Management Of Myelodysplastic Syndromes Research Articles

Diagnosis and Management of Myelodysplastic Syndrome in a Fanconi Anemia Patient: A Case Report

Diagnosis and Management of Myelodysplastic Syndrome in a Fanconi Anemia Patient: A Case Report

Cytogenetic profile and risk of transformation to acute myeloid leukemia (AML) in Indonesian patients with myelodysplastic syndrome (MDS): a pilot study

Background Cytogenetics is a fundamental examination in the course and management of myelodysplastic syndrome (MDS) since it is widely used as a diagnostic and prognostic indicator for the disease. Some cytogenetic profiles are associated with a higher risk of acute myeloid leukemia (AML) transformation. This is the first study to evaluate the cytogenetic profile of Indonesian patients with MDS. Methods This prospective cohort study was conducted at the Cancer Center and several other referral hospitals. Patients with primary MDS aged >18 years were included in the study. Clinical examination, peripheral blood smear, and bone marrow aspiration were performed, followed by cytogenetic examination. The results were further categorized into revised international prognostic scoring system (IPSS-R) scores, and cytogenetic profiles were descriptively presented. Patients were followed up for one year to evaluate AML transformation. Results A total of 28 MDS patients, aged 66±12 years, were included in this study. The majority of the patients were male (n=17;60.7%), aged 65 years or above (n=19;67.9%), diagnosed with MDS-MLD (n=14;50%), and had an intermediate cytogenetic group (n=4;14.3%). The IPSS-R score was high in 6 (21.4%) patients and very high risk in 3 (10.7%) patients. During one-year follow-up, AML transformation occurred in 3 (10.7%) patients, and 10 (35.7%) patients ceased. Monosomy 7 was observed in 6 (21.4%) patients but in one metaphase each. Deletion of chromosome 5 (del(5)(q31)), del (16)(q21.1), and del (16)(q11.2) were found in a male patient with MDS-EB1. Conclusions Monosomy 7 and deletion of chromosome 5 have been identified in Indonesian patients with MDS. MDS-EB has the highest risk of AML transformation.

Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada.

The management of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is limited and remains an unmet need. Decitabine/cedazuridine (DEC-C, ASTX727) is Canada's first and only approved oral hypomethylating agent for MDS and CMML. We characterized the real-world use of DEC-C through a Canadian compassionate use program. Demographic and clinical data from 769 patients enrolled in Taiho Pharma Canada's Patient Support Program were collected and analyzed. These patients represent a collection period from 10 November 2020 to 31 August 2022 with a median age of 76 years. Among 651 patients who started DEC-C, the median treatment duration was 4.2 cycles. The median overall and progression-free survival were 21.6 and 10.7 months, respectively. Among 427 patients who discontinued treatment, the majority (69.5%) stopped due to death (n = 164) or disease progression (n = 133). Multivariable cox regression showed that age, province of residence, blast counts, antibiotic prophylaxis, and number of dose reductions and delays were not significantly associated with overall and progression-free survival. DEC-C is a promising alternative to parenteral hypomethylating agent therapy, and it likely addresses an important unmet need for effective and convenient therapies in this setting.

Yoga As Possible Non-Medical Intervention to Improve Quality of Life of Patients with Myelodysplastic Syndromes - a Feasibility Report

Background Despite significant progress in the management of myelodysplastic syndromes (MDS), symptom-burden remains significant and patients report on impaired quality of life (QoL) [Stauder, Leukemia 2018]. There is an ongoing need to explore non-pharmacologic approaches for managing MDS symptom burden. Yoga has proved an effective method to improve various physical and psychosocial outcomes, such as fatigue, anxiety, and sleep disturbances, in patients diagnosed with solid cancers. Aims (1) To examine the practicality of an in-person 8-week yoga class; (2) To explore the feasibility of an 8-week group online yoga within an observational study; (3) Preliminary assessment of QoL parameters. Methods MDS patients from 9 medical centers in Israel were invited to participate in a yoga program, consisting of 8 one hour in-person classes (once weekly). The classes were given by certified Kundalini yoga teachers, who delivered a mild-medium intensity program combining deep breathing, physical movements, and mantras, specifically designed for this patient population. Each medical center hosted its own course. All the exercises were done while the patients were seated on a chair. All MDS patients were invited, regardless of disease risk or performance status. In the second part, patients were offered a further 8-week online program, in which a one-hour weekly session was given via zoom, within an observational study. Symptom-burden was assessed using a modified Edmonton Symptom Self-Assessment Scale (ESAS), a 10-item rating scale (0-10, with 10 being the highest degree), which has been previously recommended by the National Comprehensive Cancer Network to assess QoL in all cancer populations. Patient-reported outcomes included fatigue, sleepiness, depression, nausea, pain and other QoL measures. Questionnaires were filled out by patients before and after each meeting. Results Overall, 120 patients from 9 centers participated in at least one in-person yoga class. Participating patients, including those with poor performance status, were able to engage and complete most exercises throughout the class. Many of the patients were able to return to consequent classes, but some of them encountered barriers, mainly difficulty in commuting. Twenty-three patients signed up for the online yoga live zoom session. Of those, 11 patients were high-risk MDS and 12 were low-risk MDS, 7 were transfusion dependent. During the 8 weeks of study, 3 patients experienced disease progression. Sixteen patients participated in the online program. The main reasons for not participating included video-conferencing installing and enabling issues. Most patients filled out the questionnaires before and after each online lesson. The QoL analysis will be reported separately, but preliminary data suggests a substantial increase in general well-being and decrease in fatigue, after a class. Conclusion This in-person and live online Kundalini yoga program was well-tolerated by many MDS patients of all risk groups. Preliminary analysis suggests improved well-being after completing each class. However, we did encounter some barriers, mainly challenging transportation and software operating difficulties. Despite theses challenges, patients managed to adhere to schedule. We suggest developing a hybrid plan (in-person and live online lessons) for further exploring the benefits of yoga among MDS patients. In the future we will evaluate the effect on QoL, as well as possible effect on disease outcomes.

Uncovering Gaps in the Evaluation and Integration of New Evidence into the Treatment and Management of Myelodysplastic Syndromes: Results from a Nationwide Survey

Background Myelodysplastic syndromes (MDS) are underreported and underdiagnosed, due to their rare occurrence and ambiguous presentation. Appropriate treatment selection, in light of an expanding therapeutic landscape, is highly dependent on an accurate diagnosis and risk stratification. To identify educational gaps limiting MDS risk stratification and individualized treatment selection, we surveyed hematology/oncology providers regarding clinical evidence on new and emerging therapies and challenges in care related to MDS treatment. Methods During March 2022, a nationwide survey was conducted among 117 hematology/oncology healthcare providers (HCPs) caring for patients with MDS (Table 1). Survey questions were designed to identify knowledge and competence barriers in performing MDS risk assessment and treatment-decision making, as well as to provide a platform for HCPs to ask 'top-of-mind' questions in MDS care. Of the survey respondents, 47% were hematologists or oncologists, and providers reported an average monthly MDS caseload of 112 patients. Results HCPs identified selecting optimal therapies for individual patients (35%) and obtaining an accurate diagnosis (22%) as the most challenging issue encountered in managing patients in MDS. In addition to clinical guidelines, HCPs considered treatment effectiveness (50%) and quality of life (50%) as the top two factors in treatment-decision making. When addressing barriers to adopting new therapies, HCPs reported being uncertain about who the "right" patients for new therapies are (35%) and having difficulty differentiating the roles of new therapies in the treatment armamentarium (20%). When asking HCPs to self-report their confidence levels in various aspects of MDS treatment, HCPs reported high confidence in their ability to identify and interpret genetic or molecular tests that should be ordered for MDS patients (53%), evaluate clinical data on the safety and efficacy of novel therapies for MDS (56%), and recognize and manage adverse events related to newer targeted therapies (54%) (Figure 1). 45% of HCPs reported moderate to low confidence in their ability to distinguish patient- and disease-related factors that affect risk stratification, and of this provider population, 40% stated that interpreting the correlation between cytogenetic abnormality and prognostic value is the biggest challenge impeding high confidence. Furthermore, of the 50% of HCPs that reported moderate to low confidence in selecting appropriate therapies for individualized MDS treatment, 47% stated their reported confidence was due to the challenge of keeping up with the clinical safety and efficacy therapy for new and emerging therapies. HCPs postulated key questions to MDS experts, including insight on the value of molecular tests in selecting novel therapies, how to individualize patient treatment plans, understanding the burden of transfusion-dependent anemia, timing for stem cell transplantation, and how to balance cost management and quality of life. Conclusions HCPs disclosed key educational barriers that limit their ability to accurately diagnosis, risk stratify, develop individualized treatment plans, and manage treatment care for patients with MDS. Of note, HCPs revealed having difficulty differentiating the roles of the rapidly evolving therapies for MDS and identifying the patients that would benefit from them, which is exacerbated by limited confidence in incorporating cytogenetic findings into MDS patient risk assessment. To optimize MDS care, educational programming to inform HCPs on how to diagnose and risk stratify patients, as well as to report data on new and emerging therapies, is critical. These findings can inform future educational initiatives to close persistent gaps in quality MDS care. Study Sponsor Statement The study reported in this abstract was funded by an independent educational grant from Gilead Sciences, Inc. The grantor had no role in the study design, execution, analysis, or reporting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Role of cedazuridine/decitabine in the management of myelodysplastic syndrome and chronic myelomonocytic leukemia.

Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are clonal hematopoietic stem cell disorders. Complex disease biology has posed significant challenge to the development of novel therapeutics. Despite myriad clinical trials, none have been superior to azacitidine and decitabine (DEC) therapy. These therapies present a substantial burden for patients with 5 and 7days of parenteral treatment in an infusion clinic. To overcome this limitation, a fixed drug combination of oral DEC-cedazuridine (C-DEC), a cytidine deaminase inhibitor with documented safety profile was developed. This drug was recently approved by the US FDA, Australian TGA and Health Canada for newly diagnosed or previously treated intermediate or high risk by international prognostic scoring system, MDS and CMML. In this review, we detail the pharmacokinetic and clinical activity of C-DEC in the management of MDS and CMML.

Management of myelodysplastic syndromes after failure of response to hypomethylating agents.

Hypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndrome (MDS). However, only around 50% of patients respond to these agents, and responses tend to be transient, with loss of response frequently happening within 2 years and being associated with very poor prognosis and limited therapeutic options. Identification of patients who will respond to HMAs is challenging. Mechanisms underlying resistance to HMAs are not clear yet. Recently, absence of response has been associated with increased cell-cycle quiescence among the hematopoietic progenitor cells. There are no standard-of-care options for patients after HMA failure. However, the increasing knowledge of MDS pathogenesis has led to the development of new potential therapies, including HMAs with longer half-life and exposure, inhibition of the antiapoptotic BCL2 protein with venetoclax or inhibition of immune-checkpoint regulatory proteins such as PD-1 or CTLA-4, innate immunity and targeting of CD33/CD3 with multiple monoclonal antibodies. In addition, multiple targeted agents are opening opportunities to treat subgroups of patients whose disease harbors mutations in TP53, IDH, FLT3, and genes involved in splicing machinery. Newer formulations of intensive chemotherapy and its different combinations may be considered a valid option in selected patients after HMA failure. Finally, decision making at the time of failure of response to HMAs should be personalized, taking into account that allogenic stem-cell transplantation remains the only therapeutic approach with curative potential in these patients. In the current review, we will focus on all the above aspects.

A Feasibility Randomized Trial of Red Cell Transfusion Thresholds in Myelodysplasia

BackgroundRed cell transfusion is the most common intervention in the management of myelodysplastic syndromes (MDS). Transfusion practice in MDS is typically characterized by transfusion of multiple (usually 2 - 4) units every 3 - 4 weeks, but there is no supporting evidence for efficacy of this strategy. The aim of this trial was to explore the feasibility of (and adherence to) two standardized transfusion algorithms (liberal vs. restrictive), in order to inform future research. This trial is aligned with a Canadian study (NCT02099669).MethodsThe study was undertaken in the UK and Australia/New Zealand (ISRCTN26088319). Inclusion criteria were MDS patients with <20% bone marrow blasts, who were transfusion dependent (at least 1 red cell transfusion episode per month in the last 8 weeks) and receiving no additional MDS therapy. Randomization was to one of two red cell transfusion strategies over a 12-week period after a 4-week run-in to achieve a Hb >100 g/l prior to initiation of the allocated transfusion arm:(1) Restrictive (control arm) transfusion strategy to maintain hemoglobin concentration (Hb) between 85 and 100g/L; 2 units of packed red cell unit transfusions were transfused when Hb was <80g/L and 1 unit of packed red cell unit transfusions when Hb is 80-85g/L.(2) Liberal transfusion strategy to maintain Hb between 110 and 125g/L; 2 units of packed red cell unit transfusions were transfused when Hb was <105g/L and 1 unit of packed red cell unit transfusions when Hb is 105-110g/L.Primary outcomes were: percentage of pre-transfusion Hb concentrations below the target range of the assigned strategy, and achievement of at least a 20g/L difference between the mean pre-transfusion Hb in the two transfusion groups. It was pre-specified that the study would be considered feasible if compliance to the pre-transfusion target Hb was ≥70%, with evidence of a difference in Hb between the two arms. Secondary outcomes included quality of life questionnaires (EQ-5D-5L and EORTC QLQ-C30). The primary analysis was intention to treat and these results are reported.Results38 patients were randomized from 12 hospitals (n=20, restrictive; n=18 liberal). Median age was 79 years (IQR 69-82). Although generally well matched, there were some minor imbalances in baseline characteristics (ECOG status, WHO subtype, prior iron chelation treatment and heart failure medication). Thirty-four participants received at least one transfusion during the trial and were included in the ‘compliance to treatment threshold’ analysis. Percentage compliance (95% confidence interval) of pre-transfusion Hb being below the target range of the RBC transfusion threshold assigned were 86% (75-94) and 99% (95-100) for the restrictive and liberal arms respectively. As compliance was ≥70% in both arms, the study was declared feasible.The mean (standard deviation (SD)) pre-transfusion Hb for the restrictive and liberal arms were 80 (6) g/l and 97 (7) g/l respectively, for a significant difference between the two groups (p<0.0001). Figure 1 shows the mean (±SD) Hb by week for all randomized participants by treatment arm. The total number of red cell units transfused was 82 in the restrictive group and 192 in the liberal group. Of 8 serious adverse events reported, 1 was deemed potentially related to transfusion. Compliance for completion of EQ-5D-5L and EORTC QLQ-C30 questionnaires was good (between 70 - 80%). Although interpretation of quality of life analyses is exploratory, the numbers of participants achieving a (pre-defined) clinically meaningful increase showed small improvements favoring the liberal policy across the following domains (EQ-5D-5L descriptive; EORTC QLQ-C30: physical functioning and global health score).DiscussionThese results of this multicenter trial in an older out-patient based population support the feasibility of progressing to a definitive trial of different red cell transfusion strategies, in order to evaluate the comparative effectiveness and safety for clinically relevant outcomes of a restrictive vs liberal transfusion policy for transfusion-dependent MDS. The large difference in units transfused between the two arms challenges perceived dogma and supports the need for a cost-effectiveness component in follow-on trials. (Funding: NHSBT, ANZSBT). DisclosuresBuckstein:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

A systematic review and network meta-analysis comparing azacitidine and decitabine for the treatment of myelodysplastic syndrome

BackgroundHypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS.MethodsWe conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence).ResultsOnly four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95% CI 0.74–0.94, I2 = 89%) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95% CI 0.77–1.00, I2 = 53%). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95% CI = 0.01–0.86, very low-certainty evidence).ConclusionsAzacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.

A Case Report of a Patient with Myelodysplastic Syndrome Who Has Lower Back Pain

Objectives This case aims to describe management of a patient with myelodysplasitc syndrome who has lower back pain. Methods A 75-year-old female patient with myelodysplasitc syndrome was hospitalized from February 28, 2018 to March 14, 2018. The patient was treated with Azacitidine at Bundangjyesaeng Hospital, and lower back pain worsened without any reason. The patient was willing to undergo traditional Korean medical treatment, and Wonyuksayuk-tang was chosen considering both hematopoiesis dysfunction and lower back pain. Results The patient was diagnosed with myelodysplatic syndrome after bone marrow aspiration and biopsy at Bundangjyesaeng Hospital. After the Wonyuksayuk-tang treatment, platelet levels increased about 50% compared with initial blood test results. In addition, lower back pain and general weakness were slightly improved. Conclusion It is important to manage the quality of life of patients with myelodysplastic syndrome. This case suggests that traditional Korean medicine has a beneficial effect on the management of myelodysplastic syndrome. Keywords: myelodysplastic syndrome, lower back pain, Wonyuksayuk-tang

92 - Management of Myelodysplastic Syndromes with Erythropoiesis Stimulating Agents (ESAS) in Real-Life Experience: An Update from Recamds

92 - Management of Myelodysplastic Syndromes with Erythropoiesis Stimulating Agents (ESAS) in Real-Life Experience: An Update from Recamds

A Prospective Multicenter Single-Arm Study of Low-Dose Decitabine in Adult Patients with Immune Thrombocytopenia

Introduction: Approximately 30% of patients with immune thrombocytopenia (ITP) fail to respond to the first- and/or second-line treatments (corticosteroids, intravenous immunoglobulin, rituximab, splenectomy, and thrombopoietin-receptor agonists). For those patients, the management is challenging.Decitabine (DAC), a demethylating agent with a dual mechanism of action: the demethylating effect leading to cell differentiation at low dose and cytotoxic activity leading to cell death at high concentration, has been used in the management of myelodysplastic syndrome (MDS) with a considerable platelet response during the past decade. Recent studies proved that low-dose DAC was sufficient to show a therapeutic effect with no obvious cytotoxicity. Our previous and other studies have demonstrated that low-dose DAC could promote megakaryocyte maturation and platelet production. These findings suggest a possible therapeutic role of low-dose DAC in the management of ITP. We hereby present the preliminary results of a prospective, multicenter, open-labeled study evaluating the efficacy and safety of low-dose DAC for ITP patients.Methods: ITP patients, who failed to respond to corticosteroids, intravenous immunoglobulin, rituximab, and/or thrombopoietin-receptor agonists from 9 centers, were enrolled in the study. The study protocol was approved by the ethics committee on medical research of each participating site. All patients provided written informed consent in accordance with the Declaration of Helsinki. DAC was given intravenously at 3.5mg/m2 for 3 days/cycle for 3 cycles with a 4-week interval between cycles.The primary end points were complete response (CR), response (R), overall response (OR). All the criteria were consistent with the standardization of terminology, definitions and outcome criteria in immune thrombocytopenia proposed by the international working group (Rodeghiero F, et al. Blood, 2009, 113:2386-2393). Secondary end points were bleeding scores, time to response (TTR), duration of response and adverse events. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version3.0. This clinical trial was registered at http://clinicaltrials.gov as NCT 01568333.Results: A total of 20 ITP patients were recruited. The clinical characteristics were shown in Table 1. At the end of the 12th week of the initial treatment, CR was achieved in 1 patient (5%) and R was achieved in 9 patients (45%). The OR rate was 50%. During the follow-up period, 1 patient initially stabilized at R and subsequently improved to CR at the 20th week. Therefore, CR, R and OR rates were 10% (2/20), 40% (8/20) and 50% (10/20), respectively. In patients who achieved CR and R, the median (range) TTR was 22 days (8-38 days). The median (range) follow-up time was 24 weeks (13-40 weeks). The platelet counts of patients who achieved CR and R were shown in Figure 1. The follow-up of our study is in progress.Adverse events were observed in 2 patients, one had nausea and the other was mild fever. No adverse events exceeded grade 1.Conclusion: Although the sample size is small, with a relatively short follow-up period limited by now, our study suggests that low-dose DAC is effective and safe in the management of ITP patients. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Integrating Frailty, Comorbidity, and Quality of Life in the Management of Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a group of acquired hematopoietic stem cell disorders that manifest with progressive bone marrow failure and have a propensity to transform into leukemia. Although an increase in biologic understanding of MDS has led to improved patient risk stratification and prognostication, advances in treatment have lagged behind. While hematopoietic cell transplantation (HCT) is a potentially curative option for some, most affected patients continue to be treated with supportive care or with drugs that offer temporary palliation such as hematopoietic growth factors, DNA hypomethylating agents, or immunomodulatory therapy. For several groups, such as those with intermediate-risk disease as classified by the Revised International Prognostic Scoring System (IPSS-R) or those with higher-risk disease for whom hypomethylating agents have failed, optimal treatment remains uncertain. Inclusion of patient-related factors such as frailty and comorbid conditions into risk assessment can improve prognostication beyond the disease-associated variables included in systems such as the IPSS-R. This article focuses on approaches to assessing and integrating frailty, comorbidities, and quality of life into the treatment of patients with MDS.

Impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome.

Regular blood transfusions in the management of myelodysplastic syndrome (MDS) often lead to iron overload. The main objective of this study was to evaluate the impact of medication adherence on the effectiveness of deferasirox for the treatment of transfusional iron overload in patients with MDS. Secondary objectives were to describe treatment effectiveness and safety in daily clinical practice. A longitudinal, retrospective, observational study was carried out in a university hospital. The inclusion criteria were age over 18 years, MDS diagnosis and treatment with deferasirox for transfusion-dependent iron overload during the period of study (from January 2011 to April 2015). Treatment effectiveness was estimated by serum ferritin (SF), and adherence was measured by medication possession ratio (MPR). Clinically relevant analytical alterations during the treatment and reasons for treatment discontinuation were also assessed. Thirty-five patients were included in the study. Median SF at baseline was 1636 μg/L, and it decreased to 1399 μg/L during follow-up. The median adherence rate was 92%, although only 54·8% of the patients maintained deferasirox adherence ≥90% during the whole duration of treatment. Adherence rate was inversely correlated to SF (r = -0·288, P = 0·004). The median (p25, p75) duration of treatment was 11 (3·0, 37·8) months. The most common reasons for treatment discontinuation were renal toxicity (35%) and patient's death (25%). Deferasirox's effectiveness, measured by the decrease in SF, was significantly better in adherent patients. The most frequent reason for treatment discontinuation was renal toxicity. Developing strategies to improve deferasirox treatment adherence and monitoring renal function in those patients should be key points in pharmaceutical care.

Integrating Frailty, Comorbidity, and Quality of Life in the Management of Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of acquired hematopoietic stem cell disorders that manifest with progressive bone marrow failure and have a propensity to transform into leukemia. Although an increase in biologic understanding of MDS has led to improved patient risk stratification and prognostication, advances in treatment have lagged behind. While hematopoietic cell transplantation (HCT) is a potentially curative option for some, most affected patients continue to be treated with supportive care or with drugs that offer temporary palliation such as hematopoietic growth factors, DNA hypomethylating agents, or immunomodulatory therapy. For several groups, such as those with intermediate-risk disease as classified by the Revised International Prognostic Scoring System (IPSS-R) or those with higher-risk disease for whom hypomethylating agents have failed, optimal treatment remains uncertain. Inclusion of patient-related factors such as frailty and comorbid conditions into risk assessment can improve prognostication beyond the disease-associated variables included in systems such as the IPSS-R. This article focuses on approaches to assessing and integrating frailty, comorbidities, and quality of life into the treatment of patients with MDS.

The challenging world of cytopenias: distinguishing myelodysplastic syndromes from other disorders of marrow failure.

Over the past decade, our understanding of bone marrow failure has advanced considerably. Marrow failure encompasses multiple overlapping diseases, and there is increasing availability of diagnostic tools to distinguish among the subtypes. Identification of genetic alterations that underlie marrow failure has also greatly expanded, especially for myelodysplastic syndromes. Molecular markers are increasingly used to guide the management of myelodysplasia and may distinguish this diagnosis from other marrow failure disorders. This review summarizes the current state of distinguishing among causes of marrow failure and discusses the potential uses of multiple diagnostic and prognostic indicators in the management of myelodysplastic syndromes and other bone marrow failure disorders.

Iron chelation therapy with deferasirox in the management of iron overload in primary myelofibrosis.

Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

Management of myelodysplastic syndromes: Expert consensus opinion from the Saudi MDS Working Group

Myelodysplastic syndromes (MDSs) constitute a heterogeneous group of clonal hematopoietic disorders. A panel of Saudi hematologists representing the Saudi MDS Working Group convened with two international experts to develop the guidelines for MDS diagnosis and treatment. The recommendations were formulated on the basis of a list of real cases and therapy-related questions. The diagnostic procedures should help distinguish MDS from other causes of cytopenia and dysplasia and other clonal stem cell disorders. Blood smear, bone marrow aspirate and biopsy, and cytogenetic testing are among the mandatory diagnostic tests in MDS. Higher resolution genetic testing like mutational analysis and single nucleotide polymorphisms can be suggested for the workup depending on the clinical condition and availability of these technologies. The Working Group stressed that the heterogeneity of MDS strongly withstands a risk-adapted treatment strategy based on the international prognostic scoring system risk group of patients.

A Comprehensive Overview of the Role of Azacitidine in the Management of Myelodysplastic Syndromes and Acute Myeloid Leukaemia

Myelodysplastic syndromes (MDS) are a heterogeneous group of haematological disorders marked by progressive cytopenias and risk of transformation to acute myeloid leukaemia (AML). Best supportive care (BSC) remains the mainstay of therapy. The pyrimidine analogue azacitidine was the first drug to demonstrate that a change in the natural history of MDS is possible and was the first chemotherapeutic agent approved by the US Food and Drug Administration for the treatment of MDS. Azacitidine, a hypomethylating agent, has shown to reduce proliferation and induce apoptosis of dysplastic cells. The Cancer and Leukemia Group B (CALGB) 9221 and AZA-001 trials demonstrated superiority of azacitidine over BSC and conventional care regimen, respectively. Various studies have demonstrated that azacitidine has better tolerability with comparable efficacy in terms of conventional therapy in older AML patients. Azacitidine is well tolerated even in the elderly patients. Cytopenias were the most commonly occurring haematological adverse events. Gastrointestinal adverse events (AEs) (e.g. nausea, vomiting and diarrhoea) and injection-site reactions were the most commonly occurring nonhaematological AEs. The review summarises the current role of azacitidine in the management of MDS and AML.

Development and validation of QOL-E© instrument for the assessment of health-related quality of life in myelodysplastic syndromes

Abstract