Bone marrow transplantation is becoming an increasingly acceptable curative option for patients suffering from thalassemia. This coincides with improved access to care and management of thalassemia. There is a need for a measure to be available for the patient families, support organisations, government and donors to make a truly informed choice on whether or not the option of a bone marrow transplantation of a particular kind at a particular centre is the best option for the patient. Overall survival post transplant and disease free survival are the generally used measures.
In case of transplants for malignancies where the patient may not have good chance to survive without undergoing the transplant, measuring the overall and disease free survival alone may look sufficient. However, the context of thalassemia is different. The transplants for thalassemia are more directed at reducing the suffering resulting from chronic blood transfusion therapy, consequent complications, and with a treatment goal to restore the quality of life of the patient. If a patient ends up with a serious complication which makes the life of the patient worse than what it was with thalassemia – it cannot be called success in the context of thalassemias.
Graft versus host disease is a common complication associated with BMT. GVHD has been shown to have severe impairments to the quality of life of patients. The associated problems include fatigue, difficulty in breathing, gastrointestinal side effects, worries/anxiety and skin problems. A patient may get cured from the disease as such and yet land up with a much worse quality of life.
In this context the measure of overall survival and disease free survival are inadequate to assess what to expect post transplant. A more informative measure which is being considered is a GRFS[1-2] - the survival free of graft failure, chronic GVHD, or death. This measure is one step closer to showing how many patients reached an acceptable state of being cured after the transplantation. It allows assessment of how many patients truly benefitted from the transplant in the direction of meeting the treatment goal – to restore the quality of life.
Dr Prakash Satwani from the Columbia University retrospectively reviewed the transplant essential data submissions made to the Center for International Blood and Marrow Transplant Research database for patients who underwent transplant for Sickle Cell Disease in USA from 2000-2011[3]. It showed overall survival at 2 years of 90% (95% confidence intervals [CI] 85-95%). It was also noted that Chronic GVHD incidence was 31% (95% CI 23-38%) at 2yrs. Thus, the 2yr GRFS was 64% (95% CI 56-71%). This example leaves little doubt that since GRFS is a more indicative measure for the success of the transplantation procedure.
We as an organisation are working towards adopting GRFS in our reporting of transplantation outcomes for all our centres. We eagerly look forward to more centres sharing their treatment outcomes in a relevant manner. This may even help place emphasis on the most important thing – giving meaningful cure to each patient who is offered a bone marrow transplantation!
References:
1. Holtan SG, DeFor TE, Lazaryan A, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-1338. doi:10.1182/blood-2014-10-609032.
2. Solh M, Zhang X, Connor K, et al. Factors Predicting Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Cell Transplantation: Multivariable Analysis from a Single Center. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2016;22(8):1403-1409. doi:10.1016/j.bbmt.2016.04.006.
3. Satwani P, Brazauskas R, Arnold SD, et al. A Study of Predictors of Clinical Outcomes and Healthcare Utilization in Children with Sickle Cell Disease Undergoing Allogeneic Hematopoietic Cell Transplantation. Blood. 2015;126(23):528.