Harnessing the power of alloreactivity without triggering graft-versus-host disease: how non-engrafting alloreactive cellular therapy might change the landscape of acute myeloid leukemia treatment

Blood Reviews ◽  
2014 ◽  
Vol 28 (6) ◽  
pp. 249-261 ◽  
Author(s):  
Elizabeth F. Krakow ◽  
Julie Bergeron ◽  
Silvy Lachance ◽  
Denis-Claude Roy ◽  
Jean-Sébastien Delisle
2021 ◽  
Vol 2 (4) ◽  
pp. 01-04
Author(s):  
Toumi H ◽  
Betaouaf H ◽  
Boudia Boudia ◽  
Fettati H ◽  
Yafour N

Acute myeloid leukemia (AML) is a malignant blood disease that affects hematopoietic cells in the bone marrow. The best treatment for AML is allogeneic hematopoietic stem cell transplantation (HSC). To prevent and treat the main complication of allogeneic marrow transplant, graft versus host disease (GVHD), it is necessary to combine immunosuppressive therapy which includes ciclosporin (CsA). The objective of our work is to study the influence of hepatic GVHD on the pharmacokinetics of cyclosporin in an AMLcase. This is an allografted patient (CSH), presented to our Pharmacovigilance department at the EHU of Oran in Algeria, with the aim of carrying out therapeutic pharmacological monitoring (TPM) of ciclosporin. We proceeded to assay for residual ciclosporinaemia from D1 of the allogeneic transplant. The patient presented a fluctuation of the trough concentrations, the explanation of which was an onset of acute hepatic GVHD, confirmed by biopsy with an elevated hepatic function, which represents an incidence varying between 10 and 50% in patients receiving transplant from a genoidentical donor. Without forgetting the great inter-individual and intra-individual variability of the response to ciclosporin, the environmental and pathological factors and the numerous drug interactions which can be the cause of modification of the pharmacokinetics and the pharmacodynamics of this drug. In conclusion, the pharmacological monitoring of cyclosporin, which is the treatment of choice to prevent or treat GVHD, is mandatory due to its low therapeutic index and high inter- and intra-individual variability.


2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Koichi Murakami ◽  
Hironori Ueno ◽  
Takashi Okabe ◽  
Toshiya Kagoo ◽  
Saigen Boku ◽  
...  

Allogeneic stem cell transplantation (allo-SCT) is the only curative option for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Azacitidine (AZA) has a good toxicity profile compared with intensive chemotherapy and can be considered a pre-transplant regimen in elderly patients and in patients with comorbidities. To investigate the impact of pre-transplant AZA on patient outcome after allo-SCT, we conducted a retrospective analysis of AZA pre-treatment followed by allo-SCT in patients with high-risk MDS and AML. Twenty patients who were divided into two groups according to AZA treatment given prior to allo-SCT (AZA <em>vs</em> non- AZA group, 10 each). Overall survival, event-free survival and incidence of chronic graft-versus-host disease (GVHD) were not significantly different between the two groups. The overall incidence of grade II to IV acute GVHD in the AZA group was significantly lower than that in the non-AZA group (P=0.004). Bridging to transplant with AZA should be considered as an immunomodulator and effective treatment strategy for patients with MDS and AML.


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