The role of positron emission tomography with 18F-fluorodeoxyglucose integrated with computed tomography in the evaluation of patients with multiple myeloma undergoing allogeneic stem cell transplantation.

Positron emission tomography (PET) integrated with computed tomography (PET/CT) has been reported to be useful for screening myelomatous lesions at diagnosis in patients with multiple myeloma (MM) and for monitoring response to autologous stem cell transplantation (auto-SCT). The aim of the study was to evaluate the prognostic significance of PET/CT in MM patients who received allogeneic stem cell transplantation (allo-SCT). Patients who underwent upfront auto-SCT followed by allo-SCT, either as consolidation or salvage treatment, were studied with PET/CT before and/or within 6 months after allo-SCT. The number, the maximum standard uptake value (SUV), and the location (medullary or extramedullary) of focal lesions (FLs) were recorded and investigated as predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. Fifty-four patients had a PET/CT scan before allo-SCT. Of these, 22 patients (41%) had a negative PET/CT scan, 11 patients (20%) showed 1 to 3 FLs, and 21 patients (39%) had either a diffuse bone marrow involvement or more than 3 FLs. SUV was >4.2 in 21 patients (39%) and extramedullary disease (EMD) was present in 6 patients (11%). Multivariate analysis of prognostic factors before allo-SCT showed that persistence of EMD at transplantation was an independent predictor of poor PFS, whereas OS was negatively influenced by unrelated donor and SUV > 4.2. Fifty-nine patients had a PET/CT scan within 6 months after allo-SCT. Multivariate analysis of post-treatment variables showed that persistence of EMD and failure to obtain complete response or very good partial response after allo-SCT were strongly associated with shorter PFS and OS. Of the 46 patients with evaluable PET/CT scans both before and 6 months after allo-SCT, the 23 patients who maintained or reached a PET complete remission showed a significantly prolonged PFS and OS compared with the 23 patients with persistence of any PET positivity (2-year PFS: 51% versus 25%, P = .03; 2-year OS: 81% versus 47%, P = .001). This study indicates that PET/CT imaging before and after allo-SCT is significantly associated with the outcome, suggesting the utility of this technique for MM staging before allo-SCT and for response monitoring after the transplantation.

Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia.

We report the long-term outcome results of 57 consecutive adult patients with immune thrombocytopenia after being treated with rituximab. According to the different period of therapy, patients received either standard dose (SD) rituximab (i.e., 375 mg/m(2) weekly for 4 weeks) or low dose (LD) rituximab (i.e., 100 mg flat dose weekly for 4 weeks). Overall (OR) and complete response (CR) rates were 60 and 40%, respectively. Patients' median follow-up was 52 months, 82 months in the SD, and 44 months in the LD group; 15 out of 34 responsive patients (44%) relapsed, with median response duration of 24 months (range 3-120). The estimated 4-years event-free survival (EFS, considering events the non response status at month 2 or relapses in responders) was 30%. Patients who received SD vs. LD rituximab had better outcome with regard to short term response (OR 66 vs. 52%, CR 50 vs. 28%), relapse rate (38 vs. 54%), probability to achieve and maintain long-term response (41 vs. 24%) and estimated 4-years EFS (35 vs. 23%). Patients with a longer interval between diagnosis and rituximab therapy had worse EFS [HR = 1.005; 95%IC: (1.002-1.009), P = 0.019]. Three patients developed short-term adverse events, two-serum sickness, and one interstitial pneumonia. Four cases of malignancies and two herpes zoster reactivations were registered during long-term follow-up; one patient died for cerebral bleeding. Rituximab SD appears a safe and active agent allowing in nearly 40% of cases to achieve long-term response and splenectomy sparing effect.

Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation.

We prospectively analyzed the prognostic relevance of positron emission tomography-computed tomography (PET/CT) at diagnosis, after thalidomide-dexamethasone (TD) induction therapy and double autotransplantation (ASCT) in 192 newly diagnosed multiple myeloma (MM) patients. Presence at baseline of at least 3 focal lesions (FLs; 44% of cases), a standardized uptake value (SUV) > 4.2 (46%), and extramedullary disease (EMD; 6%) adversely affected 4-year estimates of progression-free survival (PFS; ≥ 3 FLs: 50%; SUV > 4.2: 43%; presence of EMD: 28%). SUV > 4.2 and EMD were also correlated with shorter overall survival (OS; 4-year rates: 77% and 66%, respectively). Persistence of SUV > 4.2 after TD induction was an early predictor for shorter PFS. Three months after ASCT, PET/CT was negative in 65% of patients whose 4-year rates of PFS and OS were superior to those of PET-positive patients (PFS: 66% and OS: 89%). In a multivariate analysis, both EMD and SUV > 4.2 at baseline and persistence of fluorodeoxyglucose (FDG) uptake after ASCT were independent variables adversely affecting PFS. PET/CT involvement at diagnosis, after novel agent-based induction and subsequent ASCT is a reliable predictor of prognosis in MM patients. This study is registered at www.clinicaltrials.gov as NTC01341262.

Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib.

Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation (SCT) is dismal. Immunotherapy with donor lymphocyte infusion (DLI) and imatinib are rarely and/or transiently effective. Here we describe the case of a patient with imatinib-resistant post-transplant relapse of ALL, who received a combination of standard dose nilotinib and monthly DLI infusion. Therapy was well tolerated and the patient achieved and maintained a complete molecular remission. Our case provides a rationale for the combined use of a second line tyrosine kinase inhibitor and DLI in the treatment of relapsed Ph+ ALL.

A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma.

BACKGROUND AND OBJECTIVES: Bone lesions in multiple myeloma (MM) have been traditionally detected by whole body X-ray (WBXR) survey although magnetic resonance imaging (MRI) has become the gold standard for detecting MM involvement of the spine and pelvis. The aim of this study was to compare a new technique, positron emission tomography (PET) with 18F fluorodeoxyglucose (FDG) integrated with computed tomography (18F-FDG PET-CT), with MRI and WBXR for baseline assessment of bone disease in MM. DESIGN AND METHODS: We prospectively compared 18F-FDG PET-CT, MRI of the spine-pelvis and WBXR in a series of 46 patients with newly diagnosed MM. In 23 patients who received up front autologous transplantation, we also compared post-treatment PET-CT scans with MR images of the spine and pelvis. RESULTS: Overall, PET-CT was superior to planar radiographs in 46% of patients, including 19% with negative WBXR. In 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients PET-CT enabled the detection of myelomatous lesions in areas which were out of the field of view of MRI. By combining MRI of the spine- pelvis and 18F-FDG PET-CT, the ability to detect sites of active MM, both medullary and extramedullary, was as high as 92%. Following transplantation, 15 patients had negative PET-CT scans (including 13 with a very good partial response or at least a near complete response), but only 8 had normal MRI. INTERPRETATION AND CONCLUSIONS: MRI of the spine and pelvis still remains the gold standard imaging technique for the detection of bone marrow involvement in MM. 18F-FDG PET-CT provides additional and valuable information for the assessment of myeloma bone disease in areas not covered by MRI.