294 Prognostic significance of beta 2 microglobulin in survival and transformation to acute myelogenous leukemia in patients with myelodysplastic syndrome

Abstract

s of the 11th International Symposium on Myelodysplastic Syndromes (MDS) 18 May 2011 21 May 2011 S116 Posters / Leukemia Research 35 (2011) S27–S142 294 Prognostic significance of beta 2 microglobulin in survival and transformation to acute myelogenous leukemia in patients with myelodysplastic syndrome A. Galanopoulos, A. Aggelidis, D. Gogos, A. Megalakaki, I. Kotsianidis, M. Dimou, P. Panagiotidis, N. Zoumbos, N.I. Anagnostopoulos, M. Voulgarelis, H. Papadaki, A. Symeonidis. Clinical Hematology, G. Gennimatas General Hospital, Athens, Clinical Hematology, Metaxas Hospital, Piraeus, Clinical Hematology, Dimokritio University of Thraki, Alexandroupolis, Clinical Hematology, Laikon General Hospital/National and Kapodistrian University of Athens, Athens, Clinical Hematology, University of Patras, Medical School, Patras, Clinical Hematology, University of Crete School of Medicine, Heraklion, Greece Background: Beta 2 microglobulin (b2M) is a 12 kDa light chain protein that binds to the a chain of class I MHC (MHC1) molecule. Serum b2M levels are known to reflect renal function and membrane turnover, which is associated with tumor mass and growth rate. Elevated serum levels of b2M are reported to predict poor survival in several hematologic malignancies. Purpose: To investigate the prognostic relevance of b2M with regard to survival and the risk of transformation into acute myelogenous leukemia (AML) in patients with myelodysplastic syndrome (MDS). Material and Methods: We evaluated serum b2M levels in 407 MDS patients from the Hellenic MDS Study Group. From these 152 patients were excluded from further analysis for various reasons such as serum creatinine levels greater than 1.5mg/dl, treatment with intensive therapy and blood stem cell transplantation or insufficient data. B2M and karyotype were recorded along with other hematologic, biochemical and clinical covariates. Serum b2M levels were quantified by a radioimmunoassay. The log rank test was used to compare overall survival and AML transformation. Multivariate analysis was conducted utilizing the Cox proportional hazards regression model with a stepwise backward selection. Results: Thirty patients had refractory anemia (RA), 64 refractroy anemia with excess of blasts-1(RAEB-1), 34 refractory anemia-2 (RAEB-2), 24 refractory anemia with ringed sideroblasts (RARS), 69 refractory cytopenia with multilineage dysplasia (RCMD), 13 refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS) and 11 5q− syndrome. The median value for b2M was 2.67(±1.53). The univariate analysis revealed that patients with b2M below 3mg/dl had a higher overall survival compared to patients with b2M above 3mg/dl (log-rank=7.42; p = 0.006). Other factors that exerted a statistically significant effect on overall survival were the medullary blasts (log-rank =13.5; p 15%. MDS with del(5q) was identified in 135 (6.6%) of the cases, RARS-T in 76 patients (3.7%). There were 122 (6%) cases with MDS unclassifiable, including 95 (4.7%) with 1% peripheral blasts, 26 (1.3%) with pancytopenia, and only one patient without signs of dysplasia despite chromosomal abnormalities. Survival data (months) and AML progression rates (%) at 2 and 5 years are shown in the tables. Types with unilineage Dysplasia WHO 2008 Hb g/dl PLT/ nl ANC/ ml Abnormal karyotype in % Complex karyotype in % IPSS low/ int 1/int 2 median survival in month AML progression in % after 2 years AML progression in % after 5 years RCUDbi 10.3 116 2000 50 19 30/57/13 64 9 14 RA 8.5 248 3900 40 14 91/9/0 48 2 2 RT 11.7 56 2650 57 0 80/20/0 not reached 0 11 RN 11.9 137 1300 8 0 92/8/0 141 10 10 RARS 9.5 267 3150 28 6 73/24/2 63 4 4 MDS-U-PAN 8.5 44 750 33 0 0/100/0 30 0 18 Types with multilineage Dysplasia WHO 2008 HB g/dl PLT/ nl ANC/ ml Abnormal karyotype in % Complex karyotype in % IPSS low/ int 1/ int 2 median survival in month AML progression in % after 2 years AML progression in % after 5 years RCMD 9.3 134 2030 49 19 40/51/9 36 11 17 RCMD-RS 8.8 185 2200 55 24 45/41/14 31 10 17 RARS-T 9.1 584 4750 41 18 67/33/0 55 3 8 MDS del (5q) 9.3 255 2300 100 0 73/27/0 91 4 14 MDS-U-PB 9.4 118 2300 47 20 41/52/7 35 10 13 Conclusions: 1. While RCUD carries a relatively good prognosis, pancytopenic patients (MDS-U-Pan) have a shorter survival, similar to RCMD. The separation of MDS-U-Pan therefore seems to be is justified. 2. RCUD with bicytopenia accounts for a considerable fraction (52.3%) of RCUD. The prognosis of RCUDbi is intermediate between RCUD with unilineage cytopenia and MDS-U-Pan. 3. The prognostic impact of blast cells in the peripheral blood is similar to that of pancytopenia. 4. Survival rates are not substantially different for RCMD and RCMDRS. 5. RARS-T and MDS with del5q usually present with multilineage dysplasia. From a prognostic point of view, they are similar to RCUD, but their specific pathogenetic features justify their existence as distinct subtypes in the WHO classification.