Pasquale Niscola

Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome

This study evaluated the impact of a new epoetin alfa dosing regimen on quality of life (QOL), transfusion requirements, and hemoglobin (Hb) levels in 133 patients with low-risk myelodysplastic syndrome (MDS) and Hb ≤10 g/dl. Epoetin alfa 40,000 IU was given subcutaneously twice weekly; after 4 weeks, the dose could be reduced to 40,000 IU weekly in patients achieving erythroid response. QOL was assessed using the functional assessment of cancer therapy-anemia (FACT-An) questionnaire. FACT-An scores increased on average by 7.5 after 4 weeks and by 8.8 after 8 weeks compared with baseline. FACT-An scores were positively associated with Hb values (r=0.53, P<0.01). The mean FACT-An score increase at week 8 was 10.2 in responders and 5.6 in nonresponders. The overall erythroid response rate at week 8 was 68%: 74% in transfusion-independent patients and 59% in transfusion-dependent patients. Of all responders at week 8, response was maintained in 86% at week 12, 71% at week 16, 65% at week 20, and 54% at week 24. Treatment was generally well tolerated. Our data provide new and encouraging results regarding the benefits of 40,000 IU biweekly induction doses followed by 40,000 IU weekly in improving QOL, correcting anemia, and reducing transfusion requirements in low-risk MDS patients.

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.

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.

Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic lymphocytic leukaemia after rituximab therapy.

Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic lymphocytic leukaemia after rituximab therapy

Systematic review of amifostine for the management of oral mucositis in cancer patients

PurposeThe aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients.MethodsA systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible.ResultsThirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence.ConclusionReview of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.

The use of major analgesics in patients with renal dysfunction.

Pain in patients with impaired renal function may be a significant problem requiring treatment with opioids. However, pharmacokinetic and metabolic changes associated with an impaired renal function may raise some concerns about side effects and overdosing associated with opioid agents in this patients population. In order to give recommendations on this issue, we review the available evidences on the pharmacokinetics and side effects of most common opioids used to treat pain. The results of this review show that the half-life of the parent opioid compounds and of their metabolites is increased in the presence of renal dysfunction, for which careful monitoring of the patient, dose reduction and a longer time interval between doses are recommended. Among opioids, morphine and codeine used with very caution and possibly avoided in renal failure/dialysis patients; tramadol, hydromorphone and oxycodone can be used with caution and close patients monitoring, whereas transdermal buprenorphine, methadone and fentanyl/sufentanil appear to be safe to use in patients with renal failure.

Pain Syndromes in Sickle Cell Disease : An Update

OBJECTIVE Pain has a critical role in the management of sickle cell disease (SCD). Patients may suffer from several pain syndromes, which may be or not may be associated with other clinical complications, such as anemia, organ failures, and infections. DESIGN Data for review were identified by using PubMed to search MEDLINE, limiting the search to abstract/articles in English, Italian, French, and Dutch. The key words pain, sickle cell disease, anemia, hemoglobin, hemoglobinopathy, analgesics, opioids, morphine, acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, hematology, and quality of life were variously combined in the title, abstract, and key word search list. The abstract database of most hematological congresses and the bibliographies of most relevant articles were also considered. RESULTS There are two major types of SCD pain: acute and chronic. Sometimes, mixed and neuropathic pain can be also observed. Acute pain is mostly related to vaso-occlusion. Chronic pain may be due to some SCD complications, such as leg ulcers and avascular necrosis. CONCLUSIONS Pain management in the SCD setting needs multidisciplinary approaches, given the several syndromes and the pathogenic mechanisms that are likely involved. Pain management is not standardized and often difficult, so that many patients with SCD are still poorly treated. Further efforts to develop care plans and treatment protocols as well as management guidelines are required.

Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study.

BACKGROUND The clinical presentation of myelodysplastic syndromes is highly variable and so accurate prediction of outcomes in these patients is crucial. We aimed to assess whether self-reported fatigue severity predicts overall survival beyond gold-standard prognostic indices in patients with higher-risk myelodysplastic syndromes. METHODS We did a multicentre, prospective, observational, cohort study of patients from 37 centres in Europe, USA, and east Asia. Adults (≥18 years) with myelodysplastic syndromes were consecutively enrolled within 6 months of diagnosis with an intermediate-2-risk or high-risk score according to the International Prognostic Scoring System (IPSS). Patients were enrolled irrespective of older age, comorbidities, performance status, and progression from a lower IPSS risk score category. All patients had to complete a quality of life assessment at baseline. With use of univariate and then multivariate Cox proportional hazards regression analysis, we constructed a multivariate model of how prognostic variables, including IPSS and fatigue score from the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-core 30, predicted overall survival. The primary endpoint was overall survival by baseline self-reported fatigue scale ratings. This study was registered with ClinicalTrials.gov, number NCT00809575. FINDINGS Between Nov 10, 2008, and Aug 13, 2012, we enrolled 280 patients with a median age of 71 years (IQR 64-77). The median follow-up was 15 months (IQR 8-27), and the last patient was assessed Feb 16, 2015. The median overall survival from diagnosis was 17 months (95% CI 15-19). In univariate analysis, the baseline factors that were significantly associated with reduced overall survival were increasing age, transfusion dependency (defined as having received at least one red blood cell transfusion every 8 weeks over a period of 4 months), Eastern Cooperative Oncology Group (ECOG) performance status of two or more, increased white blood cell count, high-risk IPSS score, and higher self-reported fatigue severity. In multivariate analysis, baseline factors independently associated with reduced overall survival were high-risk IPSS score (hazard ratio [HR] 2·525, 95% CI 1·357-4·697; p=0·0035) and a higher score for fatigue (1·110, 1·040-1·170, for every ten points of fatigue deterioration; p=0·0007). In further multivariate models for survival, including either the WHO-based prognostic scoring system or the revised version of the IPSS classification, fatigue remained a statistically significant independent prognostic factor with a HR of 1·120 (1·050-1·180, p=0.0003) and a HR of 1·130 (1·060-1·190, p=0·0002), respectively. INTERPRETATION In patients with newly diagnosed higher-risk myelodysplastic syndromes, self-reported fatigue severity provides prognostic information for survival independent from gold-standard risk classifications. Our findings suggest that fatigue assessment should be included in routine diagnostic investigation for these patients and considered as a standard baseline stratification factor in future randomised controlled trials. FUNDING Associazione Italiana contro le Leucemie, Linfomi e Mieloma (AIL).

Rapid loss of response after withdrawal of treatment with azacitidine: a case series in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia

In patients with myelodysplastic syndromes (MDS), the likelihood of having a sustained response to azacitidine is increased by maximizing treatment duration. This is important as prognosis postrelapse is poor. There is also the concern that early termination of treatment may result in rapid disease progression. We reviewed outcomes in 13 patients who discontinued azacitidine (decitabine in one patient) while still responding to the treatment. Most patients rapidly relapsed; median time to progression was 5.4 months. Reasons for treatment discontinuation included comorbidities, infections, and patient choice. These findings illustrate the risk of prematurely terminating azacitidine therapy in MDS.

Epidemiology, features and outcome of pain in patients with advanced hematological malignancies followed in a home care program: an Italian survey

We report on epidemiology, features, outcome, and domiciliary management of pain in patients with advanced hematological malignancies followed by an experienced hospital-based home care (HC) team. Out of 469 patients, 244 (52%) experienced a total of 284 pain syndromes. Pain intensity was rated from mild to moderate in 31% and from moderate to severe in 69% of them. The diagnosed pain mechanisms were deep somatic in 56%, superficial somatic in 15%, visceral 14%, mixed 8%, and neuropathic in 7% of pain syndromes, respectively. Incident pain was observed in 38% of all pain syndromes. In every diagnostic group, deep somatic pain was prevalent. Moreover, 85% of visceral pain syndromes were observed in patients affected by non-Hodgkin’s lymphoma (NHL). In addition, out of 284 pain syndromes, 150 (51%) were caused by bone involvement. The most frequent recognized pain provocative mechanisms were bone marrow expansions, osteolysis, lymph node enlargement, and mucositis. In our experience, an approach based on the association of causal therapies and analgesics allows optimal control of most pain syndromes. Therefore, pain is a major problem in patients affected by advanced hematological malignancies, and its management can be effective and feasible when carried out by a skilled HC team.