* INCLUSION/EXCLUSION CRITERIA:
Participants of both sexes will be considered for inclusion in this study. There will be no racial, ethnic, or sex discrimination. To be eligible to participate in the treatment portion of this study, an individual must meet all of the following inclusion criteria and none of the following exclusion criteria:
INCLUSION CRITERIA:
ALL COHORTS:
* Ability of the participant or legally authorized representative (LAR) to understand and be willing to sign a written informed consent document
* Age 18 or older
* For females of childbearing potential, stated willingness to use an accepted method of contraception for the duration of the study. Accepted methods of contraception are:
* Total abstinence
* Use of an implanted or intrauterine hormonal device for at least 30 consecutive days before study drug administration
* Use of oral, patch or injectable contraceptives or a vaginal hormonal device for at least 30 consecutive days before study drug infusion
* Use of a non-hormonal intrauterine device for at least 30 consecutive days before study drug administration
* Two barrier methods such as a diaphragm with spermicide or a condom with spermicide
* For sexually active males with a female partner of childbearing potential, stated willingness to agree to use a condom with spermicide for the duration of the study.
* Diagnosis of immune bone marrow failure (see specific cohort)
COHORT 1: RELAPSED/REFRACTORY SAA:
Meet all 3 criteria below:
Severe aplastic anemia\*:
-Bone marrow cellularity \<30% excluding lymphocytes
AND
At least two of the following:
* Absolute neutrophil count \< 0.5 x 10\^9/L
* Platelet count \< 20 x 10\^9/L
* Absolute Reticulocyte count \< 60 x 10\^9/L
* Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
* Not suitable for transplant due to age, co-morbidities, lack of suitable donor, or participant choice.
* Patients who have a documented historic diagnosis of SAA and have received an ATG-based therapy in the past and are now relapsed / refractory may be included in this cohort even if documentation of original CBC and bone marrow are unavailable.
COHORT 2: RELAPSED/REFRACTORY MODERATE AA:
Moderate AA:
* Aplastic anemia (hypocellular bone marrow for age) with no evidence for other disease processes causing marrow failure, and depression of at least two out of three blood counts below the normal values but not fulfilling the criteria for SAA:
* Absolute neutrophil count \<= l.2 x 10\^9/L
* Platelet count \<= 70 x 10\^9/L
* Anemia with hemoglobin \<= 9 g/dL and absolute reticulocyte count \< 60 x 10\^9/L or transfusion dependence
* Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
COHORT 3: RELAPSED/REFRACTORY UNILINEAGE BONE MARROW FAILURE DISORDERS:
Cytopenia in lineage as below:
-Erythroid lineage: Hemoglobin \<= 9 g/dL and reticulocyte count \< 60 x 10\^9/L or red cell transfusion dependence and bone marrow with absent or reduced red cell precursors
OR
Platelet lineage: Thrombocytopenia \<= 30 x 10\^9/L or platelet transfusion dependence and bone marrow with absent or reduced megakaryocytes
OR
Granulocyte lineage: Neutropenia \<= 0.5 x 10\^9/L and bone marrow for with absent or reduced granulopoiesis
* No evidence of viral or drug suppression of the marrow, T-LGL, dysplasia, or underproduction anemias secondary to B12, folate, iron or other reversible causes.
* Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
COHORT 4: RELAPSED/REFRACTORY T-LGL WITH CYTOPENIAS:
* Clinical history supportive of the diagnosis of T-LGL leukemia (i.e., a history of cytopenias with peripheral blood morphologic evidence of LGLs).
* Immunophenotypic studies of peripheral blood showing an increased population of T-LGLs (suggested by staining with CD3+, CD8+ and CD16+ or CD57+) or gamma-delta T cells.
* Restricted or clonal rearrangement of the T-cell receptor by PCR
AND cytopenia as follows:
Severe neutropenia (\< 0.5 x 10\^9/L);
OR
Severe thrombocytopenia (\<= 20 x 10\^9/L), or moderate thrombocytopenia (\<= 50 x 10\^9/L) with active bleeding;
OR
Symptomatic anemia with a hemoglobin \<= 9 g/dL or red blood cell transfusion dependence
-Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
COHORT 5: HYPOPLASTIC MDS:
-A diagnosis of hypoplastic MDS by WHO 2016, WHO 2022, or ICC criteria with significant cytopenias defined as:
Bone marrow hypocellular for age
AND
Either morphologic dysplasia or cytogenetic abnormality
AND
At least one of the following:
* Neutropenia: Absolute neutrophil count \< 0.5 x 10\^9/L
* Thrombocytopenia: Platelet count \< 30 x 10\^9/L or platelet transfusion dependence
* Anemia: Hemoglobin \< 9g/dL or red cell transfusion-dependence or absolute reticulocyte count \<60 x 10\^9/L
* Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
* Known diagnosis or high suspicion of constitutional marrow failure syndrome
* Evidence of a clonal disorder with poor risk cytogenetics per R-IPSS criteria involving chromosome 7 (-7del/-7), chromosome 3 (inv 3/del3/t(3)) or three or more chromosomal abnormalities (complex)
* MDS with EB-1, EB-2, AML, chronic myelomonocytic leukemia (CMML), MDS/MPN
* For MDS: Has received hypomethylating agent, chemotherapy, or immunomodulatory therapy within 8 weeks prior to study entry
* History of progressive multifocal leuko-encephalopathy (PML)
* Infection not adequately responding to appropriate therapy
* Participants with untreated or poorly controlled HIV, Hepatitis B or C
* Participants with cancer who are on active chemotherapeutic treatment
* Presence of severely impaired renal function defined by CrCl (as calculated by eGFR) less than 15 mL/min not requiring renal dialysis
* Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during this study
* Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the participant s ability to tolerate protocol therapy, or that death within 7-10 days is likely
* Inability to understand the investigational nature of the study or to give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent
* Hypersensitivity to ruxolitinib or its components
* Inability to swallow pills
* Currently breastfeeding
* Active non-melanoma skin cancer
* Acute thrombosis (myocardial infarction, ischemic heart disease requiring stents, stroke, pulmonary embolism, or deep venous thrombosis) within the last 6 months
* Patients with a PNH clone \>50% who are not taking anticoagulation or anticomplement therapy
