Bone Marrow Fibrosis Is a Not Predictor of Overall Survival in Patients with Myeloma.
Authors: Roberts P. , Paneesha S. , Freeman H. , Pratt G. , Chachalani N. , Rose P. , Borg Anton 
Published: April 2020

Abstract
Multiple myeloma is a lymphoproliferative disorder characterised by the clonal proliferation of plasma cells. Marrow interstitial fibrosis is common in myeloma. Data concerning the correlation of marrow fibrosis with clinical parameters and survival in patients with myeloma is conflicting. We have studied here the impact of marrow fibrosis at presentation in patients with myeloma on overall survival.
This study included 38 (F: 22; M: 16) patients with myeloma from two teaching hospitals between May 1995 and March 2005. The diagnosis of myeloma is made on the basis of standard clinico-morphological criteria. At diagnosis patients underwent bone marrow aspiration and trephine biopsy along with routine haematological, biochemical and radiological investigations. Iliac crest biopsies were fixed in 4% formaldehyde, decalcified in EDTA and embedded in paraffin. Conventional staining for cellular components included haematoxylin and eosin (H& E). Reticulin silver impregnation staining is employed as standard matrix stain. H & E slides were reviewed by the histopathologist for degree and pattern of plasma cell infiltration. Reticulin staining was initially independently assessed by three of the authors, which was subsequently blindly confirmed by the haematopathologists. Bone marrow reticulin is quantified as Grade 0 when no reticulin fibres, Grade 1occasional fine individual fibres, Grade 2 fine fibre network, Grade 3 diffuse fibre network with scattered coarse fibres and grade 4 diffuse coarse fibre network. Patients received either intensive or non intensive anti-myeloma therapy as per standard practise.
Median age at diagnosis was 65.3yrs (Range: 39–86 yrs) and the median follow up period was 16 months (Range: 0–121months). Para protein types were IgG: 23; IgA: 7; LC: 6; IgD: 1 & IgM: 1. 20 patients received VAD chemotherapy, 6 patients had Melphalan therapy, 5 patients were not given any therapy, 3 patients received oral Cyclophosphamide and 2 patients each received steroids and thalidomide alone as initial therapy. Bone marrow reticulin was increased in 25 patients and normal in 13 patients. Haemoglobin &lt;8gms/dl was observed in 8 (24%) patients. 23 (74%) patients were positive for Bence-Jones protein. 17 (47%) patients had elevated serum calcium. 12(57%) patients had a β2-microglobulin of &gt;4mg/ L and 6(16%) patients had renal failure. 21 patients required single line of therapy, where as 12 patients needed more than one line of therapy. Bone marrow reticulin, sex of the patient, presence of Bence-Jones protein, presence of renal failure at diagnosis did not impact on the overall survival(P values: 0.9, 0.8, 0.9 & 0.6 respectively), where as Hb&lt; 8gm/ dl, hypercalcemia and elevated β2-microglobulin at diagnosis was associated with poor overall survival(P values: &lt;0.0001, 0.2 & 0.04 respectively). Bone marrow reticulin also had no effect on the requirement for more than one line of therapy (P value: 0.7). Multivariate analysis revealed only Hb&lt;8gm/dl as the independent predictor of poor overall survival (P Value: 0.03).
Bone marrow fibrosis at diagnosis does not impact on the overall survival in patients with myeloma. Marrow fibrosis also doesn’t predict the need for more than one line of therapy in patients with myeloma. Our study also confirms the poor prognostic role of anaemia, hypercalcemia and elevated β2-microglobulin levels in patients with myeloma. Further studies are needed to confirm these and also the impact of anti-myeloma therapy on the marrow fibrosis.