Selection of conditioning regimen. The role of age and comorbidities

Haema 2016; 7(2): 169-179

by Ioanna Sakellari

Department of Haematology and Bone Marrow Transplantation, Papanikolaou General Hospital, Thessaloniki, Greece

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Allogeneic hematopoietic stem cell transplantation (HCT) has been a curative therapy for hematologic malignancies and a variety of non-malignant disorders. Allogeneic HCT has two major immune barriers: a) Host vs the Graft (HVG) alloreaction that may cause engraftment failure, and b) Graft vs Host (GVH) alloreaction that may cause GVH disease. Thus, the conditioning regimen along with the post-transplant immunosuppresion form the basis for a successful HCT. Conventional or “classic” HCT cannot be used for patients >50-60 years old, due to increased in (TRM). In patients >45-50, TRM can be 32%-41% in general, but it can reach 70% in advanced phase. If we consider that the median patient age at diagnosis of certain diseases vary from 65 to 70 years of age, it is, therefore, concluded that only a minority of patients would undergo a conventional HCT. It is therefore contra-indicated for older individuals who are mainly at risk of developing other comorbitidies. The assessment of a hematopoietic stem cell transplant (HCT)-specific comorbidity index (HCT-CI) has been developed to predict the risk of TRM in patients undergoing allogeneic HCT. The HCT specific comorbitidy index (HCT-CI) has been shown to be an effective marker to determine the risk of TRM regardless of patient age and disease status. Further, the HCT-CI has been consolidated with various disease-specific and patient-specific risk factors to refine assignments of patients to the appropriate HCT setting. As a potential solution to the problems of excessive regimen – related toxicity, the reduced intensity or non myeloablative allografts were introduced in the mid-1990s even in patients of older age with morbidities. They were not otherwise eligible for conventional HCT because they could not bear any additional organ toxicity. Each transplant procedure which includes a non-myeloablative preparative regimen is characterized as allogeneic transplantation with reduced intensity conditioning (RIC) regimen (Reduced Intensity stem Cell Transplantation, RIsT). The conventional HCT retains its role but the RIsT has led to expand the patient population to older ages and patients with comorbidities. The advantages comparing the two procedures depend on the disease, its phase and the clinical condition of the patient, taking into consideration age and comorbidities. In addition, RIsT has enabled the role of HCT in certain diseases to be reevaluated. There are major differences among malignant diseases in terms of their sensitivity to the graft versus malignancy effect and actually to the RIsT. Recent developments have created a realistic perspective of individualized therapeutic management in older patients, as “one-size-fits-all” transplantation is not further performed. Through the designing of transplant strategy it remains mandatory to identify patients of higher risk of TRM and consequently tailor the most appropriate treatment approach. Ongoing studies are addressing prospective validation of the HCT-CI. Reduced intensity conditioning regimens are heterogeneous with regards to dose of chemotherapy and radiotherapy and degree of immunosuppression regimens. The reduced intensity regimens suffer from the same limitations compared to conventional ones such as relapse, GVHD, TRM. Given that the rate of relapse depends on the disease or the inten- sity of the conditioning regimen it seems obligatory that the choice of the regimen should be based on the severity and resistance of the disease. Novel agents and strategies aimed at improving disease free survival and lowering relapse are currently under investigation.