scholarly journals Microbiota Disruption Induced by Early Use of Broad-Spectrum Antibiotics Is an Independent Risk Factor of Outcome after Allogeneic Stem Cell Transplantation

2017 ◽  
Vol 23 (5) ◽  
pp. 845-852 ◽  
Author(s):  
Daniela Weber ◽  
Robert R. Jenq ◽  
Jonathan U. Peled ◽  
Ying Taur ◽  
Andreas Hiergeist ◽  
...  
Keyword(s):  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Broad Spectrum ◽  
Independent Risk Factor ◽  
Broad Spectrum Antibiotics ◽  
Early Use

scholarly journals The Proportion of CD52/GPI Negative T Cells Early Following Alemtuzumab Conditioned Haematopoetic Stem Cell Transplantation Is an Independent Risk Factor for Acute GvHD

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4543-4543
Author(s):  
Francesca Kinsella ◽  
Charlotte F Inman ◽  
Duncan Murray ◽  
Wayne Croft ◽  
Jianmin Zuo ◽  
...  
Keyword(s):  
T Cells ◽  
Risk Factor ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Independent Risk Factor ◽  
Acute Gvhd ◽  
Cell Fraction

T cell depletion with in vivo alemtuzumab is used to ameliorate the graft versus host response and permit donor engraftment in allogeneic haematopoietic stem cell transplantation (allo-HSCT). Previous reports have shown that T cells lacking CD52 are often detectable during the period of early immune reconstitution with this protocol, but the clinical relevance of this cellular population is not understood. In a cohort of 67 consecutive patients undergoing allo-HSCT between 2013-2016 we investigated the phenotype and function of the CD52-negative T cell fraction and related their presence to clinical outcome. 47 patients (70%) had a myeloid disease (AML or MDS) while 20 patients had lymphoid disease. All patients received in vivo alemtuzumab (10mg/day from day -5 for 5 days). 63 (94%) received reduced intensity conditioning chemotherapy, while 4 (6%) received a myeloablative regimen. All patients received post-transplant ciclosporin A for GvHD prophylaxis. 6 (9%) also received methotrexate, while 2 (3%) patients also received mycophenolate mofetil. Overall survival at 2 years was 68% and relapse free survival was 48%. 29% patients experienced acute GvHD (grade 2 or above) and 15% developed chronic GvHD. CD52-negative T cells demonstrated low binding of FLAER, indicating downregulation of the glycophosphatidylinositol (GPI) anchor, although we did not detect any mutations in the PIG-A gene as is typically seen in patients with PNH. CD52-negative T cells were almost exclusively CD4+ and exhibited a dominant memory phenotype with only small numbers of CD25+ CD127lowFoxp3+ regulatory T cells. They exhibited enhanced cytotoxic responses to T cell receptor stimulation in vitro. Early after allo-HSCT, the presence of a significant population of CD52 negative T cells (comprising >51% of the T cell fraction) was found to be an independent risk factor for acute GvHD. This was confirmed in a validation cohort of 28 patients obtained between 2017-2018. These data suggest that CD52/GPI-negative T cells arise from the selective pressure of alemtuzumab in the setting of lymphopenia and homeostatic proliferation. To our knowledge this is the first study to show that CD52 negative T cells have a reduced regulatory T cell fraction, and have an association with acute GvHD. This suggests that the CD52-negative T cell fraction may represent a 'footprint' of the early alloreactive response focused within the CD4+ population, or contribute to an immune environment with reduced T cell tolerance. These data help to delineate the nature of T cell escape from alemtuzumab surveillance providing new insights into the early alloreactive immune response. Furthermore, this study informs the use of alemtuzumab in conditioning regimens for upcoming cellular immunotherapies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation

Blood ◽  
2018 ◽  
Vol 131 (13) ◽  
pp. 1464-1475 ◽  
Author(s):  
Heike Pfeifer ◽  
Katharina Raum ◽  
Sandra Markovic ◽  
Verena Nowak ◽  
Stephanie Fey ◽  
...  
Keyword(s):  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Genomic Deletions ◽  
Key Points

Key Points Genomic deletions of CDKN2A/2B are a new independent prognostic risk factor in adult Ph+ ALL.

Comparison of Empiric Versus Prophylactic Administration of Ceftazidime during Neutropenia Associated with Reduced-Intensity Allogeneic Stem Cell Transplantation (RIST).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5100-5100
Author(s):  
Kyle M. Donley ◽  
Juan C. Gea-Banacloche ◽  
Robert M. Dean ◽  
Seth M. Steinberg ◽  
Richard W. Childs ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Broad Spectrum ◽  
Conditioning Regimen ◽  
Antibiotic Use ◽  
Hematologic Malignancies ◽  
Marrow Transplant ◽  
Neutropenic Fever ◽  
Broad Spectrum Antibiotics

Abstract Broad spectrum antibiotics are sometimes used prophylactically during the neutropenic phase of stem cell transplantation, but this practice is controversial. Possible benefits include the prevention of fever and infectious episodes. Possible disadvantages include increased usage of antibiotics with associated increases in cost, toxicities and development of antibiotic resistance. OBJECTIVE: To compare prophylactic (PRO) administration of ceftazidime at the beginning of neutropenia (ANC <500) vs. empirical (EMP) initiation of ceftazidime for neutropenic fever in RIST patients during the pre-engraftment period. METHODS: Retrospective analysis of all patients who received a RIST for hematologic malignancies in two different bone marrow transplant units at the NIH Clinical Center between 2000 and 2003. The PRO group was composed of 41 patients who received prophylactic ceftazidime 2 g iv q 8h when ANC <500. The EMP group was composed of 40 patients who received ceftazidime during neutropenia only if fever developed. Both groups were comparable in terms of baseline disease, age, sex, conditioning regimen (FLU/CY) and gut decontamination. Mean duration of neutropenia was 10.8 days in the PRO group and 13.7 days in the EMP group (p < 0.05), due to differences in GVHD prophylaxis and GCSF usage. RESULTS: The PRO group presented less episodes of neutropenic fever (16/41, 39% vs. 27/40, 67.5%, p < 0.05), less microbiologically documented infections (4/41, 10% vs 17/40, 43% p < 0.05) and less episodes of bacteremia (1 vs. 7). By Kaplan-Meier analysis the median time to developing fever was significantly longer in the PRO group (9.6 vs 6.8 days p = 0.03). The PRO group received, on average, 5.5 less days of broad-spectrum antibiotics (11.8 vs 17.3). The average number of days on ceftazidime was 10 in the PRO group and 7 in the EMP group. There were no significant toxicities associated with antibiotic use. The susceptibility to ceftazidime on the bacterial isolates from both transplant units did not change significantly between 1999 and 2003, despite the different patterns of antibiotic use. CONCLUSION: Prophylaxis with ceftazidime may prevent neutropenic fever and microbiologically documented infections during the pre-engraftment phase of RIST, and may result in decreased utilization of broad-spectrum antibiotics.

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