Luspatercept With or Without Hydroxyurea for the Treatment of Myelodysplastic/Myeloproliferative Neoplasms With Ring Sideroblasts and Thrombocytosis or Unclassifiable With Ring Sideroblasts

Inclusion Criteria: * Age \>= 18 years * Patients with a World Health Organization(WHO)-defined diagnosis of MDS/MPN-RS-T or MDS/MPN-U with \>= 15% RS * Prior treatment with lenalidomide, hypomethylating agents, immunosuppressive therapy, erythropoietin stimulating agents (ESA) or investigational agent is allowed as long as patients have not received luspatercept-aamt or sotatercept. If there is prior history of investigational agent, there should be an interval equivalent to at least four elimination half-lives of the agent prior to enrollment. Note: For patients who have received prior lenalidomide, hypomethylating agents, or immunosuppressive therapy, there must be \>= 6 weeks since the last dose before luspatercept-aamt treatment is started * Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2 * Requirement of red blood cell transfusions (\>= 2 unit =\< 8-weeks prior to registration) OR symptomatic anemia with hemoglobin \< 9.5 g/dL OR hematocrit \< 30% (as long as there is documentation of adequate iron stores (ferritin \> 50 mg/L) =\< 5 weeks prior to registration). Symptomatic anemia is defined as fatigue with or without exertion, shortness of breath with or without exertion, or decrease in exercise tolerance * Hemoglobin =\< 9.5 g/dL (obtained =\< 14 days prior to registration) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration) * Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< …