The goal of this observational study is to correlate molecular alterations with outcomes including overall survival (OS), progression-free survival (PFS), response rates for patients with a new diagnosis, primary refractory or relapse, of mature T-cell and NK-cell neoplasms (TNKL). We hypothesize that machine learning can be leveraged to uncover distinct genetic vulnerabilities that underlie treatment response and resistance for patients with TNKL, thus moving towards personalized treatment solutions.

This study is a prospective, longitudinal observational study of patients with newly diagnosed or relapsed/refractory T-cell and NK-cell neoplasms, conducted across multiple participating institutions globally. Patients will be enrolled during their initial visit as new patients and will be followed for up to four years through the course of their clinical management. Data for routine demographics, baseline clinical features, including pathology, molecular information related to the tumor, radiology, treatment characteristics and quality of life (QoL) associated with their lymphoma care will be collected over the course of 4 years by clinical research teams at every participating institution. The de-identified data will be securely shared through a password protected REDCap with other participating institutions under data usage agreements of the consortium. Next generation sequencing (NGS) including but not limited to whole exome sequencing and bulk RNA-sequencing will be performed on archived lymphoma specimens, mononuclear cells, cfDNA and saliva (when feasible) for a comprehensive molecular characterization of the tumor. Molecular data will be analyzed in correlation with patient outcomes. Advanced deep learning algorithms will be applied to predict responses and survival across lymphoma subtypes, heterogeneous clinical scenarios and various potential therapeutic approaches that the patient has not been exposed to.

Inclusion Criteria:

• Untreated, relapsed, or refractory histologically confirmed mature T-cell or NK-cell neoplasm.
• All subtypes of PTCL are eligible except for T-cell large granular lymphocytic leukemia, cutaneous T-cell lymphoma such as but not limited to mycosis fungoides and transformation, Sézary syndrome, and primary cutaneous CD30+ disorders.

Exclusion Criteria:

• Precursor T/NK neoplasms, T-cell large granular lymphocytic leukemia, cutaneous T-cell lymphoma such as but not limited to mycosis fungoides and transformation, Sézary syndrome, and primary cutaneous CD30+ disorders.
• Adults who are unable to consent, individuals who are not yet adults such as infants, children and teenagers, pregnant women, and prisoners.

This is a prospective observational non-interventional study with the primary objective to define overall survival and time to next treatment, as well as determining the ability to bridge patients to stem cell transplantation for patients with a new diagnosis, primary refractory or relapse of T-cell or NK-cell neoplasm.