Optimal Outcomes in Young Class 3 Patients With Thalassemia Undergoing HLA-Identical Sibling Bone Marrow Transplantation

Gaziev, Javid; Isgrò, Antonella; Sodani, Pietro; Marziali, Marco; Paciaroni, Katia; Gallucci, Cristiano; Angelis, Gioia De; Andreani, Marco; Testi, Manuela; Alfieri, Cecilia; Ribersani, Michela; Galluccio, Tiziana; Battarra, Mariarosa; Morrone, Andrea; Lucarelli, G

doi:10.1097/tp.0000000000000928

Cited by 41 publications

(45 citation statements)

References 41 publications

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“…The stratification of risk by Lucarelli predicted poor outcome and enabled selection of those suitable for alloBMT. More recently, even high risk patients have been successfully transplanted [54]. For patients at high risk, conditioning needs to be titrated to reduce toxicity and at the same time, prevent graft rejection.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Bone Marrow Transplantationmentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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“…By contrast, hemoglobinopaties are mostly distributed in third world countries (62) where the allocation of the resources necessary to develop these therapies is challenging. This problem is only partially solved by the international programs that allow the transfer of patients from underdeveloped to developed countries to be cured such as the Mediterranean Transplantation Program that allows hemoglobinopathy patients from the Middle East to be transplanted in Italy (63). For obvious reasons, the number of patients that may benefit from these programs is limited.…”

Section: Hsc Transfusion In the Clinic At Last: Mini-transplants To Cmentioning

confidence: 99%

To condition or not to condition—That is the question: The evolution of nonmyeloablative conditions for transplantation

Migliaccio

2016

Experimental Hematology

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In 1985, Eugene Cronkite published in Experimental Hematology data indicating that five consecutive “transfusions” of high numbers of marrow cells significantly increase the number of donor-derived cells detected by day 10 spleen colony forming assay, the most primitive hematopoietic cells detectable at that time, present in the host for as long as two months post transfusion (1). These data provided the first evidence that donor hematopoietic stem cells (HSC) may at least persist in vivo for some time in recipients that were transfused and not transplanted, i.e. not subjected to treatments that deplete their marrow niches of endogenous HSC. The limited technology available at the time prevented Dr. Cronkite to pursue this observation into the development of non-myeloablated transplantation procedures and his experiment as well as the term “bone marrow transfusion” have since long been forgotten. In recent years, the scientific need to clarify HSC functions in non-stressed hosts and the clinical need to develop transplantation procedures with levels of morbidity/mortality acceptable to cure inherited hematological disorders have inspired the search for non-myeloablative transplantation procedures including methods to “outcompete” endogenous host HSC such as those pioneered by Dr. Cronkite's experiments using high transfusion doses. This review will describe the technical progress since Dr. Cronkite's insightful work that has finally provided a path to the clinic.

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“…11 All these modifications have led to significantly improved survival rates of nearly 80-90% in these high-risk patients (Table 1). 10,11,15,19,20,[23][24][25][26][27] While we have to appreciate the impact of successful alloHSCT on the lives of these patients, we need to continue to recognize the many challenges that persist with respect to the still significant morbidity and mortality associated with this procedure. All over the world a major constraint is the lack of access to this therapy related to the lack of a suitable donor.…”

Section: Allogeneic Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

“…19,20 Patients over 7 years of age with hepatomegaly of more than 5cm have been identified as an especially high-risk group who are candidates for/require novel approaches, particularly with regard to their conditioning regimen and preparation for transplant. 21,22 Two approaches have been taken in this regard, one based on pre-transplant immunosuppression using fludarabine, and the other by introducing a longer gap between the use of busulfan and cyclophosphamide during conditioning 23,24 or using less toxic myeloablative agents such as treosulfan and avoiding cyclophosphamide completely. 11 All these modifications have led to significantly improved survival rates of nearly 80-90% in these high-risk patients (Table 1).…”

Section: Allogeneic Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Cure for thalassemia major – from allogeneic hematopoietic stem cell transplantation to gene therapy

Srivastava

Shaji

2016

Haematologica

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A llogeneic hematopoietic stem cell transplantation has been well established for several decades as gene replacement therapy for patients with thalassemia major, and now offers very high rates of cure for patients who have access to this therapy. Outcomes have improved tremendously over the last decade, even in high-risk patients. The limited data available suggests that the long-term outcome is also excellent, with a >90% survival rate, but for the best results, hematopoietic stem cell transplantation should be offered early, before any end organ damage occurs. However, access to this therapy is limited in more than half the patients by the lack of suitable donors. Inadequate hematopoietic stem cell transplantation services and the high cost of therapy are other reasons for this limited access, particularly in those parts of the world which have a high prevalence of this condition. As a result, fewer than 10% of eligible patients are actually able to avail of this therapy. Other options for curative therapies are therefore needed. Recently, gene correction of autologous hematopoietic stem cells has been successfully established using lentiviral vectors, and several clinical trials have been initiated. A gene editing approach to correct the b-globin mutation or disrupt the BCL11A gene to increase fetal hemoglobin production has also been reported, and is expected to be introduced in clinical trials soon. Curative possibilities for the major hemoglobin disorders are expanding. Providing access to these therapies around the world will remain a challenge.

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Optimal Outcomes in Young Class 3 Patients With Thalassemia Undergoing HLA-Identical Sibling Bone Marrow Transplantation

Abstract: The modified treatment protocol effectively and safely prevented graft failure/rejection and significantly increased thalassemia-free survival of class 3 patients with thalassemia.

Cited by 41 publications

References 41 publications

Thalassemia 2016: Modern medicine battles an ancient disease

Thalassemia 2016: Modern medicine battles an ancient disease

To condition or not to condition—That is the question: The evolution of nonmyeloablative conditions for transplantation

Cure for thalassemia major – from allogeneic hematopoietic stem cell transplantation to gene therapy

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