Relapse after Allogeneic Hematopoietic Stem Cell Transplantation (HCT) in AML/MDS: Monocyte Chemo-Attractant Protein-1 (MCP-1) Levels Post HCT and Prediction of Relapse in Patients with Hematological Remission and Full Chimerism at Day 30

Relapse after allogeneic hematopoietic stem cell transplantation (HCT) in AML/MDS: Monocyte chemo-attractant protein-1 (MCP-1) levels post HCT and prediction of relapse in patients with hematological remission and full chimerism at day 30.

Acute myeloid leukemia/Myelodysplastic syndrome (AML/MDS) is highly heterogeneous disease and prediction of relapse at the molecular level is a challenging task post allogeneic HCT. Significant existing data supports the MCP-1/CCR2 axis expression in the majority of AML blasts and it has been shown to be involved in blasts trafficking and proliferation. To evaluate the role of MCP-1 in prediction of AML/MDS relapse post allogeneic HCT, we measured the serum values of MCP-1 at day 30 post HCT in 54 consecutive patients with AML/MDS using multiple luminex ELISA assay. The samples were collected from the patients prospectively

Results: Patients characteristic are shown in table 1. Median age at transplant was 56 year old. GVHD prophylaxis was Tacrolimus /Methotrexate for FIC and Tacrolimus/ Mycophenolate for RIC.  Thymoglobulin was added at dose of 4.5 mg/Kg total dose for matched unrelated donor recipients. All the patients engrafted with no graft failure. Full chimerism at day 30 (> 95%) was achieved in 51/54 patients supported by morphological evidence of complete remission. With median follow up of 17 months, overall survival at 1 & 2 years was 78% and 67%. Cumulative Incidence of relapse at 1 year was 31% +/- 6% while cumulative Incidence of treatment related mortality (TRM) at 2 years was 10% +/- 4%. In order to evaluate the impact of MCP-1 levels at day 30 post HCT in predicting relapse., patients with less than 95% chimerism (n=3) and patients who died as result of TRM prior to relapse (n=5) were excluded from the analysis. At day 30 post HCT, patients with full chimerism who relapsed (n=13) had higher mean MCP-1 level of 514 +/- 175 versus patients with full chimerism who did not relapse (n=33), mean MCP-1 level of 382 +/-181; P= 0.03. (Figure 1). The median time to relapse from day 30 post- transplant was 69 days (range 41-230 days). The cumulative incidence of acute GVHD grade II-IV was 44% with 10% grade III-IV. The cumulative incidence of Chronic GVHD at 2 years was 48%, with 22% extensive chronic GVHD.  Conclusion: In this cohort of patients with AML/ MDS, MCP-1 levels at day 30 post allogeneic HCT in patients who had achieved complete remission and full chimerism were predictive of relapse two months on average prior to overt hematological relapse. Larger studies may find potential role of MCP-1 in predicting relapse post- transplant and development of early strategies for prevention.

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