Summary
Background
Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess “response”.
Aim
To assess the prognostic and therapeutic implications of baseline neutrophil‐to‐lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis.
Methods
Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the receiver operating curve (AUC) analysis was performed. Kaplan‐Meier analysis was used to assess survival. Log‐rank test and odds ratio (OR) were used for comparative analysis.
Results
Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90‐day outcome (0.660), but was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety‐day survival was not affected by prednisolone treatment if NLR < 5 or > 8 but mortality was reduced with prednisolone treatment when the NLR was 5‐8 (21.0% cf. 34.5%; P = 0.012). Prednisolone treatment increased the chance of Lille response if the NLR was ≥ 5 (56.5% cf. 41.1%: P = 0.01; OR 1.86) but increased the risk of day 7 infection (17.3% cf. 7.4%: P = 0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P = 0.008; OR 3.46) if the NLR was > 8. Incorporation of NLR into a modified Glasgow alcoholic hepatitis score (mGAHS) improved the AUC to 0.783 and 0.739 for 28‐day and 90‐day outcome, respectively.
Conclusion
The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5‐8). The mGAHS has a good predictive value for 28‐ and 90‐day outcomes.
Thirty unselected patients with chronic granulocytic leukaemia (CGL), age range 22-59 years, were treated with intensive chemotherapy and G-CSF to mobilize peripheral blood progenitor cells (PBPC). Chemotherapy was well tolerated and PBPC were collected by leukapheresis early during white cell recovery. PBPC collections considered adequate for engraftment were collected in 21 patients. Cytogenetic analysis of all collections in these patients showed Ͼ75% Ph negativity (range 79-100%) in 10. Successful collections, ie those Ͼ75% Ph negative and with total cell count of Ͼ1 × 10 6 CD34+ve cells/kg or Ͼ20 × 10 4 CFU-GM/kg were further analysed by Southern blot or RT-PCR. All samples were positive for the bcr/abl transcript. Patients with a low Sokal score (Ͻ0.8) were more likely to achieve a successful collection. In contrast, there was no association between transcript expression and likelihood of successful collection. We have confirmed that it is possible to mobilize and collect Ph-negative enriched PBPC in unselected patients with CGL. This procedure is more likely to be successful earlier rather than later in the course of the disease. Whether such collections will give an advantage over unmanipulated autologous bone marrow transplantation in CGL requires further study, but our experience suggests that suitable material for autologous rescue can be obtained from approximately one third of eligible, unselected young patients.
For those patients ineligible for allogeneic bone marrow transplant and who are non-responsive to interferon, autotransplant with peripheral blood stem cells (PBSC) mobilised after intensive chemotherapy, may provide a novel approach to improve prognosis in patients with chronic granulocytic leukaemia. PBSC harvests are assessed for CD34-positive cell numbers, which serve as an indicator of engraftment potential, and are also analysed cytogenetically to ascertain tumour cell contamination. However, a more accurate assessment of PBSC harvest contamination requires investigation of the Philadelphia (Ph) status of the CD34 pos population, in which the cells that provide long-term engraftment are contained. In this study, we have analysed these levels in mobilised PBSC and also in bone marrow (BM) harvests, taken several weeks prior to mobilising chemotherapy. Using fluorescent in situ hybridisation for the bcr/abl gene fusion, we have shown that the median number of Ph negative cells in CD34 pos isolated populations was 14.95% in BM compared to 79.05% in PBSC harvests and that in all PBSC samples tested, Ph positivity in CD34 pos populations was always detectable either by FISH or one round PCR methods. In paired assessments of both PBSC and BM harvests, higher levels of Ph negative CD34 pos cells (у14%) isolated from BM harvests, taken prior to intensive chemotherapy, correlated with higher levels of Ph negative CD34 pos cells (у78.5%) in PBSC harvests. These data may aid in the selection of patients for whom PBSC harvesting, after mobilisation, is more likely to achieve an autograft product containing predominantly Ph negative CD34 pos cells and may exclude those patients for whom the risk, morbidity and expense of stem cell harvesting may have no apparent benefit over a chronic phase BM harvest.
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