vitamin-b-12 and Myelodysplastic-Syndromes

There have been several large-scale epidemiologic studies, including the National Health and Nutrition Examination Survey III (NHANES III), which have described the prevalence and impact of anemia in the elderly. The information derived has been critically important. However, given the large number of patients surveyed, these reports necessarily relied substantially on the laboratory-based screening evaluations. There are now two recent reports describing the cause of anemia in elderly outpatients, and although the numbers are smaller than the large scale surveys, they constitute comprehensive hematologic evaluations with therapeutic interventions and clinical follow-up. The purpose of this review is to compare these different analyses.. There are distinct differences and similarities in the two types of studies, which are derived from patients seen in hematology clinics. Despite comprehensive hematologic evaluation, the puzzling entity of unexplained anemia of the elderly is confirmed and found to account for 30-46% of patients. NHANES III classified iron-deficiency anemia with other nutritional anemias, a classification that might be correct in the developing third world, but in North America and Western Europe, iron deficiency is more often caused by blood loss and the cause must be sought and dealt with. The myelodysplastic syndromes are an important cause of anemia in the elderly, with a prevalence of at least 4%.. Large-scale screening studies of anemia in the elderly are of great importance, and when complemented by comprehensive hematologic evaluations, provide a more accurate picture of the clinical situation.

Topics: Aged; Aged, 80 and over; Anemia; Blood Cell Count; Folic Acid; Health Surveys; Hemoglobins; Humans; Iron; Iron Deficiencies; Iron, Dietary; Myelodysplastic Syndromes; Nutrition Assessment; Outpatients; Vitamin B 12

The discovery of hematologic improvement and bone marrow modification by the drug β-D mannuronic acid (M2000) during treatment of rheumatoid arthritis in phase 1/2/3 clinical trials prompted us to design a new trial to target hematologic deficits in myelodysplastic syndromes (MDS). In this open-label, randomized phase 2 clinical trial, the potential effect and tolerability of drug M2000 was assessed in patients with low- and intermediate-1-risk MDS. The primary efficacy end point was hematologic improvement after 12 weeks of β-D-mannuronic acid therapy. Among 34 enrolled patients, half received their conventional therapy plus β-D-mannuronic acid, and the other half received only conventional drugs. In the conventional + β-D mannuronic acid treatment group, hematologic improvement and development of transfusion independence and/or reduction in transfusion requirements were seen in 12 patients (92.3%) and 1 patient (7.7%), respectively. Moreover, 5 patients (38.5%), 2 patients (15.4%), and 1 patient (7.7%) in the β-D-mannuronic acid-treated group showed hematologic improvement of the major parameters of erythroid, neutrophil, and platelet responses, respectively, based on the International Working Group criteria), whereas in the conventional treatment group as control, no hematologic improvements including erythroid, neutrophil, and platelet response was seen. In this trial, the addition of β-D mannuronic acid to conventional treatment showed promising results in MDS patients with low and intermediate-1 risk with effects on hematologic improvements without significant adverse effect.

Topics: Administration, Oral; Erythrocyte Transfusion; Female; Folic Acid; Hemoglobins; Hexuronic Acids; Humans; Iatrogenic Disease; Immunosuppressive Agents; Infections; Male; Middle Aged; Myelodysplastic Syndromes; Neutrophils; Treatment Outcome; Vitamin B 12

Topics: Aged; Anemia, Sideroblastic; Humans; Male; Myelodysplastic Syndromes; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Diagnosis, Differential; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Female; Humans; Male; Myelodysplastic Syndromes; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Pernicious; Bone Marrow Cells; Chromosome Aberrations; Chromosome Deletion; Chromosomes, Human, Pair 3; Diagnosis, Differential; Female; Humans; Middle Aged; Myelodysplastic Syndromes; Recurrence; Remission Induction; Severity of Illness Index; Syncope; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to prospectively determine the etiology of anemia in a cohort of community-dwelling older outpatients with a comprehensive hematologic evaluation. Participants were men and women age 65 and older with anemia as defined by World Health Organization criteria recruited from outpatient hematology clinics at Stanford Hospital and Clinics (SHC) and Veterans Affairs Palo Alto Health Care System (VAPAHCS). Each participant underwent a history and physical examination, followed by a comprehensive hematologic evaluation, which in all participants included complete blood count, red cell indices, review of the blood smear, and assessment of vitamin B12, folate, iron status and renal function. Additional evaluation was obtained by clinical providers as per their discretion. 190 participants enrolled and completed the evaluation. Twelve percent of participants had iron deficiency anemia. Of those with iron deficiency in whom there was follow-up information, half normalized their hemoglobin in response to iron repletion, and half did not. Thirty-five percent of participants had unexplained anemia. Those with unexplained anemia had mildly increased inflammatory markers compared to non-anemic controls, and, at the lower hemoglobin ranges had relatively low erythropoietin levels. Sixteen percent of participants were categorized as being "suspicious for myelodysplastic syndrome." Thus, even with comprehensive hematologic evaluation, unexplained anemia is common in older anemic outpatients. Iron deficiency anemia is also common and can be difficult to diagnose, and frequently the anemia is not fully corrected with iron repletion.

Topics: Aged; Anemia, Iron-Deficiency; Blood Cell Count; Erythrocyte Indices; Female; Folic Acid; Hemoglobins; Humans; Inflammation; Iron, Dietary; Kidney Function Tests; Male; Myelodysplastic Syndromes; Outpatients; Prospective Studies; Vitamin B 12

This study presents 12 patients (7 women and 5 men) with vitamin B(12)-responsive pancytopenia who had discordant laboratory findings and were misdiagnosed as having myelodysplastic syndrome (MDS). The median hemoglobin level was 6.5 g/dl, and the leukocyte and platelet counts were 2.85 × 10(9)/l and 55.5 × 10(9)/l, respectively. The median serum lactate dehydrogenase level was high (3,204.5 IU/l). The serum vitamin B(12) levels were within normal limits at the initial evaluation, but a serial follow-up of the vitamin B(12) levels revealed either fluctuations or a gradual decrease. The patients were initially diagnosed with MDS and responded rapidly to a 7-day parenteral B(12) treatment with normal complete blood counts (CBCs). We propose that patients suspected to have MDS may suffer from vitamin B(12) deficiency and that this can be revealed by a normalization of CBCs following 7 days of treatment with parental vitamin B(12).

Topics: Blood Cell Count; Diagnostic Errors; Female; Humans; Male; Myelodysplastic Syndromes; Pancytopenia; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Female; Humans; Male; Myelodysplastic Syndromes; Pancytopenia; Vitamin B 12; Vitamin B 12 Deficiency

A diagnosis of myelodysplastic syndrome, refractory anemia subtype, was made in an elderly Indian woman on the basis of a refractory macrocytic anemia with normal vitamin B(12) and folate assays, normal thyroid function, essentially normal liver function and normal cytogenetic analysis. Disease evolution revealed that the diagnosis was erroneous.

Topics: Aged; Anemia, Macrocytic; Anemia, Pernicious; Anemia, Refractory; Diagnostic Errors; Diet, Vegetarian; Female; Humans; Myelodysplastic Syndromes; Vitamin B 12

Vitamin B12 deficiency can cause profound alterations in the bone marrow. These alterations can mimic the more serious diagnosis of acute leukemia. The two patients described in this report were originally suspected of having acute leukemia or myelodysplasia on the basis of the bone marrow smear, and induction chemotherapy was considered. However, after further studies, they were both found to have vitamin B12 deficiency, and parenteral vitamin B12 administration resulted in normalization of the bone marrow.

Topics: Aged; Anemia, Pernicious; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Vitamin B 12

Megaloblastic anemia (MA) due to vitamin B12 deficiency is a reversible form of ineffective hematopoiesis. Myelodysplastic syndrome (MDS) is an acquired, irreversible disorder of ineffective hematopoiesis, characterized by stem cell dysfunction as a consequence of DNA damage manifested in part by karyotype anomalies. Importantly, MA and MDS are generally considered mutually exclusive diagnoses. We report the case of a 73-year-old woman with a profound macrocytic anemia, monocytosis and neurologic symptoms. Low cobalamin levels and the presence of anti-intrinsic-factor antibodies definitively established a diagnosis of pernicious anemia. Replacement therapy resulted in resolution of neurologic findings and macrocytosis; however, the anemia and monocytosis persisted. Bone marrow biopsy revealed trilineage myelodysplasia, which together with the peripheral monocytosis suggested a diagnosis of chronic myelomonocytic leukemia. Karyotype analysis revealed a clone with 45, XX, +der(1;7)(q10;p10)-7 [20]. Eighteen months after documented vitamin B12 replenishment her MDS transformed to terminal acute myeloid leukemia with the same clonal abnormality. Reversible cytogenetic abnormalities have been observed with MA, occasionally including karyotypes typically associated with MDS or myeloid leukemias. These abnormalities, like the anemia, resolve with vitamin replacement. This case suggests that MA and MDS can occur simultaneously; clinicians should be aware that this phenomenon occurs. Whether acquired karyotype abnormalities from the MA were related to the MDS and subsequent myeloid leukemia in this woman is a speculative but intriguing consideration that is discussed.

Topics: Aged; Anemia, Pernicious; Autoantibodies; Biopsy; Bone Marrow; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 7; Female; Humans; Intrinsic Factor; Karyotyping; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Vitamin B 12

During a 7-month period a prospective study of 71 anaemic patients (29 males and 42 females) over the age of 50 was undertaken in order to identify patients with myelodysplastic syndrome (MDS). The mean values of mean corpuscular volume (MCV), serum ferritin, folate, vitamin B12 and red cell folate (RCF) of patients grouped according to the diagnosis were compared to those observed in age-matched blood donors. Forty-four of the 71 elderly patients showed macrocytic anaemia: 21 of them had gastric disease and the remaining 23 MDS. Two further patients with MDS showed microcytic anaemia. The 25 patients diagnosed with MDS were subclassified according to the FAB nomenclature: 9 had a refractory anaemia with excess of blasts and 16 refractory anaemia. The mean values of MCV, serum folate, ferritin, vitamin B12 and RCF were statistically different between patients with macrocytic anaemia due to gastric disease and patients with MDS. Among patients with MDS, the RCF level pathologically high was inversely correlated to the haemoglobin level (r=-0.39; p<0.05). Thus the RCF and serum folate may represent useful parameters for the diagnosis of MDS in elderly anaemic patients.

Topics: Aged; Biomarkers; Erythrocytes; Ferritins; Folic Acid; Humans; Middle Aged; Myelodysplastic Syndromes; Vitamin B 12

Forty two patients who were seen and satisfied the French-American-British (FAB) diagnostic criteria for myelodysplastic syndromes (MDS) over a 6-year period at the University of Zimbabwe's Department of Haematology, Harare, are presented. Their overall ages ranged from 29 to 75 years with a mean +/- SD of 57.8 +/- 11.2 years. Males outnumbered females with a male to female ratio of 1.2:1. Refractory anaemia (RA) occurred in 33.3%; refractory anaemia with ringed sideroblasts (RARS) in 16.7%; refractory anaemia with excess blasts (RAEB) in 21.4%; refractory anaemia with excess blasts in transformation (RAEB-T) in 16.7% and chronic myelomonocytic leukaemia (CMML) in 11.9% of the patients. In 90.5% the disease was primary and in 9.5% prior exposure to myelotoxic agents resulted in secondary MDS. The study reveals that MDS as a cause of anaemia in the African population is usually hidden in the big number of well known anaemias due to rampant malaria, malnutrition and a host of nutritional deficiencies. There is therefore the need to increase diagnostic awareness among our clinicians about the existence of these disorders.

Topics: Adult; Age Factors; Aged; Anemia; Bone Marrow; Female; Folic Acid; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Prospective Studies; Sex Factors; Vitamin B 12; Zimbabwe