Spectrum of Cerebrovascular Disease in Multiple Myeloma Patients Undergoing Chemotherapy

Abstract Introduction: The objective of study was to determine the risk factors, stroke mechanisms and outcome following a stroke in Multiple myeloma (MM) patients. Materials and Methods: We conducted a matched cohort study from a prospective database of MM patients enrolled in TT2, TT3A, TT3B protocols who developed a vascular event (transient ischemic attack, ischemic stroke and intracerebral hemorrhage) from 1998 to 2014 with age, sex and treatment matched controls. Comparison of baseline demographics, risk factors, myeloma characteristics, laboratory values and mortality between both groups was performed using Pearson's Chi-square test for categorical variables and student T test for continuous variables. Multivariate logistic regression analysis was performed to identify risk factors associated with stroke. For statistical analysis SAS 9.4 software was used and p value of ≤ 0.05 was considered significant. Strokes were classified using the modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Of 1148 patients, 46 developed a vascular event (Ischemic stroke (TIA)-33, Transient ischemic attack-11, Hypertensive intracerebral hemorrhage-2). On univariate analysis, predictors of stroke were a positive smoking history (26.1% vs 13% p=0.0381), renal insufficiency (23.9% vs 8.0% p=0.0039), hemodialysis (10.9 vs 0.7% p=0.004) and MM Stage I and II as opposed to Stage III (Stage I - 23.9% vs 9.4%, Stage II - 17.4% vs 12.3, Stage III - 58.7% vs 78.3% p=0.025). Despite the lack of significant difference in the baseline laboratory values between both groups, among the cases, there was a significant decrease in the platelet count (112.6 vs 255.2, p On multivariate analysis, independent predictors of stroke were renal insufficiency (Odds Ratio, 3.528, 95% CI, 1.36-9.14; p=0.0094) and MM Stage I and II (Odds Ratio, 2.770, 95% CI, 1.31-5.81; p=0.0073). The ischemic strokes subtypes were: Large vessel disease 6%, cardioembolic 18%, small vessel disease 21%, other known etiologies 49% (hypercoaguable state; watershed; others) and cryptogenic in 6%. Following ischemic event, antiplatelet agents were used in 16 patients, anticoagulation in 7 patients but 23 patients were ineligible for both due to thrombocytopenia. In our cohort, 78% were discharged home or rehabilitation facility, 4% were transferred to long-term nursing facility and in hospital mortality was 15%. Conclusion: In MMpatient'srenal insufficiency andMM Stage I and II were associated with increased stroke risk. Besides hypercoagulability other mechanisms like atrial fibrillation, watershed strokes and small vessel disease played major role. Table 1 . Demographic and disease characteristics of multiple myeloma patients experiencing a stroke compared to controls Variable Stroke (N=46) No Stroke (N=138) p-value Age [mean (sd)] 60.6 (7.7) 60.7 (7.8) 0.8960 Female 50.0 (23) 41.6 (57) 0.3023 Race Caucasian 95.7 (44) 90.6 (125) 0.3635# Hypertension 54.4 (25) 43.5 (60) 0.2003 HPL 33.3 (15/45) 26.1 (36) 0.3464 Diabetes 17.4 (8) 9.4 (13) 0.1409 CAD 10.9 (5) 10.9 (15) >0.99 CHF 4.4 (2) 8.7 (12) 0.5237 AFIB 17.4 (8) 9.4 (13) 0.1409 Smoking 26.1 (12) 13.0 (18) 0.0381 ETOH 2.2 (1) 1.5 (2) >0.99 Malignancy 8.7 (4) 16.1 (22/137) 0.2159 Nephropathy 23.9 (11) 8.0 (11) 0.0039 Hemodialysis 10.9 (5) 0.7 (1) 0.0040 Protocol TT2 TT3A TT3B 54.4 (25) 32.6 (15) 13.0 (6) 57.2 (79) 21.0 (29) 21.7 (30) 0.3036 MM Stage I II III 23.9 (11) 17.4 (8) 58.7 (27) 9.4 (13) 12.3 (17) 78.3 (108) 0.0182 MM Isotype IgG IgA FLC-κ FLC-λ Other 58.7 (27) 21.7 (10) 8.7 (4) 10.9 (5) 0 49.3 (68) 24.6 (34) 10.1 (14) 10.9 (15) 5.1 (7) 0.6128 MM Risk [mean (sd)] Death -0.13 (0.61; N=37) 65.2(30) 0.09 (0.67; N=88) 51.5(71) 0.0941 0.19 OSA: Obstructive sleep apnea, CAD: coronary artery disease, CHF: Congestive heart failure, AFIB: Atrial fibrillation, HPL hyperlipidemia. Table 1 . Results on multivariable logistic model Variable Odds Ratio 95% CI p-value Nephropathy 3.528 1.36 to 9.14 0.0094 MM Stage I or II 2.770 1.31 to 5.81 0.0073 Disclosures Hinduja: University of Arkansas for Medical Sciences: Employment. Limaye: University of Arkansas for Medical Sciences: Employment. Ravilla: University of Arkansas for Medical Sciences: Employment. Sasapu: University of Arkansas for Medical Sciences: Employment. Waheed: University of Arkansas for Medical Sciences: Employment.