•We present real-world data on all ruxolitinib-treated myelofibrosis patients in a 10-million-resident region, with a follow-up of 2 years.•We found no evidence of an increased risk of developing ...lymphomas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Hellström-Lindberg score (HLS) (1997) is designed to predict erythroid response to erythropoietin treatment in myelodysplastic patients. In order to test the validity of this scoring system, 58 ...patients affected by myelodysplastic syndrome, treated with a “standard dose” approach between 2001 and 2010, were analyzed. The response to erythropoietin treatment was evaluated in accordance with the “international working group” (IWG) criteria. Among the patients only two were scored “poor,” 12 “intermediate,” and 44 “good” (15 of whom were scored “3” and 29 “4”). Although the system was verified as a predictive tool for response to erythropoietin therapy, we noted that of patients scored as “good,” those with a numerical score of “4” responded more frequently than did those scored “3”, as evaluated under both the 2006- and 2000-IWG (“major response”) criteria. The modest response rate in patients scoring “3” did not show a difference in response rate in comparison to the “intermediate” group. The present data suggest that only patients scoring “4” on the scale may show an adequate response to the standard dose erythropoietin therapy, while frontline high-dose therapy should be offered to other patients. A further analysis considering endogenous erythropoietin as a possible determinant of response revealed the optimal cut-off value of 80 mIU/mL, instead of the value of 100 mIU/mL utilized by the HLS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Learning Objectives
After completing this course, the reader will be able to:
Discuss the different modalities of disease dissemination in nongastric marginal‐zone B‐cell MALT lymphoma.
Explain the ...rationale for using extensive staging in nongastric marginal‐zone B‐cell MALT lymphoma.
Assess the clinical features helpful to detect patients with nongastric marginal‐zone B‐cell MALT lymphoma who have a poor prognosis.
Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com
The aim of this study is to describe the clinical features and define the prognostic significance of disease dissemination in a large series of nongastric marginal‐zone B‐cell mucosa‐associated lymphoid tissue (MALT) lymphomas. We studied 208 patients with nongastric marginal‐zone B‐cell MALT lymphoma diagnosed and treated from 1991 to 2004. Ninety percent of the patients had a single site of MALT involvement—skin (26%), salivary glands (18%), orbit (14%), Waldeyer's ring (13%)—and 39% and 28% had nodal involvement and bone marrow involvement, respectively. After a median follow‐up of 2.7 years, the median event‐free survival (EFS) time was 2.4 years, and the median overall survival (OS) time was not reached. On univariate analysis, the features significantly associated with longer EFS and OS times were the following: single MALT site involvement (OS), localized disease (EFS and OS), no nodal disease (EFS and OS), skin and orbit lymphoma (OS), and stage IV disease without bone marrow involvement (OS). On multivariate analysis, both bone marrow and nodal involvement were associated with shorter OS. This study describes the clinical features and the natural history of nongastric marginal‐zone lymphomas and highlights that the dissemination to lymph nodes and bone marrow is associated with a poorer outcome.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A proper assessment of elderly patients is a relevant clinical problem in the onco-hematological setting. In this context, age and extra-hematological morbidity are of primary importance, but ...performance status and overall functionality related to geriatric age, as physical abilities, cognitive aspects and ability to self-management are not negligible. Thus, a defined multi-dimensional assessment is needed to differentiate between fit, unfit and frail older adults (Klepin ASH Education Program 2014).
We propose a tool to evaluate the tolerance to more or less intensive treatments in over 60 years aged patients, and to estimate the impact on the outcome. Our algorithm is based on 4 main variables universally recognized: age, performance status, comorbidities and geriatric aspects (functional, physical and cognitive).
1- As regards age, two cut-off values were considered: 70-years limit because it represents the threshold below which the allogeneic bone marrow transplantation may still run; and the 85-year limit because it denotes the edge beyond which chemotherapy (also non-intensive) should not be administered.
2- About performance status, it was chosen the ECOG (Eastern Cooperative Oncology Group) scale more or equal to 3 as the limit beyond which chemotherapy should be avoided.
3- Considering co-morbidities, the SIE, SIES GITMO group consensus-based definition of inability to intensive and non-intensive chemotherapy in acute myeloid leukemia (Ferrara et al. Leukemia 2013) was chosen to identify both patients candidate to intensive or candidate to only non-intensive chemotherapy.
4- Approaching the geriatric assessment, two levels of impairment were considered: the most important level of seriousness occurs when the Activities of Daily Living (ADL) functional scale is not overtaken; the lowest level of seriousness is verified if at least one among the functional Instrumental Activities of Daily Living (IADL) scale or the physical Short Physical Performace Battery (SPPB) scale or the cognitive Mini Mental State Examination (MMSE) scale are not overcome.
The stratification of patients works with some steps that must be excluded in order to get over the various levels of fitness (Figure 1).
We call this approach the NO-chain algorithm. It foresees that:
- Patient with at least one of the following features are considered frail: 85 or more years of age; at least 3 of ECOG; assessed functional impairment with the ADL scale <3; presence of major comorbidities including at least one of the six criteria, according to the SIE, SIES GITMO consensus-based definition of inability to non-intensive chemotherapy in acute myeloid leukemia.
- Not-frail patient with at least one of the following features are considered unfit: age over 70 years; at least one of criteria, according to the SIE, SIES GITMO consensus-based definition of inability to intensive chemotherapy in acute myeloid leukemia; at least one among functional impairment assessed by IADL scale <4 or reduced physical performance by SPPB scale <9 or intellectual deficit by the MMSE scale <24.
- All patients who get through all these steps are considered fit and potentially eligible for allogeneic stem cell transplantation.
Although the used cut-off levels might need amelioration in the practice, the basic principle of this algorithm is the definition of fitness actually correlated to the patient's condition in itself, regardless of the hematological disease. The algorithm was originally developed for elderly patients with acute myeloid leukemia (AML), but subsequently applied to patients with myelodysplastic syndrome (MDS) and to the other hematological malignancies. The application is undoubtedly different, depending on the disease the patient is affected by and its classification. For instance: an AML frail patients, regardless of biological risk, can be candidate only to supportive care; a low-risk MDS frail patients may still be candidate to pharmacological therapy as erythropoiesis stimulating agents or iron chelation therapy. The validation of this algorithm has to be carried out within each hematologic malignancy and must take into account the specific application.
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No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Severe thrombocytopenia is an uncommon event in patients (pts) with lower-risk MDS, but it may significantly affect the prognosis. No specific pharmacological approaches other than ...hypometilating agents (not licensed in Europe in lower-risk MDS), able to improve platelet count in this setting, are currently available. Trials testing efficacy and safety of Eltrombopag are ongoing (Oliva 2017). Few data were reported about danazol, an attenuated androgen, that seems to have also some effectiveness in this still unmet need (Wattel 1994; Chan 2002).
Aims: To assess the efficacy and safety of danazol in improving the platelet count in low risk MDS pts with severe thrombocytopenia.
Methods: We retrospectively reviewed 35 thrombocytopenic MDS pts treated with danazol. The initial and maximal dose was 600 mg/day for all pts, modulated according to response and toxicity. The response was evaluated according to IWG response criteria (Cheson 2006). The outcome was strictly observed every 3 months (mo) up to the 12th mo, and the platelets average number in each observation moment was described. The time to response, the response rate and the enduring of response were also recorded.
Results: Of the 35 pts, according to 2016 WHO classification, 4 pts were MDS-ULD; 19 were MDS-MLD (3 of them with medullar hypocellularity), 7 were MDS-EB1 and 5 were affected by MDS/MPN. At baseline the platelet count was lower than 20x10^3/mL in 11 pts, the median was 23x10^3/mL . At starting time of danazol therapy the IPSS-R cytogenetic class of risk was very low in 2 cases, low in 28 cases, intermediate in 3 cases and very high in 1 case. Cytogenetic was not available in one patient. In the 30 MDS pts, the IPSS-R was “very low” in 1 patient, “low” in 16, “intermediate” in 7, “high” in 4 and “very high” in 1. In 1 case it was not evaluable due to the lack of cytogenetics. Two pts were not included in the analysis because they were treated for less than 3 mo (in 1 case danazol was withdraw to permit the beginning of another therapy and in 1 case due to death for other neoplastic disease). The response rate was 63,6% (21 responders on 33 evaluable). Median time to response was 3.5 mo (range 0.3 - 12.4 mo); the average response time was 5.09 mo. In the first year of treatment, the platelet count (evaluated at baseline, 3, 6, 9 and 12 mo) changed in a significant way (F test after repeated measures ANOVA: p < 0.001 as shown in Figure 1). Pairwise comparisons of platelet count according to Bonferroni showed a significant difference for baseline vs. 3 mo (p = 0.0013), baseline vs 6 mo (p = 0.0255), baseline vs 9 mo (p = 0.0047) and baseline vs 12 mo (p = 0.0014); however, no significant differences (p ≥ 0.05) in counts were seen for all the further pairwise comparisons at 3, 6, 9 and 12 mo. The median and average duration of the response for the entire population were respectively 12,5 and 32,5 mo. Only 6 of the 21 responders (28%) lost the response (the median and average duration of response were respectively 5.8 and 12.9 mo). Within the 21 responders, the median progression free survival was not reached after 24 mo. The probability to maintain the response after 50 mo was assessed at 58.2% (C.I. 24.1% to 81.4% - Figure 2). The overall survival showed a significant difference (logrank test: p = 0.0064) between responders and non-responders (Figure 3). Adverse events recorded were as follows: moderate (grade 1 and 2) increase in transaminases in 4 cases (with reduction of danazol to 400 mg/day); 1 case of severe but reversible liver toxicity (grade 3) (with subsequently drug suspension); severe (grade 3) but reversible renal failure in 1 case (the drug was stopped); moderate (grade 1 and 2) increasing of serum creatinine in 6 case (with reduction of danazol to 400 mg/day in 2 of these); reversible cutaneous rash in 3 cases; amenorrhea in 1 case (the only fertile woman in the series); weight loss and loss of appetite in 1 case, weight gain in 1 case.
Conclusion: Even if the mechanism of action of danazol in pts with MDS is unclear, this series confirms its efficacy to improve platelet count in the most of MDS pts with severe thrombocytopenia. The response was often clinically significant. It may not be immediate but seems to be reachable after 3-6 mo of treatment. A responsive patient has a good probability to maintain a long-lasting response. The toxicity profile of this drug is acceptable. Waiting for more effective options, danazol may be a good therapeutic option for these pts.
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Riva:Jannsen and Cilag: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Reda:Celgene: Consultancy; Janssen and Cilag: Consultancy; Gilead: Consultancy; ABBVIE: Consultancy. Molteni:AMGEN: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Celgene: Consultancy; Janssen and Cilag: Consultancy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the current study, we have investigated the effects of the different modalities of treatment (volume of radiotherapy RT, previous surgery) as well as the Gleason score of prostate cancer (PC) on ...the lymphocyte composition of PC patients undergoing RT.
This is a monoinstitutional study that prospectively included PC patients that underwent RT from January 2016 until December 2017. To compare the different evaluations, the Wilcoxon signed-rank test was used among 2 times (Timepoint 0 to Timepoint 1). Percentage variation was calculated for all the lymphocyte subpopulation and was correlated with clinical parameters (previous surgery, Gleason score, and pelvic irradiation) with the χ2 test. The statistical analysis was repeated also on the stratified dataset according to the above parameters (previous surgery, Gleason score, and whole pelvic radiotherapy WPRT).
One hundred and eleven patients were included in the present analysis. All the lymphocyte subpopulations resulted significantly lower after RT. The modifications of several lymphocyte subpopulations correlated with previous surgery, Gleason score, and WPRT, although stratified analysis demonstrated that WPRT showed the greatest correlation.
Our results could be used to design a prospective trial in order to study the use of WPRT on the lymphocyte subpopulations.
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