Treosulfan Based Conditioning Regime for Allogenic HSCT in Resource Poor Setting

Abstract

Allogenic stem cell transplantation is a curative procedure for many blood disorders including haemtological malignancies. The outcomes are very dependent on the conditioning regime used. Infections from a variety of micro-organisms and graft vs host disease(GVHD) can be the other parameters affecting outcomes. Relapse rate specially in a malignant condition influences the choice of regime as does the prevention of certain conditions like veno occlusive disease- Sinusoidal obstruction syndrome.Busalfan based regimes have been used extensively but shows a high rate of veno occlusive disease (VOD) specially when used with post transplant high dose Cyclophosphamide for GVHD prevention. Also Buslfan drug monitoring is not available in many places making this kind of transplants risky. Once VOD develops, the mortality is very high and it is better prevented. The use of drugs like Defibrotide makes the transplant very expensive also. We developed a conditioning regime using Treosulfan (di hydroxy Busulfan), followed by post transplant Cyclophosphamide and did not see a single patient suffering from VOD in the 15 patients transplanted so far. These were for a variety of malignant conditions including Myelodysplasia, Acute myeloid leukaemia, Acute Lymphoblastic leukaemia, Chronic Myeloid leukaemia, Follicular Lymphoma. The age group varied from 10-58 years(median=35) and there was almost an equal sex distribution. Among the 15 patients transplanted 7 patients were in CR(complete remission)1, 6 in CR2 and 2 in CR3. The graft was a peripheral stem cell graft taken from a mix of Haploidentical donors, Matched unrelated donor and sibling donors. 10 patients are alive so far and are in CR. 2 relapses were seen who ultimately died in agressive acute myeloid leukaemia, 2 died of a secondary infection, 1 transplant related mortality due to microangiopathy was seen. 1 grade 4 GVHD was noted which was treated with steroids. In conclusion, Treosulfan gives an advantage over Busulfan in our results and with the advent of generic Treosulfan the cost of the transplant procedures have gone down also. The avoidance of medicines like Defibrotide and no requirement of drug monitoring make these procedures simple and cheaper and is much suited in a resource poor setting.