This clinical trial studies personalized dose monitoring of busulfan and combination chemotherapy in treating patients with Hodgkin or non-Hodgkin lymphoma undergoing stem cell transplant. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's peripheral blood or bone marrow and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Monitoring the dose of busulfan may help doctors deliver the most accurate dose and reduce toxicity in patients undergoing stem cell transplant.

PRIMARY OBJECTIVES:

I. To determine the feasibility of real-time therapeutic dose monitoring (TDM) for once daily intravenously (IV) busulfan administration as part of a preparative regimen for patients with lymphoma undergoing autologous stem cell transplantation.

SECONDARY OBJECTIVES:

I. To compare the incidence of adverse events including mucositis, liver toxicity, seizures, and pulmonary toxicity with TDM of once daily IV busulfan compared to historic controls.

II. To compare the 6-month progression-free survival (PFS), with TDM of once daily IV busulfan compared to historic controls.

III. To determine the proportion of patients who would not have achieved desired busulfan level with weight-based busulfan dosing and therefore required TDM.

OUTLINE:

Patients receive busulfan intravenously (IV) over 3 hours on days -9 to -6, etoposide IV continuously over 24-36 hours on days -5 and -4, and cyclophosphamide IV over 4 hours on days -3 and -2. Patients then undergo autologous stem cell transplant on day 0.

After completion of study treatment, patients are followed up for 6 months.

Inclusion Criteria:

• Patients with either Hodgkin lymphoma or non-Hodgkin lymphoma

• Patients with a previously harvested hematopoietic stem cells while in complete or partial remission, or in the case of patients with stable or refractory disease are undergoing autologous transplantation because it has been recommended by their treating physician as representing their best treatment option with a goal of at minimum of 2 x 10^6 cluster of differentiation (CD)34+ peripheral primed stem cells per kilogram of actual body weight

• Cardiac ejection fraction >= 45% or clearance by Cleveland Clinic (CCF) physician

• Diffusion capacity of the lung for carbon monoxide (DLCO) of >= 45% predicted or clearance by CCF physician

• Serum creatinine < 2.0 mg/dl

• Serum bilirubin < 2.0 mg/dl

• Females of childbearing potential must have a negative pregnancy test

• Patients of childbearing potential must agree to use an effective birth control method

• Patient must not have any other active malignancy (or malignancy must be in remission with no evidence of disease for the past 2 years) excluding nonmelanoma skin cancer

• Patients must have had at least 17 days since their most recent cytoxic chemotherapy or radiation at the time of the initiation of their preparative regimen (day -9)

• Serum glutamic oxaloacetic transaminase (SGOT) < 2 times the normal or clearance by a CCF physician

• Patients who are human immunodeficiency virus (HIV) positive:

  • Patients must be receiving concurrent HAART therapy (highly active antiretroviral therapy)
  • CD4 count must be >= 100/mm^3
  • Viral load must be =< 10,000 copies/ml
  • Patients must not have concurrent opportunistic infections

• There is no restriction on the number of prior chemotherapeutic regimens or radiation exposure with the exception of prior autologous or allogeneic stem cell transplantation

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at time of consent

• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier OR

  • Prior treatment toxicities must be resolved to =< grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

• Patients with uncontrolled seizures as defined by having any seizure activity within the 3 months prior to screening

• Patients who are receiving any other investigational agents

• Patients with untreated brain metastases should be excluded from this clinical trial

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to busulfan other agents used in this study

• Patients receiving any medications or substances that are inhibitors or inducers of specify cytochrome P450 (CYP450) enzyme(s) will be eligible for the study at the discretion of the consenting physician

• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant or breastfeeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with busulfan, cyclophosphamide, and etoposide

• Patients who have had major surgical procedures or significant traumatic injury within 28 days prior to study treatment