Acute myeloid leukemia treatment

Enzymes Degrading Macromolecules. Enzymes that degrade macromolecules such as membrane polysaccharides, stmctural and functional proteins, or nucleic acids, have all shown oncolytic activity. Treatment strategies include the treatment of inoperable tumors with pepsin (1) antitumor activity of carboxypeptidase (44) cytotoxicity of ribonudease (45—47) oncolytic activity of neuraminidase (48—52) therapy with neuraminidase of patients with acute myeloid leukemia (53) antitumor activity of proteases (54) and hyaluronidase treatment in the management of human soHd tumors (55). 

Ishii E, Kawasaki H, Isoyama K, et al. Recent advances in the treatment of infant acute myeloid leukemia. Leukemia Lymphoma 2003 44 741-748. 

Giles F, Estey E, O Brien S. (2003) Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer 98 2095-2104. 

Pagano L, Fianchi L, Caira M, Rutella S, Leone G. (2007) The role of gemtuzumab ozogamicin in the treatment of acute myeloid leukemia patients. 

Knapper S, Burnett AK, Littlewood T, Kell WJ, Agrawal S, Chopra R, Clark R, Levis MJ, Small D. (2006) A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood 108 3262-3270. 

The inhibitors available for human use, azacitidine and decitabine, have been approved for the treatment of myelodysplastic syndrome (MDS) [98, 99[. MDS summarizes a set of different conditions that affect the maturation of blood cells. It is a group of bone marrow stem cell malignancies that have a pathogenetic overlap with acute myeloid leukemia, show peripheral blood cytopenias and, in more advanced subtypes, varied degrees of maturation arrest [100]. Both drugs are approved for all subtypes of MDS. Response rates are usually around 30%. The question whether the clinical benefit results more from epigenetic effects and re-activation of silenced maturation factors or more from cytotoxic effects on the immature hyperproliferative cells remains open. 

Mongelard F, Bouvet P (2010) AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. Curr Opin Mol Ther 1 107-114... 

The general approach to the treatment of acute myeloid leukemia has consisted of an anthracycline, usually daunorubicin, and cytarabine induction regimen followed by an intensive post-remission therapy phase most frequently comprising high dose... 

H. Other considerations Neupogen has been designated an orphan product for use in the treatment of neutropenia associated with bone marrow transplant, AIDS patients with CMV retinitis being treated with ganciclovir, severe chronic neutropenia, and acute myeloid leukemia. 

Indications Treatment of patients with CD33 positive acute myeloid leukemia (AML)... 

The thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) were synthesized by Elion and Hitchings in the 1950s, and they play an important part in treatment protocols for leukemia (61,62,63,64). For no other than historical reasons, 6-MP is used in ALL while 6-TG is mainly used in acute myeloid leukemia (AML) or relapsed ALL. First-line treatment for childhood ALL usually includes several cycles of 6-MP at doses of 50-75 mg/m /d, starting as early as in consolidation/early intensification treatment until up to 36 months after diagnosis (1,2,3). 

In June 1999, phase I clinical trials of OTI-010 were initiated in cancer patients receivingchemotherapy and HSC transplantation for the treatment of high-risk hematological malignancies (including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia and non-Hodgkin s lymphoma). The multicenter studies, conducted in seven US and European cancer centers, showed OTI-010 to be safe and efficacious, with 52% of patients ( 40 patients) responding positively to the therapy [327297], [495015]. 

Bennett JM, Kaminski MS, Leonard JP, Vase JM, et al. 2005. Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and Iodine I 131 tositumomab. Blood. 1052 4576-4582. 

Changes in IAP expression modulate apoptotic response to cellular stress. For example, an antisense oligonucleotide developed by Aegera Therapeutics, Inc. (Montreal, Quebec, Canada), AEG35156, reduces expression of XIAP. Treatment with AEG3516 increases apoptosis in studies with myeloid leukemia cells, and the antisense approach currently is in phase Eli clinical trials for refractory AML (acute myeloid leukemia) in combination with chemotherapy (29). The strategy of up-regulating IAP action to inhibit apoptosis has been validated... 

Hiddemann W, Essink ME, Fegeler W, Zuhlsdorf M, Sauerland C, Buchner T. Antifungal treatment by amphotericin B and 5-fluorocytosine delays the recovery of normal hematopoietic cells after intensive cytostatic therapy for acute myeloid leukemia. Cancer 1991 68(1) 9-14. 

Voutsadakis lA. Gemtuzumab Ozogamicin (CMA-676, Mylotarg) for the treatment of CD33-I- acute myeloid leukemia. Anticancer Drugs 2002 13(7) 685-92. 

Although reversible increases in circulating blasts during GM-CSF treatment are sometimes noted and have raised concern on the possible accelerated occurrence of acute leukemia, the progression of myelodysplastic syndromes to acute myeloid leukemia has been only anecdotally reported (SEDA-19, 342) (57). There was no evidence of significant leukemic cell proliferation in patients with acute myeloid leukemia, and no increased... 

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