A proposed index of diffuse bone marrow [18F]-FDG uptake and PET skeletal patterns correlate with myeloma prognostic markers, plasma cell morphology, and response to therapy.

PURPOSE: The investigation of a semi-quantitative index in the pelvis to assess for diffuse bone marrow (BM) [18F]-FDG uptake and the investigation of PET skeletal patterns in multiple myeloma (MM) patients, in accordance with prognostic markers, clonal plasma cell (cPC) morphology, and response to therapy. METHODS: We prospectively analyzed [18F]-FDG PET/CT in 90 MM patients (newly diagnosed, 60; relapsed/refractory, 30). Among other PET/CT parameters, we calculated the ratio SUVmax pelvis/liver and examined for correlations with known MM prognostic parameters, cPC morphology (good vs. low/intermediate differentiation), and response to therapy. RESULTS: SUVmax pelvis/liver ratio was significantly lower for the group of good differentiation vs. intermediate/low differentiation cPCs (p < 0.001) and showed a positive correlation with BM infiltration rate, ß2 microglobulin, serum ferritin, international staging system (ISS), and revised ISS; no significant correlation was found with hemoglobin. A cutoff value of 1.1 showed an excellent specificity (99%) and high sensitivity (76%) for diffuse BM involvement (AUC 0.94; p < 0.001). Mixed pattern and appendicular involvement correlated with poor prognostic features while normal pattern, found in 30% of patients, correlated with good prognostic features. Presence of ≥ 10 focal lesions negatively predicted for overall response (p < 0.05; OR 4.8). The CT component improved the diagnostic performance of PET. CONCLUSION: This study showed, for the first time, that cPC morphology and markers related with MM biology, correlate with SUVmax pelvis/liver index, which could be used as a surrogate marker for BM assessment and disease prognosis; PET patterns correlate with MM prognostic features and response rates.

Extramedullary (EMP) relapse in unusual locations in multiple myeloma: Is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome?

Extramedullary relapse constitutes an uncommon manifestation of multiple myeloma (MM), characterized by highly malignant histology, special biological features, resistance to treatment and poor outcome. Its incidence has been increased during the last years, probably due to the introduction of novel strategies in the management of MM, including intensified treatment and immunomodulatory drugs. Here we report nine cases of extramedullary relapse of MM, presented in unusual locations, seven of which had previously been treated with thalidomide-containing regimens (TCR). Our aim was to explore the morphological, immunophenotypical, molecular and laboratory characteristics accompanying EMP-relapse and seek possible correlations with treatment and clinical outcome.

Non-thromboembolic pulmonary hypertension in multiple myeloma, after thalidomide treatment: a pilot study.

BACKGROUND: Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects and endothelial damage. Thalidomide has been associated with an increased risk of thromboembolic pulmonary hypertension (PH). PH in the absence of venous thromboembolism has also been described in MM patients during thalidomide treatment. AIM: Detection of clinical and subclinical nonthromboembolic PH in MM patients after thalidomide treatment. PATIENTS AND METHODS: Eighty-two patients, 46-82 years (median age 61 years), 42 males, were studied. They underwent echocardiographic study at baseline, 1 month thereafter, 6 months later and whenever symptoms indicating deterioration of cardiac function appeared. Echocardiographic signs of PH were especially identified. RESULTS: Clinical and echocardiographic evaluation revealed four patients (out of 82 patients, 4.87%) with PH. Nonimaging and imaging diagnostic methods excluded thromboembolic PH. Statistical analysis demonstrated significant correlation between structural heart disease and PH (r = 14.078; P = 0.008). No significant correlation between age (r = 0.770; P = 0.724), gender (r = 1.157; P = 0.285), International Staging System (ISS) (r = 0.316; P = 0.716) and PH was found. CONCLUSIONS: Preexisted endothelial dysfunction due to structural cardiac disease enhances the vasoactive substances release causing increased pulmonary vascular resistance. Thalidomide possibly causes a vasodilator and vasoconstriction imbalance, which may cause abnormal pulmonary vascular response interfering to a vicious circle perpetuating PH.