Phenotypic Differences amongst Subgroups of Patients with Myelofibrosis with Myeloid Metaplasia (MMM): Analysis of 458 MMM Patients.
Authors: Mesa Ruben , Niblack Joyce , Verstovsek Srdan , Barnes Sunni , Tan Angelina , Atherton Pamela , Sloan Jeffrey , Tefferi Ayalew 
Published: April 2020

Background: Debate continues as to the clinical relevance of subclassifying patients with the myeloproliferative disorder (MPD) MMM into the subgroups of agnogenic myeloid metaplasia (AMM), post-polycythemic myeloid metaplasia (PPMM), and post-thrombocythemic myeloid metaplasia (PTMM). We looked to validate previously described phenotypic variability amongst subtypes, and explore relevant and differences in constitutional symptoms.

Methods: An detailed analysis of patients with MMM whom responded to an international web based survey of MPD patients which registered responses regarding diagnosis, disease course, complete blood counts, co-morbidities (Charlson Co-morbidity index), symptoms, and fatigue (Fact-An and Brief Fatigue Inventory (BFI)).

Results: A total of 456 patients self described as MMM responded of which 32.3% had AMM (n = 148), 38.0% % had PPMM (n = 174), and 29.7% had PTMM (n = 136). Detailed breakdown of differences in demographics, clinical course, current laboratory studies, treatment history, and current symptoms are outlined in the table below.

Phenotypic Variability Amongst 458 MMM Patients Category AMM (N=148; 32.3%) PPMM (N=174; 38.0%) PTMM (N=136; 29.7%) MMM Total (N=458) Δ between groups (p = ) Hb = Hemoglobin; SCT = Stem Cell Transplant Age (Median) 61 57 57 58 0.09 Sex (% Males) 60% 49% 30% 47% &lt;0.01 Yrs from MPD Dx 5 6 8 6 &lt;0.01 Labs/ Prior History Hb (g/dL) 11.0 13.7 11.6 12.1 &lt;0.01 % with RBC Tx 43% 6% 11% 20% &lt;0.01 Leukocytes (×10(9)/L) 8.0 7.6 7.2 7.7 0.64 Platelets (×10(9))/L) 200 352 396 321 &lt;0.01 % with Splenomegaly 76% 49% 41% 54% &lt;0.01 % with Prior Thrombosis 10% 22% 31% 21% &lt;0.01 % with Prior Bleed 16% 20% 31% 22% 0.01 Treatment History for the MMM % with Prior Tx for MPD 64% 88% 77% 77% &lt;0.01 % Medical Therapy 57% 70% 75% 67% &lt;0.01 # Meds (Median (Range)) 1 (0–8) 2 (0–6) 2 (0–6) 2 (0–8) &lt;0.01 % with Splenectomy 8% 5% 6% 6% 0.48 % with SCT 6% 1% 1% 3% &lt;0.01 MMM Associated Constitutional Symptoms % with Fatigue 85% 81% 85% 84% 0.56 % with Bone Pain 51% 46% 44% 47% 0.51 % with Fevers 19% 17% 18% 18% 0.87 % with Pruritus 39% 69% 39% 50% &lt;0.01 % with Night Sweats 55% 58% 53% 56% 0.67 % with Weight Loss 30% 15% 16% 20% &lt;0.01

Overall the data suggests patients with AMM are more likely male, with greater burdens of anemia, splenomegaly, and weight loss. However they are less likely to have experienced thrombohemorrhagic complications and have received fewer MPD medications. In contrast PPMM patients (not unsurprisingly) have little trouble from anemia, but have the most pruritus. Patients with PTMM are most likely female, with the highest platelet counts, and the greatest likelihood of thrombohemorrhagic complications. Additionally, all three subgroups of MMM had significant fatigue compared to published controls for both fatigue instruments (P&lt;0.0001) yet there was no difference between MMM subtypes for the severity of fatigue.

Conclusions: A large unselected series of MMM patients supports that although constitutional symptoms are significant and similar amongst MMM subgroups, these patients have variable burdens of other MPD manifestations.