• Documented informed consent of the participant and/or legally authorized representative

‣ Assent, when appropriate, will be obtained per institutional guidelines

⁃ For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening, while the request for a translated full consent is processed

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

‣ If unavailable, exceptions may be granted with Study principal investigator (PI) approval

• Age: \>= 18 years

• Karnofsky Performance Scale (KPS) \>= 70

• Life expectancy \>= 16 weeks at the time of enrollment

• Prior allogeneic transplant allowed if \> 6 months prior to study enrollment

• Participant must have a confirmed diagnosis of active CD33+ AML de novo, or secondary OR participants who are at a high risk for disease recurrence

‣ Relapsed AML is defined as patients that had a first complete response (CR) before developing recurrent disease (increased bone marrow blasts)

⁃ Refractory AML is defined as patients that have not achieved a first CR after induction chemotherapy. For patients with AML evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy

• Research participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML

‣ CD33 positivity must be confirmed by either flow cytometry or immunohistochemistry within 90 days of study entry. Cytogenetics, flow cytometry, and molecular studies (such as FLT-3 status) will be obtained as per standard practice

⁃ Research participants who are at a high risk of disease recurrence, they must have historical bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML

• No known contraindications to lymphodepleting agents, steroids, tocilizumab and/or cetuximab, or the investigational agent

• Total serum bilirubin =\< 2.0 mg/dL

• Participants with Gilbert syndrome may be included if their total bilirubin is =\< 3.0

• Aspartate aminotransferase (AST) =\< 3 x the upper limit of normal (ULN)

• Alanine aminotransferase (ALT) =\< 3 x ULN

• Estimated creatinine clearance of \>= 60 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis

• Left ventricular ejection fraction \>= 50% within 8 weeks before enrollment

• Oxygen (O2) saturation \> 92% not requiring oxygen supplementation

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy

‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

• Research participants must have a potential donor or stem cell source identified for allogeneic transplantation, either related (7/8 or 8/8 allele matched or haploidentical)

• DONOR: The identified donor must be the original donor whose stem cells were used for the research participant's allogeneic hematopoietic stem cell transplantation (alloSCT)

• DONOR: The donor must be HIV negative

• DONOR: KPS \>= 70

• DONOR: Documented body weight