Continuous molecular remission and regression of side effects after discontinuation of salvage therapy with sorafenib and donor lymphocyte infusions in a young patient with relapsed AML

Ernst, Jochen; Schäfer, Vivien; Rinke, Jenny; Wittig, Susan; Beck, James F.; Ernst, Thomas; Gruhn, Bernd

doi:10.1007/s00277-016-2637-7

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…[20][21][22] Promising effects have been reported from combining sorafenib with hypomethylating agents, ATRA or homoharringtonin, especially in refractory AML. [23][24][25] The greatest antiproliferative and proapoptotic accuracy in preclinical trials on human leukemic cell lines was demonstrated with a composite of 3 kinase inhibitors: FLT3 (sunitinib), PI3K (PF-04691502) and GLI1/2 (GANT61). 26 The use of sunitinib with standard inductive and life-sustaining therapy showed no benefits because of toxicity.…”

Section: Low Molecular Mass Drugsmentioning

confidence: 99%

The new perspectives of targeted therapy in acute myeloid leukemia

Walasek¹

2019

Adv Clin Exp Med

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Acute myeloid leukemia (AML) is a heterogeneous disease and the results of previous treatment with cytotoxic drugs have not been satisfactory. This situation has prompted investigations into novel approaches. The breakthrough in therapy brought by all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) and tyrosine kinase inhibitors in neoplasms with the Philadelphia chromosome has encouraged the search for other effective targeted therapies. Among the tested substances are higher molecular mass drugs such as antibodies and various small molecules: kinase inhibitors, cell pathway inhibitors and epigenetic modulators. So far, the U.S. Food and Drug Administration (FDA) has approved the antibody-drug conjugate gemtuzumab ozogamycin (GO), the tyrosine kinase inhibitor midostaurin and the IDH2 inhibitor enasidenib. These studies have led to a better understanding of the mechanisms of leukemogenesis and may soon allow for differentiating treatments depending on baseline mutational complements. Some innovative drugs described in this article have strong therapeutic potential, but there is still a long way to go before actual success in targeted treatment.

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Section: Low Molecular Mass Drugsmentioning

confidence: 99%

The new perspectives of targeted therapy in acute myeloid leukemia

Walasek¹

2019

Adv Clin Exp Med

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“…A tolerable toxicity profile was reported, consisting of fatigue, hand foot skin reaction, hypertension, elevated transaminases and mild myelosuppression (19). In cases, when sorafenib was used as treatment of relapsed or refractory AML, a fast and efficient leukoreduction has been reported (20)(21)(22), suggesting that it might be of clinical benefit in the management of hyperleukocytosis, even in cases where the FLT3-ITD status in unknown.…”

Section: Introductionmentioning

confidence: 99%

Leukoreductive response to the combination of sorafenib and chemotherapy in hyperleukocytosis of FLT3-ITD mutated pediatric AML

Schmidt

Erlacher²,

Niemeyer³

et al. 2022

Front. Pediatr.

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Twelve to 22% of pediatric acute myeloid leukemia (AML) patients present with hyperleukocytosis, which is one of the main risk factors of early death due to its clinical complications: leukostasis, causing pulmonary or central nervous system injuries, tumor lysis syndrome, and disseminated intravascular coagulation. Sorafenib is a multi-kinase inhibitor that blocks the Fms-Related Tyrosine Kinase 3 receptor (FLT3) in AML patients with a FLT3-internal tandem duplication (FLT3-ITD), leading to a reduction of proliferation. Here we report four de novo diagnosed or relapsed pediatric FLT3-ITD–positive AML patients with hyperleukocytosis, which were treated with sorafenib in combination with cytoreductive chemotherapy prior to the start of the induction phase. We observed a fast reduction of white blood cells in peripheral blood and bone marrow. This resulted in a rapid clinical stabilization of the patients. Adverse side effects—such as dermatologic toxicity, elevation of transaminases and hypertension—occurred but were mild and inductive chemotherapy could be started in parallel or subsequently. This implies sorafenib as a safe and effective treatment option in combination with chemotherapy during cytoreductive prephase for children with this life-threatening condition.

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Sorafenib

2016

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Continuous molecular remission and regression of side effects after discontinuation of salvage therapy with sorafenib and donor lymphocyte infusions in a young patient with relapsed AML

Cited by 3 publications

References 9 publications

The new perspectives of targeted therapy in acute myeloid leukemia

The new perspectives of targeted therapy in acute myeloid leukemia

Leukoreductive response to the combination of sorafenib and chemotherapy in hyperleukocytosis of FLT3-ITD mutated pediatric AML

Sorafenib

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