A novel approach to treatment in childhood acute myeloblastic leukemia and myelodysplastic syndrome with high-dose methylprednisolone as a differentiation- and apoptosis-inducing agent of myeloid leukemic cells.

Differentiation-inducing therapy with all-trans retinoic acid significantly improved the outcome in children with acute promyelocytic leukemia (APL). Therefore, use of agents that induce differentiation of leukemic cells in non-APL children appears to be a highly promising therapeutic approach. Based on the experimental studies in mice, we have shown that short-course high-dose methylprednisolone (HDMP) treatment can induce terminal differentiation of leukemic cells in children with various subtypes of acute myeloblastic leukemia (AML-M1,-M2,-M3,-M4,-M7).

The role of splenectomy in children with juvenile myelomonocytic leukemia.

Splenectomy has been performed as a palliative treatment both in adults and children with myelodysplastic syndrome (MDS). However, there is no report describing the course after splenectomy in children with MDS. The aim of this study was to evaluate the impact of splenectomy on the outcome of six children with juvenile myelomonocytic leukemia (JMML) who had no HLA identical donor and who became unresponsive to chemotherapy.

Natural history and early diagnosis of LAD-1/variant syndrome.

The syndrome of leukocyte adhesion deficiency (LAD) combined with a severe Glanzmann-type bleeding disorder has been recognized as a separate disease entity. The variability in clinical and cell biological terms has remained largely unclear. We present data on 9 cases from 7 unrelated families, with 3 patients being actively followed for more than 12 years.

Myeloprotective effect of short-course high-dose methylprednisolone treatment before consolidation therapy in children with acute myeloblastic leukemia.

In our previous studies, short-course high-dose methylprednisolone (HDMP) has been shown to shorten the chemotherapy-induced neutropenic period by stimulating the CD34(+) hematopoietic progenitor cells in children with acute leukemia. In this study, we investigate the role of short-course HDMP on induction of a myeloprotective effect when administered before consolidation therapy consisting of high-dose cytosine arabinoside and daunorubicin. Thirty-four consecutive newly diagnosed children with acute myeloblastic leukemia (AML) who received 64 courses of consolidation regimen were entered into the study.

Genital ulcers after treatment with all-trans-retinoic acid in a child with acute promyelocytic leukemia.

All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment.

The effect of steroid on myeloid leukemic cells: the potential of short-course high-dose methylprednisolone treatment in inducing differentiation, apoptosis and in stimulating myelopoiesis.

Several in vitro studies have shown that dexamethasone (Dex) and prednisolone can induce differentiation of some mouse and human myeloid leukemic cells to macrophages and granulocytes. Based on in vitro experiments, we have shown that short-course (3-7 days) high-dose methylprednisolone (HDMP) (20-30 mg/kg/day) treatment can induce differentiation of myeloid leukemic cells in vivo in children with different subtypes of acute myeloblastic leukemia (AML) (AML-M1, -M2, -M3, -M4, -M7). We have also shown that induction of apoptosis of myeloid leukemic cells with or without differentiation is possible by short-course HDMP treatment.

Long-term survival in severe combined immune deficiency: the role of persistent maternal engraftment.

Two siblings with severe combined immune deficiency, one with maternal engraftment and detectable immunologic functions who was alive at the age of 8 years are presented. Both patients had the same JAK3 gene mutation, suggesting that maternal engraftment may result in immune competence leading to long-term survival in patients with severe combined immune deficiency.

Acute lymphoblastic leukemia in infants.

Between January 1978 and August 1999, 29 infants with newly diagnosed acute lymphoblastic leukemia (ALL) were treated on three consecutive protocols. Eighteen patients with infant ALL diagnosed between 1978-1991 were included in Group 1. In this group, treatment comprised a two- or three-drug induction with prednisolone, vincristine and L-asparaginase, and maintenance therapy consisted of weekly oral administration of mercaptopurine and methotrexate for three years.

Children with acute myeloblastic leukemia presenting with extramedullary infiltration: the effects of high-dose steroid treatment.

To evaluate whether children with acute myeloblastic leukemia (AML) presenting with extramedullary infiltration (EMI) have different clinical, morphologic features and prognosis from children without EMI, a 127 consecutive previously untreated children with AML were entered in this study. Fifty-one children (40%) had EMI at diagnosis and 27% of these showed multiple site involvement. Twenty-seven of 127 children (21%) presented myeloid tumors.

The potential effect of short-course high-dose steroid on the maturation and apoptosis of leukemic cells in a child with acute megakaryoblastic leukemia.

High-dose methylprednisolone (HDMP) treatment has been shown to induce differentiation of myeloid leukemic cells in children with acute promyelocytic leukemia and other subtypes (FAB AML M1-M2-M4) of acute myeloblastic leukemia. In the present study, a child with acute megakaryoblastic leukemia (AMKL) was given HDMP (30 mg/kg/day) orally in a single dose for the first 4 days of induction therapy. A marked decrease in peripheral blood blast cells and an increase in platelet count associated with a striking change in bone marrow (BM) morphology was observed following a short-course of HDMP treatment alone.

Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia.

The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.

The role of short course of high-dose methylprednisolone in children with acute myeloblastic leukemia (FAB M2) presented with myeloid tumor.

The authors have previously demonstrated a favorable effect of high-dose methylprednisolone (HDMP), which can induce differentiation and apoptosis of leukemic cells in children with acute myeloblastic leukemia (AML). Here, they evaluate the effect of short-course HDMP in 2 children with acute myeloblastic leukemia (AML-M2) presented with myeloid tumor (MT). Methylprednisolone (20 or 30 mg/kg/day) was given orally, in a single dose, without using other antileukemic agents.

The effect of short-course high-dose methylprednisolone on peripheral blood lymphocyte subsets in children with acute leukemia during remission induction treatment.

We have previously demonstrated a favorable effect of high-dose steroid in the treatment of children with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). This study was performed to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on the peripheral blood (PB) T lymphocyte subsets, and blast cells, during remission induction treatment in 23 children with newly diagnosed acute leukemia (16 with ALL, seven with AML). All patients were administered HDMP as a single daily oral dose of 30mg/kg for the first 4 days of induction therapy.

The effect of short-course high-dose methylprednisolone on peripheral blood CD34+ progenitor cells of children with acute leukemia during remission induction therapy.

This study was undertaken to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on peripheral blood (PB) CD34+ progenitor cells during remission induction treatment in 11 children with newly diagnosed acute leukemia (7 with ALL, 4 with AML) whose bone marrow (BM) cells expressed fewer than 5% CD34 at the time of diagnosis. All children who had no infection were given HDMP as a single daily oral dose of 30 mg/kg for the first four days of induction therapy. The number of CD34+ progenitor cells were determined by flow cytometry before and after four days of HDMP treatment.