Journal of Experimental Hematology % CD25. agvhd

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1 Journal of Experimental Hematology Article ID CD25 * CD25 21 Ⅱ-Ⅳ d CD25 1 mg / kg d % 4 8 cgvhd % 3 cgvhd % 90. 5% % 6 100% CD25 Ⅱ - Ⅳ CD25 R Q461 A doi /j. issn Clinical Study on Recombinant Humanized Anti-CD25 Monoconal Antibody Used for Treating Steroid-resistant Acute Graft versus Host Disease Following Allo-Hematopoietic Stem Cell Transplantation LI Xiao-Hong GAO Chun-Ji DA Wan-Ming CAO Yong-Bin XU Li-Xin WU Ya-Mei LIU Bei LIU Zhou-Yang YAN Bei LI Song-Wei YANG Xue-Liang WU Xiao-Xiong * Department of hematology The First Affiliated Hospital Chinese PLA General Hospitall Beijing China * Corresponding Author WU Xiao-Xiong Senior Physician xiongwuxiao@ sohu. com Abstract This study was purposed to investigate the efficacy and feasibility of recombinant humanized anti-cd25 monoconal antibody for treating steroid-resistant acute graft-versus-host disease following allo-hematopoietic stem cell transplantation allo-hsct. Twenty-one cases with Ⅱ-Ⅳ grade steroid-resistant after allo-hsct were treated by intravenous injection of recombinant humanized anti-cd25 monoconal antibody at a dose of 1 mg / kg d on days Injection was repeated after 1 week for the patients who did not achieve CR. The results indicaled that 13 cases 61. 9% got complete response CR 4 cases out of them have been still in disease-free survival 8 cases have been in survival with mild cgvhd 1 cases died from AML relapse 6 cases % got partial response PR 3 cases out of them have been in survival with mild cgvhd 3 case died from pulmonary infection 2 cases without response died from GVHD. Overall response rate was 90. 5% and long term survival rate was %. There were no infusion-associated sideeffects after treatment with recombinant humanized anti-cd25 monoconal antibody. It is concluded that recombinant humanized anti-cd25 monoconal antibody is effective and feasible for treatment of steroid-refractory grade Ⅱ-Ⅳ after allo-hsct. Key words recombinant humanized anti-cd25 monoconal antibody allo-hematopoietic stem cell transplantation acute graft-versus-host disease J Exp Hematol CD25-2 IL-2 *.. sohu. com

2 1536 Journal of Experimental Hematology GVHD CD25 25 mg / Ⅱ-Ⅳ A 9 BuCy Bu 0. 8 mg / kg 6h 3 d + Cy 50 mg / kg d 2 d + Arac 3. 0 g / m 2 d 2 d + VM mg /m B 6 TBI + Cy Ⅱ-Ⅳ TBI 3-4 Gy 3 d + Cy 50 mg / kg Glucksberg 1 A d 2 d + Arac 3. 0 g / m 2 d 2 d C CsA MMF 6 Flu mg / kg d 4 mg / m 2 d 4 d + Cy 500 mg /m 2 4 d mg / kg d 4 d HLA8 / G-CSF 5 μg / kg d 5-7 d Table 1. Characteristics of 21 patients received allo-hsct Case NO. Gender Age Diagosis Donor Age years HLA match HLA mismatched 1 female 15 AML brother 12 4 /6 A DRB1 2 male 25 CML blast mother 52 3 /6 A B DRB1 3 male 19 AML-M4 father 43 3 /6 A B DRB1 4 female 13 ALL father 35 4 /6 A DRB1 5 female 19 VSAA brother 25 3 /6 A B DRB1 6 Male 15 SAA fatherr 42 3 /6 A B DRB1 7 female 38 AML brother 47 3 /6 A B DRB1 8 male 4 SAA mother 33 3 /6 A B DRB1 9 female 15 ALL sister 18 3 /6 A B DRB1 10 male 24 VSAA mother 49 3 /6 A B DRB1 11 female 24 SAA mother 48 3 /6 A B DRB1 12 female 26 MDS-RCMD brother 24 3 /6 A B DRB1 13 male 17 AA-PNH mother 41 5 /6 A 14 male 18 ALL relapse father 48 4 /6 B DRB1 15 female 24 ALL relapse mather 45 3 /6 A B DRB1 16 male 54 AML-M2 sister 54 6 /6 17 male 24 NHL sistter 21 6 /6 18 male 18 CML blast sister 20 6 /6 19 male 21 AML-M5 sister 21 6 /6 20 male 49 NHL brother 47 6 /6 21 male 26 AML Un-related 23 8 /10 B DRB1 subsite

3 CD PR 1 NR 6 h human umbilical cord derived mesenchymalstem cells huc- MSC huc-msc cgvhd /kg 30 min N I H h 24 h 72 h cgvhd 6-7 GVHD X 珔 ± SD CsA + MMF + MTX + ATG + CD25 CsA 3 mg / kg d 7 d 5 mg / kg d CsA CsA allo-hsct ± d μg /L 3 GVHD d 15 5% ± d 5 12 MMF 1 g /d ± d 2 d ATG 2. 5 mg / kg d 4 d MTX 15 mg / 3 m 2 1 d 10 mg /m d CD25 1 mg / kg d 4 d ± d 3 - CSA + MMF + MTX CsA 2. 5 mg / kg d d CD25 5 d 5 mg / kg 15 d CsA 3 CD GVHD 5% MTX mg /m 2 1 d 10 mg /m d MMF 1 g /d 28 d % 4 8 GVHD cgvhd d % 3 mg / kg d 3 d cgvhd d Ⅱ-Ⅳ 9. 52% 90. 5% CD25 1 mg / kg d % ± d GVHD 100% 5 3 CMV /EBV /HSV Ⅲ CR GVHD CD d CD CD25 6

4 1538 Journal of Experimental Hematology Table 2. Characteristics and outcome of therapy in 21 patients with treated with recombinant humanized anti- CD25McAb NO. Time of incidence day before use of RH anti-cd25mcab skin liver intestine Grade of Dose of RH anti- CD25McAb 1 mg /kg /time times after use of RH anti-cd25mcab skin liver intestine Grade of Therapy response cgvhd Follow-up Survival time after HSCT months Ⅲ Ⅰ CR mild alive Ⅳ Ⅱ CR mild alive Ⅲ CR mild alive Ⅳ Ⅱ PR mild Died from pneumonia Ⅲ Ⅰ PR mild alive Ⅲ Ⅰ PR mild alive Ⅳ Ⅳ NR Died from Ⅲ CR mild alive Ⅳ CR mild alive Ⅲ CR mild alive Ⅲ CR mild alive Ⅲ CR No alive Ⅱ CR No alive Ⅳ Ⅲ PR Died from pneumonia Ⅳ Ⅲ NR Died from GVHD Ⅲ CR mild alive Ⅳ Ⅰ PR mild alive Ⅲ Ⅱ PR moderate Died from pneumonia fungle Ⅱ CR mild Died from relapse Ⅲ CR No alive Ⅲ CR No alive after transplanfation - recombinant humanized anti-cd25 McAb. Table 3. Dose and efficacy of recombinant humanized anticd25 McAb for patients with in different allo-hsct Dose of recombinant humanized anticd25 McAb for each patient 1mg /kg /time times Haploidentical HSCT 15 cases Haplor-identical related Haplor-identical unrelated Hematopoiesis failure disease 6 cases Malignant hematological disease 9 cases donors 5 cases donor 1 case CR PR NR allo-hsct allo-hematopoietic stem cell transplantation.

5 CD GVHD 2 PR 1 GVHD CR 14 1 PR 3 2 CMV 1 CD25 CD Ⅱ-Ⅳ % 21 CR 17 85% PR % NR % % 10% % 6 CR % PR % 100% NR2 10% % 2 CD25 Ⅱ % CD25 CR 2 PR NR 1 CD25 CR PR NR CD25 CD % 85. 5% 81% 75% CD25 CD25 Ⅲ-Ⅳ 33% 11% 2 Ⅲ-Ⅳ Ⅱ-Ⅳ T T 30% - 60% CD T 1 Rowlings PA Przepiorka D Klein JP GVHD with Glucksberg grade. Br J Haematol CD25 2 J i SQ Chen HR Yan HM basiliximab for prevention Ⅱ-Ⅳ 8-11 malignancies. Bone Marrow Transplant et al. IBMTR severity Index for grading acute graft2versus2host disease retrospective compa-rison et al. Anti2CD25 monoclonal antibody of graft2versus2host disease after haploidentical bone marrow transplantation for hematological

6 1540 Journal of Experimental Hematology WillenbacherW Basara N Blau IW et al. Treatment of steroid refractory acute and chronic graft versus host disease with daclizumab. Br J Haemtol Carpenter PA Appelbaum FR Corey L et al. A humanized nonfcrbinding anti-cd3 antibody visilizumab for treatment of steroid refractory acute graft-versus-host disease. Blood Ibrahim RB Abidi MH Cronin SM et al. Nonabsorable corticosteroids use in the treatment of gastrointestinal graft-versus-host disease. Biol Blod Marrow Transplant Filipovich AH We isdorf D Pavletic S et al. N I H consensus development project on criteria for clinical trials in chronic graftversus-host disease Diagnosis and Staging Working Group report. Biol Blood Marrow Transplan t Funke VAM de2medeiros CR SetubalDC al. Therapy for severe refractory acute graft-versus-host disease with basiliximab a selective interleukin-2 receptor antagonist. Bone Marrow Transp-lant Schmidt2HieberM Fietz T KnaufW et al. Efficacy of the interleukin22 receptor antagonist basiliximab in steroid refractory acute graft2versus2host disease. Br J Haematol Massenkeil G Rackwitz S Genvresse I et al. Basiliximab is well tolerated and effective in the treatment of steroid2refractory acute graft-versus-host disease after allogeneic stem cell transp-lantation. Bone Marrow Transp lant CD Kovarik J Wolf P Cisterne JM et al. Disposition of basiliximab.. aninterleukin22 receptor monoclonal antibody inrecipients of mismatched cadaver renal allografts. Transplantation

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