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Biomedical subjects

T Ruutu

Publications and source records attributed to T Ruutu.

At least 91 records · Page 5Linked to original sources
PubMed1988

Heme arginate treatment for myelodysplastic syndromes.

Heme arginate was given to 26 patients with a myelodysplastic syndrome (MDS) as infusions of 2-3 mg/kg body weight weekly for 8-12 weeks. Most of the patients first received a loading dose on four consecutive days. Six of the patients showed improvement in cytopenias during the therapy. In three of the responders severely depressed blood cell counts recovered to normal or close to normal. So far the maximum duration of a response after the cessation of the treatment is 25 months, and the two ongoing responses have lasted for 11 and 12 months, respectively. In two responders of the eight patients with more than 15% ring sideroblasts the number of ring sideroblasts decreased during the treatment but remained unchanged in six non-responders. The responders were characterized by a low or low normal heme synthase activity which increased during the treatment, whereas the non-responders showed a higher mean heme synthase activity which decreased during the treatment. In general, the responders had significantly fewer defects in heme synthetic enzyme activities than the non-responders. FAB type, karyotype or growth pattern in in vitro cultures of hematopoietic progenitors did not predict the response. Apart from one case of mild venous irritation, no other adverse effects were seen. The present study shows that heme arginate induces beneficial effects on cytopenia in some MDS patients and has very few side-effects.

Adult↗
PubMed1988

Megakaryocytic colony formation in polycythaemia vera and secondary erythrocytosis.

Megakaryocytic colony formation by progenitor cells of 18 patients with polycythaemia vera, seven with secondary erythrocytosis and four with erythrocytosis of unexplained origin was studied in vitro by the methyl cellulose culture assay. Fourteen of the 18 patients with polycythaemia vera showed spontaneous megakaryocytic colony formation, i.e. colony growth with normal human plasma as the only source of colony stimulation. None of the patients with secondary erythrocytosis or erythrocytosis of unknown origin or of the normal controls grew colonies in the presence of normal human plasma only. When the plasma of a patient with aplastic anaemia was used instead of normal human plasma and phytohaemagglutinin stimulated leucocyte conditioned medium (PHA-LCM) was added to the culture medium, two of the patients with polycythaemia vera and one with secondary erythrocytosis formed slightly increased numbers of megakaryocytic colonies, while the rest of the patients showed normal colony formation. All of the patients with polycythaemia vera but none of those with secondary erythrocytosis or erythrocytosis of unknown origin showed spontaneous erythroid colony growth. The present study shows that most patients with polycythaemia vera form spontaneous megakaryocytic colonies in vitro. This phenomenon has recently also been demonstrated in essential thrombocythaemia and it is apparently analogous to spontaneous erythroid colony growth seen in all myeloproliferative disorders.

Adult↗
PubMed1988

A new congenital dyserythropoietic anaemia.

A new dominantly inherited dyserythropoietic anaemia is described. In the bone marrow, many of the nonspecific morphological characteristics described in congenital dyserythropoietic anaemias were seen; however, dysmorphic cells were rare. The acidified serum test was positive with one out of 17 sera tested; the negative sera included two that had haemolysed HEMPAS erythrocytes in the acid Ham test. Anti-i-agglutination was negative. No aberrations of red cell membrane protein glycosylation were observed. Serum cholesterol was low. Bilirubin conjugation was deficient but icterus was resolved by treatment with phenobarbital.

Adult↗
PubMed1988

Erythroid colony formation and effect of hemin in vitro in hereditary sideroblastic anemias.

Colony formation by erythroid burst-forming units (BFU-E) and erythroid colony-forming units (CFU-E) and the effect of hemin on colony growth was studied in vitro in three Finnish families with hereditary sideroblastic anemia (HSA). Defective activity of heme synthase has been demonstrated in family A and that of delta-aminolevulinic acid synthase in family B. No biochemical defect has been recognized so far in family C. CFU-E colony growth was defective in seven of the eight persons studied. The formation of BFU-E colonies was normal in family A and increased in family C, whereas of the two members of family B one showed normal and one decreased BFU-E colony growth. Hemin in 30-120 microM concentration increased significantly both BFU-E (p less than 0.01) and CFU-E (p less than 0.005) colony formation in family C. No effect was seen in family A, and in family B the only effect was normalization of the decreased BFU-E colony growth by the highest hemin concentration in one person. This study indicates that differences exist between families with HSA in erythroid colony formation and in response to hemin in vitro, but the low number of investigated members in each family does not permit a conclusive evaluation of the impact of the carrier versus patient status or of sex on the results.

Adult↗
PubMed1988

Monocytic involvement by monosomy 7 preceded acute myelomonocytic leukemia in a patient with myelodysplastic syndrome.

Novel techniques were used to detect which cell lineages were affected by monosomy 7 in a patient who had myelodysplastic syndrome and later developed acute leukemia. The patient had had paroxysmal nocturnal hemoglobinuria for 20 years before developing refractory anemia with excess of blasts. Cytogenetic analysis at the myelodysplastic stage disclosed monosomy 7 in bone marrow mitoses. Restriction fragment length polymorphism analysis of fractionated white blood cells with the chromosome 7-specific probes MetH and MetD revealed that blood monocytes and most bone marrow erythroblasts but not blood granulocytes or lymphocytes were affected by monosomy 7. The patient later developed acute myelomonocytic leukemia with blast cells positive for markers of the myelomonocytic lineage but negative for granulocytic markers in a standard surface marker analysis. The leukemic blast cells had monosomy 7 as determined by direct cytogenetic investigation. Thus, the monocytes were found to be affected by monosomy 7 in this patient 8 months before her myelodysplastic syndrome progressed to acute myelomonocytic leukemia, and the affected cells had the same biologic markers at both stages of the disease.

Anemia, Refractory, with Excess of Blasts↗
PubMed1987

Monosomy 7 in granulocytes and monocytes in myelodysplastic syndrome.

Monosomy for all or part of chromosome 7 in bone marrow mitoses of some patients with myelodysplastic syndrome or acute nonlymphocytic leukemia has been associated with a defect in granulocyte function. To study which blood-cell lineages are affected by the monosomy, we used chromosome 7-specific DNA probes in Southern blotting experiments on DNA derived from specific cell fractions isolated from the blood of five patients. As judged by the presence or absence of two different alleles for restriction-fragment-length polymorphisms, lymphocytes of all five patients were shown to have two different chromosomes 7. Granulocytes were affected by the chromosomal abnormality in four patients (No. 1, 2, 4, and 5) and unaffected in one (No. 3). Chemotaxis was normal in Patient 3 and impaired in Patients 4 and 5. Monocytes were affected by the monosomy in two of three patients (No. 2 and 3) and mainly unaffected in one (No. 1). Thus, the granulocytes and monocytes were affected differently in different patients. We conclude that mature blood cells are derived from abnormal progenitors and that there may be heterogeneity in the involvement of different cell lineages in different patients with myelodysplastic syndrome or acute nonlymphocytic leukemia. There is an association between DNA loss and functional impairment.

Acute Disease↗
PubMed1987

Constitutional translocation t(3;6)(p14;p11) in a family with hematologic malignancies.

We describe a family with an inherited constitutional balanced translocation t(3;6)(p14;p11) and hematologic malignancies. Of two proven translocation carriers, one had acute myeloid leukemia and the other had myelofibrosis. A third member who had died of acute leukemia was a possible translocation carrier (chromosome analysis had not been performed). Five healthy translocation carriers were detected. Neither the translocation nor additional hematologic malignancies were found outside the nuclear family. It could not be definitely clarified if this constitutional translocation predisposes to hematologic malignancies. Breakpoint 3p14 has previously been implicated in recurrent cancer-associated rearrangements but 6p11 has not. We suggest that other investigators look for involvement of these breakpoints in cancer patients.

Acute Disease↗
PubMed1987

Colony formation by megakaryocytic progenitors in essential thrombocythaemia.

Colony formation by megakaryocytic progenitors (CFU-M) from the blood or bone marrow of 12 patients with essential thrombocythaemia was studied in vitro with the methyl cellulose assay. When the cultures were stimulated with plasma from a patient with aplastic anaemia and with phytohaemagglutinin stimulated conditioned medium (PHA-LCM), the patients showed a significant trend towards higher circulating CFU-M numbers when compared with the controls; three of the patients exceeded our normal range. In the bone marrow cultures there were no differences in the number or morphology of megakaryocytic colonies between the patients and the controls. When normal human plasma was the only source of colony stimulating activity, 11 out of 12 patients, but none of the controls, showed megakaryocytic colony formation. The same patients also had 'spontaneous' erythroid colony growth without the addition of exogenous erythropoietin into the cultures. Only one of the patients with essential thrombocythaemia (ET) had normal megakaryocytic and erythroid colony formation. The present study shows that, in most patients with ET 'spontaneous' CFU-M colony formation occurs in suboptimal culture conditions, a phenomenon obviously analogous to the spontaneous erythroid colony formation seen in the myeloproliferative disorders.

Adult↗
PubMed1987

Haem arginate as a treatment for myelodysplastic syndromes.

We report on two patients with a myelodysplastic syndrome in whom the blood cell counts markedly improved during treatment with haem arginate. One patient received haem arginate only, the other haem arginate in combination with low dose androgen. The drug was given as weekly infusions of 2-3 mg/kg body weight for 8-12 weeks. In one patient the percentage of ringed and other abnormal sideroblasts in the bone marrow was clearly reduced as a result of the treatment. In both patients the effect on blood cell counts lasted for several months after the cessation of the haem arginate treatment. Eleven other patients showed no clear response. No adverse effects of the infusions were observed. Further studies on the possible therapeutic role of haem arginate are indicated.

Adult↗
PubMed1987

Graft-versus-leukaemia activity associated with cytomegalovirus seropositive bone marrow donors but separated from graft-versus-host disease in allograft recipients with AML.

To elucidate whether a relationship existed between bone marrow donor cytomegalovirus (CMV) immune status and the probability of staying in remission after transplantation, a retrospective multicentre analysis was performed in 69 patients who received allogeneic bone marrow transplantation during relapse or second remission of AML, or second remission of ALL. None of 12 AML patients with CMV seropositive donors had posttransplant relapse, in contrast to 7 of 10 AML patients with seronegative donors. Kaplan-Meier estimates of the 2-yr probability of staying in remission for the two groups were 100% and 0%, respectively (p less than 0.0005). This effect was independent of disease stage, donor and recipient age, recipient pretransplant CMV immune status and the occurrence of posttransplant CMV infection in recipients, and was not mediated through an increased occurrence of overt graft-versus-host disease (GvHD) in recipients with CMV seropositive donors. The increased probability of staying in remission was associated with an increased probability of 3-yr disease-free survival (p less than 0.01). No similar effect was observed in patients with ALL. This study may suggest an allograft-versus-leukaemia effect in AML, associated with CMV seropositive donors, which seems separate from GvHD and independent of the occurrence of posttransplant CMV infection.

Adolescent↗
PubMed1987

Correlation between bone marrow karyotype and the occurrence of erythroblast micronuclei and nuclear budding in patients with myelodysplastic syndromes.

147 patients with myelodysplastic syndromes were investigated for the presence of micronuclei and nuclear budding in bone marrow erythroblasts. The patients were divided into subgroups on the basis of bone marrow karyotype, 31 healthy bone marrow donors constituted a control group. Patients with monosomy 7 or 7q- and patients with major karyotypic abnormalities (MAKA) had significantly more erythroblasts with micronuclei and nuclear budding than the control group. Patients with a 5q- chromosome as the sole karyotypic aberration had more micronuclei than the controls. For other patients with MDS the differences were statistically nonsignificant.

Adolescent↗