Objective:To investigate the efficacy of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) using post-transplantation cyclophosphamide(pt-Cy) combined with mycophenolate mofetil (MMF) as prophylaxis of graft versus host disease(GVHD).Methods:Part 1:the efficacy of HLA-matched or haploidentical allo-PBSCT using pt-Cy combined with MMF as prophylaxis of GVHD.From December 2011 to August 2015, patients with allo-PBSCT were divided into the matched group and the haploidentical group.3 Schemes for conditioning regimen.Regimen A:Flu 40mg/m2x4d(d-5--2)+BU 130mg/m2×4d(d-5~-2),used for AML、CML、MDS、β-thalassemia and pure red cell anemia;Regimen B:Flu 40mg/m2x4d(d-5~-2)+Mel 50mg/m2x4d(d-5~-2),used for ALL、CLL、MM、 NHL;Regimen C:Flu 40mg/m2x4d(d-5~-2)+Cy 0.6g/m2x4d(d-5~-2),used for aplastic anemia.Using pt-Cy (1.8g/m2, d+3/+4)+MMF for GVHD prophylaxis,MMF was administered on day +5 after transplantation,the matched group received 10mg/kg,2 times daily for 60 days,the haploidentical group received 10mg/kg,3 times daily for 90 days.Thereafter gradually reduce the dose utill 180 days stoped.Neutrophil recovery was defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) greater than 0.5×109/L. Platelet recovery was defined as a platelet count greater than 20×109/L without platelet transfusion the first of 3 consecutive days.The two are used as criteria for the reconstruction of hematopoietic function.According to the improved Glucksberg indexing method for aGVHD classification and total graduation,and Seattle standards for cGVHD typing.Follow up since the beginning of the hematopoietic stem cell transfusion.Every 1~2 months back to the hospital review till to February 2016.Part 2:the efficacy of 4 days pt-Cy combined with MMF as allo-PBSCT prophylaxis of GVHD.Select patients from October 2014 to February 2015 for allo-PBSCT.Using pt-Cy (1.8g/m2, d+3-+6)+MMF for GVHD prophylaxis.The other methods are the same as part 1.Results:Part 1:(1)A total of 99 patients were selected.The matched group included in 42 cases,including 27 males and 15 females and the median age was 23.5 years old(2~58,26.19±15.35).Among them,there are AML 14 cases, ALL 5 cases, CML 6 cases, SAA 9 cases, MDS 2 cases,4 cases of β-thalassemia,1 case of pure red cell anemia,NHL 1 case and ABO blood type matched in 19 cases (45%);The haploidentical group included in 57 cases,including 32 males and 25 females and the median age was 22 (3-63,22.40±13.70).Among them,there are AML 22 cases, ALL 10 cases, CML 3 cases, CLL 1 case,SAA 13 cases, MDS 3 cases,3 cases of β-thalassemia, MM 1 case,NHL 1 case and ABO blood type matched in 33 cases (58%).(2)Of the matched group 40 cases (95%) experienced sustained engraftment,2(5%) of them had graft failure.The median time to graft of neutrophil were 13 days (12.79±1.83 days),platelet were 14 days(13.58±3.49 days) respectively.Of the haploidentical group 55 cases (96%) experienced sustained engraftment,2(4%) of them had graft failure.The median time to graft of neutrophil were 13 days (14.65±2.47 days),platelet were 15 days(15.82±4.40 days) respectively.(3)Of the matched group the incidence of aGVHD was 47.6%(20/42),Ⅰ aGVHD was 23.8% (10/42),Ⅱ aGVHD was 7.1% (3/42),Ⅲ aGVHD was 9.6%(4/42),IV aGVHD was 7.1% (3/42) And the incidence of chronic GVHD was 14.3% (6/42),including 4 cases of localized type and 2 cases of extensive type.Of the haploidentical group the incidence of aGVHD was 43.9%(23/57),Ⅰ aGVHD was 3.5 % (2/57),Ⅱ aGVHD was 22.8%(13/57),Ⅲ aGVHD was 12.3%(7/57),Ⅳ aGVHD was 5.3%(3/57).And the incidence of chronic GVHD was 22.8%(13/57) including 3 cases of localized type and 10 cases of extensive type.(4)Of the matched group had 3 cases (7.1%) of mucositis and 9 cases (21.4%) of HC after the application of Cy.12 cases was died,the NRM and OS was 21.4% and 71.4% respectively.Of the haploidentical group had 9 cases (15.8%) of mucositis and 8 cases (14.0%) of HC after the application of Cy.18 cases was died,the NRM and OS was 22.8% and 68.4% respectively.(5)There was no statistically significant difference of the incidence of Ⅱ~Ⅳ aGVHD (23.8% vs 40.3%, P=0.084),Ⅲ~Ⅳ aGVHD (16.7% vs 17.5%, P=0.909)、 cGVHD(14.3% vs 22.8%, P=0.287)、NRM(21.4% vs 22.8%, P=0.769)、OS (71.4% vs 68.4%, P=0.692) between the matched group and the haploidentical group.Part 2:(1)There are 10 patients were selected.1 case(10%) received HLA-matched transplantation,9 cases (90%) received haploidentical transplantation. Of the 10 patients there are 4 males and 6 females and the median age was 21 years old (5-38).Among them,there are AML 4 cases, ALL 2 cases, CML 1 case, MDS 1 case, 1 case of β-thalassemia,1 case of Glanzmann thrombasthenia and ABO blood type matched in 8 cases (80%).(2)Of the 10 patients 9 cases(90%)experienced sustained engraftment,l(10%) of them had graft failure.The median time to graft of neutrophil were 17 days (12-35 days).platelet were 25 days(11~36 days) respectively.The incidence of aGVHD was 60%(6/10),Ⅰ aGVHD was 10% (1/10),Ⅱ aGVHD was 30%(3/10),Ⅲ aGVHD was 10%(1/10),Ⅳ aGVHD was 10%(1/10).And the incidence of chronic GVHD was 30%(3/10) including 1 cases of localized type and 2 cases of extensive type.Of the 10 patients had 4 cases (40%) of mucositis and 4 cases (40%) of HC.5 cases was died,the NRM and OS was 40% and 50% respectively.Conclusions:1.Pt-Cy combined with MMF can be used for HLA-matched or haploidentical allo-PBSCT as prophylaxis of GVHD. The scheme can reduce the incidence of severe aGVHD and cGVHD,improve survival rate and its toxicity can be accepted.2.The efficacy for patients after haploidentical transplantation with Pt-Cy combined with MMF is comparable with HLA-matched transplantation.There was no statistically significant difference of the incidence of Ⅱ~Ⅳ aGVHD、cGVHD、NRM and OS between the matched group and the haploidentical group.3.Compared to Cy given on day +3、+4,4 days Cy had no advantage to prevent the GVHD, and the toxicity increased.Therefore, we view that the best application time of Cy is given on day +3、+4. |