Could a stem cell transplant tame VEXAS syndrome?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* INCLUSION CRITERIA: Non-disease related * Age \>= 18-year-old and \<= 75-year-old * Availability of an 8/8 or 7/8 HLA-matched related or unrelated donor, or a haploidentical related donor * Karnofsky performance status of \>= 40% * Adequate end-organ function, defined as follow: 1. Left ventricular ejection fraction \> 35%, preferably by 2-D echocardiogram (ECHO) obtained within 60 days prior to treatment initiation. 2. Creatinine \<= 2.0 mg/dl and creatinine clearance \>= 30 ml/min; 3. Serum conjugated bilirubin \< 3.0 mg/dl; serum ALT and AST \<= 5 times upper limit of normal. * Pulmonary function tests: FEV1 and DLCO \>30% * Ability of subject to understand and the willingness to sign a written informed consent document. * As therapeutic agents used in this trial may be harmful to a fetus, individuals of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry and for at least one-year post-allo HCT. Should an individual become pregnant or suspect they are pregnant while she or her partner is participating in the study, she should inform her treating physician immediately. * Willingness to remain in the NIH hospital or, if discharged, live within 2 hours drive from the NIH, for a minimum of 100 days after transplant or longer, if there are complications. If outpatient in the first 100 days after transplant, participant must commit to having an adult caregiver with them at all times. Disease related * Somatic mutation in UBA1 performed by a CLIA or CAP certified laboratory. NOTE: Participants without a mutation or unknown mutation status may be eligible if they have a clinical history that is characteristic of an individual with VEXAS syndrome including two or more of a-e below. * Inflammatory clinical phenotype for VEXAS syndrome with at least one VEXAS disease manifestation below: 1. constitutional symptoms including fevers, fatigue, and weight loss 2. cutaneous symptoms of VEXAS including biopsy proven neutrophilic dermatosis, cutaneous vasculitis, periorbital inflammation 3. pulmonary symptoms of VEXAS with pulmonary infiltrates, pleural effusion 4. musculoskeletal or cartilaginous involvement including inflammatory arthritis, ear chondritis, and nasal chondritis 5. inflammatory disease in other major organ systems including cardiac, gastrointestinal, ocular, etc. * Presence of cytopenia defined as at least one of the following: i. Absolute neutrophil count \<=1000/ microliter ii. platelet count \<= 75,000/microliter or platelet transfusion dependence (at least 4 platelet transfusions in the 8 weeks prior to study entry iii. hemoglobin \<= 10.0g/dL or red cell transfusion-dependence (at least 4 units of PRBCs in the 8 weeks prior to treatment initiation) or meeting criteria for myeloid neoplasm (MN) by updated 2022 WHO criteria or 2022 International Consensus Classification (ICC) of myeloid neoplasms and acute leukemia OR: -Participants who have failed standard medical management (requiring \>= 0.5mg/kg per day of prednisone for the above listed inflammatory condition or intolerance or refractory to use of corticosteroids and/or steroid sparing medications as well as biological response modifiers over the last 6 months), or when no standard medical treatment is available. EXCLUSION CRITERIA: * HCT Comorbidity Index \>= 5. Note: Comorbidities that are specifically addressed in the inclusion criteria will not be included in the calculation of HCT-CI score. * Participants with multiple myeloma. Note: participants with low risk smoldering multiple myeloma or monoclonal gammopathy of unknown significance will not be excluded) * Participants who are receiving any other investigational agents within the last 30 days before treatment initiation. * HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (steroids, cyclophosphamide, busulfan, tacrolimus, MMF, filgrastim or filgrastim biosimilar) used in the study. * Pregnant individuals are excluded from this study because the study agents have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated with the study agents. * Uncontrolled intercurrent illness or social situations (as determined by a licensed master social worker) that would limit compliance with study requirements. * Presence of active uncontrolled infections that in the opinion of the PI would make it unsafe to proceed with transplantation. * Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol.