Where does it hurt?
When you get right down to it, myeloproliferative neoplasms (MPNs) may involve complex hematopoietic events but for patients, MPNs are about symptoms.
Symptoms are what drive patients to the doctor’s office for diagnosis. The progression or reduction of symptoms indicates whether therapy is working or not. Symptoms can affect physical abilities, emotional and psychological state, social interactions and overall quality of life.
Some symptoms are annoying, some like fatigue, bone pain, weight loss can be indicative of something more serious. The question is which MPN symptoms are most significant. And how can we determine their relative impact on our quality of life.
Until recently, even though examining physicians listened to patient reported symptoms, the real determination of n MPN phenotype staget a precise level was dependent on lab results, bone marrow biopsy, and genetic testing.
Patient Reported Symptoms: The Evolution from Fatigue to Myelofibrosis to Myeloproliferative Neoplasm
The history of symptom stratification to determine relative severity of an MPN with clinically tested precision has a long history. An early attempt leading to our current assessment scales is the Brief Fatigue Inventory developed at MD Anderson in 1999. The Mayo Clinic expanded on this work in a pivotal 2006 publication, (The Burden of Fatigue and quality of life in myeloproliferative disorders , (MPDs) In this Mayo Clinic work, a leading MPN patient and advocate, Joyce Niblack, was a driving force.
The first formal full MPN symptom assessment form (MFSAF) was published in Leukemia Research in 2009, debuting as “an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis,
Drawing on that experience, , two years later , Dr. Robyn Scherber and the Dr. Ruben Mesa group at the Mayo Clinic in Scottsdale, Arizona, tested their 18 item MPN symptom assessment instrument, 
including the Brief Fatigue Inventory, against an international cohort of 402 patients. Their findings:”The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): International Prospective Validation and Reliability Trial in 402 patients | Blood | American Society of Hematology (ashpublications.org) THE MPN-SAF correlated strongly with existing clinical responses and “The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally.”
The Mayo Clinic (Phoenix) group set out to produce a short form questionnaire that would aid physicians and patients figure out where they were along the continuum of symptomatic response to MPNs. If successful that tool could help drive the choice of therapeutic interventions and monitor patient progress.
The result, published in 2012, was a 10 question plain English form, the MPN Symptom Assessment Form Total System Score (MPN-SAF TSS). This new instrument derived from the original 18 symptom MPN-SAF, took the nine most clinicnally relevlant symptoms plus a BFI question. Subjected to rigorous international testing of 1408 patients across the three WHO-identified MPN groups – essential thrombocythemia (ET), polycythemia vera (PV) . and myelofibrosis (MF), the MPN-SAF TSS showed remarkable correlation with two previously validated QOL scales. As anticipated, MPN-SAF TSS scores were progressively higher in the more acute MPNs.
What’s your number?
The MPN-TSS is computed as the average of the observed items multiplied by 10 to result in a possible range of 0-100 where 0 represents no issue and 10: worst imaginable. The tool is designed to provide a fast and accurate assessment of the severity of MPN symptons in order to track the progress of disease and provide guidance for therapeutic intervention.
A sample of the MPN-SAF-10 TSS you can try out is at The Hematologist.
Originally the 10 question TSS was graded on a three level scale assessing Quality of life. Scoring a mean of 4 of ean indicated low level impacts, 6 of 10, Moderate and 7 of 10 Severe. Subsquent research produced more nuanced scales. Here are three key documents for details and deeper study:
(1) Symptom burden as a driver for therapy
(2) MPN SAF Symptom Response Thresholds (e.g., Quartiles abstract
This is the analysis that looked at the different quartiles (Overall MPN-SAF TSS scores of 0 – 7 were designated as Q1, 8 – 17 as Q2, 18 – 31 as Q3, and ≥ 32 was as Q4.). According to Dr. Scherber, “This is a much better way to look at scores rather than some other arbitrary “low, int, high” type scale.”
(3) Determining meaningful change in MFSAF