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Analysis of factors affecting initial cyclosporine level and its impact on post transplant outcomes in acute leukemia

In Journal of Cancer Research and Therapeutics
By: Gupta A.
Contributor(s): Punatar S | Gawande J | Mathew L | Kannan S | Khattry N.
Material type: materialTypeLabelArticlePublisher: 2017Description: .Subject(s): Cyclosporine level | Acute leukemia In: Journal of Cancer Research and TherapeuticsSummary: BACKGROUND: Trough cyclosporine (CsA) blood level can influence incidence of graft-versus-host disease (GVHD) and relapse in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplant (HSCT). We sought to determine factors affecting initial trough CsA level (CsA-1) and its impact on transplant outcome in acute leukemia. MATERIALS AND METHODS: Seventy-seven patients underwent HSCT for acute leukemia between January 2008 and March 2013 and were included. GVHD prophylaxis included CsA + methotrexate. (MTX) in 53 patients and CsA + mycophenolate mofetil (MMF) in 24 patients CsA-1 was measured on day 3-5 of starting CsA and subsequent dose was modified to achieve therapeutic level of 150-200. ng/mL. According to CsA-1, patients were divided into three groups - 27 in Group A (dose escalated), 13 in Group B (dose de-escalated), and 37 in Group C (same dose continued). RESULTS: On univariate analysis, cyclophosphamide with total-body irradiation (TBI) based conditioning regimen and lower body mass index (BMI) were associated with lower CsA-1, while use of fludarabine and higher BMI were associated with higher CsA-1. On multivariate analysis, only fludarabine use and BMI affected CsA-1. Incidence of acute and chronic GVHD (aGVHD and cGVHD), transplant-related mortality, relapse incidence, and relapse-free and overall survival (OS) were similar in the three groups. CONCLUSION: While fludarabine use in conditioning regimen and higher BMI leads to higher CsA-1, transplant outcomes are not affected by CsA-1.
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BACKGROUND:
Trough cyclosporine (CsA) blood level can influence incidence of graft-versus-host disease (GVHD) and relapse in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplant (HSCT). We sought to determine factors affecting initial trough CsA level (CsA-1) and its impact on transplant outcome in acute leukemia.

MATERIALS AND METHODS:
Seventy-seven patients underwent HSCT for acute leukemia between January 2008 and March 2013 and were included. GVHD prophylaxis included CsA + methotrexate. (MTX) in 53 patients and CsA + mycophenolate mofetil (MMF) in 24 patients CsA-1 was measured on day 3-5 of starting CsA and subsequent dose was modified to achieve therapeutic level of 150-200. ng/mL. According to CsA-1, patients were divided into three groups - 27 in Group A (dose escalated), 13 in Group B (dose de-escalated), and 37 in Group C (same dose continued).

RESULTS:
On univariate analysis, cyclophosphamide with total-body irradiation (TBI) based conditioning regimen and lower body mass index (BMI) were associated with lower CsA-1, while use of fludarabine and higher BMI were associated with higher CsA-1. On multivariate analysis, only fludarabine use and BMI affected CsA-1. Incidence of acute and chronic GVHD (aGVHD and cGVHD), transplant-related mortality, relapse incidence, and relapse-free and overall survival (OS) were similar in the three groups.

CONCLUSION:
While fludarabine use in conditioning regimen and higher BMI leads to higher CsA-1, transplant outcomes are not affected by CsA-1.

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