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A Clinical Study of Unrelated Donor Allogeneic Bone Marrow Transplantation by Using CD25 Monoclonal Antibody for Acute GVHD Prophylaxis and Graft Failure

Author: ShouLiHong
Tutor: HuangHe
School: Zhejiang University
Course: Clinical
Keywords: CD25 monoclonal antibody unrelated donor bone marrow transplantation acute graft versus host disease engraftment failure
CLC: R457.7
Type: Master's thesis
Year: 2005
Downloads: 39
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Abstract


Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curial treatment of hematologic malignancies. Unfortunately, fewer than 30% of patients have a human leukocyte antigen (HLA)-matched sibling. The increasing use of unrelated donors enlarged alternative source of stem cells. Compared with HLA-identical sibling transplantation, grafting with unrelated donor (URD) associated with more complications and higher mortality rate. Severe acute graft-versus-host disease (GVHD) and graft failure are the main causes of transplant-related mortality in this setting. 78% patients developed Ⅱ Ⅳ acute GVHD in HLA-matched URD allo-HSCT with foundational prophylaxis, and 36% developed Ⅲ acute GVHD, reported FredHutchinson cancer research center. To further cut down severe acute GVHD, 10 patients carrying out URD allo-BMT received additional humanized CD25 monoclonal antibody (daclizumab) for acute CVHD prophylaxis. The outcomes of transplantation were compared with those with basal prophylaxis.1. Objective:To compare the clinical outcome of additional humanized CD25 monoclonal antibody for acute GVHD prophylaxis with no application of CD25 monoclonal antibody in unrelated donor bone marrow transplantation. To explore the impact of CD25 monoclonal antibody on URD-BMT.2. Materials and Methods2.1 PatientsPatients received URD-BMT for acute leukemia and chronic myeloid leukemia in our hospital between October 2003 and July 2004. 10 patients in the study group received transplantation after March 2004, the rest in the controls.2.2 MethodsIn the control group mycophenolate mofetil (MMF), CsA and MTX were given to prevent acute GVHD; additional CD25 monoclonal antibody were given to the patients in the study group, 1mg/kg each intravenous infusion in 24 hours before transplantation and on the 4th daypost transplantation. Conditioning regimens were Bu16mg/kg plus Cy120mg/kg, and prostaglandin E1 were given to prevent hepaticveno-occlusive disease (VOD), piperacillin and amikacin were used toprevent bacteria infection, Foscarnet Sodium、 Ganciclovir et al were usedto prevent CMV infection.2.3 StatisticsContinuous variables were compared by median of theIndependent-Samples T Test and One-factor Analysis of Variance.Differences in distribution were compared by the Chi-square test orFisher’s exact test if appropriate.3. Results:All patients show 100% donor-typed hematopoietic cells after transplantation by cytogenetic evidence. The follow-up duration was 712 months in study group and 1217 months in control group. In the study group, 2 patients experienced secondary graft failure; no patient replased; 1 patient developed VOD; 9 patients suffer from infections. In the control group, 2 patients experienced secondary graft failure; 2 patients replased; 2 patient develop VOD; 10 patients suffer from infections. 4 out of 10 patients developed acute GVHD in the study group and 8 patients in control group. There were no and 5 patients experienced Ⅱ acute GVHD in the two groups respectively (P < 0.05).The percent of CD3 CD25 cells in the study group was 3.23%, 0.54%、 0.29%、 0.66%、 1.88% at the day 0、 day 15、 day 30、 day 60、 day 90 after transplantation respectively. All percentage were low, especially on the day 15、 day 30、 day 60 (vs day 0, P < 0.05). The content of soluble interleukin-2 receptor was Ong/L and 1.22ng/L in the study group on the day 15, day 30 after transplantation, being 6.76 ng/L and 3.12 ng/L in the control group (P < 0.05). 4. Conclusions:Using CD25 monoclonal antibody for acute GVHD prophylaxis in URD allo-BMT is effective in preventing severe acute GVHD and not change engraftment, relapse, infection. CD25 monoclonal antibody was bind to α-unit of IL-2 receptor in activated T lymphocyte and improve the prognosis of the transplantation.

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CLC: > Medicine, health > Clinical > Therapy > Blood Therapy > Bone marrow transplant
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