Prognostic significance of tumor burden assessed by whole-body magnetic resonance imaging in multiple myeloma patients treated with allogeneic stem cell transplantation.

Allogeneic stem cell transplantation is a therapeutic option under dispute but nonetheless chosen with increasing frequency for patients suffering from multiple myeloma in Europe. To study possible predictors of survival, 79 patients were investigated using whole-body magnetic resonance imaging to assess the visible tumor burden before and after allogeneic stem cell transplantation. Statistical analysis of clinical and imaging parameters included Cox regression models and distribution of survival time estimates (Kaplan-Meier method). Log rank test was used to determine the prognostic impact of the presence of focal lesions on survival. A higher tumor burden according to the lesion count was associated with a shorter overall survival (univariable/multivariable Cox regression: 1st magnetic resonance imaging P=0.028/P=0.048; 2nd magnetic resonance imaging P=0.008/P=0.024). Focal infiltration pattern itself seemed to be an additional adverse prognostic factor for overall survival (2nd MRI P=0.048), although no definite cut-off could be defined. Kaplan-Meier estimates at 60 months of follow up show a significant difference (Log rank P=0.04) for overall survival rates between patients with focal infiltration (32%) and those without (75%). Since this subgroup of patients may benefit from maintenance therapy, adoptive immunotherapy, or local interventions, whole-body imaging is an appropriate and highly recommendable diagnostic approach for detection of prognostically relevant lesions before and after treatment.

High-dose chemotherapy and autologous stem cell transplantation of patients with multiple myeloma in an outpatient setting.

BACKGROUND: High-dose (HD) chemotherapy with melphalan and autologous blood stem cell transplantation (ABSCT) for treatment of symptomatic multiple myeloma (MM) on an outpatient basis has been well established in the USA and Canada, whereas in Germany and Western Europe an inpatient setting is the current standard. We report on a German single-centre program to offer the procedure on an outpatient basis to selected patients. METHODS: Major requirements included: patients had to have family and/or other caregivers, had to be able to reach the hospital within 45 min and have an ECOG performance score of 0-1. Patients with severe co-morbidities were not included. RESULTS: From September 2012 until April 2016, 21 patients with MM stage IIIA were enrolled. All engrafted within the expected time range (median 14 days), and no severe adverse events occurred. 14 patients (67%) had an episode of neutropenic fever and blood cultures were positive in 4 patients (19%). Although rather liberal criteria for hospital admission were applied, 14 patients (67%) were treated entirely on an outpatient basis. CONCLUSIONS: HD chemotherapy and ABSCT on an outpatient basis is safe and feasible if it is conducted in an elaborate surveillance program. The feedback from patients was very positive, thus encouraging further expansion of the program.

Association between magnetic resonance imaging patterns and baseline disease features in multiple myeloma: analyzing surrogates of tumour mass and biology.

OBJECTIVE: To assess associations between bone marrow infiltration patterns and localization in magnetic resonance imaging (MRI) and baseline clinical/prognostic parameters in multiple myeloma (MM). METHODS: We compared baseline MM parameters, MRI patterns and localization of focal lesions to the mineralized bone in 206 newly diagnosed MM patients. RESULTS: A high tumour mass (represented by International Staging System stage III) was significantly associated with severe diffuse infiltration (p = 0.015) and a higher number of focal lesions (p = 0.006). Elevated creatinine (p = 0.003), anaemia (p < 0.001) and high LDH (p = 0.001) correlated with severe diffuse infiltration. A salt and pepper diffuse pattern had a favourable prognosis. A higher degree of destruction of mineralized bone (assessed by X-ray or computed tomography) was associated with an increasing number of focal lesions on MRI (p < 0.001). Adverse cytogenetics (del17p/gain1q21/t(4;14)) were associated with diffuse infiltration (p = 0.008). The presence of intraosseous focal lesions exceeding the mineralized bone had a borderline significant impact on prognosis. CONCLUSIONS: Diffuse bone marrow infiltration on MRI correlates with adverse cytogenetics, lowered haemoglobin values and high tumour burden in newly diagnosed MM whereas an increasing number of focal lesions correlates with a higher degree of bone destruction. Focal lesions exceeding the cortical bone did not adversely affect the prognosis. KEY POINTS: • Diffuse MRI correlates with adverse cytogenetics, lowered haemoglobin and high tumour burden. • Higher numbers of MRI focal lesions correlate with increasing degree of bone destruction. • Focal lesions exceeding the cortical bone borderline significantly influence survival. • Moderate/severe diffuse infiltration and more than 23 focal lesions adversely affect survival.

A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma.

Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated. Compared to salt and pepper/minimal diffuse infiltration, moderate/severe diffuse infiltration had a negative prognostic impact on both progression-free survival (P<0.001) and overall survival (P=0.003). More than 25 focal lesions on whole-body magnetic resonance imaging or more than seven on axial magnetic resonance imaging were associated with an adverse prognosis (progression-free survival: P=0.001/0.003 and overall survival: P=0.04/0.02). A magnetic resonance imaging-based prognostic scoring system, combining grouped diffuse and focal infiltration patterns, was formulated and is applicable to whole-body as well as axial magnetic resonance imaging. The score identified high-risk patients with median progression-free and overall survival of 23.4 and 55.9 months, respectively (whole-body-based). Multivariate analyses demonstrated that the magnetic resonance imaging-based prognostic score stage III (high-risk) and adverse cytogenetics are independent prognostic factors for both progression-free and overall survival (whole-body-based, progression-free survival: hazard ratio=3.65, P<0.001; overall survival: hazard ratio=5.19, P=0.005). In conclusion, we suggest a magnetic resonance imaging-based prognostic scoring system which is a robust, easy to assess and interpret parameter summarizing significant magnetic resonance imaging findings in transplant-eligible patients with multiple myeloma.