Tumor-Specific Clonotype, Metabolic Profile, and PET/CT in Predicting Chemotherapy Response in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Inclusion Criteria:

* Subject/legal representative willing and able to provide written informed consent
* Histologically confirmed aggressive B-cell DLBCL, including follicular lymphoma (FL) transforming to DLBCL and high grade B-cell lymphoma
* Willing to provide existing relapse-confirmatory DLBCL tumor sample
* Relapsed from or refractory to at least one treatment containing a CD20 monoclonal antibody combined with anthracycline-based chemotherapy
* CT scans showing involvement of 1 or more clearly demarcated lesions with a long axis \> 1.5 cm and short axis \>= 1.0 cm
* Baseline FDG-PET/CT scans must demonstrate at least one hypermetabolic lesion as defined by the Deauville criteria localizing to CT-defined anatomical tumor sites
* Suitable candidate for therapy with standard salvage chemotherapy and autologous stem cell transplant (ASCT) as determined by the treating physician
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Life expectancy of \>= 12 weeks as estimated by the treating physician
* Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
* Hemoglobin \>= 8.5 g/dL
* Absolute neutrophil count (ANC) \>= 1500/mm\^3
* Platelet count \>= 75,000/mm\^3
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 x institutional upper limit of normal (ULN) for cases involving liver metastasis and =\< 3 x institutional ULN for all other cases
* Bilirubin =\< 2 x ULN (unless related to lymphoma) or =\< 5 x ULN for subjects with documented or suspected Gilbert's disease
* Serum creatinine =\< 1.5 x ULN or calculated creatinine clearance (CrCl) \>= 50 mL/min as determined by the Cockcroft-Gault equation

Exclusion Criteria:

* Any condition that, in the opinion of the investigator, would interfere with the interpretation of study results or subject safety including non-malignant FDG avid diseases such as sarcoidosis or other granulomatous disease
* Uncontrolled diabetes mellitus
* Concurrent enrollment in another clinical study where they are receiving non-standard salvage chemotherapy, (i.e., concurrent enrollment is allowable if the patient is receiving standard salvage chemotherapy and research imaging is allowed)
* Any chemotherapy, radiotherapy, immunotherapy, biologic, or investigational therapy for treatment of lymphoma within 14 days prior to treatment
* Symptomatic congestive heart failure