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.
Patients with hematological malignancies and past serological evidence of hepatitis B are at risk for HBV reactivation. In myeloproliferative neoplasms, continuous treatment with the JAK 1/2 ...inhibitor ruxolitinib confers a moderate risk of reactivation (1-10%); nevertheless, no prospective randomized data are available to strongly recommend HBV prophylaxis in these patients. Here, we report a case of primary myelofibrosis and past serological evidence of HBV infection, treated with ruxolitinib and concomitant lamivudine, developing HBV reactivation due to premature withdrawal of prophylaxis. This case underlines the potential need for persistent HBV prophylaxis in the setting of ruxolitinib treatment.
We describe a case of second primary malignancy in a 65-year-old patient affected by polycythemia vera treated with the JAK 1/2 inhibitor ruxolitinib. The latter is recognized as a risk factor for ...the onset of non-melanoma skin cancers in many retrospective and perspective studies, but the concomitant use of ruxolitinib with new immunotherapies is very rarely reported, and the safety of this association is still not clear. In our case, ruxolitinib combined with the anti-PD-L1 avelumab demonstrated both safety and efficacy for hematological disease control and underlying carcinoma remission.
This case report presents a 3-year-old female patient initially diagnosed with polycythemia vera (PV) in 2001. The patient exhibited elevated red blood cell (RBC) counts, high hemoglobin (Hb) levels, ...hyperleukocytosis, and moderate thrombocytosis, with sporadic abdominal pain and significant splenomegaly. Despite various treatments, including phlebotomies, hydroxyurea, and alpha-interferon, the patient struggled to maintain optimal hematocrit levels and experienced persistent symptoms. Subsequent genomic analysis revealed a rare
G301R mutation alongside the canonical
V617F mutation, potentially contributing to disease severity. In 2023, the patient started Ropeginterferon alfa-2b, leading to improved hematological parameters and symptom relief. The case underscores the challenges in managing PV, particularly in young patients, and highlights the potential clinical significance of additional
mutations/variants and the potential benefits of Ropeginterferon alfa-2b in achieving better disease control.
Tyrosine kinase inhibitors (TKIs), the backbone of treatment for chronic phase chronic myeloid leukemia patients (CP-CML), have changed the long-term outcome of the disease. Nonetheless, over 20% of ...patients fail front-line therapy due to intolerance or resistance. A head-to-head comparison of dasatinib and nilotinib as second-line treatment outside of sponsored clinical trials has not been reported. We retrospectively analyzed 131 CP-CML patients who, after front-line imatinib failure, switched to a second-line therapy with nilotinib (59, 45%) or dasatinib (72, 55%). Median duration of second-line treatment was 33 months (range 2–100). The reason for switching therapy was resistance in 83.2% and intolerance in 16.8% of patients. The overall survival of the entire cohort at 7 years was 78.9%, while it was 72% and 85.6% for patients treated with dasatinib and nilotinib, respectively (
p
=0.287). With regard to efficacy after 12 months of treatment, 108 patients were evaluable for molecular response: 47% achieved a major molecular response and 18.2% a deep molecular response with dasatinib, compared to 38% and 16.2% with nilotinib (
p
=ns). We observed 35% of grade 3–4 adverse events, more frequently in the dasatinib group (47%) compared to the nilotinib group (22%), without affecting molecular responses. Our study suggests that, in the real-life setting, dasatinib and nilotinib used as second-line treatment in CP-CML are equally effective, with high molecular response rates and an acceptable tolerability.
Elderly patients represent the most challenging and hard-to-treat patient population due to dismal characteristics of the disease, such as secondary-acute myeloid leukemia (AML), enrichment of ...unfavorable molecular genes (TP53) and comorbidities. We conducted a multicentric retrospective study to evaluate activity and safety in a real-life setting of hypomethylating drugs (HMAs) in patients older than 75 years with AML. Between September 2010 and December 2021, 220 patients were treated, 164 (74.5%) received AZAcitidine and 56 DECitabine; most patients (57.8%), received more than four cycles of HMAs. The best response obtained was CR in 51 patients (23.2%), PR in 23 (10.5%) and SD in 45 (20.5%); overall transfusion independence was obtained in 47 patients (34%), after a median of 3.5 months. The median OS (mOs) was 8 months (95% CI 5.9–10.2), with 1- and 2-years OS of 39.4% (95% CI 32.7–46) and 17.4% (95% CI 11.7–23.1), respectively; similar mOS was observed according to HMA treatment (AZA 8.3 vs. DEC 7.8 months, p = 0.810). A subset of 57 long survivors (44 in AZA group and 13 in DEC group) received at least 12 cycles of HMAs, their mOS was 24.3 months. In multivariate analysis, age (≥80), Charlson comorbidity index (≥3), creatinine clearance and the type of best response (≥PR) during treatment maintained independent significance in predicting survival. Infectious complications, most frequently pneumonia (35) and septic shock (12), were lethal in 49 patients (22.2%). Our data show that HMAs have similar efficacy compared to pivotal trials and are well tolerated in a setting of very elderly patients with several co-comorbidities.
While the outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly ...population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients.
We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients.
The median age at diagnosis was 80 years (range: 75-96). In the first line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third line, and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In the first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e., 3-month
< 10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, respectively, with 16.6%, 35.7%, and 51.7% achieving a deep molecular response (DMR) at the same time points. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade ≥ 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (
= 0.033). Overall, the median follow-up was 46.62 months (range: 1.8-206.2), and 43 patients died due to non-CML-related causes. Three patients died due to disease progression to advanced (
= 1) and blastic (
= 2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63-0.81), with no significant difference between the patients treated with standard doses of TKIs compared to those treated with reduced doses (
= 0.35).
TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.
The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia.
From February 2003 ...to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E).
Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected median QOL-E standardized score 54, interquartile range 46-70; median EORTC global score 50, interquartile range 41-66. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients' perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores.
Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.
Aims: To define the peculiar features of patients with the deletion of the chromosome 20 long arm (del20q), data from 69 patients with myelodysplastic syndromes (MDSs) and isolated del20q, followed ...by the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L) and Ospedale Torrette of Ancona, were collected and compared with those of 502 MDS patients with normal karyotype (NK-MDS). Results: Compared to the NK-MDS group, patients with del20q at diagnosis were older (p = 0.020) and mainly male (p = 0.006). They also had a higher rate of bone marrow blast < 5% (p = 0.004), a higher proportion of low and int-1 risk according to IPSS score (p = 0.023), and lower median platelet (PLT) count (p < 0.001). To date, in the del20q cohort, 21 patients (30.4%) received no treatment, 42 (61.0%) were treated with erythropoiesis-stimulating agents (ESA), 3 (4.3%) with hypomethylating agents, and 3 (4.3%) with other treatments. Among 34 patients evaluable for response to ESA, 21 (61.7%) achieved stable erythroid response according to IWG 2006 criteria and 13 (38.2%) were resistant. Nine patients (13.0%) progressed to acute myeloid leukaemia (AML) after a median time from diagnosis of 28 months (IR 4.1−51.7). The median overall survival (OS) of the entire cohort was 60.6 months (95% CI 54.7−66.4). the 5-year cumulative OS was 55.9% (95% CI 40.6−71.2). Conclusion: According to our results, we hypothesize that MDSs with isolated del 20q may represent a distinct biological entity, with peculiar clinical and prognostic features. The physio-pathological mechanisms underlying the deletion of the chromosome 20 long arm are still unclear and warrant future molecular analysis.
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.
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