Myeloproliferative Neoplasm (MPN) and the MAGIC risk assessment tools

MAGIC, the MPN Assessment Graphic Internet Calculator,  is a convenient and graphic means to summarize broad clinical experience in assessing overall risk-associated condition for myelofibrosis, polycythemia vera and essential thrombocythemia.

For Myelofibrosis

MAGIC relies on two commonly used and validated scales developed by the International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). Together, the DIPSS (Dynamic International Prognostic Scoring System) and the DIPSS + assess the degree of myelofibrosis risk.*

There are four MF Risk Levels (Low, Intermediate-1, Intermed-2, and High) Each Risk Level carries a mean approximation of overall survival (OS) expressed in years and months. The OS is only a guideline.   Mean survival is the midpoint between the number of those who will live longer and those who will die earlier.”

Myelofibrosis is a complex and still largely unexplored disease whose etiology and progression is only partially understood. Beyond the clinical elements measured by our scales, some factors influencing survival include genetics, environment, co-morbidities, diet, lifestyle, epigenetics, geography, occupation, and , emotional, social and psychological elements.

The MAGIC results are significant , however, in revealing a patient’s underlying general risk status and can serve as a guide to undertake minimal or more aggressive therapies.

 

For Polycythemia Vera, Essential Thrombocythemia and MF.

MAGIC includes reference to two clinically validated patient reported symptom scales, the MF-SAF and the MPN-SAF TSS, the myelofibrosis symptom assessemenz form and the MPN symptom assessment form — Total System Score.

A brief history of the symptom burden assessment tools,  along with sample forms, test scoring procedures and links to updates can be found here:

The Mutational Component 

MAGIC provides the option for patients to select their known current MPN mutations. Calculation of the relative weight of these mutational selections has not been clinically validated.  MAGIC  currently relies only on the clinically validated DIPSS scales and the MPN-SAF to determine Risk Levels and Overall Survival averages for myelofibrosis and the MPN-SAF TSS scale for PV and ET.

The mutational landscape however provides vital prognostic information that may be applicable to selection of therapeutic options.  In addition to the Notes on Individual Mutations included in the MAGIC text,  links to new on-line calculators that do incorporate clinical, cytogenetic and mutational data are provided. Two of the most promising instruments that have already published results of extensive testing are the MIPSS70  and MIPSS70+ (P. Guglielmelli et al., Journal of Clinical Oncology, 2017.) and the MPN Personalized Risk Calculator (J. Grinfeld et al. New England Journal of Medicine, 2018).

Much has been learned about the role mutations play in the creation and driving of myeloproliferative neoplasms. Two recent studies – Vainchenker, Kralovics et al. and Grinfeld, Nangalia, et al. – were a primary basis for selecting commonly occurring driving and passenger mutations. And while there are both deadly and relatively benign mutations there remains some question as to the specific impact of any individual mutation. However, the presence of multiple mutations arising in an unstable genetic environment that includes MPN driving mutations generally predicts poor outcomes.

Three known MPN driving mutations – JAK2, CALR and MPL – are indicated in the tool’s graphic display with large, red markers. All other mutations are given equal weight although some are known to participate more often in progression to AML and others are more benign. Details and a full listing of all these mutations notes can be found in Notes on MPN Mutations an integral resource for MAGIC .

The real value of the MAGIC calculator lies in sharing its results with the patient’s hematologist as an aid to developing an optimal treatment plan. If genomic testing has not yet been done and mutational load is unknown MAGIC will still yield significant Risk Level Results.


  • DIPSS: This model considers age older than 65 years, hemoglobin level lower than 10 g/dL, white blood cell count more than 25 × 109/L, peripheral blood blasts equal to or higher than 1%, and constitutional symptom.
  • DIPSS+ is a scale that adds three additional factors: platelet levels, transfusion dependence, and chromosome abnormalties (Karyotypes)