Combining Active and Passive DNA Hypomethylation

Prior treatment

• Patient eligible for allogeneic stem cell transplantation
• Prior therapy with hypomethylating agents
• Any matter constituting an exclusion criterion for treatment with azacitidine
• Therapeutic radiation or chemotherapy within the past 6 months
• Unwillingness to discontinue any and all use of vitamin C medication/supplementation including multivitamin at least 3 days (but preferably longer) prior to inclusion and baseline sampling
• Planned azacitidine treatment after allogeneic stem cell transplantation

Other illness

• History of allergic reactions to ascorbic acid
• History of kidney or urinary tract stones requiring intervention within the past year

Lab values

• Patient receiving other active cancer treatment, including investigational agents, with the exception of hydroxyurea for white blood cell (WBC) control, G-CSF, and low permanent doses of steroid (≤ 25 mg oral prednisolone per day) for inflammatory disorders
• Uncontrolled comorbidity including impaired hepatic function (total serum bilirubin \>1.5 × upper limit of the normal range (ULN), serum alanine transaminase \>3 × ULN, chronic hepatitis with decompensated cirrhosis), disabling psychiatric disease, severe neurologic disease, severe metabolic disease, or severe cardiac disease (NYHA class 3-4)

Other

• Lack of ability to understand the information given, or lack of willingness to sign a written informed consent document
• Unwillingness to comply with the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status ≥3

• Patients eligible for treatment with azacitidine with one of the following diagnoses according to World Health Organization 2016:
• MDS Higher-risk MDS according to the IPSS-R, i.e., intermediate- to very high-risk (IPSS-R score \> 3)
• CMML CMML with 10-29 percent marrow blasts without myeloproliferative disorder
• AML AML with 20-30 percent blasts (low-blast count AML)
  • Note: Patients with therapy-related MDS are eligible if they have not received radiation or chemotherapy for six months.