Treatment of Agitation With Lorazepam in Clinical Practice: A Systematic Review.

Acute agitation is a frequent occurrence in both inpatient and outpatient psychiatric settings, and the use of medication to calm a patient may be warranted to mitigate the situation. Lorazepam is a benzodiazepine that is widely used for management of acute agitation. Despite its widespread use, there is remarkably little clinical evidence for the benefits of lorazepam in acute agitation. We performed a systematic review with focus on lorazepam, including all randomized clinical trials on lorazepam in mental and behavioral disorders, excluding studies on dementia and pediatric patients and in mixed conditions. A total of 11 studies met inclusion criteria, and all were in patients with mental and behavioral disorders. Most trials generally found improvements across a variety of outcomes related to agitation, although there was some disparity if specific outcomes were considered. In the five studies with haloperidol, the combination of lorazepam and haloperidol was superior to either agent alone, but with no differences between monotherapy with the individual agents. In the study comparing lorazepam to olanzapine, olanzapine was superior to lorazepam, and both were superior to placebo. As expected, the safety of lorazepam among the different studies was consistent with its well-characterized profile with dizziness, sedation, and somnolence being the most common adverse events. Based on this structured review, lorazepam can be considered to be a clinically effective means of treating the acutely agitated patient.

Patients with juvenile idiopathic arthritis become adults: the role of transitional care.

Most juvenile idiopathic arthritis (JIA) patients need to attend adult rheumatology centres to continue the clinical management of their disease and to receive adequate long-term treatment. Transition from the paediatric to the adult health care team is a critical moment in the clinical history of these patients, but unfortunately, about 50% of the transfer processes to adult rheumatology are not successful, putting these patients at high risk of unfavourable outcomes. There are several obstacles to the success of transitional care for JIA patients, such as the absence of specific criteria for the assessment of disease activity, the lack of specific treatment recommendations for JIA adult patients, the poor adolescent-specific training for adult rheumatologists, and the shortage of resources. The improvement in the transition process in medical care has become a priority in many health care systems, but not many studies evaluating transition models, and common methodologies for measuring transition outcomes are available. The aim of this review is to identify and describe the models of transitional care in JIA, providing insights and recommendations to develop effective transitional care models in this disease.

Prospective study of hepatitis B virus reactivation in patients with hematological malignancies.

BACKGROUND AND AIM: The best strategy for managing patients with resolved hepatitis B virus infection (HBsAg negative, anti-HBc antibodies positive with or without anti-HBs antibodies) and hematological malignancies under immunosuppressive therapies has not been defined. The aim of this study was to prospectively analyze the risk of hepatitis B virus reactivation in these patients. MATERIAL AND METHODS: Twenty-three patients (20 positive for anti-HBs) were enrolled. Eleven patients underwent hematopoietic stem cell transplantation (autologous in 7 cases, allogeneic in 4 cases) while the remaining 12 were treated with immunosuppressive regimens (including rituximab in 9 cases). RESULTS: During the study no patient presented acute hepatitis. However, three anti-HBc/anti-HBs positive patients who were treated with allogeneic hematopoietic stem cell transplantation demonstrated hepatitis B virus reactivation within 12 months from transplant. No one of the remaining patients showed hepatitis B virus reverse seroconversion. CONCLUSIONS: Allogeneic hematopoietic stem cell transplantation is a high risk condition for late hepatitis B virus reactivation in patients with resolved infection. Reverse seroconversion seems to be a rare event in anti-HBc/anti-HBs positive patients submitted to autologous hematopoietic stem cell transplantation or systemic chemotherapy with or without rituximab.

Recombinant human erythropoietin in very elderly patients with myelodysplastic syndromes: results from a retrospective study.

Myelodysplastic syndromes (MDS) are common in elderly patients. Recombinant human erythro-poietin (rHuEPO) has been widely used to treat anemia in lower risk MDS patients, but few data are known about rHuEPO treatment in the very elderly patient group. In order to investigate the role of rHuEPO treatment in terms of response, overall survival (OS), and toxicity in a very elderly MDS patient group, 93 MDS patients treated with rHuEPO when aged ≥80 years were selected among MDS cases enrolled in a retrospective multicenter study by the cooperative group Gruppo Romano Mielodisplasie (GROM) from Jan 2002 to Dec 2010. At baseline, median age was 82.7 (range 80-99.1) with a median hemoglobin (Hb) level of 9 g/dl (range 6-10.8). The initial dose of rHuEPO was standard (epoetin alpha 40,000 IU/week or epoetin beta 30,000 IU/week) in 59 (63.4 %) patients or high in 34 (36.6 %) (epoetin alpha 80,000 IU/week) patients. We observed an erythroid response (ER) in 59 (63.4 %) patients. No thrombotic event was reported. Independent predictive factors for ER were low transfusion requirement before treatment (p = 0.004), ferritin <200 ng/ml (p = 0.017), Hb >8 g/dl (p = 0.034), and a high-dose rHuEPO treatment (p = 0.032). Median OS from rHuEPO start was 49.3 months (95 % CI 27.5-68.4) in responders versus 30.6 months (95 % CI 7.3-53.8) in resistant patients (p = 0.185). In conclusion, rHuEPO treatment is safe and effective also in the very elderly MDS patients. However, further larger studies are warranted to evaluate if EPO treatment could be worthwhile in terms of quality of life and cost-efficacy in very old patients.

A retrospective study on 73 elderly patients (≥75years) with aggressive B-cell non Hodgkin lymphoma: clinical significance of treatment intensity and comprehensive geriatric assessment.

OBJECTIVE: The clinical outcome of elderly (≥75years) patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL) is not firmly established because few studies have specifically addressed this issue. In addition, the usefulness of a comprehensive geriatric assessment (CGA) in B-NHL still needs to be deeply explored. MATERIALS AND METHODS: We evaluated the prognostic factors of 73 patients aged ≥75years (median age: 78) with B-NHL treated by clinical judgment with curative anthracycline-based approaches (n=36) or with conservative treatments without anthracyclines (n=37). Analysis of clinical outcomes also included baseline CGA stratification. RESULTS: The curative approaches resulted in a better clinical outcome than conservative approaches [overall response rate: 91.2% vs. 69.7%, P=0.003; 2-year progression-free survival: 47.2% vs. 21.6%, P=0.006; and 2-year overall survival (OS): 58.3% vs 24.3%, P=0.003] with similar safety profiles. Independent of treatment type, patients classified as "fit" and "intermediate" by CGA presented with better OS compared to patients classified as "frail" (P<0.001). Patients classified as "fit" and "intermediate" who were receiving curative treatments presented with a significantly better OS when compared with those treated conservatively on the basis of clinical judgment. A curative anthracycline-based therapy (P=0.048), the response to treatment (P=0.017) and a "frail" condition (P=0.031) were the only factors affecting OS in multivariate analysis. CONCLUSIONS: Present data indicates that even in elderly patients with B-NHL curative anthracycline-based therapies are more effective than conservative approaches. However, choice of treatment should rely more on objective than on subjective parameters. Therefore, further prospective trials are warranted to better define the CGA role in hematopoietic malignancies.

Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database.

PURPOSE: The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior. PATIENTS AND METHODS: We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data. RESULTS: We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis. CONCLUSION: Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.

The potential role of pre-transplant HBcIgG seroposivity as predictor of clinically relevant cytomegalovirus infection in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation: a study from the Rome Transplant Network.

Despite the increased use of intensive immunosuppressive chemo-immunotherapies in patients with lymphoma observed in the last decade, current data on cytomegalovirus (CMV) infection following autologous stem cell transplantation (Auto-SCT) are very limited. To address this peculiar aspect, a retrospective study on a cohort of 128 adult patients consecutively transplanted for lymphoma in three Hematology Institutions was performed with the aim to determine the incidence of and the risk factors for CMV symptomatic infection and/or end-organ disease. Sixteen patients (12.5%) required specific antiviral therapy and 4/16 died (25%); transplant-related mortality (TRM) was significantly influenced by CMV infection (P = 0.005). In univariate analysis, a pre-transplant HBcIgG seropositivity, HBV infection according to clinical-virological definitions, a pre-transplant Rituximab treatment, a diagnosis of B-cell non-Hodgkin lymphoma, and age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection. In multivariate analysis, only a pre-transplant HBcIgG seropositivity (P = 0.008) proved to be an independent predictor of a clinically relevant CMV infection. These results suggest that a pre-transplant HBcIgG seropositivity could be considered as an independent predictor factor of clinically relevant CMV infection after Auto-SCT.

FCR (Fludarabine, Cyclophosphamide, Rituximab) regimen followed by 90Yttrium ibritumomab tiuxetan consolidation for the treatment of relapsed grades 1 and 2 follicular lymphoma: a report of 9 cases.

BACKGROUND: This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR. METHODS: The median age was 63 yrs (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25 mg/m2x 3 days), C (1 gr/m2 day 1) and R (375 mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with < 25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. RESULTS: Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 34 months (range 13-50) the current analysis has shown that overall survival (OS) is 89% at 2 years, 76% at 3 years and 61% at 4 years. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection. CONCLUSIONS: Our experience indicate feasibility, tolerability and efficacy of FCR regimen followed by 90Y-RIT in patients relapsed with grades 1 and 2 FL with no unexpected toxicities. A longer follow up and a larger number of patients with relapsed grades 1 and 2 FL are required to determine the impact of this regimen on long-term duration of response and PFS.

Standard- versus high-dose lenograstim in adults with hematologic malignancies for peripheral blood progenitor cell mobilization.

BACKGROUND: The aim of this retrospective, multicenter study was to compare high- versus standard-dose lenograstim after chemotherapy in collecting target dose of CD34+ peripheral blood progenitor cells (PBPCs) in adult candidates for autologous transplant. STUDY DESIGN AND METHODS: A total of 166 consecutive patients (28 acute leukemias [ALs], 77 lymphomas, 61 multiple myeloma [MM]) underwent 182 mobilization procedures. Only the first were analyzed. The CD34+ cell target was at least 2×10(6) , 4×10(6) , and 8×10(6) /kg and lenograstim started on days +19, +1, and +5 from the end of chemotherapy for AL, lymphomas, and MM, respectively. Eighty-seven and 79 patients, respectively, received 5 and 10µg/kg/day lenograstim subcutaneously (sc). An analysis to evaluate factors predicting satisfactory procedures and outcome of transplants performed with first-mobilization-procedure PBPCs was conducted. Most patients received 6mg of pegfilgrastim or 5µg/kg/day lenograstim sc after transplant. RESULTS: In multivariate analysis, high-dose lenograstim (p=0.053) in MM and male sex (p=0.028) were positive predictive factors for reaching cell target. Fludarabine negatively influenced stimulation length (p=0.002). Apheresis, CD34+ cells mobilized and collected, blood volume processed, side effects, transplants performed, and engraftment time were similar between lenograstim cohorts. Pegfilgrastim versus lenograstim delayed platelet (PLT) recovery times (13 days vs. 11 days, p=0.036). CONCLUSIONS: High-dose lenograstim more efficiently mobilized MM patients requiring the highest PBPC target but did not influence transplants performed and engraftment time. Male patients mobilized more efficiently. Fludarabine negatively influenced stimulation length. Finally, pegfilgrastim seems to delay PLT recovery.

Budd-Chiari syndrome as the first manifestation of polycythemia vera in young women with inherited thrombophilic state: an aggressive form of myeloproliferative disorder requiring multidisciplinary management.

The Budd-Chiari syndrome (BCS), characterized by the obstruction and occlusion of the suprahepatic veins, is a rare but typical complication occurring in patients with polycythemia vera (PV). We describe three young women who developed BCS as first manifestation of PV, in association with an inherited thrombophilic state and in the absence of concomitant use of oral contraceptives. Our report illustrates the existence of an aggressive form of myeloproliferative disorder, which requires prompt recognition and immediate therapeutic intervention including cytostatic drugs and anticoagulant treatment. Furthermore, we suggest the need of routine screening for thrombophilic state in young women affected by PV.

Clinico-pathological characteristics of myeloid sarcoma at diagnosis and during follow-up: report of 12 cases from a single institution.

The aim of this study was to describe the presenting features, the frequency and outcome of myeloid sarcoma (MS) diagnosed in our Institution from January 1995 to December 2000. Twelve MS were seen and the frequency account for only 2% of all acute myeloid leukemia (AML) patients observed in our department in the same period. Median age was 45 years (range: 4-84). All had been initially misdiagnosed as malignant lymphoma (ML) and a median of 2.9 months (range: 1-6) elapsed between the misdiagnosis and the correct of MS, effectuated in our department. At that time, a bone marrow examination revealed a myelodysplastic condition in seven patients, an infiltration by blast cells >30% in two patients, and normal features in the other three. In the non-leukemic patients a median of 5 months (range: 2-44 months) elapsed between the diagnosis of MS and acute leukemia. In all, 10 patients received intensive treatment. A total of seven patients (70%) achieved MS complete remission (CR). Patients who presented isolated skin localization and received only radiotherapy, obtained a MS-CR, but subsequently developed AML. Only in patients who were treated within 4 months from the initial ML diagnosis we achieved complete remission of both MS and leukemia, whereas in patients who were treated after this time, we obtained a complete disappearance of MS without response at the bone-marrow level, irrespectively of the specific therapy regimen. Median survival time from MS diagnosis was 7 months (range: 1-49 months), and only one patient is still alive, 49 months after bone marrow transplantation. Our data stress the importance of an accurate and prompt identification of this rare form of AML, and suggest that, even in patients with isolated MS, the early administration of AML-like intensive chemotherapy followed by bone marrow transplantation might reduce the risk of subsequently developing systemic disease.

Granulocytic sarcoma of the pancreas successfully treated with intensive chemotherapy and stem cell transplantation.

A case of preleukemic granulocytic sarcoma of pancreas is presented. Pancreas is a well described site of secondary metastasis of solid tumors, but occasionally it has been reported as the primary site of leukemia. Like other cases reported in the literature, the present case was initially misdiagnosed as malignant lymphoma. We highlight the importance of an accurate immunohistochemical diagnosis and of an early and intensive acute myeloid leukemia-like treatment for these cases representing an uncommon and aggressive form of acute leukemia.

Cutaneous pleomorphic T-cell lymphoma coexisting with myelodysplastic syndrome transforming into acute myeloid leukemia: successful treatment with a fludarabine-containing regimen.

The coexistence of a primary myelodysplastic syndrome (MDS) and a T-cell cutaneous non-Hodgkin's lymphoma is an extremely rare event, which has so far only been reported in a single instance in the literature. We describe herein an additional case in which the lymphoid disease was combined with an MDS at the time of its evolution into acute myeloid leukemia (AML). Both diseases were successfully treated with a regimen containing fludarabine. We discuss possible pathogenetic mechanisms and suggest the use of nonalkylating drugs, such as fludarabine, for the treatment of this rare association of malignancies usually characterized by a very poor response to therapy.