Pre-Transplant Consolidation and Cost Effectiveness of RIC Allogeneic SCT in Patients of AML-CR1 in India

An allogeneic SCT (alloSCT) with a reduced intensity conditioning regimen (RIC) in first remission (CR1) is an attractive option to fulfill the requirements of relatively low cost without compromising efficacy. The need for consolidation chemotherapy prior to offering a RIC alloSCT for AML CR1 remains controversial. To evaluate these aspects we undertook a retrospective analysis of patients with AML CR1 who received a RIC alloSCT from multiple centers in India.

Data from 8 centers in India was collected between 2005 and 2013. A total of 138 patients fulfilled the criteria of AML CR1 having received an alloSCT with a RIC regimen. The median age was 34 years (range: 2 – 63) and 60% were males. The median time from diagnosis of AML to transplant was 99 days (range: 41 – 504). 123 (89%) were HLA matched related donors, 3 (2.1%) were MUD transplants and the rest were HLA mismatched related donors. 70 (51%) received chemotherapy consolidation prior to transplant, 61 (44%) did not and data was not available in 7 (5%). 68% of those that received consolidation received intermediate or low dose cytosine based regimens. Fludarabine with melphalan (140mg/m²) (128{93%}) was the most commonly used regimen. All patients received a PBSC graft with a median CD34 cell dose of 9.1x10⁶/kg (range: 1.3 – 43). With the exception of one, all patients engrafted (97% of these achieved complete chimerism at one month post transplant). The median time to ANC >500/mm³was 13 days (range: 7 – 22) and platelet count of >20,000/mm3 was 15 days (range: 0-33). Acute GVHD Grade 2-4 was seen in 29% and of patients evaluated 62% had chronic GVHD, the majority of these being limited (61%). The 100 day treatment related mortality (TRM) was 7.5% and the one year TRM was 25.6%. At a median follow up of 24 months the 5 year EFS and OS was 64.0±5.07 and 71.1±4.0 respectively. The 5 year cumulative incidence of relapse was 21.8%. The baseline characteristics as mentioned above were not significantly different between the group that received consolidation and the group that did not. The use of consolidation therapy prior to alloSCT did not have a significant impact on EFS or OS. 

On a multivariate analysis (after adjusting for those significant on univariate analysis and for conventional risk factors) only CMV reactivation (RR 2.0; 95% CI 1.03-3.87; P-value 0.042) and fungal infection (RR 7.1; 95%CI 3.154-16.12; P-value 0.000) had a significant adverse impact.

The mean costs of induction chemotherapy for these patients was US$ 9239±3596 (n=74) and for alloSCT it was 18138±13826 (n=118; costing up to 1 year post transplant). Induction chemotherapy followed by HLA matched RIC alloSCT is likely to be the most cost effective and affordable treatment option for young adults with AML in CR1 in India. With an average gross net income in India of US$3500/year the limitation still remains the cost of treatment and number of centers that can offer this therapy.