• Previously untreated biopsy-confirmed CD20-positive monomorphic post-transplant lymphoproliferative disorder (or CD20-positive lymphoma associated with immune deficiency) arising after solid organ or hematopoietic stem cell transplant. This may be defined by either the 2016 World Health Organization classification of lymphoid neoplasms or the 2022 International consensus Classification of Mature Lymphoid Neoplasms or the 2022 World Health Organization classification.

• At least 18 years of age.

• ECOG performance status ≤ 3.

• Adequate hematologic and organ function (unless due to underlying lymphoma per the investigator) as defined below:

‣ Absolute neutrophil count ≥ 1.0 K/cumm

⁃ Platelets ≥ 75 K/cumm

⁃ Hemoglobin ≥ 8.0 g/dL

⁃ Total bilirubin \< 1.5 x IULN

⁃ AST(SGOT)/ALT(SGPT) \< 2.5 x IULN

⁃ Creatinine clearance \> 30 mL/min measured or by Cockcroft-Gault

• Note: Patients with extensive bone marrow involvement by lymphoma and/or disease-related cytopenias may be enrolled if the following criteria are met:

‣ ANC ≥ 0.5 K/cumm

⁃ Platelets ≥ 50 K/cumm

⁃ Hemoglobin ≥ 7.0 g/dL

• The effects of polatuzumab vedotin and rituximab on the developing human fetus are unknown. For this reason, 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 participant become pregnant or suspect pregnancy while participating in this study, the participant must inform the treating physician immediately.

• Ability to understand and willingness to sign an IRB approved written informed consent document.