Andrea Tendas

A prospective study comparing quantitative Cytomegalovirus (CMV) polymerase chain reaction in plasma and pp65 antigenemia assay in monitoring patients after allogeneic stem cell transplantation

BackgroundLow levels of Cytomegalovirus (CMV) viral load are frequently detected following allogeneic stem cell transplantation (SCT) and CMV disease may still develop in some allogeneic SCT patients who have negative pp65-antigenemia (pp65-Ag) or undetectable DNA. Pp65Ag is a sensitive method to diagnose CMV infection. Quantitative CMV-DNA PCR assay in plasma has been proposed to monitor CMV infection in SCT patients. We evaluated the clinical utility of pp65Ag and PCR assay in plasma of SCT recipients.MethodsIn a prospective longitudinal study, 38 consecutive patients at risk of CMV infection (donor and/or recipient CMV seropositive) were weekly monitored for CMV infection by both quantitative CMV-PCR in plasma (COBAS AMPLICOR CMV MONITOR) and pp65 Ag, during the first 100 days after SCT.ResultsA total of 534 blood samples were simultaneously analysed for pp65Ag and PCR. Overall, 28/38 patients (74%) had active CMV infection within 100 days from SCT. In 16 patients, CMV was first detected by pp65 Ag alone; in 5 patients by both methods and in 6 by PCR assay alone; one patient had CMV biopsy-proven intestinal disease without pp65Ag and PCR assays positivity before CMV disease. Overall, three patients developed intestinal CMV disease (7.9%): one had negative both pp65Ag and PCR assays before CMV disease, one had disease and concomitant positivity of both methods, while in the remaining patient, only pp65Ag was positive before CMV disease.ConclusionPlasma PCR(COBAS AMPLICOR CMV MONITOR) and pp65Ag assays were effective in detecting CMV infection, however, discordance between both methods were frequently observed. Plasma PCR and pp65Ag assays may be complementary for diagnosis and management of CMV infection.

Breakthrough fusariosis in a patient with acute lymphoblastic leukemia receiving voriconazole prophylaxis.

nema pallidum antibody, and a diagnosis of relapsed secondary syphilis was made. Syphilitic hepatitis was suspected on the basis of a 2-fold increase in the level of alkaline phosphatase from previously normal levels, a 2-fold increase in the level of liver enzymes from baseline, a 5-fold increase in total bilirubin to 1200 mmol/L, and the exclusion of other etiologies, including viral hepatitis (A and B) and alcohol abuse. Two hours after the patient received intramuscular penicillin V, his temperature increased to 39.0ЊC. Within 24 h, the AST and ALT levels had increased to 1331 U/L and 328 U/L, respectively, and by 36 h, the patient was encephalopathic, with an international normalized ratio of 2.16, a total bilirubin of 364 mmol/L (direct bilirubin, 197 mmol/L). A diagnosis of Jarisch-Herxheimer reaction was made. Over the next week in the intensive care unit, the patients condition and liver status stabilized. Further antibiotic therapy for syphilis was administered without incident. The patient was eventually discharged but died of decompensated liver disease 6 months later. Syphilitic infection of the liver is well documented [4–6]. This case illustrates the potential for hepatic complications resulting from syphilitic infection and its treatment in cases of HIV-HCV coinfec-tion. Liver injury due to syphilis is thought to be immune mediated, although obstruction of portal lymph nodes by syph-ilitic adenitis has been proposed. The histological findings are variable and non-specific and include portal inflammatory infiltrates, hepatocellular necrosis, granu-loma, and cholestatis. There is insufficient knowledge of the effects of HIV infection, if any, on the histological manifestations of syphilitic hepatitis. The Jarisch-Herxheimer reaction is clearly life-threatening in patients with preexisting cirrhosis and limited hepatic synthetic reserve. The rapid lysis of spi-rochetes releases heat-stable pyrogen, which produces this febrile illness. It is unclear what influence HIV-related immune suppression has on the severity of this reaction. It is noteworthy that among an HIV-seropositive cohort with syphilitic hepatitis (), no one developed a Jar-n p 7 isch-Herxheimer reaction [7]. Acute hepatitis C in HIV-infected men who have sex with men. HIV Med 2004; 5:303–6. 4. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 27-1983: a 25-year-old homosexual man with persistent fever and liver disease. Sir—Voriconazole is a broad-spectrum triazole antifungal drug with excellent activity against Aspergillus species, most Candida species, and several less-common invasive fungi but with limited activity against pathogenic Zygomycetes. Reports on the successful use of voriconazole therapy for patients …

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.

P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemia

Summary. Concurrent resistance mechanisms, such as P‐glycoprotein (PGP) and bcl‐2, may contribute to a worse outcome in adult acute lymphoblastic leukaemia (ALL). Between 1990 and 2000, we analysed PGP and bcl‐2 by flow cytometry, using two anti‐PGP (C219 and JSB‐1) monoclonal antibodies (mAbs) and an anti‐bcl‐2 mAb in 115 de novo adult ALL patients. Both a longer overall survival (OS) and longer disease‐free survival (DFS) were observed in PGP‐negative patients (23%vs 0% at 3 years, P = 0·011 and 29%vs 0% at 2 years, P = 0·006 for C219 respectively; 42%vs 0% at 1·5 years, P = 0·004 and 53%vs 0% at 8·5 months, P = 0·00006 for JSB‐1 respectively). Bcl‐2 positivity was associated with a significantly higher complete remission rate (90%vs 66%, P = 0·01). Moreover, in 69 patients not presenting with either t(9;22) or B‐mature immunophenotype, PGP negativity (JSB‐1) maintained its significant favourable prognostic impact with regard to OS (41%vs 0% at 1·5 years, P = 0·009) and DFS (83%vs 0% at 6 months, P = 0·0005). Importantly, within a subset of 62 patients with normal (n = 31) or unknown (n = 31) karyotype, PGP (JSB‐1)‐negative patients showed both a significantly longer OS and DFS (63%vs 0% at 1·4 years, P = 0·018 and 84%vs 0% at 6 months, P = 0·001 respectively). In multivariate analysis, JSB‐1 (P = 0·008) and cytogenetics (P = 0·02) were found to be independent prognostic factors with regard to DFS. Therefore, in adult ALL, PGP and bcl‐2 represent sensitive indicators of clinical outcome, and potential targets of novel molecules aimed at overcoming chemoresistance and recurrent relapses.

Pain and anxiety associated with bone marrow aspiration and biopsy: a prospective study on 152 Italian patients with hematological malignancies

Dear Editor, Pain and anxiety associated with bone marrow aspiration and biopsy (BMAB) are frequently encountered by hematologists in daily clinical practice [1–5], about which we have read with much interest what was reported by Degen and colleagues in a previous issue of the journal [6]. In order to address this issue, we have performed a singlecenter prospective survey on patients affected by hematological malignancies (HM) and submitted to BMAB. Between January and June 2010, pain and anxiety were assessed in all adult patients who underwent BMAB. There were 152 HM patients (M/F) with a median age of 54 years (range, 22–91). The main demographic data, hematological diagnoses, and procedure characteristics are reported in Table 1. A careful clinical assessment, including examination of past medical history, allergies, mental status, and review of current medications was performed before the procedure. Adequate information about the scope and indication of the invasive diagnostic maneuver and about all the steps involved in performing it were given by the hematologists at their best; again, patients were invited to formulate any questions about the procedure. All patients were properly informed and gave their written consent to participate in the study. In accordance with our institutional standard operating procedures, BMAB was performed under local anesthesia with 5 ml of lidocaine hydrochloride 1% aqueous solution in the left and/or right posterior superior iliac crest by a skilled hematologist with adequate technical experience. Other than local anesthesia, no other premedication was given. Anxiety before and pain during the procedure were assessed by patient interview 10 min before and 10 min after the procedure, respectively. A numerical rating system (NRS) scale, ranging from 0 (no symptom) to 10 (the worst), was administered to score symptom intensity. In order to explore correlation between anxiety before and pain during the procedure, the incidence of moderate–severe pain (NRS=4–10) in different anxiety severity populations of the cohort was examined. Statistical analysis was performed using Pearsons chi-square test. All 152 patients were evaluable for analysis (Table 2). Anxiety was experienced by 108/152 (71%) patients and scored as mild (1–3), moderate (4–7), and severe (8–10) in 29 (27%), 47 (44%), and 32 (29%) of them, respectively; median anxiety NRS value was 4 (range, 0–10). Pain was reported in 118/152 (78%) patients and scored as mild (1–3), moderate (4–6), and severe (7–10) in 63 (53%), 41 (35%), and 14 (12%) of them, respectively; median pain NRS value was 3 (range, 0–10). By using median anxiety NRS G. A. Brunetti (*) : E. Meloni :D. Mancini : P. Maggiore : C. Cartoni :G. Alimena Division of Hematology, Department of Cellular Biotechnologies and Hematology, University “La Sapienza”, Rome, Italy e-mail: brunetti@bce.uniroma1.it

Hemorrhagic complications in patients with advanced hematological malignancies followed at home: an Italian experience.

Patients with advanced hematological malignancies may experience many troublesome hemorrhagic complications requiring hospitalisation during a palliative home care (HC) program. We report on the feasibility of the management of bleeding at home in patients with haematological malignancies admitted in a domiciliary HC program. The occurrence of a major hemorrhage episode (>1 WHO grade) was registered among 469 patients with hematological malignancies in the terminal phase of their disease followed at home. Number, sites, domiciliary treatment (local hemostatic measures, platelet units, hemostatic drugs, packed red blood cells) and outcome of hemorrhagic complications were evaluated. Out of 469 patients, 123 (26%) experienced a bleeding complication; the overall number of hemorrhagic episodes was 232 (49%) with a median number of 2 episodes per patient. Patients with a platelet count lower than 20 × 109/L (P < 0.00005) or with a diagnosis of acute leukemia or in blast crisis of myeloprolypherative disorders (P < 0.00005) showed a significant higher incidence of hemorrhages than other patients. Resolution of bleeding at home was obtained in 206 (88%) of the 232 episodes; platelet units were transfused at home in 188 (81%) cases. Bleeding was the cause of hospitalisation in four cases. Death occurred in 447 of 469 patients: in 26 of them (6%), it was caused by bleeding complications (11 brain hemorrhage, 2 hematemesis, 3 hemoptysis and 10 melena). In this group of patients, bleeding was a relevant clinical problem However, by implementing a domiciliary palliative care program, home management of hemorrhages proved to be a safe and effective choice.

Pain management in multiple myeloma.

Pain is a prominent feature of multiple myeloma (MM) and may be caused by different underlying causes and mechanisms. Indeed, pain may be due to disease-related complications, iatrogenic causes or may be associated with other unrelated medical conditions. This symptom may be particularly devastating and can negatively affect the quality of life of the afflicted patients and their functional status. For most MM patients suffering from continuous nociceptive pain, the WHO’s three-step analgesic ladder can provide adequate relief with oral options, although the high prevalence in MM patients of difficult-to-treat pains, such as pains due to skeletal mechanical instability or sustained by neuropathic mechanisms, makes the treatment approach a challenging concern. The management of pain in this setting requires a multidisciplinary approach integrating analgesics and causal interventions. This review focuses on the most common syndromes afflicting MM patients, attempting to provide an understanding of the underlying pain mechanisms and a discussion of the most commonly used treatment strategies.

Disability and physical rehabilitation in patients with advanced hematological malignancies followed in a home care program

Dear Editor, Hematological malignancies (HM) in their advanced course may be progressively complicating by debilitating deteriorations of the personal status, physical deconditioning, and several forms of motor disability (MD), often leading to severe limitations in performing activities of daily living and in the loss of the individual independence. Although hematologists are faced with problems arising from functional decline in their daily clinical practice, little information about the exact burden of disability in the HM setting are available, and very few experiences on the role of physical rehabilitation, a part of the management of these patients, have been reported [1, 2]. In order to address this issue, we evaluated the incidence of MD and the feasibility of a rehabilitation program in a group of patients with advanced HM followed by a specialized home care service [3–5]. In this regard, MD was assessed monthly using Barthel index (BI) [6] and was classified as: mild (BI>66%), moderate (BI: 33–66%), and severe (BI<33%). Patients with a BI reduction and life expectancy of more than 3 months were evaluated for a rehabilitative home-based program. Exclusion criteria were: patient refusal, contraindications to mobilization (untreatable osteolytic lesions and skeletal instability), moderate to severe respiratory insufficiency, and severe cognitive impairment. Rehabilitative program was tailored on patient target; feasibility of the program was evaluated by assessing the administered-intensity/planned-intensity ratio. From April 2008 to February 2009, 136 patients entered the study. Median age was of 81 (range, 25–96), 84 males and 52 female. Diagnoses were as follows: acute leukemia, 31; lymphoma/chronic lymphocytic leukemia, 24; multiple myeloma, 13; myelodysplastic/myeloproliferative disorders, 50; and other diagnosis, 18. Out of 136 evaluable patients, 52, 60, 11, 5, and 8 were patients in advanced disease, chronic disease, complete/partial remission (CR/PR), relapse/progression/new diagnosis, and undefined status, respectively. MD was observed in 122/136 patients (90%), being mild, moderate, and severe in 48/122 (39%), 46/122 (38%), and 28 (23%), respectively. Given the burden of disability recorded by us, a pilot interventional study was launched, and 18 patients were offered a rehabilitation program; out of these, three were not eligible, while 15 patients (nine male) with a median age of 75 (range, 37–92) received the planned treatment. Among them, five patients were affected by multiple myeloma, four by myelodysplastic syndromes, two by acute myeloid leukemias, and four by A. Tendas : P. Niscola (*) :M. Ales : L. Baraldi : C. Boschetto : E. Caiazza : L. Cupelli :M. Giovannini : L. Scaramucci : P. de Fabritiis Hematology Unit, S.Eugenio Hospital, Rome, Italy e-mail: pniscola@gmail.com

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

To investigate whether patient‐reported symptoms provide independent prognostic information for survival in patients with hematological malignancies.

Standard dose and prolonged administration of azacitidine are associated with improved efficacy in a real-world group of patients with myelodysplastic syndrome or low blast count acute myeloid leukemia

Azacitidine is the standard of care for higher‐risk myelodysplastic syndromes (MDS). We evaluated factors affecting the outcome of azacitidine treatment in 196 ‘real‐world’ patients, retrospectively collected by two Italian cooperative groups.