Mixed (Umbilical Cord Blood And Bone Marrow) Transplantation in Thalassaemia: An Experience from Eastern India

Background: Bone marrow transplant is often the preferred method of treatment for a variety of blood disorders including leukaemias, aplastic anaemia, inborn errors of metabolism and certain haemoglobinopathies (thalassaemia, sickle cell disease). Recently, several investigations have shown that cord blood is a rich source of pluripotent stem cells and it can be used effectively in place of BMT. Cord blood transplantation as a therapeutic option is a recent phenomenon in India. To date umbilical cord blood has been used in sibling and other related donors in a few centers in India. Cord blood transplant can also be used in case of a large number of patients for whom no acceptable family donor is available. The aim of our study is to see the effectiveness of umbilical cord blood as a source of stem cell transplant.

MATERIAL AND METHODS: We recruited 5 patients for the sibling CBT, from July 2002 – June 2008, at our institute, which is a tertiary level cancer research institute in eastern India. The patients were properly screened for Lucarelli staging and HLA matching prior to the procedure. Out of the 5 cases 3 were fully HLA matched and 2 were mismatched. Three (3) children were in Lucarelli stage 1 and 2 were in stage 1. The sibling CBT was done at a median age of 4.5 yrs (range 3 – 12 yrs). In all the cases, cord blood was obtained shortly after the birth of the donor child, employing the closed system of collection. About 100 – 120 ml of blood was collected in each case. The blood obtained was tested for several infectious diseases including HIV and hepatitis. The blood was then sent to the appropriate laboratory for storage where it was cryopreserved at −80°C and then stored in liquid nitrogen (− 192°C) for future use. The mean no of nucleated cells infused were 2.8 × 10⁷/kg (Range:1.2 – 7.2 × 10⁷/kg)and the mean number of CD4+ cells infused were 3.2 × 10⁶/kg (Range: 2.2 – 7.8 × 10⁶/kg). The infused CFU-GM for our cases were 6 ×10⁴/kg (4.1 – 9.2 ×10⁴/kg).

RESULTS: The median number of days to achieve engraftment was 13 days (range 9 – 13 days) for neutrophil, 33 days(range 24 – 48 days) for platelets and 80 days (33 – 148 days) for the red blood cells. All 3 patients who received HLA identical cord blood transplant engrafted, but rejection of the graft was seen in 2 patients later on at day + 180 and day + 250. Two patients who received 4/6 and 5/6 mismatched cord blood only had a partial engraftment. Out of the 3 pts who received HLA identical transplants 1 developed Gr 1 AcuteGVHD and no GVHD was seen the 2 patients who received HLA non identical CBT. Complete engraftment was seen in 2 HLA matched patients with a second transplant with the bone marrow of the same sibling. With a median follow up of 3.6 years (3 months – 6 years) all the patients are surviving – 3 being disease free(transfusion independent),2 with infrequent transfusion.

CONCLUSION: In conclusion, it appears that umbilical cord blood transplant appears to be a viable option in terms of providing a cure for thalassaemia major and other haemoglobinopathies, provided it is combined with bone marrow of a matched sibling donor. In the future, we are intending to perform a mixed transplant (stored umbilical cord blood and bone marrow) if a HLA matched sibling donor is available. If no matched donor is available we will consider mismatched related or unrelated cord blood transplant.