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Figure 1. Factors to be considered in deciding hematopoietic cell transplant versus gene therapy. GvHD: graft-versus-host disease.
Editorials
1) Once again it has been confirmed that transplantation in thalassemia should be performed as soon as possible, not only to maximize transplant outcome, but also to min- imize long-term complications. The data on spontaneous puberty make this issue very clear.2
2) Long-term complications are less than those expected in medically-treated thalassemia12 and, with the exception of hypogonadism, are of limited incidence with a quality of life similar to that of a matched normal population.13
3) Several reports of spontaneous maternities have been published, but this is the first report with epidemiology data including probability of maternity and paternity after an analysis of almost the entire transplanted population.
4) For the first time, the issue of adolescents being over- weight is reported post transplant for a congenital disease. Clearly this observation requires more in-depth analysis and prospective dedicated studies with comparison to normal population data.
5) The problem of iron overload in the post-transplant setting has been resolved, and most patients can easily achieve normal iron burden5 thus avoiding long-term iron toxicity complications.14
6) Like iron overload, other complications related to tha- lassemia can be treated after transplantation, such as hep- atitis C and B virus infection, with the therapies available today.
7) Specific follow-up guidelines and screening recom- mendations can be proposed and can be used specifically for this category of patients in order to prevent / cure the complications that are known today.15,16
8) Recent data on the emerging gene therapy approach clearly indicate that a myeloablative preparative regime is necessary to allow gene-modified autologous stem cell engraftment. Therefore, if the long follow up confirms current safety data on the cellular product,17 complications relating to the conditioning regimen, such as those report- ed here, can be foreseen and similar screening programs can be set up.
Lastly, this article provides a further contribution to the debate on the therapeutic decision-making process for thalassemia patients. This debate, which has so far been limited to medical therapy and transplantation, will soon be carried forward by another great innovation in the treatment of this disease: gene therapy.17 Even if this approach has so far only demonstrated complete clinical effectiveness in non β0/β0 thalassemia, the door has been left ajar and will certainly be thrown wide open soon.
Regardless of the problem of gene therapy costs, which will probably significantly compromise its wide applica- bility, these data reporting long-term limited complication and no cancer after HCT can be of enormous help in establishing the correct therapeutic approach.
As discussed by many authors, transplantation, medical therapy, and now gene therapy, is an individual and highly personal decision.18 Because of this, there have been no randomized prospective trials and it is likely that none will ever be performed. Several different medical, person- al, and socio-economic aspects must be considered, taking into account the impressive epidemiology and the social conditions of countries were this disease is prevalent.19 Figure 1 reports the factors to be considered today in approaching transplantation or gene therapy for the cure of transfusion-dependent thalassemia.
In my personal opinion, this report by Rahal et al.2 rein- forces the position of transplantation in this difficult deci- sion-making process, particularly in the case of young chil- dren when an HLA identical sibling donor is available.
References
1 Baronciani D, Angelucci E, Potschger U, et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010. Bone Marrow Transplant. 2016;51(4):536-541.
2. RahalI,GalambrunC,BertrandY,etal.Lateeffectsafterhematopoiet- ic stem cell transplantation for beta-thalassemia major: the French national experience. Haematologica. 2018;103(7):1143-1149.
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