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Immune thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. iTTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (vWF)-cleaving protease, due to anti-ADAMTS13 autoantibodies. Early diagnosis and treatment reduce the mortality. Front-line therapy includes daily plasma exchange (PEX) with fresh frozen plasma replacement and immunosuppression with corticosteroids. Caplacizumab is recently added to the front-line therapy. Caplacizumab is a nanobody that binds to the A1 domain of vWF, blocking the interaction of ultra-large vWF multimers with the platelet, and thereby preventing the formation of platelet-rich thrombi. Caplacizumab reduces mortality due to ischemic events, refractoriness and exacerbations after PEX discontinuation. Until now, the criteria for response to treatment mainly took into account the normalization of platelet count and discontinuation of PEX, now with the use of caplacizumab, leading to rapid normalization of platelet count, it has been necessary to redefine the response criteria, taking into account also the underlying autoimmune disease. Monitoring of ADAMTS13 activity is important to identify cases with low value of activity (

Introduction: The NPM1mut identification by RQ-PCR at diagnosis is important for AML risk stratification and represents a reliable marker to track minimal residual disease (MRD) and to early detect relapse. We retrospectively analyzed clinical and biological features of NPM1mut AML pts consecutively treated with intensive therapy in our Institution to evaluate the role of MRD monitoring in relation to overall survival (OS) and disease free survival (DFS). Methods: We analyzed 104 NPM1mut AML pts eligible for intensive therapy, diagnosed between 2008 and 2018. Median age was 52 years (y) (range, 8-75). NPM1mut was detected in the bone marrow (BM) by RQ-PCR at diagnosis and at different time points. MRD levels were expressed as a percentage (ratio of the NPM1 copies-cp to the housekeeping gene ABL cp × 100); MRD positivity was defined as any level above 0.01%. FLT3mut was detected in 50 pts (48.1%) (7 FLT3-TKD; 43 FLT3-ITD). All pts received intensive treatment according to local institutional standard. After induction and consolidation, pts received either high-dose (HD) chemotherapy followed by autologous stem cell transplantation (ASCT) or 2/3 further cycles of HDAra-C if not eligible for ASCT. Results: Eighty-nine pts achieved a complete remission (CR) (85.6%), 7 proved refractory (6.7%), while 8 died during induction (7.7%). After induction, MRD was available for 50 pts (61.7%): 8 (16%) were MRD negative (-) (7 FLT3wt; 1 FLT3mut) and 42 (84%) were MRD positive (+) (18 FLT3wt; 24 FLT3mut); MRD evaluation after I consolidation was performed in 52 pts (64.2%): 16 (30.8%) were MRD- (9 FLT3wt; 7 FLT3mut), 36 (69.2%) were MRD+ (16 FLT3wt; 20 FLT3mut). For the whole cohort, the 5y-OS was 40.8% (95% CI, 31.5-52.9%) and 5y-DFS was 38.2% (95% CI, 28.8-50.7%). Achieving an MRD- after induction or I consolidation, identified pts with better 5y-DFS than pts with persisting MRD+ (85.6% and 65.5% vs 40% and 26%; p= 0.015, p= 0.032). This also translated into significant differences in 5y-OS (100% and 75.8% vs 44% and 30.5%; p= 0.009, p= 0.045); 5y-cumulative incidence of relapse (CIR) was 43.7% (95% CI: 30.2-54.6%). No statistically significant differences were observed in OS (p= 0.535) and DFS (p= 0.224) according to FLT3 status. However, the CIR was higher in FLT3mut pts (p= 0.063). In the whole cohort, ASCT were 24, allogenic (allo)SCT were 26. Reasons for alloSCT in CR1 were: 1) FLT3-ITDmut; 2) secondary-AML; 3) raising MRD levels, 4) slow clearance of MRD reduction; 5) primary refractory pts. MRD- pts before alloSCT showed a trend towards better OS (p= 0.074) and DFS (p= 0.065) than MRD+ pts. Conclusions: Our study underlines the clinical relevance of achieving an early molecular response in NPM1mut AML. MRD monitoring is a valuable tool for the early identification of pts who might benefit from alloSCT/new drugs and pts with molecular relapse. The most relevant time points for collecting samples and the prognostic MRD thresholds remain to be defined.

The occurrence of acute myeloid leukemia (AML) within six months from a diagnosis of breast cancer (BC) is rarely reported in the literature, and it is associated with a poor prognosis. We report herein the case of a 40-year-old woman referred to our centre affected by BC and simultaneous AML. The patient proved refractory to first line therapy and achieved complete remission (CR) with a clofarabine-based regimen followed by allogeneic stem cell transplantation (ASCT). Both during salvage chemotherapy and after ASCT, the patient presented severe infectious complications ( acute cholecistytis and Nocardia pneumonia, respectively) treated with surgery, and currently she is alive in CR for both diseases after 29 months of follow-up. The case highlights the importance of a diagnostic assessment of any unexplained cytopenia in association with solid neoplasia under treatment, underlining the feasibility and priority of a timely treatment of the haematological neoplasm in order to achieve long-term survival.

Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy.

Mucormycosis is the third cause of invasive mycosis after candidiasis and aspergillosis in AML patients, representing a poor prognostic factor associated with a high rate of fatal outcome. We report a case of a patient with AML and a concomitant pulmonary mucormycosis at diagnosis, who obtained a complete remission both of her AML and of the fungal infection. The incidence of the infection at the onset of leukemia is extremely unusual, and, to our knowledge, the sporadic cases reported in the literature are included in heterogeneous series retrospectively examined. In our case, Liposomal Amphotericin B as single agent appeared incapable of controlling the infection, so anti-infective therapy was intensified with posaconazole and simultaneously antileukemic treatment with 5-azacitidine was started, with the understanding that the only antifungal treatment would not have been able to keep the infection under control for a long time if not associated with a reversal of neutropenia related to the disease. We observed a progressive improvement of the general conditions, a healing of pneumonia and a complete remission of the leukemic disease, suggesting that a careful utilization of the new compounds available today, in terms of both antifungal and antileukemic treatment, may offer a curative chance a patient who would have otherwise been considered unfit for a potentially curative therapeutic strategy.

Long-term survival of relapsed/refractory acute myeloid leukemia (AML) remains a major problem, particularly in patients not eligible for transplantation. We hereby evaluated the feasibility and efficacy of adding Gemtuzumab Ozogamicin to salvage chemotherapy (Ara-C, Idarubicine, Peg-Filgrastim) in relapsed/refractory AML. The main endpoints were: the rate of complete remissions (CR) and the proportion of patients capable of undergoing a stem cell transplant. Fourty-two patients were enrolled. The overall CR rate was 76% and no induction deaths were reported. In 56% of patients, a transplant procedure could be performed. The treatment schedule proved feasible and well tolerated, providing a high CR rate and a useful bridge to transplant.

Background Posaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia.Design and Methods The impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs.Results Proven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs.Conclusions Primary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a “real-life” scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous.

Long-term survival of relapsed/refractory acute myeloid leukemia (AML) remains a major problem, particularly in patients not eligible for transplantation.We hereby evaluated the feasibility and efficacy of adding Gemtuzumab Ozogamicin to salvage chemotherapy (Ara-C, Idarubicine, Peg-Filgrastim) in relapsed/refractory AML. The main endpoints were: the rate of complete remissions (CR) and the proportion of patients capable of undergoing a stem cell transplant.Fourty-two patients were enrolled. The overall CR rate was 76% and no induction deaths were reported. In 56% of patients, a transplant procedure could be performed. The treatment schedule proved feasible and well tolerated, providing a high CR rate and a useful bridge to transplant.

Background and Objectives Follow-ups of patients with mediastinal lymphoma are not accurate if they rely on computed tomography (CT). Positron emission tomography (PET) has been suggested to be useful in several lymphoma settings, such as initial staging, evaluation of residual masses after therapy, and assessment of response early in the course of treatment. The aim of this retrospective study was to verify the reliability of positive PET scans of the mediastinum in following up patients wirh mediastinal lymphoma, using histological findings as a comparison.Design and Methods From January 2002 to July 2005, 151 patients with mediastinal lymphoma (57 with Hodgkin’s disease [HD] and 94 with aggressive non-Hodgkin’s lymphoma [NHL]) were followed-up after the end of front-line treatment. Patients with a positive PET scan of the mediastinum underwent CT scanning and surgical biopsy.Results In 30 (21 HD and 9 NHL) out of 151 patients (20%) a suspicion of lymphoma relapse was raised based on positive mediastinal PET scanning. Histology confirmed this suspicion in 17 (10 HD and 7 NHL) out of 30 patients (57%), whereas either benign (9 fibrosis, 3 sarcoid-like granulomatosis) or unrelated neoplastic conditions (1 thymoma) were demonstrated in the remaining 13 patients (43%). SUVmax was significantly higher among patients who had signs of relapse (17 true positive cases) than among those who stayed in remission (13 false positive cases), the median values being 5.95 (range, 3.5–26.9) and 2.90 (range, 1.4–3.3), respectively (p=0.01).Interpretation and Conclusions We suggest that a positive PET scan of the mediastinum of a patient being followed-up for a mediastinal lymphoma should not be considered sufficient for diagnostic purposes in view of its lack of discrimination. Histological confirmation can safely be carried out with various biopsy techniques, the choice of which should be made on the basis of the findings of the clinical and imaging studies of the individual case.