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HDMPHigh-Dose Methyl Prednisolone
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Despite the fact that the patients in the present study that responded to HDMP had very severe group AA, among those that responded to ATG and CsA, 3 had moderate AA, 1 had severe AA, and 1 had very severe AA.
Combined IST with ATG, CsA, and low-dose methylprednisolone was an effective treatment option for our pediatric patients without an HLA-identical donor; however, in patients that cannot be given ATG HDMP treatment can be used as an alternative to 1ST, as it is an inexpensive and safe treatment Option.
We have also shown that induction of apoptosis of myeloid leukemic cells with or without differentiation is possible with HDMP treatment in vivo and in vitro [26,49,51].
Therapeutic effects of HDMP in children with AML Effect of HDMP on blast cells
During our long-term clinical studies, in a short-period (24 or 48 hours) after administration of HDMP treatment alone, dramatic clinical improvement (improved activities; resolution of bone pain and unexplained high fever) was observed in most of the AML children who had not received HDMP previously.
More importantly, dramatic decreases in the size of extramedullary leukemic infiltration (orbita, gingiva and soft tissue) were detected in 24 hours to 7 days after initiation of HDMP treatment [43-45,58,61].
In our previous study reported in 1992, addition of HDMP to mild antileukemia regimens (adriamycin and Ara-c) increased the CR rate to 84.
Since an early blast cell clearance by remission induction therapy is a major independent prognostic factor, the improved outcome in our patients could be related with the initial striking decrease in leukemic cells in the bone marrow and in the extramedullary site obtained with HDMP as a differentiating- and apoptosis-inducing agent.
Significant blast reduction with hematological and cytogenetic remission following HDMP (1000 mg/day) treatment alone was also demonstrated by Shimohakamada et al [70] in an adult AML patient who had pulmonary infection.
The stimulation of normal myelopoiesis with HDMP treatment would be an additional benefit in the treatment of these patients.
On the other hand, we obtained promising results in children with various subtypes of MDS (refractory anemia with excess blast (RAEB), RAEB in transformation, juvenile myelomonocytic leukemia (JMML) and CMML) with the addition of HDMP to cytotoxic chemotherapy [66,78,79], with the exception of patients with JMML and monosomy 7.
Based on these studies, HDMP combined with chemotherapy followed by autologous stem cell transplantation can be considered as an alternative therapeutic approach in children with MDS who are not suitable for bone marrow transplantation.