Updated Outcomes of NF-08-TM Protocol in HSCT for Patients with b-Thalassemia Major: A Large Prospective Study from Single Center

Background: The optimization of both erythrocyte transfusion and iron chelating has resulted in a remarkable improvement in the life expectancy of patients with thalassemia major (TM). However, only curative therapy remains allogeneic hematopoietic stem cell transplantation (HSCT). HLA matched sibling transplant (MST) has been commonly used for TM patients with well results. However, this option is unavailable to many patients as a result of a lack of compatible MS, especially in China. Matched unrelated-donor transplant (MUT) and Haploidentical-donor transplant (HIT) have be well performed in malignant disease. But in few thalassemia patients because of high risk of transplantation so far. To expand donor pool and to lower risk of HSCT from alterative donor, we designed a NF-08-TM protocol for MST, MUT and HIT for TM patients since 2009. Outcomes before June 2011 have published in “Blood” in 2012. Here we updated these outcomes.

Aims: to check stability and reliability of NF-08-TM protocol in MST, MUT and HIT for thalassemia patients.

Methods: 293 consecutive patients with TM underwent HSCT between January, 2009 and December, 2013 in our center, including 143 in MUT, 21 in HIT (≥ one HLA mismatch) and 105 in MST. Rate of male to female is 185:108. The median age at transplant was 6 years (rang:0.6-16), The median follow-up time is 29 months (range: 6-64). All patients received the NF-08-TM protocol, which included a new risk classification to adjust dose of IV Busulfex (Bu) and Cyclophosphamide (Cy), and a conditioning regimen of Bu following Cy instead of Cy following Bu. Simultaneously, a intensify graft versus host disease (GVHD) prophylaxis consisted of ATG, Cs A, MMF and short MTX was given.

Results: The estimated 5-year overall survival and TM-free survival were 92.6%, 89.5% and 94.1%, and 90.5%, 89.5% and 92.2% in the MUT, HIT and MST, respectively. The cumulative incidence of graft rejection was 2.1% in total. The cumulative transplant-related mortality was 7.4%, 10.5% and 5.9%, respectively, in the MUT, HIT and MST. Incidence of cytopenia post-transplant (white cell count less than 3.0x10⁹/L for 4 weeks or longer but CMV infection) was 20.6%.

Conclusion: Our large sample prospective study provides results comparing MUT or HIT with the MST for TM patients, which showed that MUT or HIT was comparable with MST when using NF-08-TM-HSCT protocol.