with an informed choice, with the aim of cure of the disease rather than freedom from disease, relapse free survival or OS. Furthermore, understanding the immune signature for response to IST and the immunological responses to somatic mutations and clonal progression to MDS/AML may help define the future indication for upfront HCT and a precision medicine approach to therapy.