Myelodysplastic syndromes/neoplasms (MDS): Overview of diagnosis and management

INTRODUCTION — 

Myelodysplastic syndromes/neoplasms (MDS) comprise a diverse group of clonal hematologic malignancies that manifest as one or more cytopenias (ie, anemia, neutropenia, and/or thrombocytopenia) typically accompanied by morphologic changes in bone marrow and blood cells. The diseases are predominantly acquired with rare/some germline predisposition.

Most patients with MDS experience symptoms related to anemia, bleeding, and/or infection, but some patients are asymptomatic. There are variable rates of progression of MDS that occur over months or years, including transformation to acute myeloid leukemia (AML) and bone marrow failure.

Cytogenetic and molecular features at diagnosis and through disease course figure prominently in classification, prognosis, and management of MDS:

●Classification – MDS should be classified according to either the World Health Organization 5^th edition (WHO5) or the International Consensus Classification (ICC). Both systems are informed by cytogenetic, molecular, and/or pathologic findings, and they share many features, but they differ in certain aspects of organization, diagnostic criteria, and category labels. Either WHO5 or ICC is acceptable, but they supersede and should replace earlier classification systems. (See 'MDS classification' below.)

●Prognosis – Outcomes for patients with MDS vary widely. Broadly, patients can be categorized as having lower-risk versus higher-risk prognoses according to specific bone marrow, peripheral blood, or cytogenetic and molecular features. (See 'Prognostic category' below.)

●Management – Alleviating MDS-related symptoms, improving the quality of life, and prolonging survival, while minimizing treatment-related toxicity, are important goals for management in all patients with MDS.

Treatment options are guided by the nature and severity of symptoms, MDS prognostic category, and medical fitness for treatment. (See 'Overview of management' below.)

Related topics that present more detailed discussions of aspects of MDS include:

●(See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)".)

●(See "Prognosis of myelodysplastic syndromes/neoplasms (MDS) in adults".)

●(See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)".)

●(See "Myelodysplastic syndromes/neoplasms (MDS): Treatment of higher-risk MDS".)

EVALUATION — 

Clinical evaluation and laboratory testing are required in patients with cytopenia-related symptoms or laboratory abnormalities who are suspected to have MDS.

●Suspicion for MDS – MDS should be considered in any patient with unexplained symptoms related to anemia, infections, or bleeding/bruising, particularly in older adults. MDS should also be suspected when laboratory studies demonstrate unexplained cytopenias, dysplasia of blood or bone marrow cells, circulating blasts, bone marrow failure, or characteristic cytogenetic or molecular abnormalities. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'Diagnosis'.)

●Epidemiology of MDS – Most cases are seen in older adults, and the incidence of MDS rises with age. However, rare cases of MDS may be encountered in children in association with inherited or germline predisposition syndromes. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'Epidemiology'.)

Clinical evaluation — Clinical manifestations of MDS are variable. Most patients experience symptoms related to low blood counts (cytopenias), while others come to medical attention because of asymptomatic abnormal blood counts or other laboratory studies.

●History – The patient should be asked about symptoms related to anemia, such as fatigue, dyspnea, palpitations, and pallor; symptoms related to thrombocytopenia, such as unusual bleeding or bruising; and symptoms related to neutropenia, such as recurrent, severe, or unusual infections.

Other potential causes for cytopenias and/or dysplasia should be evaluated, including nutritional status, alcohol and drug use, medications, toxic exposures, autoimmune conditions, antineoplastic agents or radiotherapy, and risk factors for human immunodeficiency virus (HIV) infection. Prior blood transfusions and other treatments for cytopenias should be documented.

Comorbid conditions that might affect management, such as heart, lung, kidney, or liver dysfunction, should be evaluated.

●Physical examination – Physical examination may reveal pallor, tachycardia, tachypnea, or dyspnea. Liver, spleen, and lymph nodes should be examined clinically.

Skin and mucosal surfaces are examined for ulceration; infections; bleeding; bruising; and for red, tender papules, plaques, or nodules of acute febrile neutrophilic dermatosis (Sweet syndrome).

Details of clinical evaluation are presented separately. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'History and physical examination'.)

MDS associated with inherited/germline disorders may be associated with other hematologic abnormalities and/or other cancers in the patient or relatives; somatic abnormalities (eg, skin, hair, nail, mucosal findings; short stature; congenital skeletal organ abnormalities; unexplained liver or lung disorders); and other findings. A careful family history for other cancers should be obtained, with particular attention to cancers that arose at younger ages. While these disorders are primarily encountered in children, they may also present in adults, especially in those diagnosed with MDS at younger ages. Evaluation and diagnosis of MDS in association with inherited/germline disorders are discussed separately. (See "Familial disorders of acute leukemia and myelodysplastic syndromes".)

Laboratory and other testing — Screening laboratory studies evaluate the nature and degree of cytopenias, evidence for organ dysfunction, and potential alternative explanations for the hematologic findings.

●Hematology – Complete blood count, including differential count and red blood cell (RBC) indices.

Peripheral blood smear is examined for bilobed neutrophils (picture 1), dysplasia (picture 2), blasts (picture 3), and nucleated RBCs.

●Chemistries – Complete metabolic panel, including liver and kidney function tests, lactate dehydrogenase (LDH).

Tests for serum erythropoietin; iron, ferritin, and total iron binding capacity (TIBC); RBC folate; vitamin B12; thyroid stimulating hormone (TSH); and/or copper should be considered, if not previously done.

●Infectious – HIV testing.

●Other clinical testing – Evaluation for heart, lung, or other organ dysfunction that might affect treatment is performed, as clinically applicable.

Bone marrow examination — Bone marrow aspiration and biopsy are performed, if not done previously or recently.

●Aspirate – Evaluation includes microscopy for cellular features, dysplasia, iron staining to look for ring sideroblasts; percentage of blasts and other abnormal forms; cytogenetics by standard karyotyping; flow cytometry (eg, for paroxysmal nocturnal hemoglobinuria or for immunophenotype of blasts, if present); mutation analysis.

Either bone marrow or blood can be used for molecular evaluation (eg, gene panel testing for somatic mutations of genes associated with MDS), whereas bone marrow should be used for karyotyping.

●Biopsy – Cellularity, bone marrow architecture, reticulin stain for fibrosis, and exclusion of other causes of cytopenias (eg, infiltration by solid cancer).

Details of microscopy, immunophenotyping, cytogenetics, and molecular testing are presented separately. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'Bone marrow examination'.)

MEDICAL FITNESS — 

Medical fitness is determined by clinical and laboratory evaluation, performance status, and severity of comorbid conditions.

In judging medical fitness, it is important to recognize that age, per se, does not determine medical fitness. Additional information for judging medical fitness, especially in older patients, is discussed separately. (See "Pretreatment evaluation and prognosis of acute myeloid leukemia in older adults".)

Clinical and laboratory studies are described above. (See 'Clinical evaluation' above.)

Fitness assessment instruments — Assessment of medical fitness can be judged by the following instruments:

●Performance status – Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status scale (table 1) can be used to assess activities of daily living (ADL).

Instruments, such as the QALMS and the Vulnerable Elders Survey, can be used to assess quality of life and vulnerability [1,2].

●Physiologic fitness – We use the Charlson comorbidity index (table 2) to assess the severity of comorbid conditions, ADL, physical performance tests, and cognition. Other instruments, such as the short physical performance battery (SPPB), are also acceptable.

For some older patients, a comprehensive geriatric assessment and geriatric consultation may aid an assessment of medical fitness, as discussed separately. (See "Pretreatment evaluation and prognosis of acute myeloid leukemia in older adults", section on 'Pretreatment evaluation'.)

Fitness categories — We classify patients according to fitness for treatment, based on ECOG performance status (table 3) and physiologic fitness (eg, Charlson comorbidity index (table 2)), as described above.

There are no clear distinctions among fitness categories, and some measures of fitness can apply to different categories of fitness. Chronic comorbid conditions should be weighed more heavily than transient medical complications of the leukemia itself (eg, infection due to neutropenia, heart failure exacerbated by anemia).

●Medically fit – Patients who are able to tolerate intensive treatment, such as that for acute myeloid leukemia (AML).

•Both of the following:

-ECOG performance status: 0 to 2

-Charlson comorbidity index: 0 to 2

●Medically unfit but not frail – Patients unlikely to tolerate intensive treatments because of comorbidities or impaired fitness.

This category includes a broad range of physical function; some patients have only modest, recent, or transient impairment of functional status, while others have substantial comorbidities, cognitive impairment, or other conditions that may affect their ability to tolerate treatment.

•Either of the following:

-ECOG performance status: 3

-Charlson comorbidity index: 3

●Frail – Patients whose debility or comorbid conditions would not permit treatment aimed at modifying the disease course.

•Both the following:

-ECOG performance status: >3

-Charlson comorbidity index: >3

DIAGNOSIS AND CLASSIFICATION — 

MDS is a clinical and pathologic diagnosis.

Clinical presentation and laboratory findings that suggest a diagnosis of MDS are described above. (See 'Evaluation' above.)

Diagnosis — Diagnosis of MDS requires [3]:

●Persistent cytopenia(s) – One or more cytopenias (typically for ≥4 months) that cannot be explained by a drug, toxin, nutritional abnormality, or other comorbid condition:

•Hemoglobin <12 g/dL (females) or <13 g/dL (males)

•Absolute neutrophil count <1800/microL

•Platelets <150 x 10⁹/L

●Myeloblasts – Bone marrow with 5 to 19 percent blasts or blood smear with 2 to 19 percent blasts plus either:

•MDS-defining cytogenetic or molecular features

or

•Qualifying dysplasia (≥10 percent in one or more hematopoietic lineages) or ring sideroblasts ≥15 percent (or ≥5 percent in presence of SF3B1 mutation)

Either the World Health Organization 5^th edition (WHO5) [4] or the International Consensus Classification (ICC) [5] can be used to diagnose and classify MDS. Note that ICC includes a category (MDS/acute myeloid leukemia [AML]) of hematologic malignancies with >10 percent myeloblasts.

Detailed diagnostic criteria for MDS are presented separately. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'Diagnosis'.)

Differential diagnosis — The differential diagnosis of MDS includes other causes of cytopenias/dysplasia (eg, nutritional deficiencies, medications, toxic exposures, infections, autoimmune conditions, inherited/germline disorders), and other causes of clonal hematopoiesis (eg, leukemias, myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, clonal cytopenia of undetermined significance [CCUS], clonal hematopoiesis of indeterminate potential [CHIP]) should be excluded.

Details of conditions that must be distinguished from MDS are discussed separately. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'Differential diagnosis'.)

MDS classification — MDS can be classified according to either ICC or WHO5 criteria [4,5].

Broadly, MDS is classified according to cytogenetic, molecular, and morphologic features [4,5]. Both ICC and WHO5 use bone marrow blast count, degree of dysplasia, and cytogenetic and molecular abnormalities for categorizing MDS. However, they differ regarding their overall organization, category labels, diagnostic criteria, distinctions between MDS and AML, and classification of treatment-related MDS and MDS associated with germline genetic abnormalities.

Details of MDS classification are presented separately. (See "Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS)", section on 'Classification'.)

PROGNOSTIC CATEGORY — 

Management of MDS is stratified according to the risk category, which is determined by clinical and cytogenetic features.

We favor IPSS-M (International Prognostic Scoring System-Molecular) to estimate risk in patients with MDS [6]. An online calculator offers a personalized risk score; assigns the patient to a prognostic category; and provides estimates of overall survival (OS), leukemia-free survival (LFS), and transformation to acute myeloid leukemia (AML).

IPSS-R (IPSS-Revised) is an acceptable alternative model (table 4) (calculator 1), but it is less precise, and it does not incorporate molecular features [7]. The original IPSS model is no longer acceptable because it is based on outmoded diagnostic criteria, and it lacks the prognostic accuracy of IPSS-M and IPSS-R; however, indications for azacitidine and erythropoiesis-stimulating agents to treat MDS in Europe are based on the original IPSS.

We stratify MDS management according to the following broad categories (the corresponding IPSS-M and IPSS-R subcategories are listed):

●Higher-risk MDS

•IPSS-M: Moderate-high, high, very high

•IPSS-R: High, very high, intermediate (≥3.5 points)

●Lower-risk MDS

•IPSS-M: Very low, low, moderate-low

•IPSS-R: Very low, low, intermediate (3 points)

Details of these and other prognostic models for MDS are presented separately. (See "Prognosis of myelodysplastic syndromes/neoplasms (MDS) in adults", section on 'IPSS (Original IPSS)'.)

OVERVIEW OF MANAGEMENT — 

MDS is a heterogeneous disease, and treatment must be individualized. We encourage participation in a clinical trial, when possible.

●Goals of care – Alleviation of MDS-related symptoms, improving the quality of life, and prolonging survival are important goals for all patients with MDS.

Goals of care and patient expectations should be established in conversations between the clinician and patient at the time of diagnosis and periodically through the course of the disease. When appropriate, relatives and/or loved ones should also participate in conversations about goals, management, and prognosis.

●Treatment stratification – Broadly, management is stratified according to the prognostic category (see 'Prognostic category' above):

•Lower-risk MDS (see 'Lower-risk MDS' below)

•Higher-risk MDS (see 'Higher-risk MDS' below)

Selection of treatment is informed by the severity of symptoms and cytopenias, MDS category, medical fitness, and patient preferences.

Our approach is similar to those proposed by the National Comprehensive Cancer Network (NCCN), the European LeukemiaNet, European Society of Medical Oncology, and other expert panels [3,8-11].

LOWER-RISK MDS — 

For patients with lower-risk MDS, we offer treatment based on the severity of cytopenias and related symptoms.

We consider symptomatic patients to manifest any of the following:

●Anemia – Symptoms related to anemia (eg, dyspnea, fatigue, weakness) and hemoglobin (Hb) <10 g/dL; note that Hb <10 g/dL without associated symptoms is not an indication for treatment.

●Thrombocytopenia – Platelets <20,000/microL or excessive bleeding or bruising with platelets <50,000/microL.

●Neutropenia – Recurrent and/or severe infections in the setting of persistent absolute neutrophil count (ANC) <500 neutrophils/microL or ANC <1000 neutrophils/microL with recurrent infections. Although a low ANC without infections is not an indication for treatment, vaccinations and other prophylactic measures may be warranted.

Asymptomatic — For asymptomatic patients, we generally offer monitoring rather than immediate treatment because there is no evidence that early treatment of asymptomatic lower-risk MDS improves long-term survival, and the deferral of treatment avoids potential treatment-related adverse effects (AEs).

Asymptomatic patients are followed expectantly to evaluate the tempo of disease; receive supportive care, if needed (eg, antibiotics for bacterial infections, transfusions for critical cytopenias prior to surgery); and have age-appropriate health maintenance (eg, counseling for smoking cessation, healthy diet, weight control, screening for other cancers). (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)", section on 'Response monitoring and surveillance'.)

Symptomatic — Symptomatic patients with lower-risk MDS are treated according to the severity of cytopenias and symptoms, such as ongoing transfusion requirements, progressive cytopenias, or a declining quality of life.

●Lower-intensity therapies – For most symptomatic patients with lower-risk MDS, we treat with a lower-intensity therapy, supplemented by supportive care as needed. Lower-intensity treatments can lessen symptoms, improve the quality of life, and may lengthen survival, but they are not curative.

The choice of a lower-intensity treatment is guided by the affected cell lineages, laboratory findings (eg, serum erythropoietin), MDS classification, drug availability, and patient preference, as discussed separately. (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)".)

Examples of lower-intensity treatments include growth factors (eg, erythropoiesis-stimulating agents, thrombopoietin receptor agonists), hypomethylating agents (eg, azacitidine, decitabine), luspatercept, immunosuppressive therapy, lenalidomide, imetelstat, and targeted agents (eg, IDH inhibitors). These treatments are generally administered in the outpatient setting, and they have a low risk of treatment-related morbidity and mortality.

●Intensive treatments – Some younger, fit patients with more advanced lower-risk MDS or adverse pathologic features may choose intensive approaches that can alter the natural history of MDS, like those used to treat acute myeloid leukemia. Intensive remission induction chemotherapy and/or allogeneic hematopoietic cell transplantation may be selected because the patient places greater value on a prompt treatment response and/or long-term disease control/potential cure. Such treatments are associated with substantial morbidity and possible early mortality, and many patients with MDS are not eligible for intensive treatments because of comorbidities, age, and impaired functional status.

Intensive treatments for such patients are like those for higher-risk MDS, as discussed separately. (See "Myelodysplastic syndromes/neoplasms (MDS): Treatment of higher-risk MDS".)

●Supportive care alone – Some patients may decline specific treatment for MDS and opt for supportive care alone, based on frailty or personal preferences. (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)", section on 'Supportive care'.)

HIGHER-RISK MDS — 

Treatment choices for patients with higher-risk MDS are informed by medical fitness, pathologic features, and personal preferences. Assessment of medical fitness is discussed above. (See 'Medical fitness' above.)

Allogeneic hematopoietic cell transplantation (HCT) has the greatest potential for long-term disease control/cure, but most patients with MDS are not transplant candidates because of comorbidities, advanced age, and/or lack of a suitable transplant donor. Eligibility for allogeneic HCT is discussed separately. (See "Allogeneic hematopoietic cell transplantation: Indications, eligibility, and prognosis".)

Medically fit — A range of treatment options is available to medically fit patients with higher-risk MDS.

There is no optimal therapy for all patients, and the preferred approach varies by institutional approach and the clinical scenario. The choice of therapy is individualized, with consideration of pathologic features (eg, TP53 mutation, adverse cytogenetic abnormalities), mutations that are amenable to a targeted agent (eg, IDH inhibitors) (algorithm 1), availability of a suitable transplant donor, and patient preference.

Age, per se, does not govern the choice of treatment, but caution is appropriate when considering intensive remission induction therapy and/or approaches for patients ≥75 years because their benefits and toxicities have been defined primarily in younger patients. We encourage early evaluation by transplant specialists to determine eligibility for allogeneic HCT. (See "Allogeneic hematopoietic cell transplantation: Indications, eligibility, and prognosis".)

Broadly, treatments for medically fit patients with higher-risk MDS are:

●Intensive treatments – Intensive remission induction chemotherapy, with or without allogeneic HCT. Such approaches have the greatest potential to achieve long-term disease-free survival, but they are associated with considerable short-term and long-term toxicity. Intensive therapies, outcomes, and adverse effects are presented separately. (See "Myelodysplastic syndromes/neoplasms (MDS): Treatment of higher-risk MDS".)

●Lower-intensity therapies – Lower-intensity therapies, such as hypomethylating agents (HMAs; ie, azacitidine, decitabine) and/or targeted agents are effective, and they are associated with more modest toxicity than intensive treatments. Lower-intensity therapy can provide symptom relief, improve quality of life, and extend survival, but they are not curative. Some patients may seek allogeneic HCT after induction therapy with lower-intensity therapy. (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)".)

Medically unfit but not frail — This fitness category includes a wide spectrum of patients. Most are treated with lower-intensity therapies, while others may choose supportive care alone. Impaired fitness that is related to MDS may improve with treatment.

Selection of treatment is informed by the patient's goals of care and personal preferences, institutional approach, and genetic features of the MDS cells:

●Patients who are not candidates for intensive treatments are generally treated with lower-intensity therapy, such as an HMA, with or without venetoclax and/or targeted agents. (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)".)

●Some patients choose supportive care alone, as described for frail patients. (See 'Frail' below.)

Frail — Frail patients are unlikely to tolerate treatment other than supportive care.

Transfusions and other treatments to alleviate symptoms related to cytopenias are discussed separately. (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)", section on 'Supportive care'.)

MONITORING — 

Patients should be evaluated to determine the response to therapy, monitor for disease progression, and assess possible treatment- or disease-related complications.

●Response to therapy – Response assessment varies according to the type of treatment and the goals of therapy. International Working Group criteria for response have been developed for both lower-risk and higher-risk MDS [12,13]. For patients enrolled in a clinical trial, response assessment and monitoring for treatment-related adverse effects (AEs) are guided by the treatment protocol. There is a balance to be achieved between consistent, on-schedule treatment to achieve response and avoidance of undue toxicity from therapy [14].

•Intensive therapy – Bone marrow examination is performed to assess treatment response to intensive remission induction therapy, especially if allogeneic hematopoietic cell transplantation (HCT) is planned. Response assessments are akin to those for acute myeloid leukemia (AML). (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'Remission status'.)

•Lower-intensity treatments – Response to therapy is primarily assessed by the alleviation of symptoms, improved blood and/or blast counts, reduced transfusion needs, and improved quality of life. (See "Acute myeloid leukemia: Management of medically unfit adults", section on 'Response assessment'.)

Most patients respond slowly to lower-intensity agents, and a meaningful improvement may require three or more months of treatment. Blood counts are monitored, but routine bone marrow examinations are generally not required. We perform a bone marrow examination if there is suspicion of disease progression (eg, unanticipated deterioration of blood counts, worrisome clinical findings) or prolonged, unexplained pancytopenia.

●Monitoring – The schedule and protocol for follow-up is individualized according to the severity of symptoms and cytopenias and concerns on the part of the patient and clinician.

We perform a focused history and physical examination, complete blood count with differential, and other laboratory studies, as clinically indicated. Patients should be educated regarding potential complications of MDS and asked to call the office promptly if they develop a fever or bleeding.

RELAPSED/REFRACTORY MDS — 

For patients who do not respond adequately to initial therapy or have worsening symptoms or disease progression after an earlier response, we select management based on fitness, prior therapy, and patient preference.

●Evaluation – For patients who relapse after an initial response to therapy, re-evaluation is guided by the clinical presentation and severity of laboratory abnormalities. For sudden or dramatic changes in blood counts or increased circulating blasts, we perform a bone marrow examination to assess disease progression. For modest changes in blood counts or symptoms, repeating a bone marrow examination is generally not necessary.

●Treatment – Patients should be encouraged to participate in clinical trials, when available. Treatment options for patients with refractory or recurrent disease are influenced by prior therapy, as described separately. (See "Treatment of lower-risk myelodysplastic syndromes/neoplasms (MDS)", section on 'Second-line therapy'.)

CLINICAL TRIALS — 

Often there is no better therapy to offer a patient than enrollment onto a well-designed, scientifically valid, peer-reviewed clinical trial. Additional information and instructions for referring a patient to an appropriate research center can be obtained from the United States National Institutes of Health (www.clinicaltrials.gov).

For interested patients, relatives, and physicians, the MDS Foundation (https://www.mds-foundation.org) and the Aplastic Anemia and MDS International Foundation maintain websites (www.aamds.org) that contain additional information and listings of clinical trials in this disorder.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Myelodysplastic syndromes".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Myelodysplastic syndromes (MDS) (The Basics)" and "Patient education: Autologous bone marrow transplant (The Basics)")

●Beyond the Basics topics (see "Patient education: Myelodysplastic syndromes (MDS) in adults (Beyond the Basics)" and "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Description – Myelodysplastic syndromes/neoplasms (MDS) are diverse hematologic malignancies that manifest as ≥1 cytopenia (ie, anemia, neutropenia, thrombocytopenia), dysplasia, and predisposition to acute myeloid leukemia (AML) or bone marrow failure.

●Evaluation – MDS should be considered in patients with unexplained symptoms or laboratory abnormalities related to cytopenias, dysplastic blood/marrow cells, circulating blasts, bone marrow failure, or characteristic cytogenetic or molecular abnormalities.

•Clinical evaluation and laboratory studies assess MDS-related symptoms and comorbid conditions. (See 'Evaluation' above.)

•Bone marrow aspirate/biopsy is assessed by microscopy (including blast percentage), cytogenetics, and molecular studies. Testing can be performed using peripheral blood in some cases. (See 'Bone marrow examination' above.)

●Diagnosis and classification – Diagnosis and classification of MDS are based on either the World Health Organization 5^th edition (WHO5) system or the International Consensus Classification (ICC). (See 'Diagnosis and classification' above.)

●Prognosis – Prognosis is evaluated using IPSS-M (International Prognostic Scoring System-Molecular) or IPSS-R (IPSS-Revised) (table 4) (calculator 1), which uses clinical, cytogenetic, and molecular features. These models should replace earlier prognostic models. (See 'Prognostic category' above.)

Patients are broadly categorized as having either lower-risk MDS or higher-risk MDS.

●Fitness

•Medical fitness is determined by clinical evaluation, performance status (table 3), and comorbid conditions (table 2). (See 'Fitness assessment instruments' above.)

•Patients are classified as (see 'Fitness categories' above):

-Medically fit

-Medically unfit but not frail

-Frail

●Overview

•Alleviation of MDS-related symptoms, improving the quality of life, and prolonging survival are goals for all patients with MDS. (See 'Overview of management' above.)

•Treatment is stratified according to prognostic category:

-Higher-risk MDS

-Lower-risk MDS

●Lower-risk MDS – Management is guided by symptoms and cytopenias (see 'Lower-risk MDS' above):

•Asymptomatic – We offer monitoring rather than immediate treatment to avoid treatment-related adverse effects (AEs). (See 'Asymptomatic' above.)

•Symptomatic – Management is focused on the alleviation of cytopenia-related symptoms and often includes transfusions. (See 'Symptomatic' above.)

Erythropoiesis-stimulating agents, hypomethylating agents (HMAs; eg, azacitidine, decitabine), immunosuppressive therapy, lenalidomide, imetelstat, luspatercept, or targeted agents may reduce transfusion requirements and alleviate symptoms with only modest AEs. The choice is guided by clinical/laboratory findings and pathologic features.

Some patients choose intensive approaches that can alter the natural history of MDS, but they are associated with substantial morbidity and mortality. Other patients may opt for supportive care alone, based on frailty or personal values.

●Higher-risk MDS – Treatment is informed by medical fitness, pathologic features, and personal values. (See 'Higher-risk MDS' above.)

•Medically fit – Treatment is individualized and may include intensive remission induction or lower-intensity treatments (eg, HMA- and/or venetoclax-based therapies), eligibility for allogeneic hematopoietic cell transplantation, and patient preference. (See "Myelodysplastic syndromes/neoplasms (MDS): Treatment of higher-risk MDS".)

•Medically unfit but not frail – We favor lower-intensity therapy, such as an HMA-based therapy, with or without venetoclax and/or targeted agents, based on pathologic features, convenience, and patient preference. (See 'Medically unfit but not frail' above.)

•Frail – Supportive care is provided. (See 'Frail' above.)

●Monitoring – Response assessment and monitoring for AEs and disease progression are described above. (See 'Monitoring' above.)

●Relapsed/refractory disease – Evaluation and management of relapsed or refractory MDS are discussed above. (See 'Relapsed/refractory MDS' above.)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Elihu H Estey, MD, who contributed as an author for this topic review.

The editors of UpToDate acknowledge the contributions of Stanley L Schrier, MD as author on this topic, his tenure as the founding Editor-in-Chief for UpToDate in Hematology, and his dedicated and longstanding involvement with the UpToDate program.