Objective To enhance engraftment by infusing two partially matched cord blood (CB) units from unrelated donors simultaneously. Methods Two patients with high-risk leukemia(1 case of ALL and 1 case of CML-BC) received total body irradiation with antithymocyte globulin (ATG) and then were transplanted with two HLA-mismatched CB units from unrelated donors. A combination of cyclosporine A, methylprednisonelone and mycophenolate mofetil (MMF) was administered for graft-versus-host disease (GVHD) prophylaxis. Results Two patients were all engrafted and the time to neutrophil≥ 0.5 ?10 9/L and platelet≥20?10 9/L were 21, 22 days and 51, 28 days post-transplant respectively, and DNA analysis showed only one donor DNA was detectable after engraftment. There was no serious GVHD. And these 2 patients are still alive and disease free for more than 34 and 30 months repectively. Conclusion Double units cord blood from unrelated donors can restore hematopoiesis and is suitable in adults without bone marrow donors.

Objective To evaluate the efficacy and safety of micafungin in the treatment of invasive fungal infections (IFI) in patients with acute leukemia.Methods A total of 133 IFI patients with acute leukemia received micafungin 150 mg once daily for 14 days.The clinical and mycological efficacies were evaluated on (7±2) days and(14±2) days of treatment.Meanwhile,the adverse events were recorded.The normally distributed data was compared using analysis of variance and nonnormal distributed data was analyzed using Wilcoxon rank-sum test.Results Among 133 IFI patients with acute leukemia,116 finished the 14-day micafungin treatment.The total clinical efficacy was 94.8% and the total mycological efficacy was 75.0% at (14±2) days of treatment.The fungus eliminate rates were 82.9%,66.7% and 55.6% against Monilia,Aspergillus and others,respectively.The clinical and mycological efficacies of (14±2)-day treatment were both higher than those of (7±2)-day treatment(X2=6.060,34.416.both P<0.05).The clinical efficacy was not related with age,sex,IFI diagnose,types of leukemia and combinative drugs (X2=26.541,P<0.05).The incidence of drug-related adverse events of micafungin was 3%among 133 patients,which included skin rash in 3 eases, diarrhea in 1 case. Only one case was discontinued because of severe skin rash and micafungin was well tolerant in other patients. Conclusion Treatment of micafungin 150 mg daily for 14 days is effective and safe in IFI patients with acute leukemia.

Objective To explore the incidence and risk factors of hepatic events and overall survival among HBsAg positive leukemia patients after allo-hematopoietic stem cell transplantation (allo-HSCT). Methods A retrospective clinical study was conducted at the bone marrow transplant unit in our hospital between March 2001 and November 2006. A total of 26 HBsAg positive leukemia patients were included in the study.18 patients received HLA-identical sibling allo-HSCT, 7 patients received HLA-mismatched related and 1 patient received HLA-identical unrelated. All the patients were free from hepatitis C infection before and after allo-HSCT. HBV serologic markers,including HBsAg、HBeAg、HBsAb、HBeAb and HBcAb were tested. 2 patients were positive for HBV-DNA before allo-HSCT. Results The cumulative incidence for acute graft vs host disease(aGVHD) grades Ⅰ-Ⅳ was 50.0%. The cumulative incidence for chronic GVHD was 25.0%. 15(57. 7%)of all the patients had abnormalities of liver function after allo-HSCT. The types of hepatic disease were reactivation of HBV and hepatic GVHD. The cumulative incidence in 5 years for hepatitis B reactivation was 33.4%, the median day of hepatitis B reactivation was 82th(65th-159th)day. The virologic and clinical outcomes were compared between two groups:one received lamivudine as prophylactic(group 1)and the other did not receive lamivudine(group 2). After transplantation,1 patient in group 1 and 7 patients in group 2 had hepatitis due to reactivation of HBV. The cumulative incidence for hepatitis B reactivation was statistically different between the two groups(P=0.006). None in group 1 but 4 in group 2 died of HBV-related hepatic failure. 10 of the 26 patients died after transplantation. The overall survival(OS) in 5 years was 59.0%. The causes of death included hepatic failure(5 cases), lung infection(3 cases) and relapse of leukemia(2 cases). By multivariate Cox analysis, development of hepatic failure was a significant predictor of mortality(P=0.000). Conclusion HBsAg positive leukemia patients often suffered from hepatic injury after allo-HSCT. The principal cause of hepatic damage was the reactivation of HBV. Hepatic failure caused by HBV was the principal reason of death. Prophylaxis with lamivudine in HBsAg positive leukemia recipients can reduce the reactivation of HBV.

ObjectiveTo investigate the efficacy of haploidentical blood and marrow transplantation (haplo-BMT) in the treatment of advanced chronic myeloid leukemia (CML).MethodsFrom November 2002 to October 2007,35 patients with advanced CML received haplo-BMT.Eleven patients achieved the second chronic phase (CP2) after treatment with imatinib or chemotherapy or both before pre-conditioning,but there were 13 cases in accelerated phase (AP) and 11 patients in blast phase (BP) at the time of transplantation.By the last follow-up date October 31,2011,the median follow-up time among living patients was 67 months (range,49 to 100 months).ResultsThe cases of HLA-antigen mismatched between donors and recipients as 1,2,and 3 antigens were 1,12,and 22 respectively.The number of mean mononuclear cells and CD34+ cells was (7.19+ 1.37) × 108/kg and (2.54± 1.50) × 106/kg,respectively.All but one patient achieved durable hematopoietic reconstitution. Hyperacute graft-versus-host disease (GVHD) occurred in 28.6％ (10/35) patients.The cumulative incidence of grade Ⅱ to Ⅳ acute GVHD was 48％.Among 27 patients who survived longer than 100 days after transplant,16 (60 ％) had chronic GVHD.Fiveyear overall survival (OS) rate was 46.2％ and 45.5％ in CML-AP and BP (P =0.97),respectively.Five-year probability of OS rate was 81.8％,30.8％ and 27.3％ in patients with CML-CP2,CML-AP and BP at transplant,respectively.The OS of CML-CP2 was significantly higher than CML-AP and BP at transplant (P＜0.01 ).ConclusionHaplo-BMT is a feasible therapeutic mean for patients with advanced CML who have no matched donors available.It is better to perform haplo-BMT at CML-CP2 other than CML-AP or BP.

OBJECTIVETo investigate the application of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in the treatment of hematologic malignancies.

METHODSBetween October 1995 and August 2001, fifty-one patients with hematologic malignancies (median age 34 years, range 5.5 approximately 52 years) received allo-PBSCT from HLA-identical (50) or 1-antigen mismatched sibling donors with conditioning regimens of TBI + CY or modified BU/CY2. Thirty-one patients were acute leukemia (AL) (15 in CR(1), 7 in CR(2) or greater, 10 in relapse including 2 relapse after allo-BMT and the other one never achieved remission); 12 chronic myeloid leukemia (CML) (CP 5, AP 2, BC 4 and relapse after allo-BMT 1); 7 MDS (RAEB 1, RAEB-T 1, AL secondary to MDS 5); Burkitt's lymphoma 1. A combination of cyclosporine and methotrexate was administered for GVHD prophylaxis.

RESULTAll patients were engrafted. The median time (range) to neutrophil >/= 0.5 x 10(9)/L and platelet >/= 20 x 10(9)/L was 14 (10 approximately 20) and 11 (7 approximately 45) days post-transplant, respectively. Grade II approximately IV acute GVHD occurred in 20/51 (39%) and grade III approximately IV aGVHD in 2 patients. Clinical chronic GVHD was diagnosed in 23 of 44 (52%) evaluable patients. Fourteen patients died: 8 died of transplant related complications, 6 of relapse. Thirty-seven patients are alive with a median follow-up of 399 (75 approximately 2 176) days, and among them 34 are in continuous complete remission, the other 3 relapsed. The 2-year probability of overall survival, disease-free survival (DFS) and relapse is 64%, 61% and 24%, respectively.

CONCLUSIONAllogeneic PBSCT is safe for both donors and recipients, and results in a rapid and stable engraftment without increase in incidence or severity of acute GVHD.

Acute Disease ; Adolescent ; Adult ; Child ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematologic Neoplasms ; mortality ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Survival Analysis ; Survival Rate ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.

METHODSTwenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9).

RESULTSFive patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.

CONCLUSIONDonor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

Adolescent ; Adult ; Bone Marrow Transplantation ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Recurrence

Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.