Retinoic acid and steroid in acute promyelocytic leukemia.
Explore the source record for details and available documents.
Dexamethasone↗
Biomedical subjects
G Hiçsönmez
Publications and source records attributed to G Hiçsönmez.
The analysis of eosinophil and lymphocyte phenotype following single dose of high-dose methylprednisolone in two siblings with marked hypereosinophilia.
The effect of single high-dose methylprednisolone (HDMP) on eosinophil and lymphocyte phenotype in two siblings with marked hypereosinophilia was investigated. Since conventional dose steroids failed to produce a haematological and clinical response in case one, both children were given HDMP (20 mg/kg/day). Eosinophils and lymphocytes showed an activated state before treatment, characterized by marked expression of CD11b, CD18, CD45RO on eosinophils and increased HLA-DR, CD95, CD18, CD38 on lymphocytes. Twenty-four hours after administration of HDMP a dramatic reduction in peripheral blood eosinophil count was observed in both patients associated with phenotypic changes characterized by decreased expression of CD11b, CD18, CD13 and increased CD95 expression in one. Furthermore, HDMP treatment induced a drop in the expression of CD95 and CD18 on lymphocytes. These changes may suggest a suppressive role for HDMP on eosinophil and lymphocyte activation which may have contributed to the haematological and clinical response.
Antigens, CD↗
Effect of short-course, high-dose steroid therapy in a child with myelodysplastic syndrome.
High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML). Here the beneficial effect of short-course HDMP therapy in a child with myelodysplastic syndrome (MDS) is reported. Oral methylprednisolone sodium succinate (Prednol-L) was administered at a single daily dose of 30 mg/kg for 5 days to a 4-year-old girl with refractory anemia with excess of blasts and hypocellular bone marrow before the initiation of chemotherapy. In addition to dramatic clinical improvement, the patient's white blood cell count increased from 2.3 x 10(9)/L to 5.0 x 10(9)/L, and peripheral blood blast cells disappeared 4 days after HDMP treatment. Repeated bone marrow aspirate 1 week after the initiation of HDMP disclosed increased cellularity with no blasts. Furthermore, short-course HDMP treatment stimulated the increase in the number of peripheral blood lymphocytes and CD3+, CD4+, CD8+, CD19+, CD34+, and NK cells. Results obtained with HDMP from the previous studies and the present case suggest that high-dose methylprednisolone is a promising agent in the treatment of AIDS and it is recommended as an initial treatment especially for MDS children with hypocellular bone marrow at presentation.
Anemia, Refractory, with Excess of Blasts↗
Evaluation of children with myelodysplastic syndrome: importance of extramedullary disease as a presenting symptom.
Thirty-three children diagnosed with primary myelodysplastic syndrome (MDS) in a single institution over an 8 year period were evaluated with special emphasis on children who presented with extramedullary disease (EMD). EMD was present at diagnosis in 12 (36%) of the 33 children with MDS. Three patients with juvenile myelomonocytic leukemia (JMML) and 2 patients with chronic myelomonocytic leukemia (CMML) presented with pleural effusion. Pericardial effusion was present in 3 of these patients, two of whom also had thrombosis. Pyoderma gangrenosum, relapsing polychondritis were the initial findings in another two cases with JMML. Lymphadenopathy (n=1), gingival hypertrophy (n=2), orbital granulocytic sarcoma (n=1) and spinal mass (n=1) were the presenting findings in 5 patients with refractory anemia with excess of blasts in transformation. Since high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) has been shown to induce differentiation and apoptosis of myeloid leukemic cells in children with different morphological subtypes of acute myeloid leukemia in vivo and in vitro, 25 children with de novo MDS were treated with combined HDMP and cytotoxic chemotherapy. Dramatic improvement of EMD and decrease in blast cells both in the peripheral blood and bone marrow were obtained following administration of short-course HDMP treatment alone as observed in children with AML. HDMP, combined with low-dose cytosine arabinoside and mitoxantrone were used for the remission induction. Remission was achieved in 8 (80%) of 10 children who presented with EMD and in 9 (60%) of 15 children without EMD. Long-term remission (>6 years) was obtained in 4 (two with JMML and two with CMML), three of whom presented with EMD. In conclusion EMD can be a presenting finding in childhood MDS as observed in adults. In addition, the beneficial effect of HDMP combined with more intensive chemotherapy should be explored as alternative therapy in children with MDS not suitable for bone marrow transplantation.
Adolescent↗
CD34/CD117 co-expression in childhood acute leukemia.
CD117 protein is expressed by the primitive CD34 positive haemopoietic stem cells and also demonstrated on the blasts of 30-100% of AML cases, but rarely on lymphoblasts. Therefore several investigators have used CD117 expression to exclude lymphoblastic origin of blasts. However, conflicting results exist in the literature. We investigated CD34 and CD117 status at initial presentation of 232 children with acute leukemia. CD34 was commonly expressed in all types of acute leukemias, whereas CD117 molecule seemed to be a more specific marker for leukemia of myeloid origin being demonstrated on > 5% of blasts in 60 out of 73 cases of AML patients, but rarely detected in ALL (9/140 patients). Moreover, co-expression of CD34/CD117 was extremely rare on lymphoblasts with only 3/140 ALL patients demonstrating > 5% co-expression of CD34 and CD117, and therefore we suggest that it should be used in the exclusion of ALL.
Adolescent↗
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.
Adolescent↗
Differentiation of leukemic cells induced by short-course high-dose methylprednisolone in children with different subtypes of acute myeloblastic leukemia.
Differentiation of myeloid leukemic cells to mature granulocytes by high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) with a favorable antileukemic effect has previously been demonstrated in children with acute promyelocytic leukemia and acute myeloblastic leukemia (AML) M4. In the present study, three children with other morphological subtypes of AML (two AML M1, one AML M2) were given methylprednisolone (30 mg/kg/day) orally in a single dose. After a short-course (3 or 7 days) of HDMP treatment alone, a striking decrease in blast cells associated with an increase in maturing and abnormally nucleated polymorphonuclear-like cells some containing Auer rods were detected in all patients in peripheral blood or bone marrow smears. During HDMP treatment, in parallel to morphological improvements, marked increases in the percentage of cells expressing granulocytic antigen (CD15) were observed. The increase of CD15 expression on myeloid cells, together with the steady expression of CD34 and CD117 antigens in Casel(AML M1) , is suggestive of aberrant CD34 + CD117 + CD15 + cells, which may indicate the leukemic origin of the maturing myeloid cells. These results suggest that HDMP treatment may induce differentiation of myeloid leukemic cells in some children with different morphological subtypes of AML, and that the differentiation-inducing effect of HDMP should be explored in other malignant diseases.
Administration, Oral↗
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.
Hepatomegaly↗
Dramatic resolution of pleural effusion in children with chronic myelomonocytic leukemia following short-course high-dose methylprednisolone.
High-dose methylprednisolone (HDMP) which can induce--differentiation and -apoptosis of myeloid leukemic cells has been shown to be very effective in the treatment of extramedullary infiltration (EMI) of children with acute myeloblastic leukemia (AML). In the present study 2 children with chronic myelomonocytic leukemia (CMML) who had pleural effusions were given a single daily dose of oral methylprednisolone (20 mg/kg or 30 mg/kg). In addition to dramatic improvement of respiratory symptoms, pleural effusions disappeared in four days in both patients possibly due to apoptotic cell death induced by HDMP treatment. Further studies are needed to determine whether high-dose corticosteroids are also effective on the resolution of pleural effusions associated with other malignant disease.
Adolescent↗
Effect of short-course high-dose methylprednisolone treatment on serum IL-2 levels in children with myelodysplastic syndromes: a pilot study.
Promising results in children with myelodysplastic syndromes (MDS) have been reported with high-dose methylprednisolone (HDMP) as a differentiation inducer, combined with cytotoxic chemotherapy. HDMP treatment has been shown to stimulate some cytokines in patients with acute leukemia. In the present study the effect of HDMP treatment on serum levels of interleukin 2 (IL-2) was evaluated in five children with MDS. Remarkable increases in serum IL-2 levels were observed 3 and 7 days after HDMP (30 mg/kg per day) treatment in three patients with chronic myelomonocytic leukemia (CMML). There was no correlation between the peripheral blood absolute lymphocyte counts and serum IL-2 levels. The results of this preliminary study indicate that the use of short-course HDMP treatment might be beneficial to increase the serum IL-2 level in patients with CMML.
Adolescent↗
High-dose methylprednisolone for children with acute lymphoblastic leukemia and unfavorable presenting features.
In an attempt to improve treatment outcome high-dose methylprednisolone (HDMP, 20-30 mg/kg, once a day orally) was used instead of a conventional dose of steroid (2 mg/kg/d, in 3 divided doses) in children with acute lymphoblastic leukemia (ALL) with increased risk factors. HDMP combined with cytotoxic agents (vincristine and L-asparaginase) resulted in an improved complete remission rate (94%) in 48 newly diagnosed children with ALL compared to 81% in 86 historical controls receiving standard dose steroid combined with the same treatment regimen. The bone marrow relapse rate was lower in patients who received HDMP (31%) than in controls (56%). Treatment was discontinued in 56% of 48 patients receiving HDMP and in 35% of 86 controls. The difference was significant (p < 0.05). The 5-yr continuous complete remission rate was significantly greater in patients received HDMP compared with the control patients (60% vs. 43%, p < 0.05). HDMP treatment was well tolerated without significant adverse effects. Moreover, during induction therapy the duration of leukopenia (< 2 x 10(9)/L) was shorter in patients receiving HDMP. We conclude that HDMP combined with other antileukemic agents increased the CR rate and prolonged the duration of remission in children with ALL who had increased risk factors. However, the optimal dosage of HDMP and its role in maintenance therapy should be determined in future, randomized studies.
Anti-Inflammatory Agents↗
Serum TNF-alpha, gamma-INF, G-CSF and GM-CSF levels in neutropenic children with acute leukemia treated with short-course, high-dose methylprednisolone.
High-dose methylprednisolone (HDMP, 20-30 mg/kg/day po) treatment has been shown to increase the number of bone marrow and peripheral blood CD34 positive progenitors and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in patients with ALL and AML. To investigate the effect of HDMP on some other hematopoietic regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (gamma-INF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were studied by microplate ELISA technique in 15 chemotherapy-induced neutropenic episodes of 14 children with acute leukemia (eight with ALL and six with AML) in whom HDMP was given alone (30 mg/kg/day po) for 4 days. The absolute neutrophil counts increased significantly in all neutropenic episodes on the fourth day of HDMP treatment. The TNF-alpha was 93.5 +/- 161 pg/ml in ALL and 78.3 +/- 61.4 pg/ml in AML before treatment and 76.1 +/- 160 pg/ml in ALL and 19.1 +/- 39.8 pg/ml in AML after treatment. The gamma-INF was 204.1 +/- 210.3 pg/ml in ALL and 130.8 +/- 138.3 pg/ml in AML before treatment and 28.6 +/- 50.5 pg/ml in ALL and 23.3 +/- 20.4 pg/ml in AML after treatment (P<0.05). Serum G-CSF and GM-CSF levels increased in all episodes (100%). The GM-CSF levels increased from 12.2 +/- 10.9 pg/ml to 36 +/- 24.7 pg/ml after treatment in ALL (P<0.05) and from 13.3 +/- 4 pg/ml to 45 +/- 48.1 pg/ml in AML (P<0.05). Serum G-CSF levels increased from 13.3 +/- 11.7 pg/ml to 83.3 +/- 86.8 pg/ml after treatment in ALL (P<0.05) and from 6.6 +/- 12.1 pg/ml to 28.3 +/- 11.3 pg/ml in AML (P<0.05). However, IL-6 levels were undetectable in all patients before and after therapy. These preliminary data suggest that short-course HDMP treatment could decrease serum TNF-alpha and gamma-INF and increase G-CSF and GM-CSF levels.
Adolescent↗
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.
Apoptosis↗
The effect of short-course high-dose corticosteroid therapy on peripheral blood CD34+ progenitor cells in children with acute leukemia.
High-dose methylprednisolone (HDMP) treatment has been shown to induce the differentiation of myeloid leukemic cells to mature granulocytes in patients with acute promyelocytic leukemia and other subtypes of acute myeloblastic leukemia (AML). HDMP administration has also been shown to accelerate the recovery of leukocytes and increase bone marrow hematopoietic CD34+ progenitor cells in patients with acute lymphoblastic leukemia (ALL). In the present study, we evaluated the effect of short-course (4-day) HDMP treatment on peripheral blood (PB) CD34+ cells in patients with acute leukemia (AL). Fourteen children with AL who were receiving maintenance therapy were enrolled in this study. Methyl-prednisolone was given orally as a single daily dose of 30 mg/kg for only 4 days to nine children (three AML, six ALL) in whom chemotherapy-induced leukopenia (< 2 x 10(9)/L) was observed. Circulating CD34+ progenitor cells were determined by flow cytometry before (day 0) and 4 and 7 days after HDMP treatment. On days 4 and 7 after initiation of HDMP treatment, the number of PB CD34+ cells increased significantly (p < 0.05). Hematopoietic CD34+ progenitor cells were also determined in five patients with AL (two AML, three ALL) and chemotherapy-induced leukopenia who did not receive HDMP. The number of CD34+ cells was found to be significantly (p < 0.05) higher in the patients who received HDMP than in those who did not. Along with PB CD34+ progenitor cells, white blood cells (WBC), polymorphonuclear cells (PMN), and monocytes also increased significantly (p < 0.05) in patients treated with short-course HDMP. In conclusion, short-course HDMP treatment can be used to shorten the chemotherapy-induced leukopenic period in patients with AL, possibly by increasing the number of hematopoietic progenitor cells. Further studies are needed to evaluate the effect of this treatment on leukopenic patients with other malignancies.
Adolescent↗
Effects of steroids on acute myeloblastic leukaemia.
Explore the source record for details and available documents.
Cell Division↗
Giant dysplastic neutrophils: possible morphologic evidence of in vivo differentiation of leukemia in acute myeloblastic leukemia.
Explore the source record for details and available documents.
Cell Differentiation↗
High-dose methylprednisolone for remission induction in hypoplastic acute myeloid leukemia.
Explore the source record for details and available documents.
Acute Disease↗
Reactive plasmacytosis and plasmacytic skin infiltration in a patient.
Explore the source record for details and available documents.
Adolescent↗