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DURATION OF IMIPENEM-CILASTATIN AND/OR PIPERACILLIN-TAZOBACTAM IS PREDICTIVE FOR ACUTE GRAFT VS HOST DISEASE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION
Author(s): ,
Nour Ben Abdeljelil
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Wafa Chanbeh
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Anouar Barhoumi
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Linda Essakly
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Cyrine Ellouz
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Ons Ben Dhia
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Rym El Fatmi
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Amel Lakhal
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Dorra Belloumi
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Lamia Torjemane
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
,
Saloua Ladeb
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
Tarek Ben Othman
Affiliations:
Centre National de Greffe de Moelle Osseuse de Tunis,Tunis,Tunisia
(Abstract release date: 05/17/18) EHA Library. Adejlil N. 06/14/18; 216677; PB2458
Assoc. Prof. Nour Ben Adejlil
Assoc. Prof. Nour Ben Adejlil
Contributions
Abstract

Abstract: PB2458

Type: Publication Only

Background

Allogeneic stem cell transplantation (ASCT) is associated with a high risk for developing graft-versus-host disease (GVHD). 

Aims
The aim of the study is to determine if duration of imipenem-cilastatin and/or piperacillin-tazobactam exposure is an independent risk factor for grade II-IV acute GVHD.

Methods

A retrospective study was conducted in adults patients who underwent ASCT from HLA-identical sibling donors between January 2014 and December 2016 to evaluate the impact of duration of imipenem-cilastatin or piperacillin-tazobactam exposure on grade II-IV acute GVHD. Patients with lymphoid malignancy were conditioned with fludarabine/busulfex/cyclophosphamide or TBI/etoposide. Myeloid malignancies were conditioned with busulfex/cyclophophamide. Patients with aplastic anemia received  ATGAM/cyclophosphamide or fludarabine/thymoglobulin/cyclophosphamide regimens. Gut decontamination with polymixin E, gentamicin and amphotericin B was used in all recipients. Graft-versus-host disease prophylaxis consisted of cyclosporine and a short course of methotrexate. No patient received antibiotic prophylaxis. GVHD was confirmed by biopsy and classified according to Glucksberg criteria. Patients who did not receive imipenem-cilastatin or piperacillin-tazobatam or received them less than 24 hours were excluded. The odds ratios and 95% confidence intervals as determined by multivariate analysis for 7 variables (selected based on a P value <0.15 in univariate analysis).

Results

Seventy-nine patients underwent ASCT (47men and 32 women). Median age was 35 years (range, 18-56y). Diagnosis included AML (n=27, 34.2%), ALL (n=23, 29.1%), Aplastic anemia (n=18, 22.8%), other hematologic malignancies (n=11, 13.9%). Stem cell source were BM in 34 patients (43%) and PBSC in 45 patients (57%). Twenty-four patients received piperacillin-tazobactam only (30.4%, group 1), 23 patients received imipenem-cilastatin only (29.1%, group 2) and 32 patients received both (40.5%, group 3).The median duration of antibiotic exposure was 17days (range, 4-64 days). One patient experienced primary graft failure. Non-relapse mortality (NRM) was 17.4%. One patient had early NRM. Twenty-six patients (32.9%) developed grade II-IV acute GVHD at a median of 23 days (range, 14-100 d). The frequency of grade II-IV acute GVHD was comparable in the three groups (33.3%, 23.8% and 40.6% in groups 1, 2 and 3, respectively, p=0.45). Acute gut GVHD occurred in 16 patients (20.7%). Three-year overall survival was 66%. In univariate and multivariate analysis, the risk of acute grade II-IV GVHD increased significantly with duration of antibiotic exposure. Exposure for ≥25 days increases the risk by nearly six times (OR=5.8, 95% CI:  1.8- 18.68, p= 0.003).

Conclusion

Duration of broad-spectrum antibiotics exposure is associated with an increased risk of acute GVHD. Limiting the use of antibiotics post-ASCT may reduce the occurrence of acute GVHD.

 

Session topic: 23. Stem cell transplantation - Clinical

Abstract: PB2458

Type: Publication Only

Background

Allogeneic stem cell transplantation (ASCT) is associated with a high risk for developing graft-versus-host disease (GVHD). 

Aims
The aim of the study is to determine if duration of imipenem-cilastatin and/or piperacillin-tazobactam exposure is an independent risk factor for grade II-IV acute GVHD.

Methods

A retrospective study was conducted in adults patients who underwent ASCT from HLA-identical sibling donors between January 2014 and December 2016 to evaluate the impact of duration of imipenem-cilastatin or piperacillin-tazobactam exposure on grade II-IV acute GVHD. Patients with lymphoid malignancy were conditioned with fludarabine/busulfex/cyclophosphamide or TBI/etoposide. Myeloid malignancies were conditioned with busulfex/cyclophophamide. Patients with aplastic anemia received  ATGAM/cyclophosphamide or fludarabine/thymoglobulin/cyclophosphamide regimens. Gut decontamination with polymixin E, gentamicin and amphotericin B was used in all recipients. Graft-versus-host disease prophylaxis consisted of cyclosporine and a short course of methotrexate. No patient received antibiotic prophylaxis. GVHD was confirmed by biopsy and classified according to Glucksberg criteria. Patients who did not receive imipenem-cilastatin or piperacillin-tazobatam or received them less than 24 hours were excluded. The odds ratios and 95% confidence intervals as determined by multivariate analysis for 7 variables (selected based on a P value <0.15 in univariate analysis).

Results

Seventy-nine patients underwent ASCT (47men and 32 women). Median age was 35 years (range, 18-56y). Diagnosis included AML (n=27, 34.2%), ALL (n=23, 29.1%), Aplastic anemia (n=18, 22.8%), other hematologic malignancies (n=11, 13.9%). Stem cell source were BM in 34 patients (43%) and PBSC in 45 patients (57%). Twenty-four patients received piperacillin-tazobactam only (30.4%, group 1), 23 patients received imipenem-cilastatin only (29.1%, group 2) and 32 patients received both (40.5%, group 3).The median duration of antibiotic exposure was 17days (range, 4-64 days). One patient experienced primary graft failure. Non-relapse mortality (NRM) was 17.4%. One patient had early NRM. Twenty-six patients (32.9%) developed grade II-IV acute GVHD at a median of 23 days (range, 14-100 d). The frequency of grade II-IV acute GVHD was comparable in the three groups (33.3%, 23.8% and 40.6% in groups 1, 2 and 3, respectively, p=0.45). Acute gut GVHD occurred in 16 patients (20.7%). Three-year overall survival was 66%. In univariate and multivariate analysis, the risk of acute grade II-IV GVHD increased significantly with duration of antibiotic exposure. Exposure for ≥25 days increases the risk by nearly six times (OR=5.8, 95% CI:  1.8- 18.68, p= 0.003).

Conclusion

Duration of broad-spectrum antibiotics exposure is associated with an increased risk of acute GVHD. Limiting the use of antibiotics post-ASCT may reduce the occurrence of acute GVHD.

 

Session topic: 23. Stem cell transplantation - Clinical

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