Ruxolitinib is approved for polycythemia vera (PV) patients after failure to previous cytoreductive therapy, based on durable results observed in phase 3 trials. We report a multicenter retrospective ...study demonstrating the efficacy and safety of ruxolitinib in real-life setting. Eighty-three patients were evaluated. Median follow-up was 24.5 months (IQR 14.0–29.3). At a 3-month response assessment, ruxolitinib provided significant benefit in reducing hematocrit (HCT) level (
p
< 0.001), phlebotomy requirement (
p
< 0.001), leucocytes (
p
= 0.044), and disease-related symptoms (
p
< 0.001). The exposure-adjusted rates (per 100 patient-years) of infectious complications, thromboembolic events, and secondary malignancies were 6.9, 3, and 3.7, respectively. Non-melanoma skin cancers (NMSC) were the most frequent (40%) SM type. Lymphoproliferative disorders were not detected. Five (6%) patients permanently discontinued ruxolitinib treatment and four (5%) evolved in myelofibrosis (MF), but none in acute leukemia. The rate of MF evolution per 100 patient-years of exposure was 2.8. In our experience, ruxolitinib confirmed its efficacy and safety outside of clinical trials.
Summary
Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX‐IOL’ study retrospectively collected 69 MF ...patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX‐ or DFX‐related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion‐independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.
One out of ten patients with Philadelphia‐negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of ...MPN‐specific therapies. Data were therefore extracted from an international nested case‐control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person‐years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1‐6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head‐and‐neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non‐poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88‐3.81), the SC prognostic group (2.57; 1.86‐3.55), SC relapse (1.53; 10.6‐2.21), MPN evolution (2.72; 1.84‐4.02), anemia at SC diagnosis (2.32; 1.49‐3.59), exposure to hydroxyurea (1.89; 1.26‐2.85) and to ruxolitinib (3.63; 1.97‐6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38‐0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti‐platelet drugs in modulating patient survival after the occurrence of a SC.
Objectives
Aim of the study was to evaluate the role of a Domiciliary Hematologic Care Unit (DHCU) compared to standard DH setting in the active frontline treatment with hypomethylating agents (HMAs) ...+/− venetoclax of frail patients with acute myelogenous leukemia/high‐risk myelodysplastic syndromes (AML/HR‐MDS).
Methods
All patients with newly diagnosed AML/HR‐MDS unfit for intensive care and treated frontline with HMAs from January 2010 to April 2021 were retrospectively included.
Results
Among 112 patients (62 AML/50 HR‐MDS), 69 (61.6%) were treated in a standard DH setting and 43 (38.4%) were followed by DHCU, allocated to DH or DHCU by responsible physician. Overall response rate was 29/69 (42.0%) in DH versus 19/43 (44.1%) in DHCU (p = .797). Median response duration was 8.7 months (95%CI 7.0–10.3) in DH versus 13.0 months (95%CI 8.3–17.6) in DHCU (p = .460). Infections were also equally reported. Median overall survival of patients treated in DH was 13.7 months (95%CI 9.9–17.4) compared to 13.0 months (95%CI 6.7–19.3) of patients managed by DHCU (p = .753).
Conclusions
Home care management of HMA is feasible and effective, with results similar to standard DH setting: this approach is thus adequate to offer active therapies in frail patients with AML/HR‐MDS considered up to now ineligible.
The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute ...promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed.
Patients with Philadelphia-negative myeloproliferative neoplasm (MPN) are prone to the development of second cancers, but the factors associated with these events have been poorly explored. In an ...international nested case-control study, we recruited 647 patients with carcinoma, nonmelanoma skin cancer, hematological second cancer, and melanoma diagnosed concurrently or after MPN diagnosis. Up to 3 control patients without a history of cancer and matched with each case for center, sex, age at MPN diagnosis, date of diagnosis, and MPN disease duration were included (n = 1234). Cases were comparable to controls for MPN type, driver mutations and cardiovascular risk factors. The frequency of thrombosis preceding MPN was similar for cases and controls (P = .462). Thrombotic events after MPN and before second cancer were higher in cases than in controls (11.6% vs 8.1%; P = .013), because of a higher proportion of arterial thromboses (6.2% vs 3.7%; P = .015). After adjustment for confounders, the occurrence of arterial thrombosis remained independently associated with the risk of carcinoma (odds ratio, 1.97; 95% confidence interval, 1.14-3.41), suggesting that MPN patients experiencing arterial events after MPN diagnosis deserve careful clinical surveillance for early detection of carcinoma. This study was registered at www.clinicaltrials.gov as NCT03745378.
•In a case-control study, the frequency of thrombosis was higher in patients with MPN with second cancer than in matched MPN controls.•The occurrence of arterial thrombosis was associated with a twofold increased risk of carcinoma.
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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.
P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised patients and the factors associated with a bad outcome are poorly understood. A retrospective analysis on Pj pneumonia (PjP) ...cases occurring in Tor Vergata University Hospital, Italy, during the period 2011-2015. The patients' demographic, clinical and radiological characteristics and the Pj genotypes were considered. The study population included 116 patients, 37.9% of whom had haematological malignancy or underwent haematological stem cell transplantation (HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining 12.1% had a miscellaneous other condition. At univariate analysis, being older than 60 years was significantly correlated with a severe PjP (OR 95%CI 2.52 0.10-5.76; p = 0.031) and death (OR 95%CI 2.44 1.05-5.70; p = 0.036), while a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly associated with a less severe pneumonia (OR95%CI 0.35 0.15-0.84, p = 0.023); moreover, death due to PjP was significantly more frequent in patients with CLD (OR95%CI 3.26 1.17-9.05; p = 0.019) while, admission to the Infectious Diseases Unit was significantly associated with fewer deaths (OR95%CI 0.10 0.03-0.36, p = 0.002). At multivariate analysis, a better PjP outcome was observed in patients taking TMP/SMX prophylaxis and that were admitted to the Infectious Diseases Unit (OR95%CI 0.27 0.07-1.03, p = 0.055, OR95%CI 0.16 0.05-0.55; p = 0.004, respectively). In conclusion, in our study population, TMP/SMX prophylaxis and infectious disease specialist approach were variables correlated with a better PjP outcome.
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