Solving Riddles Through Sequencing

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

Inclusion Criteria:

* Patients having been investigated with a suspected hematological disorder and:
* Having unclear diagnosis after internal routine diagnosis
* Unusual clinical course
* Unusual r/r status or non-responder
* Multiple parallel hematological conditions
* Difficult/rare therapy associated/secondary neoplasms
* Current diagnostic workup is not satisfactory in terms of (1) accuracy (2) clinical behavior
* Only samples of patients min. 18 years of age will be used
* Material with a minimum of 20% tumor content in bone marrow or peripheral blood sample
* Patient´s informed consent

Exclusion Criteria:

* Sample is not fit for state-of-the-art diagnosis, fails initial quality control. For quality insurance we will exclude samples with wrong anticoagulant sent. Samples with damage due to meteorological reasons (freeze-thaw damage or elevated temperature) will be excluded.
* Samples with to scarce material jeopardizing routine gold-standard diagnosis will be excluded (tumor content \< 20 %).

Conditions7

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