Updates in acquired aplastic anemia: Can we do more for our patients?

The purpose of this work is to present the results of allogeneic stem cell transplantation as therapy for patients diagnosed with acquired aplastic anemia in the Department of Bone Marrow Transplantation of Fundeni Clinical Institute and to elaborate an algorithm of treatment in aplastic anemia starting with the observations obtained from our clinical practice and following the European treatment guidelines in this group of patients.

Aplastic Anemia (AA) is a rare hematological disease characterized by pancytopenia and a hypocellular bone marrow. The paradigm of bone marrow failure syndromes, aplastic anemia is a diagnosis of exclusion despite the precision of its diagnosis criteria. Although AA is not a malignant disease, but an autoimmune disorder, the grave consequences of pancytopenia and clonal transformation into acute leukemia make it a potentially fatal condition.

The management of AA patients is challenging and necessitates a very well established treatment plan from the diagnosis.

We present the treatment algorithm for AA patients with recommendations based on both recent guidelines in the field and on our experience treating AA patients with allogeneic stem cell transplant. Therapeutic procedure algorithm comprises different approaches for different patient populations, age categories and availability of immunosuppression therapy or different types of donors.

According to the recent EBMT recommendations the treatment of choice for young patients (younger than 40 years) who have a matched sibling donor is hematopoietic stem cell transplantation (HSCT). For those patients who don’t have a matched sibling donor or are not candidates for HSCT due to older age, the immunosuppression with ATG and cyclosporine is an efficient treatment. The supportive care has an important role and the patients with aplastic anemia should be managed by a multidisciplinary team. For patients older than 40 years, the choice between immunosuppressive therapy (IST) and upfront transplant with HLA identical sibling donor remains a key question. However, the standard approaches for this category of patients is front line immunosuppression with ATG and cyclosporine and if they become refractory to at least one course of IST the allogeneic stem cell transplant using fludarabine-based conditioning is the second-line treatment option.

In our institution there were eleven AA patients treated with allogeneic stem cell transplantation from 2009 till 2015. They were all young patients with age between 19 and 42 years old and all had severe acquired aplastic anemia with transfusion dependence. Six cases were transplanted from a matched sibling donor and five patients had undergone an unrelated matched donor transplant. The allogeneic HSCT procedure was done both as front line therapy in the case of three patients and as second treatment choice in the rest of eight patients. Four patients died, three of them due to transplant related toxicity and one patient experienced severe autoimmune reaction with transfusion inefficacy complicated with intracerebral haemorrhage at four months from transplant.

In our opinion the most challenging aspect in treating AA patients is choosing the best treatment option taking into account the patient age and performance status, the severity of the disease and the availability of a donor for allogeneic HSCT.

Although the treatment strategy must be individualized in every patient case, it is necessary to make a standardization of treatment procedures in AA and to follow the evidence based recommendations available in the management of this rare disease.