Solving Riddles Through Sequencing

Condition(s) studied

Investigational drug(s) / intervention(s)

Next Generation Sequencing: NON-Interventional Observation only study comparing sequencing-only approaches to classical diagnostic methods

Study summary

During the last decades hematologists have excelled at improving and refining the classification, diagnosis, and thus ultimately the therapeutic decision-making process for their patients. This continuous evolution proceeded in parallel to seminal discoveries in basic science such as FISH, PCR and NGS. So far, the current WHO classification serves as reference to diagnostic decision making and is largely based on 5 diagnostic pillars: cytomorphology of peripheral blood and/or bone marrow smears, histology and immunohistochemistry of bone marrow trephine biopsies or lymph nodes, immunophenotyping, chromosome banding analysis supplemented by FISH analysis, molecular genetics including PCR and targeted panel sequencing via NGS. This leads to a swift diagnosis in 90 % of all cases. The leftover 10 % remain a challenge for hematopathologists and clinicians alike and are resolved through interdisciplinary teams in the context of specialized boards. With the advent of high throughput sequencing (mainly WGS and WTS) the possibility of a comprehensive and detailed portrait of the genetic alterations - specifically in challenging cases - has become a realistic alternative to classical methods. In SIRIUS the investigators will prospectively challenge this hypothesis to address the question of how often a better or final diagnosis can be delivered by WGS and/or WTS and if unclear cases can be efficiently resolved.

Eligibility

Primary outcome measure(s)

• sequencing only versus gold standard diagnosis — Time Frame of Outcome: At diagnosis for each case/patient throughout the complete duration of study for approximately 1 year.
  The primary endpoint will be assessed as follows: unclear cases will be subjected to three diagnostic algorithms: 1. Inhouse at referring site by histopathological diagnosis in the context of a hematological tumor board according to current standards 2. Current gold-standard diagnostic workup as performed routinely by the MLL 3. WGS and WTS sequencing plus matching to nearest digital sibling in 5,5k cohort We will compare the accuracy for approach #3 for each patient/case by comparing the sequencing results with the therapy guiding approach in domo and Current gold-standard diagnostic workup as performed routinely by the MLL. Accuracy and overlap or discordance will be measured in percentage (%) of total cohort. Time Frame of Outcome: At diagnosis for each case/patient throughout the complete duration of study for approximately 1 year.

Trial sites (1)

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