Latest news with #SF3B1
Medscape
2 days ago
- Health
- Medscape
Fast Five Quiz: Low-Risk Myelodysplastic Syndrome
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders, each with varying levels of prognosis. Risk stratification is an important component of MDS; however, even lower-risk variants require a nuanced approach to management, and certain factors can further affect patient risk after diagnosis. What do you know about low-risk MDS? Check your knowledge with this quick quiz. Among the gene mutations identified that can influence the prognosis in MDS, SF3B1 mutation is strongly associated with favorable clinical outcomes. Other mutations such as such as TP53 , ASXL1 , EZH2 , ETV6 , and RUNX1 typically lead to poorer clinical outcomes. The National Comprehensive Care Network (NCCN) notes that combining analysis of these mutations in MDS with International Prognostic Scoring System (IPSS) can improve risk stratification beyond the strengths of the IPSS alone, which is standard practice in some treatment centers. Learn more about cytogenic studies for MDS. Data have shown that hypocellular bone marrow is one of several factors that predict good response to IST in patients with lower-risk MDS. The NCCN specifically recommends IST in select patients, generally those 'aged ≤60 years and with ≤5% marrow blasts, or those with hypocellular marrows, PNH clone positivity, or STAT-3 mutant cytotoxic T-cell clones.' Other factors associated with predicted benefit from IST include presence of dysplasia, young age (< 60 years), presence of HLA DR15, female sex, absence of ring sideroblasts, presence of trisomy 8, and relatively short duration of transfusion need. Learn more about hypocellular marrow in MDS. A study of patients with very low- and low-risk MDS found that mutations in three genes, IDH1 , IDH2 , and NPM1 , are more common among those patients with direct transformation to AML. NPM1 mutations are the most frequently-seen mutation in AML and are found in approximately 30%-35% of cases among adults. Mutations in ASXL1 , CBL , and TP53 were found to be associated with progression to higher-risk MDS but not with transformation to AML. Learn more about cytogenetics in MDS. According to a review published in JAMA , the median survival time for patients with low and very low risk MDS is 5.3 years and 8.8 years, respectively. This is consistent with other recent data. Collected data from the same JAMA review indicated that the median age for MDS diagnosis is approximately 70 years and is more common in males; chemotherapy and radiation therapy exposure are also reported significant risk factors. Further, the IPSS, revised-IPSS, and WHO classification-based prognostic scoring system are the most frequently used scoring systems for MDS risk. Learn more about MDS risk staging. Due to longer survival, patients with low-risk MDS might be given multiple red blood cell transfusions as part of their management (which could potentially lead to iron overload). To decrease iron overload, the NCCN recommends consideration of daily iron chelation with subcutaneous deferoxamine or oral deferasirox after > 20-30 transfusions. This approach is especially recommended for patients with lower-risk MDS or those who are potential candidates for transplantation. Learn more about iron chelation in MDS. Editor's Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
Medscape
3 days ago
- Health
- Medscape
Skill Checkup: Woman With Persistent Anemia and Fatigue
A 72-year-old woman presents with persistent anemia and fatigue. Her height is 5 ft 2 in (1.57 m) and weight is 131 lb (59.42 kg; body mass index of 24). She was diagnosed with low- to intermediate-risk myelodysplastic syndrome (MDS) with ring sideroblasts 2 years ago when she presented with unexplained macrocytic anemia. Bone marrow biopsy at the time showed blasts were 5%-7%, and her specimen tested positive for SF3B1 mutation and negative for del(5q) . Her erythropoietin levels were < 400 and she received erythropoiesis-stimulating agent (ESA) therapy, requiring ≥ 2 red blood cell (RBC) units over 8 weeks. However, despite ESA therapy, the patient presents with symptomatic anemia; her hemoglobin is 10.1 g/dL. There are no blasts in the blood; 16% of erythroid precursors with ring sideroblasts are identified. Because this patient's anemia is not responding to treatment, the likely diagnosis is MDS with ESA-refractory anemia. ESAs are a potential therapy for the treatment of patients with MDS. However, most patients with MDS either do not respond to ESAs or eventually will develop resistance to these agents. Progression to acute myeloid leukemia (AML) in myelodysplastic syndrome is defined by the presence of ≥ 20% blasts in the peripheral blood or bone marrow (World Health Organization criteria). In this case, the patient has no blasts in the blood and had 5%-7% blasts at diagnosis, which is consistent with MDS but not AML. Copper deficiency can cause a sideroblastic-like anemia, but it is typically associated with neurologic symptoms (eg, ataxia, paresthesias), leukopenia, and a history of risk factors such as zinc overuse, malabsorption, or gastric surgery. This patient has a known diagnosis of MDS with ring sideroblasts and a pathogenic SF3B1 mutation, strongly supporting a clonal myeloid neoplasm rather than a nutritional deficiency. Although symptomatic anemia is a major morbidity of MDS, the anemia described in the present case, refractory anemia with ring sideroblasts (MDS-RS), is a subtype often associated with SF3B1 mutations, which lead to defective RNA splicing and secondary mitochondrial iron accumulation. This results in the formation of ring sideroblasts. SF3B1 is the most frequently mutated splicing factor gene in MDS-RS, and it is associated with better outcomes and longer survival. In this case, the presence of this mutation confirms a diagnosis of MDS over secondary causes of ring sideroblasts. Anemia in MDS might or might not be symptomatic at presentation and varies in degree, from mild to severe. Clinical symptoms of MDS, including fatigue as described by this patient, arise because of low peripheral blood counts, usually from anemia, but also can occur from thrombocytopenia or neutropenia. Features predictive of ESA response include a lower baseline serum erythropoietin (EPO) level (< 500 IU/mL), a low transfusion burden (< 2 units a month), a fixed-dose regimen, shorter time from diagnosis to starting treatment, and diagnosis of refractory anemia or MDS-RS. Although the patient in the present case is in fact diagnosed with refractory anemia or MDS-RS, response rates to ESA therapy are variable in patients with lower-risk MDS, ranging from 30%-60%. In this patient population, close monitoring of hemoglobin level is recommended to avoid increases to > 12 g/dL (as it is associated with a risk for systemic hypertension and thrombosis). In addition, the immunomodulatory agent lenalidomide can reduce transfusion requirements in patients with lower-risk MDS and a normal karyotype. In MDS, anemia is usually anisocytic, with a normal or a hypochromic microcytic population coexisting with the macrocytes. It is also generally macrocytic (mean cell volume, > 100 fL) with RBCs that are oval-shaped (macro-ovalocytes). Punctate basophilia is observed in RBCs. Symptomatic anemia in MDS frequently presents as a hypoproductive macrocytic anemia, often associated with suboptimal elevation of serum EPO levels. The National Comprehensive Cancer Network (NCCN) guidelines advise that during MDS workup, cytogenetics, bone marrow aspiration with iron stain, biopsy, serum EPO, and other coexisting causes should be ruled out. For MDS to be classified as MDS-RS, as in the present case, anemia should be present but with low blasts in the blood; for bone marrow, either ≥ 15% of erythroid precursors with ring sideroblasts must be identified, or if SF3B1 mutation is present, ≥ 5% ring sideroblasts. The same guidelines also make recommendations for additional testing of symptomatic anemia with MDS. These include flow cytometry to evaluate for large granular lymphocyte and paroxysmal nocturnal hemoglobinuria clone. Human leukocyte antigen typing offers clinical value if the patient is a hematopoietic cell transplant candidate. Because the patient in the present case is considered lower risk, she probably is not at this juncture. Recombinant fusion protein, such as luspatercept, is the most appropriate option for this patient, given its approval for the treatment of anemia in patients with lower-risk MDS-RS who have not responded to treatment with ESAs. In patients with lower-risk MDS and symptomatic anemia, treatment is usually guided by cytogenetic findings, serum EPO levels, and the presence of ring sideroblasts or SF3B1 mutations. For patients with del(5q) , lenalidomide remains the preferred treatment regardless of EPO level. For those with SF3B1 mutations or ring sideroblasts ≥ 15% (or ≥ 5% with a mutation), luspatercept is preferred, with imetelstat recommended if EPO is > 500 mU/mL and the patient is ineligible for ESAs. In patients without these features, ESAs plus granulocyte colony-stimulating factor or imetelstat may be considered on the basis of EPO levels, with follow-up based on response. Escalation to agents like ivosidenib or enasidenib is recommended only in the presence of IDH mutations. Neither hypomethylating agents or allogeneic transplant are included in this lower-risk anemia-focused treatment pathway. Further, intensive induction chemotherapy is not typically utilized in this setting.
