Patient description: The patient is a 23-year-old man who came to the hospital with high blood pressure (175/95 mmHg) and signs of septicemia. He developed respiratory failure requiring mechanical ventilation and renal failure requiring hemodialysis. His blood smear showed microangiopathic hemolytic anemia and thrombocytopenia. His blood tests revealed elevated lactate dehydrogenase and reduced human complement C3 levels with a normal coagulation profile. He was diagnosed with atypical hemolytic uremic syndrome. He was treated with plasma exchange and corticosteroids. He has been previously vaccinated with meningococcal group ACWY conjugate vaccine and meningococcal group B vaccine. The genetic survey revealed ADAMTS13 >10%.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic Adult subjects ≥18 years of age who are able to understand and comply with study procedures, and provide written informed consent before any study-specific procedure Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification Performance status (ECOG) of 0-2 Previously treated MDS or CMML, defined as prior treatment with at least one hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high risk MDS or CMML whose disease progressed or relapsed as follows: 1. Subject received HMA for at least 6 cycles and was still transfusion dependent (as defined in 5b below). 2. Subject had disease progression prior to Cycle 6 defined as ≥50% increase in bone marrow blasts from pretreatment levels to >5%, or ≥2 g/dL reduction of Hgb from pretreatment levels with transfusion dependence after at least 2 cycles of HMA. Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed Subjects must have either: 1. Bone marrow blasts >5% at randomization, OR 2. Transfusion dependence, defined as having had transfusion (in the setting of active disease) of 2 or more units of RBC or platelets within 8 weeks prior to randomization Creatinine clearance or glomerular filtration rate ≥30 mL/min estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration) Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child while receiving treatment with guadecitabine, LDAC, or IC and for at least 3 months after completing treatment  Subjects who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20% Subjects who may still be sensitive to repeated treatment with decitabine or azacitidine such as subjects who had response to prior decitabine or azacitidine treatment, but relapsed >6 months after stopping treatment with these agents Prior treatment with guadecitabine Hypersensitivity to decitabine, guadecitabine, or any of their excipients Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy Treated with any investigational drug within 2 weeks of the first dose of study treatment Total serum bilirubin >2.5 ULN (except for subjects with Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol Refractory congestive heart failure unresponsive to medical treatment, active infection resistant to all antibiotics, or advanced non-MDS associated pulmonary disease requiring >2 liters per minute oxygen