Myelodysplastic syndrome patients present more severe respiratory muscle impairment and reduced forced vital capacity: Is disordered inflammatory signaling the culprit?

BACKGROUND/OBJECTIVES: The ageing process is associated with gradual decline in respiratory system performance. Anemia is highly prevalent among older adults and usually associated with adverse outcomes. Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies with increasing incidence with age and characterized by anemia and other cytopenias. The main objectives of this study were to evaluate respiratory muscle strength and lung function in elderly patients with anemia, compare data between myelodysplastic syndromes and non-clonal anemias and evaluate the influence of serum IL-8 level and NF-kB activity on deteriorate pulmonary function in this specific population. PARTICIPANTS: Individuals aged 60 and older with anemia secondary to MDS, non-clonal anemia and healthy elderly individuals. MEASUREMENTS: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/ FVC ratio were measured by spirometry. Respiratory muscle strength was evaluated by maximal static respiratory pressures measurement. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. RESULTS: Mean Hb concentration was comparable between patients with anemia. Significant differences were detected between all patients with anemia and controls for maximum-effort inspiratory mouth pressure (PImax) and also for maximum-effort expiratory mouth pressure (PEmax). The MDS group recorded a significantly lower PImax and PEmax percent predicted when compared to non-clonal anemia group. For FVC and FEV1, a significant difference was found in anemic patients, with even significantly lower values for FVC and FEV1 in MDS group. No significant differences were detected for PImax and PEmax and spirometry parameters when anemic patients were stratified according to the degree of anemia. A significant negative impact in FVC (% pred), PImax (% pred) and PEmax (% pred) was observed in patients with MDS and higher levels of IL-8 or increased activity of NF-kB. CONCLUSION: A negative impact of anemia, independent of its degree, was demonstrated in respiratory muscle strength and lung function particularly in MDS. The well known elevated proinflammatory cytokines in MDS patients were proposed to play a role as was demonstrated by detrimental effect of higher IL-8 and NF-kB in pulmonary function tests in this population.

Myelodysplasia and the leukemias.

The armistice after World War II marked the beginning of an era that was to last to the end of the present century. It was an era in which many changes in medicine and nursing combined to alter the entire philosophy of managing malignant disease. More specifically, the fluid-phase tumors, which comprise myelodysplasia and the leukemias, were singled out for special attention. First there was the ease with which blood and bone marrow could be sampled, making serial investigations simple and practical. Second, cytotoxic drugs became available ranging from nitrogen mustard through cytosine arabinoside, the anthracycline antibiotics, and the epi-podophyllotoxins. Although cytomorphology of the hematopoietic tissue had been exquisitely defined with the use of Romanowsky stains coupled with electron microscopy, the diagnosis of leukemia was, before 1945, a death sentence for want of effective therapy. This changed dramatically with the introduction of the folate antagonists, and progress was unremitting as the range of new products expanded. Suddenly responses could be obtained with single agents, and fairly rapidly combinations were developed for cumulative antitumor effect. Many agents had undesirable toxicity among different organs. Although slightly different for myeloblastic or lymphoblastic variants, this approach produced apparent disease eradication. The concept of complete remission, both clinical and hematologic, was born. Some of our early enthusiasm has had to be tempered with the somber appreciation that not all patients can improve and many others experience relapses. Where then do we stand? Leukemic cells themselves seldom kill. It is the relentless and uncontrolled expansion of a neoplastic clone that leads to bone marrow failure, albeit at different rates in the various subtypes. In the acute forms, the common presentation remains symptomatic anemia, neutropenic sepsis, and thrombocytopenic bleeding. Differentiation from marrow aplasia may not be possible at first on clinical grounds, although bone tenderness, gingival hypertrophy, and skin infiltration are among the general useful differential signs. Findings in the circulation and the marrow are of cardinal importance in diagnosis; they provide the basis for classification. Improved accuracy has followed the introduction of cytochemical stains, and a widening range of monoclonal antibodies, and greater recourse to karyotyping, have enhanced diagnostic acumen. Treatment decisions rest on many variables or prognostic factors that include age, performance status, comorbidity, and disease category, with an ever increasing regard for the part played by cellular and molecular genetics. Despite skillful utilization of this wealth of information for optimal management, outcome often leaves much to be desired. Myelodysplasia encompasses a number of different syndromes in which the refractory anemias are indolent, whereas those with excess blasts progress toward overt leukemia. Considerable judgment is necessary in selecting patients for whom supportive therapy alone is appropriate and recognizing others, up to one third of patients for whom use growth factors that include erythropoietin, granulocyte or granulocyte monocyte-colony stimulating factors, and thrombopoietin can be justified. The often unfavorable result has been a stimulus to current investigations that examine the value of intensive chemotherapy or the more innovative bone marrow transplantation and its peripheral blood equivalent. Autografting is a newer alternative that does not have proved potential. Acute leukemia, whether myeloblastic or lymphoblastic, has been managed with mixed success. Remission rates have steadily increased and, notably among children, moved toward 100% in certain groupings. The downside of nonspecific drug regimens is that some patients simply may not respond, whereas others experience remissions and then relapses. (ABSTRACT TRUNCATED)

Sequelae and complications related to dental extractions in patients with hematologic malignancies and the impact on medical outcome.

OBJECTIVE: The purpose of this retrospective study was to evaluate sequelae and complications after dental extractions and to analyze their impact on medical treatment in patients with myelodysplastic syndrome, acute and chronic leukemia, and multiple myeloma during a 3-year period. STUDY DESIGN: The study population included 388 patients with hematologic malignancies. All medical and dental charts were reviewed in a retrospective fashion to identify patients who received dental extractions. Preexisting dental disease and intervention (extraction) were evaluated, and parameters such as days of hospitalization and survival rate were compared with those of the remainder population who did not receive dental extractions. RESULTS: Of the 388 patients, 69 underwent dental extractions and 9 had sequelae and complications after the intervention. The resulting complication rate of 13% was reported. Although some patients did experience delay of chemotherapy or bone marrow transplant (BMT), or both, no significant difference was found in the number of days in the hospital for BMT and the survival rate for the patients with sequelae and complications (n = 9) and for the remainder population (n = 319) ( >.05). CONCLUSION: Dental extraction intervention provided in the prechemotherapy and pre-BMT time frame did not have a negative bearing on medical outcome.

Oral manifestations in myelodysplastic syndrome. Review of the literature and report of a case.

Gingival hyperplasia in a patient with myelodysplastic syndrome is described. Gingival infiltration was the first sign of acceleration of a stable disease process and was followed by development of a more aggressive phase of chronic myelomonocytic leukemia that was not responsive to therapy. Oral and dental assessment of patients with the myelodysplastic syndromes should be a part of routine management.