Gönül Hiçsönmez

Retrospective Analysis of 78 Children with Chronic Idiopathic Thrombocytopenic Purpura: Follow-up from 1976 to 1996

In this retrospective study of 20 years, 78 children with chronic idiopathic thrombocytopenic purpura (ITP) were analyzed. Patients were followed for 1-17 years (median 2.7 years). Every application that required therapy was accepted as an attack. Seventy-eight patients received therapy in 236 attacks. Immediate platelet responses to high-dose methylprednisolone (HDMP), prednisone, and splenectomy were 69.3% (in 53 patients), 48.3% (in 35 patients), and 84.6% (in 29 patients) of attacks, respectively. Because 31 patients were lost to follow-up, the rate of remission was calculated on the basis of 47 patients. The remission rates for patients who underwent remission spontaneously, after steroid therapy, and after splenectomy were 29.78, 6.38, and 14.89%, respectively. Of 78 adolescent patients, 11.5% had intracranial hemorrhage (ICH), being after splenectomy. One patient died because of ICH. These data indicate that chronic ITP is still a serious problem during adolescence and splenectomy still seems to be a current choice of therapy.

Morphologic Evidence of Apoptosis in Childhood Acute Myeloblastic Leukemia Treated with High-Dose Methylprednisolone

We have previously demonstrated that various subtypes of AML children respond to high-dose methylprednisolone (HDMP; 20-30 mg/kg/day) which could induce in vivo differentiation of myeloid leukemic cells to mature granulocytes. In this study we have evaluated whether apoptosis occurs in AML cells of patients treated by HDMP using morphological criteria. For light and electron microscopic examination bone marrow aspirates were obtained four days and two weeks after methylprednisolone (30 mg/kg/day) treatment from two children with newly diagnosed AML (AML-M3 and AML-M4). In both patients maturation of leukemic cells has previously been reported four days (in patient with AML-M3) and two weeks (in patient with AML-M4) after HDMP treatment. Electron microscopy revealed the characteristic ultrastructural changes of various stages of apoptosis four days after HDMP treatment in a case with AML-M3. Morphologic evidence of apoptosis induced by HDMP were also detected on Wright-stained and toluidine blue stained semithin sections of BM preparations in a patient with AML-M4 and AML-M3 respectively. These findings suggest that HDMP which could induce in vivo terminal differentiation in myeloid leukemic cells is also able to induce apoptosis in patients with AML. The possibility of HDMP-induced apoptosis should be evaluated in a larger series of patients with AML and other types of malignant tumors.

Effects of methylprednisolone on human myeloid leukemic cells in vitro

We have demonstrated previously that high‐dose methylprednisolone treatment induces differentiation and apoptosis of leukemic cells in patients with different morphological subtypes of acute myeloblastic leukemia (AML) in vivo. In the present study, we investigated the in vitro effects of high (10−3 M) and low (10−6 M) concentrations of methylprednisolone (MP) on freshly isolated bone marrow leukemic cells from nine newly diagnosed patients with AML by light and electron microscopy (EM) and agarose gel electrophoresis. A marked increase in MP‐induced apoptosis of leukemic cells, with a maximum effect at 24 hr of exposure to both low and high concentrations of MP (10−6 M and 10−3 M), was demonstrated by light microscopy in cultures of four (three with AML‐M1 and one with AML‐M7) of the nine patients. In three cases, the increase in the number of apoptotic cells induced by high‐concentration MP was approximately twice that observed when the lower concentration was used. A few apoptotic cells were detected in the cultures from the other five patients. However, a typical DNA ladder pattern of apoptosis was observed on gel electrophoresis of MP‐treated leukemic cells from one patient (AML‐M1) after 2 hr of incubation with both high‐ and low‐MP concentrations. In two patients, a nonspecific DNA smear was observed only when high‐concentration MP was used. The increase in differentiated leukemic cells induced by MP was also dose dependent, and was observed in cultures from all but one patient. Morphological features of apoptosis and differentiation were also confirmed by EM studies. The results of the present study, together with our previous clinical experience, suggest that MP, especially at high doses, could have a significant role in the treatment of some AML patients by inducing apoptosis and differentiation of leukemic cells. Am. J. Hematol. 60:255–259, 1999.

Platelet Counts in Children with Iron Deficiency Anemia

Platelet count was evaluated in 30 children with iron deficiency anemia. It was found elevated when compared with 40 normal controls. No significant difference was found between the platelet counts in patients with hemoglobin levels higher or lower than 7 g/dl. Although no relation was observed between platelet count and transferrin saturation, it was correlated with serum iron values. After oral and/or parenteral iron therapy platelet count decreased insignificantly, while reticulocytes were found to be increased.

Myelodysplastic syndrome associated with Griscelli syndrome

Myelodysplastic syndrome (MDS) in children has been reported to be associated with various constitutional anomalies; however, it has not been described previously in patients with Griscelli syndrome (GS). In this report, we present a case with GS and refractory anemia with an excess of blasts. We believe that careful evaluation of peripheral blood and bone marrow could increase the number of patients who are found to have GS-associated MDS.

Effect of Cancer Chemotherapy Drugs on Platelet Aggregation in Children

The effect of vincristine (VCR), cytoxan and actinomycin-D on platelet aggregation was studied in 30 children with solid tumors. 2 h after administration of these drugs, a statistically insignificant reduction in the primary wave of aggregation was observed with the exception of ADP-induced aggregation after VCR injection. Unobtainable secondary wave aggregation was seen in 28, 33 and 40% of the patients after administration of VCR, cytoxan and actinomycin-D, respectively. However, none of the patients had clinical bleeding. It was concluded that after the intravenous administration of therapeutic dosages of these drugs, the bleeding tendency caused by inhibition of aggregation is not to be expected.

Reticuloendothelial Phagocytic Function in Children with β-Thalassemia Major

Reticuloendothelial phagocytic capacity (REPC) was determined in 14 children with β-thalassemia major, by means of technetium 99m sulfur colloid uptake, who had not had splenectomy. No difference was observed in the REPC between patient and controls. The REPC of liver and spleen were evaluated separately by determining the half-time for the clearance of 99mTc from the blood. The REPC of both liver and spleen in patients was expected to be decreased when compared with controls; however, we found that the REPC of the liver was increased in patients and that there was no difference between patients’ and controls’ spleen values. This suggests that chronic anemia and hemosiderosis do not alter the REPC in β-thalassemia major.

Goodpasture's Syndrome (Pulmonary Hemosiderosis with Nephritis)

papiledema and retinal bleeding on the right. Other findings were not remarkable. Chest x-rays showed bilateral lung infiltrations. The Hb level was 6 gm, Hct 21 per cent, reticulocytes 9 per cent. Apart from 3 per cent normblasts, differentials were within normal limits. His red cells showed polychromasia, poikilocytosis, and mild hypochromia. Urine sediment contained few red cells and proteinuria. Serum iron level was low, Coombs test negative. Total serum bilirubin was 1.1 mg, NPN, 43-47 mgm. Spleen aspiration biopsy revealed myeloid metaplasia. Other laboratory tests were within normal limits.

Hemoglobin H-β-Thalassemia

A Turkish child with Hb H-β-thalassemia and a clinical picture of thalassemia major, is described. His father and brother have α-β-thalassemia with hematologic findings no more severe than would be expected if they had either trait alone, and his mother has α-thalassemia alone. History revealed that 3 siblings have died from a similar illness in early infancy, perhaps indicating the severity of the combination in this family

Hereditary Persistence of Fetal Hemoglobin and β-Thalassemia in a Turkish Child

A Turkish boy with hereditary persistence of fetal hemoglobin- β -thalassemia combination is described. His Hb F was very much elevated and no Hb A could be shown in his hemolyzate. H