Silvia M. M. Magalhães

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM)

A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS.

Time-dependent changes in mortality and transformation risk in MDS

In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.

Confirmation of the utility of the International Staging System and identification of a unique pattern of disease in Brazilian patients with multiple myeloma

Multiple myeloma (MM) is one of the most frequent hematologic malignancies, and its incidence varies worldwide. Except for occasional case series or correlative biological studies, little is known about the incidence and clinical features of MM in Latin America. In Brazil, national estimates for the

14 Revised International Prognostic Scoring System (IPSS-R), developed by the International Prognostic Working Group for Prognosis in MDS (IWG-PM)

14 Revised International Prognostic Scoring System (IPSS-R), developed by the International Prognostic Working Group for Prognosis in MDS (IWG-PM) P. Greenberg, H. Tuechler, J. Schanz, F. Sole, J.M. Bennett, G. Garcia-Manero, A. Levis, L. Malcovati, M. Cazzola, G. Sanz, J. Cermak, C. Fonatsch, M. LeBeau, M. Slovak, O. Krieger, M. Luebbert, S. Magalhaes, Y. Miyazaki, M. Pfeilstocker, M. Sekeres, J. Maciejewski, R. Stauder, S. Tauro, A. van de Loosdrecht, U. Germing, P. Fenaux, D. Haase. Hematology, Stanford University Cancer Center, Stanford, CA, USA; Hanusch Hospital, Vienna, Austria; University of Goettingen, Goettingen, Germany; Hospital del Mar, Barcelona, Spain; Wilmot Cancer Center, Rochester, NY, MD Anderson Cancer Center, Houston, TX, USA; Arrigo Hospital, Alessandria, University of Pavia Medical School, Pavia, Italy; Hematology, Hospital Universitario La Fe, Valencia, Spain; Institute of Hematology and Blood Transfusion, Prague, Czech Republic; Medical University of Vienna, Vienna, Austria; Hematology/Oncology, University of Chicago Cancer Research Center, Chicago, IL, Quest Diagnostics, Chantilly, VA, USA; Elisabethinen Hospital, Linz, Austria; University of Freiburg, Freiburg, Germany; Federal University of Ceara, Fortaleza, Brazil; Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Cleveland Clinic Foundation, Cleveland, OH, USA; Medical University of Innsbruck, Innsbruck, Austria; University of Dundee, Dundee, UK; VU Medical Center, Amsterdam, The Netherlands; Hematology/Oncology, University of Duesseldorf, Duesseldorf, Germany; Hopital Avicennes, Paris, France

Bone marrow lymphoid aggregates in myelodysplastic syndromes: incidence, immunomorphological characteristics and correlation with clinical features and survival

Lymphoid aggregates (LA) are a common finding in bone marrow biopsies but little is known about their clinical implications and biological significance. We found LA in 51/206 patients with myelodysplastic syndromes (MDS). There was no correlation with age, disease progression or overall survival. The group with LA had lower hemoglobin values (P=0.03), and was associated with an increase in reticulin fibres (P=0.01). Although they were more frequent in RAEB, this did not reach statistical significance. Most LA had a benign morphology and showed CD20 expression in three distinct patterns: central, perinodular or diffuse. No evidence of an association with lymphoproliferative disease was observed. LA probably represent an ongoing immune stimulation and are probably related to an altered bone marrow microenvironment, with no impact on prognosis.

Cytopenia levels for aiding establishment of the diagnosis of myelodysplastic syndromes.

To the editor: The recent article by Arber et al[1][1] detailing the 2016 revision of the World Health Organization (WHO) classification of myeloid malignancies and AML was timely and germane. Regarding myelodysplastic syndromes (MDS), the authors indicate diagnostic criteria that include levels of

Efeito da bomba de infusão de soluções sobre o grau de hemólise em concentrados de hemácias

The lyses of red blood cells, both for immune or non-immune reasons, can cause an elevation in plasmatic hemoglobin, inducing harmful effects mainly in the kidneys and cardiovascular system. This work aims at identifying the possible hemolytic effect, related to mechanical trauma due to the use of different models of infusion pumps, on red blood cells transfused after up to ten days of storage. Three models of pumps were studied (Nutrimat, Infusomat Compact and Volumed), (four devices of each model) with three infusion speeds being tested (120 mL/h, 240 mL/h and 360 mL/h). The parameters used to report the degree of hemolysis were the percentile of hemolysis, hemoglobin levels and free potassium in the plasma. Samples were collected before infusion of red blood cells using the pumps, half way through infusion (1/2 T) and at the end of infusion (T), for the three different speeds. Significant variations were not seen in the analyzed parameters between the control samples and those collected at different speeds, using different models of pumps and infusion mechanisms and among pumps of the same brand and at different infusion times. The greatest variation found involved free potassium, probably due to the different levels found in red blood cell concentrates seen when control samples were compared to values obtained half way through and at the end of infusion for each pump. In agreement with the obtained results changes in the percentile of hemolysis were not found after infusion of the cells using the different infusion pumps.

Post-transfusion red cell alloimmunisation in patients with acute disorders and medical emergencies

Alloimmunisation following red cell transfusion is a complication in patients with chronic diseases requiring multiple transfusions. The aim of this study was to determine the frequency of alloimmunisation, to identify involved alloantibodies, to establish risk factors and to quantify the alloimmunisation risk in patients with acute disorders who received red cell transfusion at the Instituto Dr. Jose Frota from January 1999 to January 2001. Of the 5,690 recipients who received 16,547 units of red blood cells, 4,025 were men and 1,665 were women. Recipients with previous alloimmunisation or with time of hospital stay less than one week were excluded (n = 501). Red cell alloantibodies were detected in 120 recipients (2.1%): 60 men (1.49%) and 60 women (3.60%). Alloimmunisation was 2.4 fold more frequent in women and 93.33% of the women were pregnant prevously. The average number of units transfused in the alloimmunised recipients was 4.68: 4.97 units in men and 4.40 units in women. In non-alloimmunised recipients the average was 2.87 units and the risk of alloimmunisation was 0.83%: 0.59% in men and 1.44% in women. The most frequent allo-antibodies were: anti-E (18.25%) and anti-D (16.06%) from a total of 137 allo-antibodies detected. The median time for detection of allo-antibodies was 20.88 days. The risk of alloimmunisation detected was high considering the average number of units transfused. The age of recipients and the longer life expectancy increase the probability of further transfusion requirements in this group. Our findings point out the necessity of modifications in the current medical transfusion support indication, including in patients with acute disorders in order to prevent alloimmunisation.

Síndromes mielodisplásticas: diagnóstico de exclusão

Myelodysplastic syndromes are common in elderly people. Laboratory presentation includes isolated macrocytosis, anemia, isolated or combined cytopenias and dysplastic bone marrow. Diagnosis depends on exclusion of non-clonal and reversible disorders. Especially in lowest grade of the disease, with no blast excess, no ringed sideroblasts, no clonal cytogenetic abnormalities the diagnosis requires an exclusion protocol. Recent exposure to toxin, cytotoxic drugs or growth factor therapy and vitamin B12 or folate deficiency are considered absolute exclusion factors precluding the definite diagnosis. Alcohol abuse, chronic inflammatory states, auto-immune disorders, metabolic dysfunctions, hormonal disorders and viral infections must all be ruled out or interpreted with caution. Some diseases of the pluripotential stem cell must also be considered especially in hypocellular MDS. Moreover, in some cases a 6-month follow-up is necessary before a diagnosis be established.

Síndromes mielodisplásicas: protocolo de exclusão

Myelodysplastic syndromes are clonal hematological diseases with heterogeneous clinical and laboratorial presentations, which result in progressive bone marrow failure and evolve to acute leukemia. Anemia is a common symptom. In elderly patients, it is not attributed to the normal aging process and the cause is identified in most cases. The presence of cytopenias associated with bone marrow dysplastic disorders may also be due to secondary and reversible non clonal disorders. Cytogenetic abnormalities found in a proportion of patients with myelodysplastic syndromes may be helpful in the differential diagnosis and to evaluate the prognosis. Ancillary laboratory tests to show clonality are not usually available. The diagnosis of myelodysplastic syndromes is, therefore, made by exclusion, sometimes helped by the passage of time. Considering the proposed multistep myelodysplastic syndrome pathogenesis, patients at the lowest grade, presenting minimal dysplastic features may be difficult to diagnose. Vitamin B12 and/or folate deficiency, recent exposure to heavy metals and recent cytotoxic or growth factor therapy should be considered absolute exclusion factors precluding the definite diagnosis. Alcohol use, chronic inflammatory states, auto-immune disorders, chronic liver or kidney diseases, hormonal disorders and viral infections including HIV must be ruled out or interpreted with caution. Some diseases of the pluripotential stem cells must also be distinguished from myelodysplastic syndromes. Exclusion of paroxysmal nocturnal hemoglobinuria and aplastic anemia may be difficult in the less common hypocellular myelodysplastic syndromes. Dysplastic abnormalities of the bone marrow, therefore, do not in themselves establish a diagnosis of myelodysplasia and a protocol of exclusion should be carried out.