Myelofibrosis and the MAGIC risk assessment tool

MAGIC, the Myelofibrosis Assessment Graphic Internet Calculator,  is a convenient and graphic means to summarize broad clinical experience in assessing MF overall risk-associated survival times.

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 MAGICresults 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.

MAGIC is an upgrade of the original Spectrum Stem Cell Transplantation Tool designed to help high risk MF patients determine optimal SCT timing. This upgrade incorporates a mutational status component.

The Mutational Component 

MAGIC provides the option for patients to select their known current MPN mutations. Calculation of the weight of these mutational selections is not incorporated within MAGIC which currently relies only on the clinically validated DIPSS scales to determine Risk Levels and Overall Survival averages.  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)