الفهرس 
Introduction and aim of the work
The aim of the workOnly 14 pages are availabe for public view
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Abstract
MDS is mainly a disease of older population, however, recently the incidence of MDS has markedly increased also affecting young age and this may be mainly attributed to genetic alterations in this subset of patients.
There are different modalities of treatment of MDS as supportive care including RBC, platelet transfusions and antibiotic therapy, ESAs, immunosuppressive agents, immunomodulatory drugs, IPSS and SCT which is the only available curative treatment for MDS, however, it may not be suitable for older patients.
One of the attempts to decrease the high mortality rate of transplant in older patients is the use of RIC regimen instead of myeloablative conditioning regimens (widely used in transplant procedures).
Aim of the work:
The aim of this study is to determine the outcome of different types of treatment of MDS in Egyptian patients.
Primary endpoint:
OS in the transplant group and OR to treatment in the conventional group.
Secondary endpoints:
• Disease free survival rates after transplant.
• Rates of non relapse mortality.
• Incidence of relapse.
• Incidence of neutrophil and platelet engraftment.
• Incidence of acute and chronic GVHD.
• Incidence of progression to acute leukemia in the conventional group.
In order to determine the outcome of different treatment modalities in MDS patients; 45 patients were enrolled in this study with the following eligibility criteria: Patients with MDS, performance Status < 2 according to ECOG, normal organ function by ultrasonography, echocardiography, liver and kidney functions, no coincident disease and informed consent by the patient.
Treatment plan:
A. Patients with low risk disease(low and INT-1 IPSS):
Patients with hypercellular or normocellular marrow received treatment in the form of ESAs and danazol , patients with hypocellular marrow received immunosuppressive agent in the form of cyclosporine A and patients with low risk disease who showed no response to conventional treatment, became transfusion dependant and who had a HLA identical sibling donor were treated with allogeneic SCT.
B. Patients with high risk disease:
Patients with high risk disease who were in remission after receiving chemotherapy and had an available HLA identical sibling donor were treated with allogeneic SCT.
The patients were divided in two groups : conventional group including patients receiving ESAs and immunosuppressive agents and transplant group including patients with high risk disease and patients with low risk disease who failed to show a response to conventional treatment both with available HLA identical sibling donor.
The conventional group consisted of 22 patients with a median age of 45 years (range, 16-65) and a male to female ratio of 0.8, including 15 patients (68.2%) with RA , 4 patients (18.2%) with RCMD and 3 patients (13.6%) with RAEB-1. Sixteen patients received treatment with ESAs and Danazol and 6 patients received immunosuppressive therapy. The overall erythroid response in patients receiving conventional treatment was 36.3%. The response in patients with low IPSS score was 22% and in patients with int-1 IPSS score was 50%. The erythroid response in patients receiving ESAs was 25%. According to IPSS score, the response in patients with low risk score was 22% and in patients with int-1 score was 33%. Only one patient of the whole group progressed to AML nine months after treatment. The Kaplan Meier estimated probability of progression to acute leukemia at 2 years was 5%.
Twenty-three patients received allogeneic PBSCT with a median age of 35 years (range 9-53) and a male to female ratio of 1, including 10 patients (43.5%) with RA, 7 patients (17.3%) with RCMD, 3 patients (13%) with RAEB-1 and 6 patients (26%) with RAEB-2. 18 patients received RIC transplant using FLU/BU conditioning regimen and 5 patients received MA transplant using BU/CY regimen.
The median time to neutrophil recovery was 13 days (range, 7-29) and the median time to platelet recovery was 15 days (range, 8-26). The median requirement for RBCs transfusion was 7 units (range, 0-29) and for platelet transfusion was 3 transfusions (range, 0 - 24).
The incidences of acute and chronic GVHD in all patients were 26% and 13%, respectively. However, in patients receiving RIC transplant, 28 % of patients experienced grade II-IV acute GVHD and in patients receiving MA transplant 20% of patients experienced acute GVHD.
The Kaplan-Meier estimated probability of acute GVHD in RIC was 31% and in MA transplant was 20% but the difference was not statistically significant.
In RIC transplant, one patient developed extensive chronic GVHD, and in MA transplant two patients developed chronic GVHD post transplant, one limited and one extensive chronic GVHD.
The Kaplan-Meier estimated probability of extensive chronic GVHD in RIC transplant was 20 % and in MA transplant was 25% but the difference was not statistically significant.
In the whole group treated with allogeneic SCT, 8 patients died as a consequence of transplant procedure. The causes of death were severe acute GVHD in 4 patients, sepsis in 2 patients, TRALI in one patient and primary graft rejection in one patient. The Kaplan-Meier estimated probability of NRM at 2 years was 39%.
The Kaplan-Meier estimated probability of NRM at 2 years in RIC transplant was 43% and in MA transplant was 20% but the difference between them was statistically non significant.
Allogeneic peripheral blood stem cell transplant resulted in CR in 60% of patients with RA, 25% of patients with RCMD, 66.6% of patients with RAEB-1 and 83.3% of patients of RAEB-2. Five patients relapsed post transplant 3 patients with RA and 2 patients with RAEB-2. The Kaplan-Meier estimated probability of relapse in the whole transplant group at 2 years was 32%. The Kaplan-Meier estimated probability of relapse at 2 years in RIC transplant was 43.5%, however, no patients in MA transplant had relapsed so far.
The Kaplan-Meier estimated 2 year OS in the whole transplant group was 57%. In RIC transplant, the Kaplan-Meier estimated 2 year OS was 49% and in MA transplant was 80% but the difference between them was statistically non significant.
The Kaplan-Meier estimated probability of 2 year DFS for the transplant group was 43.5%. In RIC transplant, the Kaplan-Meier estimated 2 year DFS was 33% and for MA transplant was 80%.
In conclusion, treatment of MDS is based on prognostic factors that predict survival and progression to AML. The most widely used prognostic system is the IPSS. MDS patients with lower risk disease usually have cytopenias and are treated with conventional treatment as ESAs and immunosuppressive agents. The data of the present study demonstrated that a proportion of patients had substantial clinical benefit from treatment with these agents without evidence of significant adverse events. Allogeneic HSCT for patients with MDS is the only currently available treatment strategy with proven curative potential and with long term survival probabilities. The outcomes of RIC transplant in this study were similar to MA transplant despite their having worse prognostic factors. These factors included higher proportion of older patients and a trend towards a higher risk score except for the cumulative incidence of relapse which was higher in RIC transplant. Many novel modalities of treatment of MDS is being widely explored in the world but in Egypt, due to limited resources, this is not possible.