This phase II trial tests how well ruxolitinib as a maintenance medication works to prevent relapse and graft-versus-host disease (GVHD) for patients who have undergone stem cell transplantation for T-cell lymphoma. GVHD is a common problem that may occur after a blood stem cell transplant. The "graft" is the donor blood cells that patients get during the transplant. The "host" is the person receiving the cells. GVHD is when the donor graft attacks and damages some of the transplant recipient's tissues. Ruxolitinib is a type of drug called a Janus kinase (JAK) inhibitor which works by decreasing the immune response of cells in the body. It is also a cancer growth blocker that blocks the growth factors that trigger the cancer cells to divide and grow. Ruxolitinib works by blocking a gene, called JAK2, that is important in the production of cancer cells.

PRIMARY OBJECTIVES:

I. Determine the effect of ruxolitinib phosphate (ruxolitinib) on relapse at 1-year after autologous (auto) stem cell transplant (SCT) in T-cell lymphoma (TCL).

II. Determine the effect of ruxolitinib on graft versus host disease (GvHD) and relapse free-survival (GRFS) at 1-year for allogeneic (allo) SCT in TCL.

SECONDARY OBJECTIVES:

PRIMARY OBJECTIVES:

I. Determine the effect of ruxolitinib phosphate (ruxolitinib) on relapse at 1-year after autologous (auto) stem cell transplant (SCT) in T-cell lymphoma (TCL).

II. Determine the effect of ruxolitinib on graft versus host disease (GvHD) and relapse free-survival (GRFS) at 1-year for allogeneic (allo) SCT in TCL.

SECONDARY OBJECTIVES:

I. Survival (progression free survival [PFS]/overall survival [OS]) of patients with ruxolitinib maintenance (auto-SCT, allo-SCT, whole cohort).

II. Determine the safety and feasibility of ruxolitinib maintenance post-SCT. III. Determine the effect of ruxolitinib on the cumulative incidence (CI) of grade II-IV acute GVHD (alloSCT), chronic extensive GVHD, non-relapse mortality (NRM) (auto-SCT and allo-SCT).

EXPLORATORY OBJECTIVES:

I. Determine the effect of maintenance ruxolitinib compared to matched historical controls using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry.

II. Determine the effect of ruxolitinib on immune modulation and reconstitution post-allo-SCT and upon disease relapse.

OUTLINE:

Starting day +35 to day +120 post-SCT, patients receive ruxolitinib orally (PO) twice daily (BID) on days 1-30 of each cycle. Cycles repeat every 30 days for 1 year post-SCT, in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)-computed tomography (CT) scan and blood sample collection throughout the study. Patients may undergo bone marrow biopsy and/or tissue biopsy throughout the study, at time of progression.

After completion of study treatment, patients are followed up at 18 and 24 months then yearly until 5 years and at progression.

Inclusion Criteria:

1. Adult patients with T-cell lymphoma [PTCL (all subtypes), T-PLL, ATLL, and CTCL (all subtypes)] in partial or complete remission between day +35 and +120 from auto-SCT or allo-SCT
2. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
3. Adequate hematologic function defined by absolute neutrophil count (ANC) > 1000/mm3 without granulocyte colony-stimulating factor (G-CSF) for at least 3 days, platelets > 50K/mm3 without transfusion for at least 3 days and hemoglobin (Hb) > 8.0 g/dL without transfusion for at least 3 days.
4. Adequate organ function defined by total Bilirubin < 1.5 x ULN, alanine aminotransferase (ALT) </= 3 x ULN, CKD-EPI eGFR ≥ 30 ml/min, SpO2 > 92% without supplemental oxygen.
5. Able to tolerate oral or enteral medications.
6. Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.
7. Able to read and sign informed consent.

Exclusion Criteria:

1. Anaplastic lymphoma kinase (ALK)+ or Dual specificity 22 (DUSP22)+ ALCL with low international prognostic index (IPI) score (<2) in first complete remission.
2. Progressive disease or any other systemic therapy post-SCT (radiation allowed)
3. Disease progression to Ruxolitinib previously
4. GvHD requiring systemic therapy.
5. Active uncontrolled infections.
6. Active thrombotic active microangiopathy requiring therapy.
7. History of veno-occlusive disorder post-transplant
8. Use of platelets antiaggregant or anticoagulants deemed to be unsafe to be held in case of thrombocytopenia.
9. History of life-threatening bleeding defined as any bleeding that required invasive procedures or involving central nervous system.
10. Pregnancy (positive Beta HCG test in a woman with childbearing potential defined as not postmenopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
11. Uncontrolled Hepatitis B/C, HIV, tuberculosis, mycobacterium, or fungal infection.
12. Exposure to other investigational drugs within 4 weeks before enrollment.
13. Grade ≥ 3 non-hematologic toxicity from SCT that has not resolved to grade ≤ 2.
14. Myocardial infarction or stroke within 1 year of study entry.
15. Any uncontrolled medical problem at the discretion of the investigator that would pose a risk to the patient.