Anagrelide in Essential Thrombocythemia (ET): Results from 150 patients over 25 years by the "Ph1-negative Myeloproliferative Neoplasms Latium Group".

BACKGROUND AND AIMS: Anagrelide is a drug effective in reducing platelet counts in essential thrombocythemia (ET) and Ph1-negative myeloproliferative neoplasms. The aim of this study was to evaluate the real-life use of anagrelide in patients with ET followed over 25 years at the Haematological Institutes belonging to "Ph1-negative Myeloproliferative Neoplasms Latium Group." PATIENTS AND METHODS: Eligibility criteria were diagnosis of ET and treatment with anagrelide. Data were collected through an ad hoc case report form. RESULTS: One hundred and fifty patients received anagrelide for a median time of 7.4 years (0.1-23.2). Anagrelide was administered as first-line therapy in 34.7% of patients, as second-line in 52% and as third-line in 13.3%: 85.4% responded to therapy. Sixty-eight/136 evaluable patients reported side effects: palpitations, peripheral vasodilation, anaemia, diarrhoea and gastric distress. Fourteen thrombotic (arterial 10, venous 4) and 51 bleeding events (minor 48, major 3) occurred. Sixteen/150 (10.6%) patients developed secondary myelofibrosis and 3/150 (2%) an acute myeloid leukaemia. CONCLUSIONS: In our experience, anagrelide is an effective drug in reducing platelet levels in a high percentage of patients with ET. It is especially addressed to younger people. A careful assessment of the thrombotic risk and monitoring of cardiac function, at diagnosis and during follow-up, is mandatory.

Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients.

The clinical outcome, response to treatment, and occurrence of acute complications were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and correlated with serological characteristics and severity of anemia at onset. Patients had been followed up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly direct antiglobulin test negative). The latter 2 categories more frequently showed a severe onset (hemoglobin [Hb] levels ≤6 g/dL) along with reticulocytopenia. The majority of warm AIHA patients received first-line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants, and rituximab. The cumulative incidence of relapse was increased in more severe cases (hazard ratio 3.08; 95% confidence interval, 1.44-6.57 for Hb ≤6 g/dL; P < .001). Thrombotic events were associated with Hb levels ≤6 g/dL at onset, intravascular hemolysis, and previous splenectomy. Predictors of a fatal outcome were severe infections, particularly in splenectomized cases, acute renal failure, Evans syndrome, and multitreatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians.

Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease.

The main objective of this study was to compare health-related quality of life (HRQOL) of primary immune thrombocytopenia (pITP) patients with that of general population, overall, and by patient group (i.e., newly diagnosed, persistent, and chronic patients). Fatigue was also investigated as a secondary objective. Overall, 424 adult patients were enrolled in a multicenter observational study and the control group consisted of a representative sample from the general population. Propensity score matching plus further multivariate linear regression adjustment was used to compare HRQOL outcomes between pITP patients and general population. Mean age of patients was 54 years. Of those with HRQOL assessment, 99 patients (23.6%) were newly diagnosed, 53 (12.6%) were persistent, and 268 (63.8%) were chronic pITP patients. Comparison by patient group versus their respective peers in the general population revealed greater impairments in persistent pITP patients. Persistent pITP patients reported clinically meaningful impairments in physical functioning (-15; 95% CI -24.1 to -5.8; P = 0.002), social functioning (-15.3; 95% CI -25.5 to -5.1; P = 0.004), role physical (-28.4; 95% CI -43.1 to -13.7; P < 0.001), role emotional (-23.9; 95% CI -40.1 to -7.7; P = 0.004), and mental health scales (-11.3; 95% CI -21.2 to -1.4; P = 0.026) of the SF-36 questionnaire. Higher fatigue severity was associated with lower physical and mental HRQOL outcomes. Our findings suggest that the burden of the disease and treatment might depend on the disease phase and that persistent pITP patients are the most vulnerable subgroup. Am. J. Hematol. 91:995-1001, 2016. © 2016 Wiley Periodicals, Inc.

Caring for terminal patients in haematology: the urgent need of a new research agenda.

Although major therapeutic advances have led to improved survival for many hematologic malignancies in recent years, survival remains poor for some disease subtypes and a substantial proportion of patients are ultimately destined to die from their disease and/or related complications. Despite this, there is evidence that patients are not always referred to palliative/home care services as often as those with other cancers, although this situation may be improving in some areas. More research is needed, however, to explore reasons for this and identify whether patients may consequently have unmet needs that impact on their quality of life at this time.

Predicting survival in advanced hematologic malignancies: do patient-reported symptoms matter?

OBJECTIVE: To investigate whether patient-reported symptoms provide independent prognostic information for survival in patients with hematological malignancies. STUDY DESIGN AND SETTING: Overall 119 patients with various diagnoses were recruited in an observational study and symptoms were assessed with the M.D. Anderson Symptom Inventory (MDASI). Key potential socio-demographic, biomedical, and physician-reported prognostic candidates were also considered. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. Additional sensitivity analysis, based on 500 bootstrap-generated simulation datasets, was also performed to confirm the results obtained with the Cox regression model. RESULTS: The median survival of the entire cohort was 4.8 months (range 0-28 months). The MDASI was completed at baseline by 91% of patients. The final multivariate model retained two parameters as independent prognostic factors for survival: clinical prognostic group and patient's self-reported severity of drowsiness. The following hazard ratios (HR) were found for curable vs. terminal: 0.055 (95% CI, 0.022-0.136; P < 0.001) and 0.193 (95% CI, 0.103-0.362: P < 0.001) for advanced vs. terminal. Patient's self-reported severity of drowsiness independently predicted survival with a HR of 1.801 (95% CI, 1.044-3.107; P = 0.033). Additional sensitivity analysis confirmed the independent prognostic value of variables identified in this study. CONCLUSION: The results suggest that patients' self-reporting of symptoms provides independent prognostic information for survival in patients with hematologic malignancies. These findings underscore the value of collecting patient-reported symptom data in routine clinical practice.

Controlled-release oxycodone for the treatment of bortezomib-induced neuropathic pain in patients with multiple myeloma.

PURPOSE: Bortezomib, a proteasome inhibitor drug very effective against multiple myeloma, may induce the so-called bortezomib-induced peripheral neuropathy (BIPN), hardly manageable with common analgesic drugs. This study assessed the effectiveness of controlled-release (CR) oral oxycodone in controlling pain and its interference on daily functions of patients with hematologic malignancies affected by BIPN. METHODS: Forty-six patients (median age, 62 years) affected by myeloma and lymphoma, complaining of BIPN-related pain of moderate-to-severe intensity and unresponsive to previous analgesic treatments, were treated with CR oxycodone. The intensity of continuous and brief pain (BP) along with interference of pain with the common daily dimensions of feeling and function were evaluated by using an 11-point numerical rating scale (NRS); a global patient evaluation of efficacy was also performed. RESULTS: The daily average dose of CR oxycodone administered was 28.46 mg (range, 20-80 mg). The pain intensity decreased from a mean NRS value of 7.6 at baseline to 1.3 on day 14. The frequency of BP was reduced from 61 to 47% of patients and its intensity from 7.4 to 3.1 NRS score. A similar trend to decreasing values was observed for all the daily life functions. Slight- or mild-intensity side effects were observed in 23 patients (51%). At the end of the study, 75% of patients found the treatment effective or very effective. CONCLUSION: CR oxycodone for relief of BIPN-related pain was effective and well tolerated. The pain control significantly improved also the quality of the daily life functions, which are usually compromised in these suffering patients.

[Membranous glomerulonephritis secondary to allogeneic stem cell transplant: review of the literature]. / La glomerulonefrite membranosa secondaria al trapianto allogenico di cellule staminali: rassegna della letteratura.

Renal injury associated with hematopoietic stem cell transplant (HSCT) may be related to a combination of factors. Chronic graft-versus-host disease (cGVHD) is the most common complication of allogeneic HSCT. Although the kidneys are not considered the primary target organs for GVHD, chronic impairment of renal function may occur in 20% to 60% of HSCT patients. Membranous glomerulonephritis (MG) is the most frequent renal complication observed in patients who develop nephrotic syndrome after allogeneic HSCT. In this setting, the pathogenesis of MG is not clearly understood and the most appropriate treatment approach has not been established. In order to summarize the current knowledge on this issue, a review of the pertinent literature has been performed. The available data on MG diagnosed in patients submitted to allogeneic HSCT were identified using the MEDLINE database (last accessed: Jan 30, 2012). Fifty-nine patients with allogeneic HSCT-related MG with a median age of 43 years were identified. MG occurred at a median time of 17 months after allogeneic HSCT. A history of acute or concomitant clinically apparent cGVHD was present in 69% and 31% of cases, respectively. cGVHD, nonmyeloablative conditioning regimens, immunosuppression withdrawal, and the use of peripheral blood stem cell grafts were identified as risk factors. Among the 53 patients with available outcome data, complete remission, partial response, and inefficacy of treatment were recorded in 65%, 22% and 13% of cases, respectively. MG after allogeneic HSCT seems to be etiologically related to subclinical or overt cGVHD, which flares up after discontinuation of immunosuppression. The available measures can induce sustained long-term remission in about two-thirds of affected patients.

[Opioid analgesics in patients with chronic renal failure: principles for use and current guidelines]. / Analgesici oppioidi in pazienti con insufficienza renale cronica: principi d'impiego e raccomandazioni correnti.

The treatment of pain in patients with impaired renal function may be problematic, especially when opioid drugs need to be used. In the presence of renal failure, significant changes occur in the metabolism and pharmacokinetics of these drugs, which can lead to adverse reactions due to the accumulation of parental compounds and active metabolites. This paper presents and discusses the available evidence concerning the optimal use of the most frequently employed opioid analgesics to treat pain in patients with renal impairment.

Long-term favorable results by arteriovenous graft with Omniflow II prosthesis for hemodialysis.

AIMS AND METHODS: In order to decrease arteriovenous graft (AVG) failure and improve long-term patency, we used Omniflow II to perform AVG for hemodialysis access in 38 patients with very compromised vessels who were not suitable for other forms of AVG. RESULTS: At a median follow-up of 38 (range 6-55) months, 31/38 (81%) patients were still alive. At 6, 12, 18 and 24 months, the primary patency was 83, 80, 68 and 60%, whereas the secondary patency was 92, 83, 78 and 75%,respectively [corrected].The cumulative 38-month prosthetic AVG patency was 70%. No infective event related to the vascular prosthesis occurred. Neither AVG thrombosis nor modifications in thrombophilic pattern were observed; these findings confirm the high hemocompatibility of this prosthetic vascular device. CONCLUSION: Our experience is extremely encouraging for the use of new biosynthetic devices such as Omniflow II.