Journal of Experimental Hematology 2013 21 6 1535-1540 Article ID 1009-2137 2013 06-1535 - 06 1535 CD25 * 100037 CD25 21 Ⅱ-Ⅳ 1 4 8 d CD25 1 mg / kg d 1 13 61. 9% 4 8 cgvhd 1 6 28. 57% 3 cgvhd 3 2 9. 52% 90. 5% 71. 48% 6 100% CD25 Ⅱ - Ⅳ CD25 R457. 7 Q461 A doi 10. 7534 /j. issn. 1009-2137. 2013. 06. 032 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 100037 China * Corresponding Author WU Xiao-Xiong Senior Physician E-mail 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 1 4 8. 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 28. 57% 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 71. 48%. 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 2013 6 1535-1540 CD25-2 IL-2 *.. E-mail xiongwuxiao @ sohu. com 2013-07 - 10 2013-10 - 11
1536 Journal of Experimental Hematology 2013 21 6 GVHD 2011 4 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-26 300 mg /m 2 2011 4 2013 3 21 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 30 2 3 2 mg / kg d 4 mg / m 2 d 4 d + Cy 500 mg /m 2 4 d + 15 9 6 2. 5 mg / kg d 4 d HLA8 /10 1 5 14 7 21 4-54 1 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
CD25 1537 PR 1 NR 6 h human umbilical cord derived mesenchymalstem cells huc- MSC huc-msc 4 2. 87 cgvhd - 10 10 6 /kg 30 min 4 2005 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 300 21 allo-hsct 28. 81 ± 12. 79 d 10-69 μg /L 3 GVHD d 15 5% 9-24. 53 ± 8. 50 d 5 12 MMF 1 g /d 7 100 43. 4 ± 14. 5 d 2 d ATG 2. 5 mg / kg d 4 d MTX 15 mg / 3 m 2 1 d 10 mg /m 2 3 6 11 d CD25 1 mg / kg d 4 d 21 8. 2 ± 5. 61 d 3 - CSA + MMF + MTX CsA 2. 5 mg / kg d 22. 5 d CD25 5 d 5 mg / kg 15 d CsA 3 CD25 3. 47 GVHD 5% MTX 1. 6 15 mg /m 2 1 d 10 mg /m 2 3 6 11 d MMF 1 g /d 28 d 4. 17 3 13 61. 9% 4 8 GVHD cgvhd 1 14 3 d 2 6 28. 57% 3 mg / kg d 3 d cgvhd 3 2 5 d Ⅱ-Ⅳ 9. 52% 90. 5% CD25 1 mg / kg d 71. 48% 9. 79 ± 5. 41 2. 3-1 4 8 d 1 22. 5 6 GVHD 100% 5 3 CMV /EBV /HSV Ⅲ CR GVHD CD25 1 4 8 d CD25 1 2 3 CD25 6
1538 Journal of Experimental Hematology 2013 21 6 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 1 + 13 3 0 3 Ⅲ 3 1 0 0 Ⅰ CR mild alive 20. 5 2 + 22 2 3 4 Ⅳ 3 1 1 0 Ⅱ CR mild alive 8. 5 3 + 24 3 0 3 Ⅲ 3 0 0 0 0 CR mild alive 6. 7 4 + 23 3 2 4 Ⅳ 4 2 1 2 Ⅱ PR mild Died from pneumonia 4. 1 5 + 28 2 1 3 Ⅲ 4 0 0 1 Ⅰ PR mild alive 14 6 + 20 3 0 3 Ⅲ 2 0 0 1 Ⅰ PR mild alive 6 7 + 10 4 4 3 Ⅳ 3 4 4 3 Ⅳ NR Died from 2. 3 8 + 35 3 0 3 Ⅲ 6 0 0 0 0 CR mild alive 13 9 + 42 3 1 4 Ⅳ 3 0 0 0 0 CR mild alive 12 10 + 32 3 0 3 Ⅲ 5 0 0 0 0 CR mild alive 10. 5 11 + 25 2 0 3 Ⅲ 4 0 0 0 0 CR mild alive 8. 3 12 + 35 2 1 3 Ⅲ 2 0 0 0 0 CR No alive 22. 5 13 + 18 3 0 2 Ⅱ 4 0 0 0 0 CR No alive 16. 8 14 + 21 2 3 4 Ⅳ 3 1 2 3 Ⅲ PR Died from pneumonia 3 15 + 25 2 2 4 Ⅳ 3 2 3 3 Ⅲ NR Died from GVHD 4 16 + 39 3 3 0 Ⅲ 1 0 0 0 0 CR mild alive 11. 9 17 + 69 3 0 4 Ⅳ 2 0 0 1 Ⅰ PR mild alive 8. 9 18 + 34 3 2 2 Ⅲ 2 1 0 1 Ⅱ PR moderate Died from pneumonia fungle 8. 5 19 + 40 3 1 0 Ⅱ 1 0 0 0 0 CR mild Died from relapse 14 20 + 35 3 1 3 Ⅲ 2 0 0 0 0 CR No alive 10. 7 21 + 20 3 1 3 Ⅲ 3 0 0 0 0 CR No alive 5. 3 + 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 4. 17 3 1. 6 3 CR 4 5 3 1 PR 2 2 2 NR 0 2 0 allo-hsct allo-hematopoietic stem cell transplantation.
CD25 1539 2 GVHD 2 PR 1 GVHD CR 14 1 PR 3 2 CMV 1 CD25 CD25 2011 4 Ⅱ-Ⅳ 21 20 95% 21 CR 17 85% PR1 0. 05% NR2 90. 5% 71. 48% 10% 21 19 90. 1% 6 CR13 61. 9% PR4 19. 1% 100% NR2 10% 21 7 33% 2 CD25 Ⅱ 4 19. 5% CD25 CR 2 PR NR 1 CD25 CR PR NR CD25 CD25 12 50% 85. 5% 81% 75% CD25 CD25 Ⅲ-Ⅳ 33% 11% 2 Ⅲ-Ⅳ Ⅱ-Ⅳ T T 30% - 60% CD25-2 - 2 T 1 Rowlings PA Przepiorka D Klein JP GVHD with Glucksberg grade. Br J Haematol 1997 97 4 CD25 2 J i SQ Chen HR Yan HM basiliximab for prevention Ⅱ-Ⅳ 8-11 malignancies. Bone Marrow Transplant 2005 36 4 et al. IBMTR severity Index for grading acute graft2versus2host disease retrospective compa-rison 855-864. et al. Anti2CD25 monoclonal antibody of graft2versus2host disease after haploidentical bone marrow transplantation for hematological 349-354.
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