scholarly journals Clofarabine-based regimen as useful bridge therapy for stem cell transplantation in refractory or relapsed pediatric leukemia

2020 ◽  
Vol 11 (2) ◽  
pp. 2303-2307
Author(s):  
Elham Alshammari ◽  
Anfal Alshammari

Acute leukemia is often regarded as a popular malignancy affecting children. Noticeable enhancements in the treatment of childhood acute lymphoblastic leukemia, as well as acute myeloid leukemia have resulted in an upsurge in the cure rates. Presently, 80% of the children affected by acute lymphoblastic leukemia and 50% of those affected by acute myeloid leukemia can benefit from long-term remission. However, salvage routines have been very poor in some cases. Some of these cases include those that entail primary refractory disease, multiple relapses, as well as early systematic relapse. Relapsed leukemia is the fourth most popular malignancy affecting children, and there is need to develop novel therapeutic alternatives that can cater for this primary group of patients. With this perspective in mind, clofarabine remains to be the original and only anticancer drug that was certified for use in children and has been in use for over 10 years even before it was actually used in adults. There is need to include clofarabine in reduced-intensity conditioning (RIC) allogenic hematopoietic stem cell transplantation (HSCT) in the treatment of severe leukemia. Such an inclusion could possibly enhance the treatment outcomes. It is also necessary to design research that can examine the outcome of clofarabine based regimen as bridge therapy to stem cell transplant in young patients with refractory or relapsed leukemias.

1970 ◽  
Vol 1 (1) ◽  
pp. 43-49
Author(s):  
Pritesh Patel ◽  
Santosh Saraf ◽  
Damiano Rondelli

Outcomes for elderly patients with acute myeloid leukemia (AML) remain poor with standard therapies. Historically this age group has been excluded from treatment with allogeneic stem cell transplantation (allo-SCT) due to worries of excessive treatment related morbidity and mortality. However, transplantation outcomes have dramatically improved in the last decade due to the widespread use of less ablative conditioning regimens, improved supportive care, and improved patient selection based on prognostic tools such as the hematopoietic cell transplant specific comorbidity index. These have all led to an increasing acceptance of allo-SCT as a potential treatment modality in elderly patients with AML. This review addresses current strategies for patient selection and efficacy data for allo-SCT in elderly patients with AML. DOI: http://dx.doi.org/10.3126/jaim.v1i1.5840 Journal of Advances in Internal Medicine. 2012; 1(1): 43-49


Author(s):  
Linus Angenendt ◽  
Isabel Hilgefort ◽  
Jan-Henrik Mikesch ◽  
Bernhard Schlüter ◽  
Wolfgang E. Berdel ◽  
...  

AbstractLow intake of magnesium has been associated with the occurrence of lymphomas and decreased magnesium levels suppress the cytotoxic function of T cells and natural killer cells in patients with “X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia” (XMEN) syndrome. These cell types are also important mediators of immune-mediated effects after allogeneic hematopoietic stem cell transplantation. Here, we show that high posttransplant magnesium levels independently associate with a lower incidence of relapse, a higher risk of acute graft-versus-host disease, and a higher non-relapse mortality in 368 patients with acute myeloid leukemia from our center. Magnesium serum levels might impact on donor-cell-mediated immune responses in acute myeloid leukemia.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingya Cui ◽  
Chongsheng Qian ◽  
Nan Xu ◽  
Liqing Kang ◽  
Haiping Dai ◽  
...  

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.


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