REVIEW HEMATOLOGY

Haploidentical stem cell transplantation in adults: novel strategies and future directions

Summary

Haploidentical stem cell transplantation is an attractive form of alternative donor transplantation because of the immediate donor availability, ease of stem cell procurement, and the possibility to collect donor cells for further cellular therapy. T-cell depleted haploidentical transplantation (the Perugia approach) has been limited by a high nonrelapse mortality related to infectious complications as a result of delayed immune reconstitution posttransplantation. Research in this field is focusing on improving immune reconstitution by immunotherapy with different types of T-cells that do not cause graft-versus-host disease. A more recent modality (Hopkins approach), resulting in a decreased risk of graft-versus-host disease, is the use of T-cell replete haploidentical stem cells in combination with posttransplantation high-dose cyclophosphamide to eliminate expanding alloreactive T-cells. Research with this approach is focusing on the prevention of disease relapse posttransplantation. It seems that the most important barriers against successful haploidentical transplantation can now be overcome. This review evaluates the opposing modalities (T-cell replete versus T-cell depleted approach) and future directions of haploidentical stem cell transplantation in adults.

(BELG J HEMATOL 2012;3:74–81)

Cost-effectiveness of anticoagulants

Summary

Anticoagulants reduce blood clotting and are effective in preventing and treating venous thromboembolism, stroke and myocardial infarction. New oral agents such as dabigatran and rivaroxaban have recently been approved for these indications. Dabigatran and rivaroxaban benefit from oral administration, but have a higher potential for drug interactions than low molecular weight heparins. As compared with warfarin, dabigatran and rivaroxaban have a rapid onset of action and a predictable anticoagulant effect, obviating the need for routine coagulation monitoring. Although there are few economic evaluations of anticoagulants, the existing evidence suggests that the cost-effectiveness of anticoagulants depends on the alternative with which the anticoagulant is compared and on the specific disease.

(BELG J HEMATOL 2012;3:82–87)

Less veno-occlusive disease after intravenous versus oral busulfan for autologous haematopoietic stem cell transplantation: the Belgian paediatric experience

Summary

Busulfan is commonly used in preparative conditioning regimens prior to haematopoietic stem cell transplantation in children and young adults for malignant and non-malignant disorders. For many years busulfan was only available in oral form, resulting in large inter- and intra-patients variability in plasma exposure, associated with higher graft failure rate as well as higher toxicity such as veno-occlusive disease. With the development of an intravenous formulation of busulfan, a more accurate control of both the inter- and intra-patient variability has been provided. The goal of this study was to evaluate the use and efficacy of intravenous busulfan in comparison with the oral formulation in children undergoing an autologous transplantation after conditioning with busulfan. Despite the small number of patients, this study confirmed the apparent benefit of intravenous busulfan in children undergoing an autologous HSCT. The use of a five-level dose schedule defined by body weight resulted in an efficient engrafitment with marked reduction in the incidence of veno-occlusive disease compared with oral busulfan. In terms of disease-free outcome, survival and event-free survival, similar results have been obtained in both groups. The choice of this formulation of busulfan should therefore be considered.

(BELG J HEMATOL 2012;3:34–40)

Pseudohyperkalaemia in T-ALL: how to avoid life-threatening hypokalaemia

Summary

Tumour lysis syndrome is a well-known life-threatening complication in children with acute leukaemia and hyperleukocytosis. It is characterised by hyperkalaemia but it should be distinguished from pseudohyperkalaemia. Various underlying factors for this phenomenon of pseudohyperkalaemia have been suggested. Here, we describe two children with T-cell acute lymphoblastic leukaemia who presented with hyperleukocytosis and hyperkalaemia, in whom the diagnosis of pseudohyperkalaemia was made. We demonstrate that in extreme leukocytosis the use of a vacuum system, pneumatic transport, and sample centrifugation contribute all together to pseudohyperkalaemia. As the leukocyte count decreases, plasma potassium levels are more reliable. Based on our results we suggest to measure potassium in a whole blood sample immediately brought to the laboratory for minimising false results due to ex vivo cell lysis.

(BELG J HEMATOL 2012;3:12–6)

Musculoskeletal manifestations in children with acute lymphoblastic leukaemia

Summary

Acute lymphoblastic leukaemia (ALL) is the most common kind of childhood malignancy. Although the vast majority of patients are presented with medullary signs and symptoms such as an abnormal blood count, about one third will initially be presented with musculo-skeletal complaints (with or without radiological abnormalities) as the only apparent abnormality. These skeletal manifestations in ALL are not pathognomonic and may mimic several orthopaedic conditions, such as juvenile rheumatoid arthritis, osteomyelitis, septic arthritis and transient synovitis. This may therefore contribute to a delay in diagnosis, resulting in higher morbidity and mortality rates. However, musculoskeletal manifestations in leukaemia are usually associated with a precursor-B-ALL and have a good prognosis.

The purpose of this review is to highlight the diagnostic pitfalls in this type of ALL. ALL should always be considered as a differential diagnosis in any child with unexplained or persistent bone pain and a bone marrow examination is highly recommended when steroid therapy is being considered.

(BELG J HEMATOL 2012;3:3–11)