Tagraxofusp in Treating Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm After Stem Cell Transplant

Inclusion Criteria:

* Eligible patients will be aged \>= 18 years. Pediatric patients age 2 years and older will be considered on a case by case basis.
* Diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) according to World Health Organization (WHO) classification or confirmed by hematopathology
* The patients must be in partial response or better
* \> 30 days post-transplant without active or chronic infections
* Karnofsky performance status \>= 60%; Lansky \>= 60
* Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal by multigated acquisition (MUGA) scan or echocardiogram within 30 days of first protocol treatment
* Diffusion capacity of the lung for carbon monoxide (DLCO) \> 40% of predicted value (corrected for hemoglobin) within 3 months of registration
* Forced expiratory volume in 1 second (FEV1) \> 40% of predicted value within 3 months of registration
* Forced vital capacity (FVC) \> 40% of predicted value within 3 months of registration
* Serum creatinine =\< 1.5 mg/dL (133 mmol/L)
* Serum albumin \>= 3.2 g/dL (or \>= 32 g/L) without IV albumin within the previous 72 hours
* Bilirubin =\< 1.5 x the upper limit of normal (\[ULN\] except patients with Gilbert syndrome in whom bilirubin level of \> 1.5 x ULN will be allowed)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times ULN
* Hemoglobin \>= 8 g/dL with or without transfusion in the last 7 days
* Absolute neutrophil count (ANC) \>= 1000 without granulocyte colony stimulating factor (GCSF) or granulocyte-macrophage colony-stimulating factor (GMCSF) in the last 2 weeks prior to screening
* Platelets \>= 50,000micro/mL
* For allo-HCT, no \>= grade 2 visceral (gut or liver) acute graft versus host disease (GVHD) and no \>= grade 3 or any other acute GVHD (patients with chronic GVHD will be allowed at the discretion of the investigator)
* Patient agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 2 months after the last tagraxofusp infusion
* Woman of child bearing potential (WOCBP) with a negative serum or urine pregnancy test within 14 days of tagraxofusp treatment
* Patient or patient's legal representative, parent(s) or guardian able to sign informed consent
* The patient can adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment

Exclusion Criteria:

* The patient has persistent clinically significant non-hematologic toxicities \>= grade 2 (excluding alopecia, nausea, and fatigue)
* Evidence of central nervous system (CNS) involvement
* Uncontrolled and active pulmonary disease
* Requirement for oxygen treatment
* Receiving chemotherapy, radiotherapy or other anti-cancer therapy within 14 days of first dose of study drug. There must be at least a 6-week interval from the last immunotherapy therapy
* Uncontrolled infection
* Human immunodeficiency virus (HIV)/hepatitis B and/or C
* Any history of invasive malignancy in the last 2 years excluding any malignancy such as cervical cancer or skin cancer (excluding melanoma) that is considered cured at the time of screening
* Pregnant or breast-feeding woman
* Patient has uncontrolled intercurrent illness or medical/psychiatric condition that would limit compliance with study requirements or that would in the investigator's opinion place the patient at an unacceptably high risk for toxicities
* Clinical significant cardiopulmonary disease including uncontrolled or New York Heart Association (NYHA) class 3 or 4 congestive heart failure, uncontrolled angina, uncontrolled hypertension, uncontrolled arrhythmia, myocardial infarction or stroke within 6 months of first protocol treatment or corrected QT (QTc) \> 480 ms