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PubMed1987

Varying probability of the development of acute nonlymphoblastic leukemia in refractory anemia patients with an excess of blasts.

The cumulative leukemia-free survival rate of refractory anemia with excess of blasts was fitted to three parametric failure time models, i.e., the usual exponential and Weibull, and exponential mixture models. Among the three, the best fit model was the exponential mixture model, which was 119 times more likely to assume that samples came from the exponential mixture distribution than to assume that those were from the usual Weibull distribution. This strongly suggests that refractory anemia with excess of blasts consists of subgroups with very high and very low probability to develop acute nonlymphoblastic leukemia. The estimated proportion of the very low probability group was about 30%. Analysis by the exponential mixture model with covariates revealed that the probability of a patient to develop acute nonlymphoblastic leukemia could be estimated by three covariates, i.e., bone marrow blast percentage; abnormal granules of granulocytes; and mononuclear large megakaryocytes. The estimated probabilities ranged from 17 to 99%, according to the model.

Acute Disease↗
PubMed1990

[Chronic myelomonocytic leukemia transformed from refractory anemia with ring sideroblasts with a rare abnormal chromosome, inv (12)].

We report here a rare transformation from refractory anemia with ring sideroblasts (RARS) to chronic myelomonocytic leukemia (CMML). A rare karyotype, inv (12), was also seen at the phase of CMML. A 76-year-old female consulted a physician because of hoarseness in June, 1983. An anemia was found and blood transfusions were made. In August, 1983, she was referred and admitted to Tsukuba University Hospital for a further examination of anemia. A diagnosis of MDS (RARS) was made by hematological examinations, and pyridoxamine was administered from September, 1983. The monocyte counts in the peripheral blood increased above 1,000/microliters continuously from June, 1985, and an exacerbation of anemia was also seen. At the second admission to our hospital in August, 1988, the diagnostic criteria for CMML by the FAB co-operative group was fulfilled. At that time, chromosomal analysis revealed an abnormal karyotype; 46XY, inv (12) (p13.3 q15). Even at the phase of CMML, ringed sideroblasts were also seen in 2.2% of nucleated cell count in the bone marrow. To our knowledge, only 12 cases have been reported as transformation from another type of MDS to CMML. The present case is thought to be a rare case of transformation of MDS. On the other hand, 8 cases with inv (12) associated with malignant hematological disorders have been reported previously. Four of the above 8 cases were MDS. A relationship between development of MDS and inv (12) was suggested.

Aged↗
PubMedDate not supplied

Refractory anemia with ringed sideroblasts in children: two diseases with a similar phenotype?

Three pediatric patients with refractory anemia with ringed sideroblasts (RARS) are presented. Bone marrow aspirates were examined using Romanowsky and Prussian blue iron stains in all three patients, and electron microscopic analysis was performed in one patient. All three patients had cytogenetic analysis of the bone marrow. Other studies included analysis of serum iron, total iron-binding capacity, ferritin, copper, vitamins B6 and B12, and folate levels. Antibody titers to Parvovirus, HIV, and other viruses were measured. The patients had contrasting clinical courses. Patients 1 and 2 had dysplastic hematopoietic features and cytogenetic findings (with either partial or one allele loss of chromosome 7), suggestive of myelodysplastic syndrome. Patient 1 experienced acute myeloid leukemia (AML) and had a good response to AML-directed therapy. Patient 2 had prolonged cytopenias and underwent bone marrow transplantation (BMT). Patient 3 had features suggestive of refractory anemia associated with mitochondrial cytopathy, including normal cytogenetics with pronounced vacuolization of marrow precursors. His anemia regressed spontaneously a few months after diagnosis. These patients represent two subgroups of pediatric RARS. Patients with the myelodysplastic syndrome (MDS) type may progress to cytopenias or leukemia and may require aggressive therapy; the type is characterized by clonal cytogenetic findings. The non-MDS type, which may relate to mitochondrial cytopathy, often shows spontaneous regression and requires only supportive treatment; it has normal cytogenetic findings.

Adolescent↗
PubMed1989

[Refractory anemia with ringed sideroblasts complicated with delta beta-thalassemia-like hemoglobinopathy].

A 73 year-old man suffering from marked anemia for several years admitted in our hospital. Diagnosis was immediately made of refractory anemia with ringed sideroblasts by the existence of ringed sideroblasts. Hemoglobin analysis revealed a high fetal hemoglobin, a low hemoglobin A2, a decreased beta/alpha synthetic ratio, and a decreased G gamma/A gamma synthetic ratio. This acquired hemoglobinopathy resembled delta beta-thalassemia. His anemia was remarkably improved because of the responsiveness to anabolic steroid hormone, and this abnormal globin synthetic pattern was identical as those of the normal adult. We consider this hemoglobinopathy may due to an abnormal expression of globin mRNA.

Aged↗
PubMed2000

Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor alpha levels.

Amifostine increases in vitro burst-forming unit-erythroid and colony-forming unit-granulocyte/granulcoyte-macrophage cultured from bone-marrow cells from patients with myelodysplastic syndrome (MDS). Several small clinical studies give divergent informations about the potential of amifostine as single agent to improve hematopoiesis in MDS patients. In these studies, patients with refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-T) were analyzed together, resulting in response rates varying from 8% to 30%. The present multi-center study evaluated whether treatment with amifostine is of clinical benefit in patients with RA who are transfusion dependent. The effect on transfusion frequency as well as on platelets and absolute neutrophil count (ANC) was examined in 14 patients with RA [median age 67 years (55-72 years), male:female 9:5]. Four treatment cycles were planned, each consisting of intravenous amifostine at 200 mg/m2/day three times per week followed by a 2-week interval. Since tumor necrosis factor (TNF) alpha is a main suppressive cytokine for hematopoiesis in RA patients, serum samples for analyzing endogenous levels of TNF alpha were collected prior to the study and after four treatment cycles. In three patients (21%), reduced transfusion requirement with prolongation of the transfusion interval from 4 weeks to 8 weeks (two patients) and 4 weeks to 6 weeks was seen. An increase in ANC from 400/microliter to 2600/microliter and 200/microliter to 3400/microliter was observed in two patients. Platelets increased from 129,000/microliter to 277,000/microliter in an additional patient. In one patient, disease progression from RA to RAEB was observed. Serum TNF alpha levels were increased in MDS patients compared with normal controls (18.8 pg/ml vs 9.1 pg/ml), and there was no change during the treatment with amifostine (17.5 pg/ml). In conclusion, treatment with amifostine as a single agent was of limited benefit in patients with RA. The serum TNF alpha levels were unchanged during treatment with amifostine in RA patients.

Aged↗