Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin’s lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.
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.
In the March 2016 issue of the Lancet Haematology, the editorial office published a paper stating the roadmap for European research in hematology, based on the European Hematology Association (EHA) consensus document that outlines the directions in hematology for the following years across the continent. The meeting entitled “Insights in hematology” is organized a support for the initiative of a roadmap for European hematologists regarding research, may it be basic research or clinical research, but this consensus should not be focused mainly on European institutions, but rather form the backbone of global research between Europe and the United States, Japan or any other country. This will allow Europeans to learn as well as to share their experience with the rest of the scientific and medical community. And the Cluj-Napoca meeting should be followed by other such meetings all across the EU.
In the past decade, there has been significant progress in clinical hematology with the discovery of targeted molecules and thus the achievement of both hematologic and molecular responses. Nevertheless, chemotherapy remains the treatment of choice for many types of hematological malignancies. Aggressive chemotherapy leads to immunosuppression, accompanied by a high rate of infections and an increased rate of treatment-related mortality. Invasive fungal infections as well as more common bacterial and viral infections are frequent in immunocompromised patients as they are difficult to diagnose and treat. Pleuropulmonary infections in immunocompromised patients are diagnosed using clinical examination, imaging and laboratory tests. Many laboratory tests are run for several days before a final result is given and are expensive. Computer tomography is a reliable technique, but it is encumbered by high irradiation and high cost, and can assess lesions larger than 1 cm. Transthoracic ultrasound is a modern method, used in the diagnostic algorithm of pleuropulmonary pathology. It allows the diagnosis of small lesions, can be performed at the patients’ bedside, with acceptable costs and no irradiation. A fast, informed and accurate medical decision is essential for a favorable outcome in immunosuppressed patients with an adjacent infection. In the current case series we present the implementation of a new protocol for the follow-up of immunocompromised patients using transthoracic ultrasonography, of great potential use in the clinic.