The Kinetic Of Bone Marrow Fibrosis Regression Predicts Outcome In Myelofibrosis Patients After Allogeneic SCT
Authors: Kröger Nicolaus , Alchalby Haefaa , Zabelina Tatjana , Kvasnicka Hans-Michael , Thiele Juergen , Büsche Guntram , Kreipe Hans 
Published: October 2019

Abstract

Introduction
Bone marrow fibrosis is a hallmark of primary or post ET/PV myelofibrosis. Recent studies have shown that allogeneic stem cell transplantation induces rapid bone marrow fibrosis regression suggesting that fibrosis is more a dynamic rather than a static process. So far, no data are reported if fibrosis regression influences outcome after transplantation.

Methods and patients
We studied 94 patients with myelofibrosis who received allogeneic stem cell transplantation at the University Medical Center Hamburg between 2002 and 2010. In 57 patients the complete bone marrow histology prior transplantation and/or on day+30 and +100 after transplantation were available. The median age was 57 years (r: 33–73) and patients were classified as IPSS low-risk (n = 1), intermediate-1 (n = 5), intermediate-2 (n = 18), and high-risk (n = 33). Donor source was unrelated (n = 46) or related (n = 11) and of these 38 were HLA-matched while 19 were HLA-mismatched. 41 had primary and 16 post ET or post PV myelofibrosis. The median number of blasts was 1% (r: 0–17%) and gender was male (n = 32) and female (n = 25). All patients received busulfan-based dose-reduced conditioning regimen. Bone marrow fibrosis was graded according to the European consensus and WHO (MF-0 – 3), respectively, and evaluated by experienced hematopathologists.

Results
Before transplantation 41 patients (72%) had MF grade 3 and 16 (28%) MF grade 2. After engraftment on day+30 (± 10 days) (n = 48), 3 (6%) had complete regression (MF-0) and 7 (15%) near complete regression of bone marrow fibrosis while 17 (35%) had MF-2 and 21 (44%) had MF-3. On day+100 (± 20 days) complete regression (MF-0) was noted in 11 (25%) and near complete regression (MF-1) in 13 (29%) while 12 (27%) and 8 (18%) had still MF-2 or MF-3, respectively. Patients with complete and near complete regression (MF-0 and MF-1) on day +30 had a 5-year estimated overall survival of 100% and those with MF-2 and MF-3 of 75% (p = 0.09). Patients with complete or near complete regression on day+100 had a 5-year estimated survival of 95% in contrast to 60% for those with MF-2 or MF-3 (p = 0.04).
If analyzed by regression by grade at day+100 7 (16%) had a reduction of 3 grades (e.g. MF-3 to MF-0), 12 (27%) of 2 grades, 16 (36%) of 1 grade, and 9 (21%) had no grade reduction at day+100.
Reduction of 2 or 3 grades at day+100 resulted in 95% survival at 5 years while reduction of 1 or no grade had a survival of 70% however this difference did not reach statistical significance (p = 0.1). There was no difference of fibrosis regression at day+100 between high risk IPSS and low/intermediate risk patients. Furthermore, in those patients with JAK2V617F mutation and complete or near complete regression 42% still had detectable JAK2V617F mutation level in peripheral blood. In contrast, 81% had complete donor cell chimerism if bone marrow fibrosis was MF-0/MF-1 while only 31% had complete chimerism at day+100 if fibrosis was classified as MF-2 or MF-3.

Conclusion
This data on fibrosis regression after allogeneic stem cell transplantation suggests that a more rapid regression - independently of IPSS risk score - resulted in a favorable survival and may be used as an early predictive factor for excellent survival.

Disclosures:
No relevant conflicts of interest to declare.