Low-Dose Aldesleukin and Extra-Corporeal Photopheresis in Treating Patients with Steroid-Refractory Chronic Graft-versus-Host Disease

Inclusion Criteria

• Recipients of 7-8/8 human leukocyte antigen (HLA) matched adult donor allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
• Participants must have steroid-refractory cGVHD; steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms; patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible
• Stable dose of corticosteroids for 4 weeks prior to enrollment; exception permitted with overall principal investigator (PI) approval
• No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4 weeks prior to enrollment; the dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
• Estimated life expectancy greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Total bilirubin < 2.0 mg/dl-exception permitted in patients with Gilbert’s syndrome
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x upper limit of normal [ULN]), unless hepatic dysfunction is a manifestation of presumed cGVHD
• For patients with abnormal liver function tests (LFTs) as the sole manifestation of cGVHD, documented GVHD on liver biopsy will be required prior to enrollment; abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD, and a liver biopsy will not be mandated in this situation
• Serum creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• Forced expiratory volume in one second (FEV1) >= 50% or diffusing capacity of the lungs for carbon monoxide (DLCO) (hemoglobin [Hb]) >= 40% of predicted, unless pulmonary dysfunction is deemed to be due to chronic GVHD
• Absolute neutrophil count (ANC) > 1000/mm^3 without growth factors or transfusions
• Platelets > 50,000/mm^3 without growth factors or transfusions
• No myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
• The effects of IL-2 on the developing human fetus are unknown; for this reason and because chemotherapeutic agents are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
• Concurrent use of calcineurin-inhibitors plus sirolimus; either agent alone is acceptable
• History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
• Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
• Extra-corporeal photopheresis (ECP) or rituximab therapy within 4 weeks prior to enrollment
• Any contraindication to ECP, i.e. contraindication to heparin or methoxsalen (8-MOP)
• Post-transplant exposure to any novel immunosuppressive medication (e.g., alemtuzumab) within 100 days prior to enrollment
• Donor lymphocyte infusion within 100 days prior to enrollment
• Active malignant relapse
• Active uncontrolled infection
• Inability to comply with IL-2 treatment regimen
• Uncontrolled cardiac angina or symptomatic congestive heart failure (NYHA class III or IV)
• Organ transplant (allograft) recipient
• Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic hematopoietic Stem cell transplantation (HSCT); in addition, these individuals are at increased risk of lethal infections; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
• Individuals with active hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after HSCT
• Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the Principal Investigator
• Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued