What do we know about long-term outcomes of bone marrow transplantation for the cure of thalassemia?

- Dr. Lawrence Faulkner. Director Sankalp-People Tree Hospitals Bone Marrow Transplant Unit, Bangalore, India and Medical Coordinator Cure2Children Foundation Florence, Italy.

The first bone marrow transplantation (BMT) for thalassemia was performed in 1980, since than over 4.000 have been done, so what do we know about people who have undergone BMT many years back?

In a recent report in Blood [1], the official journal of the American Society of Hematology and one of the most reputed in the field, La Nasa and collaborators summarized the experience on 109 patients (44 females and 65 males) assessed over 20 years from transplant. The mean age at BMT was 12 year (range 1-36) and 34 years (21-48) at time of study. Long-term health-related quality of life (HRQoL), employment status and birth rates were similar to the general population. Relevant variables affecting HRQoL where the presence of extensive chronic Graft Versus Host Disease (cGVHD) (6% of cases), age at BMT (better if less than 15 years), and the presence of health problems related to iron overload at transplant. A matched group of 124 thalassemia patients receiving conventional treatment showed poorer HRQoL outcomes. The frequency of second malignancies, which might result from the use of chemotherapeutic agents such as busulfan and cyclophosphamide, did not seem to be increased unless cGVHD was present. The observation that birth rates where similar to the general population, however, does not necessarily imply that fertility is preserved in all transplanted patients, this because of the relatively low baseline birth rate of the study population (in Sardinia, a region of Italy), compared to that of many developing countries where thalassemia is most common. Nevertheless it is safe to assume that at least 50% of individuals who have undergone BMT (at least with the combination of busulfan and cyclophosphamide) may bear children, a figure most likely superior to the current birth rates for individuals with thalassemia undergoing long-term supportive care [2]. This may not apply to the use of different BMT preparative treatments using combinations possibly less fertility-spearing like thiotepa and treosulfan.

The impact on HRQoL might be even more evident in Low- and Middle-Income Countries (LMICs) where often health issues are compounded by financial distress and social stigmata. In an analysis from the BMT unit of the Children’s Hospital at the Pakistan Institue of Medical Sciences on 24 BMTs compared to 51 patients undergoing supportive care for severe thalassemia, Tariq S. points out how BMT, too often considered inaccessible or too expensive while in fact is highly cost-effective, not only can restore normal health and HRQoL but it’s actually safer than most people and health care professionals dealing with thalassemia children are aware of. This study suggests that BMT can also have profound effects on the mental well-being of families particularly in a developing country setting like Pakistan [3].

Morbidity and mortality related to thalassemia have been reduced significantly with modern medical treatment, and HRQoL should be considered an integral part of any report on long-term results related to thalassemia care[4].

In conclusion, even if BMT in the best circumstances is still a procedure which carries a small but sizable risk of morbidity and mortality, probably in the 5-10% range, it can restore normal long-term HRQoL in the majority of transplanted children and relieve their families from major financial and psychological burden, particularly in LMICs.

[1] La Nasa G., Caocci G., Efficace F., et al. Long-Term Health-Related Quality of Life Evaluated More than 20 Years after Hematopoietic Stem Cell Transplantation for Thalassemia.” Blood 122:2262–70, Sept. 2013.
[2] Zafari M. and Mehrnoush K. Marriage and Child Bearing in Patients with Transfusion-Dependent Thalassemia Major. The Journal of Obstetrics and Gynaecology Research 40:1978–82. Aug 2014.
[3] Tariq S, Health-Related Quality of Life (HRQoL) assessment of severe thalassemia after bone marrow transplantation and on conventional supportive care. Dissertation for Master of Science in Public Helath, Health Services Academy Quaid-i-Azam University, Islamabad, Pakistan, 2015
[4] Panepinto J.A. Health-Related Quality of Life in Patients with Hemoglobinopathies.Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program 284–89, Dec 2012.
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