Lymphadenopathies before and during the Pandemic COVID-19: Increasing Incidence of Metastases from Solid Tumors.

Since December 2019, the world has experienced a pandemic caused by SARS-CoV-2, a virus which spread throughout the world. Anti-COVID19 measures were applied to limit the spread of the infection, affecting normal clinical practice. In 2020, studies on the possible impact of the pandemic considering the screening programs for early diagnosis of cancer were conducted, resulting in a prediction of delayed diagnosis of cancer. We performed a retrospective monocentric study on patients who present with the onset of lymphadenomegalies evaluated at our Hematological Department from February 2019 to October 2021 and undergoing excisional lymph-node biopsy. Three periods were considered: pre-pandemic, first pandemic period and second pandemic period (Group A, B and C). We included 258 patients who underwent a surgical biopsy and received a histological diagnosis. Hematological evaluation of outpatients sent by the general practitioner and surgical biopsies did not decrease among the three groups, despite limitations placed during this pandemic as well as new diagnoses of hematological malignancies. However, the diagnosis of metastatic cancer significantly increased from 2019 (7.8%) to 2021 (22.1%) (p = 0.042). Our data supports the hypothesis that the pandemic affected the national screening programs of early cancer detection.

Utility of procalcitonin and C-reactive protein as predictors of Gram-negative bacteremia in febrile hematological outpatients.

This study was designed to determine the utility of procalcitonin (PCT) and C-reactive protein (CRP) as predictors of Gram-negative bloodstream infection (GN-BSI) in hematological febrile outpatients at the time of the emergency unit admission. Overall, 286 febrile episodes, which included 42 GN-BSI (16%), were considered. PCT levels at patient admission were statistically higher in GNB-BSI when compared to Gram-positive bacteria BSI (median 4.06 ng/ml (range 1.10-25.04) vs 0.88 ng/ml (0.42-10), p<0.03) and to all other fever etiologies. For CRP, differences within fever etiologies were less profound but statistically significant, except for GN-BSIs vs GP BSIs (p=0.4). ROC analysis of PCT showed that an AUC of 0.85 (95%CI 0.79-0.95) discriminated GN-BSI from all other fever etiologies, with a best cut-off of 0.5 ng/ml, a negative predictive value (NPV) of 98%, and a negative likelihood ratio (negLR) of 0.1. ROC analysis of CRP showed an AUC of 0.67 (95%CI 0.53-0.81) with a best cut-off of 6.64 mg/dl, a NPV of 94%, and a negLR of 0.33. This study confirms that 0.5 ng/ml represents the PCT best cut-off to differentiate the cause of fever and rule out a GN-BSI in febrile hematologic outpatients at the time of the emergency unit admission. Therefore, introducing PCT testing could be a valid measure in order to tailor a more precise prompt antimicrobial therapy to the febrile outpatient while waiting for blood culture results.

Early Palliative Home Care versus Hospital Care for Patients with Hematologic Malignancies: A Cost-Effectiveness Study.

Background: There is paucity of data on the potential value of early palliative home care for patients with hematologic malignancies. Objective: To compare costs, use of resources, and clinical outcomes between an early palliative home care program and standard hospital care for active-advanced or terminal phase patients. Patients and Methods: In this real-life, nonrandomized comparative study, the allocation of advanced/terminal phase patients to either home or hospital was based on pragmatic considerations. Analysis focused on resources use, events requiring blood unit transfusions or parenteral therapy, patient-reported symptom burden, mean weekly cost of care (MWC), cost-minimization difference, and incremental cost-effectiveness ratio (ICER). Results: Of 119 patients, 59 patients cared at home were more debilitated and had a shorter survival than the 60 in hospital group (p = 0.001). Nevertheless, symptom burden was similar in both groups. At home the mean weekly number of transfusions (1.45) was lower than that at hospital (2.77). Higher rate of infections occurred at hospital (54%) versus home (21%; <0.001). MWC for hospitalization was significantly higher in a 3:1 ratio versus home care. Compared with hospital, domiciliary assistance produced a weekly saving of € 2314.9 for the health provider, with a charge of € 85.9 for the family, and was cost-effective by an ICER of € -7013.9 of prevented days of care for avoided infections. Conclusions: Current findings suggest that costs of early palliative home care for patients with hematologic malignancies are lower than standard hospital care costs. Domiciliary assistance may also be cost-effective by reducing the number of days to treat infections.

Catheter-associated bloodstream infections and thrombotic risk in hematologic patients with peripherally inserted central catheters (PICC).

PURPOSE: The use of peripherally inserted central catheters (PICC) as an alternative to other central venous access devices (CVAD) is becoming very frequent in cancer patients. To evaluate the impact of complications associated to these devices in patients with hematologic malignancies, we revised the catheter-related bloodstream infections (CRBSI) and the catheter-related thrombotic complications (CRTC) observed at our institute between January 2009 and December 2012. METHODS: A total of 612 PICCs were inserted into 483 patients at diagnosis or in subsequent phases of their hematologic disease. PICCs were successfully inserted in all cases. The median duration of in situ PICC placement was 101 days (interquartile range, 48-184 days). RESULTS: A CRBSI occurred in 47 cases (7.7 %), with a rate of 0.59 per 1000 PICC days. A CRTC was recorded in 16 cases (2.6 %), with a rate of 0.20 per 1000 PICC days. No serious complication was associated to these events. Cox regression analyses of variables associated to CRBSIs and to CRTCs showed that only the type of disease (acute leukemia compared to other diseases) was significantly associated to a higher incidence of CRBSIs, while no feature was predictive for a higher risk of CRTCs. CONCLUSIONS: PICCs represent a useful and safe alternative to conventional CVAD for the management of patients with hematologic malignancies.

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.

Pain management in hematological patients with major organ dysfunctions and comorbid illnesses.

BACKGROUND: Organ dysfunctions and medical complications, such as renal failure, liver impairment, coagulation disorders, cardiovascular and respiratory illnesses, may hamper an adequate pain management in haematological patients. AIM: To summarize current knowledge on pain management in hematological patients presenting major organ dysfunctions and comorbidity. We also attempted to provide recommendations to optimize analgesia and to minimize side effects in the setting of medically compromised and frail haematological patients. METHODS: A systematic search of the literature, using relevant key words, was conducted in PubMed. RESULTS AND CONCLUSIONS: Pain in hematological patients is a common symptom and is often multi-factorial. Most pharmacotherapeutic measures, including causal therapies, analgesics and adjuvant agents routinely applied in pain management, may also be used in the setting of clinical frailty and medical comorbidities; however, comprehensive clinical and functional patient's evaluations and a careful consideration of expected benefits and potential adverse events are required.

Transfusions at home in patients with myelodysplastic syndromes.

We report descriptive data of a home care (HC) program, throughout a 5-years period (2006-2010), focusing on the reliability and the safety of transfusions at home in 211 patients affected by myelodysplastic syndromes (MDS). Our results outline the potentially relevant role of a specifically dedicated HC service in the global management of frail MDS patients for which transfusions at home may represent a valuable option to maintain a good quality of life and avoid the possible discomfort due to hospital admissions and outpatient visits.

Management of Peritoneal Dialysis within a Home Care Program for Hematological Malignancies: Concerns and Perspectives Illustrated by a Case Report.

The case of an 86-year-old man suffering from acute myeloid leukemia and end-stage renal disease, managed at home, with continuous peritoneal dialysis regimen, is described.

Anticoagulant and Anti-thrombotic Treatments in the Management of Hematological Malignancies in a Home Care Program.

AIM: Anticoagulants (AC) and anti-platelet (AP) agents are widely administered to patients with hematological malignancies (HM). However, HM patients may be at high risk of bleeding and hemorrhagic complications, because of different form of coagulopathies and several degrees of thrombocytopenia. MATERIALS AND METHODS: A prospective evaluation of the use of anticoagulant and anti-thrombotic agents as well as of bleeding and thrombotic complications in a consecutive cohort of patients, which were followed during the first semester of 2010 by our home care service, was performed. In this regard, three pharmacological class of agents, such as oral anticoagulants (warfarin and acenocumarine), low molecular weight heparin (LMWH) and anti-platelet (AP) drugs were considered. RESULTS: Out of 129 patients, 26 (20%) were treated with AC/AP drugs. Warfarin, acenocumarine, LMWH as well as AP were used in 7, 11 and 12 patients, respectively. Adverse events (bleeding) were observed in 3 patients (11.5%), 2 cases being on warfarin (replaced by LMWH) and 1 being AP (suspension without replacement); out of the 3 patients with bleeding, none presented thrombocytopenia. CONCLUSIONS: Despite the frequent findings of hemostatic disorders in a population of frail patients managed in a home care setting, our experience demonstrated that the use of AC/AP drugs has been very rarely responsible for significant complications.

Management of the 2009 A/H1N1 influenza pandemic in patients with hematologic diseases: a prospective experience at an Italian center.

Data derived from epidemiologic surveillance adopted at our center in hematologic and stem cell transplant patients during the 2009 influenza A (H1N1)v pandemic are reported. Of the 52 patients with influenza-like disease we observed, 37 underwent a real-time PCR evaluation and 21 had a confirmed diagnosis. Of the RT-PCR-confirmed cases, 23.8% were children (age <18 years) and 9.5% were >65 years; 47.6% presented with a pulmonary infiltrate and 33.3% with respiratory failure. Pulmonary involvement was observed more frequently in patients with comorbidities. All patients received a course of oseltamivir therapy starting an average of 1 day (range <1-2) after the onset of symptoms. No patient was transferred to the intensive care unit. The viral disease had a generally favorable outcome despite the high frequency of pulmonary involvement. A prompt clinical evaluation with an early antiviral and supportive therapy may have played a beneficial role in the outcome.

Management of hematological malignancies in patients affected by renal failure.

The management of hematological malignancies (HM) in renally impaired patients may be a difficult task. Indeed, the kidney represents a major elimination pathway for many chemotherapeutic agents and their metabolites, whose serum levels are not usually measured in daily clinical practice. In addition, many antineoplastic drugs have a narrow therapeutic index for which they require dose adjustment when administered to patients with renal failure. Only limited data regarding the use of chemotherapy in patients with renal impairment and in those on dialysis are available. Indeed, renal patients with HM are often excluded from most clinical trials. Thus far, in order to provide recommendations, we have reviewed the pertinent literature, gathering information from published guidelines regarding chemotherapy in patients with kidney dysfunction and from articles describing the use of individual agents in renal patients with HM.

Pain in malignant hematology.

Pain is frequently experienced by patients with hematological malignancies, although it often receives little attention. Different underlying causes and mechanisms may sustain several pain syndromes in hematological malignant patients. Pain may be due to disease itself, to disease-related complications, to iatrogenic causes or may be associated with unrelated medical conditions. The management of pain in this setting requires a multidisciplinary approach, integrating analgesics and causal interventions. An accurate diagnostic assessment and the identification of the underlying causes and pathogenetic mechanisms may dictate the treatment approach. For most pain patients, the WHO's three-step analgesic scale for cancer pain relief can provide adequate relief with oral options, although difficult-to-treat pain syndromes, requiring a more complex treatment approach, may also be observed.

Case reports: zoster pain in haematological malignancies: effective pain relief with oxycodone in patients unresponsive to other analgesic measures.

Varicella zoster virus (VZV) outbreak is a significant cause of morbidity in patients suffering from blood-related malignancies, occurring mostly among those affected by lymphoproliferative disorders and in those receiving haematopoietic stem-cell transplantation. The elucidated pathological mechanisms of VZV-related painful complications have provided the rationale for acute zoster pain (AZP) and post-herpetic neuralgia (PHN) treatment with antiviral therapy combined with neuroactive agents, such as tricyclic or anticonvulsant agents. The role of opioids in this setting is less clearly established. We successfully treated (with oxycodone) 12 consecutive patients suffering from AZP and long-lasting PHN resistant to several agents, including anticonvulsants and analgesics. Our experience is reported together with a brief overview of the management of these often distressing and intractable complications.

Cost analysis of a domiciliary program of supportive and palliative care for patients with hematologic malignancies.

The costs of home care (HC) programs may be tailored to the specific needs of patients with hematological malignancies. The aim of this study was to analyze the use of resources and the costs of a program of HC for four different prognostic groups of patients subdivided according to disease status. Over 2 years, 144 patients with hematological malignancies were assisted at home. Patients were subdivided according to disease status and life expectancy in the following groups: (i) terminal phase, with a life expectancy of 3 months or less; (ii) advanced phase, with a life expectancy of 6 months or less; (iii) chronic phase, with a life expectancy of more than 6 months; (iv) discharged early from the hospital with curable disease, following anticancer chemotherapy. Median mean monthly costs (MMC) in Euro (x) have been compared with the costs of hospitalization (DRG). Among the 4 groups of patients, those discharged early and in terminal phase required the highest mean monthly number of home visits (27.2 and 24.1), transfusions (6.1 and 6.8) and days of care (22.8 and 19.7) respectively. MMC were affected by the following variables: disease status and transfusion requirements. MMC for terminal patients (4,232.50x) and those discharged early (3,986.40x) were higher than those for advanced (2,303.80x) and chronic patients (1,488,30x). The cost of HC was lower than the corresponding DRG charges, but exceeded the district fares for HC of cancer patients. In hematological patients, the costs of HC differ according to disease status and transfusion requirements. For some categories of patients, costs of HC are lower than those of hospitalization, although higher than the current national fares for HC programs.

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.