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Objective: To study the safety and effect of G-CSF mobilized donor hematopoietic stem cells infusion (GPBSCI) as the therapy for the failure of platelet recovery after allogeneic hematopoietic stem cell transplantation., Methods: The clinical data of 15 patients with acute or chronic leukemia undergoing GPBSCI 16 times, 9 males and 6 females, aged 33 (14 approximately 48), were retrospectively analyzed., Results: The median number of mononuclear cells (MNC) from bone marrow was (4.21 +/- 1.91) x 10(8)/kg (1.50 x 10(8)/kg approximately 7.46 x 10(8)/kg). The median number of MNCs from peripheral blood was (3.27 +/- 1.40) x 10(8)/kg (1.13 x 10(8)/kg approximately 5.90 x 10(8)/kg). The median CD34+ count was (2.13 +/- 1.69) x 10(6)/kg (0.24 x 10(6)/kg approximately 5.67 x 10(6)/kg). All the patients had achieved white cell engraftment. 8 patients with primary failure of platelet recovery and 7 patients with secondary failure of platelet recovery received donor peripheral stem cells infusion. The median day of infusion was +113 days (43 approximately 384 days). The median number of infused mononuclear cells was (3.09 +/- 1.54) x 10(8)/kg (1.35 approximately 5.99) x 10(8)/kg. Only 1 patient had transfusion related GVHD. Clinical efficacy was seen in 9 patients (56.3%). The efficacy of infusion within 100 day after transplantation was 87.50%, significantly higher than that conducted 100 days after the transplantation (25.00%, P = 0.012)., Conclusion: With minimal side effect, GPBSCI may be an effective strategy for the therapy of failure of platelet recovery.

Objective: To analyze the incidence and risk factors of hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: The medical records of 250 patients undergoing allogeneic HSCT in Peking University Institute of Hematology from Sep. 2003 to Sep. 2005 were analyzed., Results: HC occurred in 72 of the 250 patients within 180 days after transplantation with a cumulative incidence of 28.8% (SE 0.3%). None of early-onset HC was developed in the cohort. The median time of onset was 33 days after HSCT (range 14 - 170 days) and the median duration of HC was 35 days (range 3 -186 days). There were HC of grade I - II in 51/72 cases (70.83%) and of grade III - IV in 21/72 (29.17%). Univariate analysis indicated that age younger than 25, high risk disease, CMV reactivation, ATG usage, graft from MUD or MMRD and GVHD grade IL - IV were associated with the occurrence of HC, while in multiple regression analysis only GVHD grade II - IV (RR = 2.75; 95% CI 1.63 -4.66; P < 0.01) and donor type (RR = 2.60; 95% CL 1.52 - 5.20; P < 0.01) were independent risk factors. Kaplan-Meier survival analysis indicated HC not increasing the mortality (RR = 0.67, 95% CI 0.33 - 1.36)., Conclusion: HC post allo-HSCT is a common complication, GVHD grade II - IV and donor type are the independent risk factors.

In this study, we tested the efficacy and safety of donor lymphocyte infusion (DLI) with granulocyte colony-stimulating factor (G-CSF) priming in patients who relapsed after haploidentical hematopoietic stem cell transplantation (HSCT). Twenty patients received DLI at a median of 177 days after HSCT. Eight patients survived in complete remission for a median of 1118 days. The 2-year probability of leukemia-free survival was 40%. Acute graft-versus-host disease (GVHD) grade 3-4 occurred in six patients after DLI. GVHD prophylaxis reduced the incidence of acute GVHD. Our primary data showed that G-CSF-primed DLI with GVHD prophylaxis was a potentially effective therapeutic option for patients who relapsed after haploidentical HSCT.

The aim of study was to investigate the pharmacokinetics and distribution of antithymocyte globulin (ATG) in recipients of partially HLA-matched hematopoietic stem cell transplantation. Fifteen patients with hematological disorders were received hematopoietic stem cell transplantation from partially HLA-matched related donor between October 2003 and October 2004 in the Institute of Hematology and People Hospital, Peking University. All patients including 5 cases of AML, 6 cases of CML, 3 cases of ALL, 1 case of AA were consecutively enrolled in the present study after providing written informed consent. Antithymocyte globulin was administered before allogeneic hematopoietic stem cell transplantation at a dose of 2.5 mg/kg daily for 4 consecutive days (total dose of 10 mg/kg) in the conditioning regimen. The concentration of rabbit ATG in the serum of 15 patients was measured using a new enzyme-linked immunoabsorbent assay (ELISA) for the Fc portion of rabbit IgG. The results showed that the washout phase of ATG elimination was analyzed over 0 - 120 days, results were well-fitted by a single exponential decay giving a mean elimination half-life (t(1/2) beta) of 29.67 +/- 2.60 days. A mean value for the apparent volume of distribution of ATG (V) obtained by analysis of data was 0.12 +/- 0.02 L/kg body weight. The serum concentration of ATG increased up to 44.8% at 5 day before transplantation, peak concentration of ATG was 136.0 +/- 10.3 mg/L, its concentration slowly descend at 0 day, fall up to 7.1 +/- 0.06 microg/ml at 90 day after dosing; t(max) 4.8 +/- 0.7 days; According to AIC (Akaike's information criterion), two compartment model of ATG was estimated. It is concluded that the conditioning regimen containing the dosage of 10 mg/kg of ATG is effective and safely in recipients of partially HLA-matched hematopoietic stem cell transplantation. There is no racial difference in the pharmacokinetics of ATG.

Objective: To evaluate the value of serum galactomannan (GM) detection for diagnosis of invasive aspergillosis (IA) in hematopoietic stem cell transplant recipients., Methods: The serum GM concentration in 167 sera from 46 patients was detected by Platelia Aspergillus double-sandwich enzyme linked immunosorbent assay (PADSELISA). According to the diagnostic criteria of invasive fungal infections in China, the diagnostic changes were evaluated, the sensitivity, specificity and predictive values were calculated., Results: The sensitivity and specificity of the PADSELISA were 81.8% and 93.3% and the positive and negative predictive values were 90.0% and 87.5% respectively. There were 15 positive cases, and 31 negative cases, and the probable IA cases were increased from 11 to 19 after the GM detection. Moreover, the serous level of galactomannan was correlated with the prognosis of the IA., Conclusions: The PADSELISA for GM detection is a reliable method for early diagnosis and treatment of IA in hematopoietic stem cell transplant recipients.

Objective: To analyze the etiology and clinical features of late onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: The medical records of 200 patients undergoing allogeneic HSCT from 2004 to 2005 were analyzed retrospectively., Results: HC developed in 57 patients within 180 days after the transplantation with a cumulative incidence of 28.8%. The etiology of 31 patients (54.39%) was infection, caused by infection of cytomegalovirus (CMV) or adenovirus and cured by anti-virus therapy, thus the cause of disease could be classified as infection agent. Viremia was seen in 12 patients (21.53%) with CMV and disappeared in urine after anti-virus therapy but bleeding still persisted. For these patients the cause of disease was classified as infection agent combined with non-infection factor. Evidence of infection agent could not be discovered in 14 patients (24.56%) and they failed to respond to anti-infection therapy. For them the cause of disease was classified as non-infection agent. 13 patients with refractory HC underwent tentative treatment with corticosteroids, 9 of them achieved a complete remission, 2 of them achieved partial remission, and 2 of them remained non-responsive., Conclusion: LOHC after allo-HSCT is a common complication and caused by multiple factors. Differentiation of the possible causes may benefit its clinical outcome.

Objective: To investigate the effect of intravenous itraconazole on fungal infections in patients undergoing allogeneic hematopoietic stem cell transplantation., Methods: Seventy-five such patients treated with itraconazole from October, 2002 to October, 2005 were studied. The diagnosis of fungal infection was made according to the criteria recommended by Chinese workshop on invasive fungal infection (IFI). Four patients were definitely diagnosed as IFI, twenty-two patients probably and 49 patients possibly., Results: Fifty-seven of the 75 patients showed response to itraconazole therapy including 3 definite, 18 probable and 36 possible cases., Conclusion: Fungal infections in patients undergoing allogeneic stem cell transplantation diagnosed according to the criteria recommended by Chinese workshop on IFI can be successfully treated with itraconazole.

Objective: To explore the indication and optimum time for treating myelodysplastic syndrome (MDS) by allogeneic hematopoietic stem cell transplantation (allo-HSCT) with HLA identical sibling grafts., Methods: From June 1997 to Sep. 2004, a total of 30 patients with MDS were treated with allo-HSCT from HLA-identical sibling donors in our institute. On HSCT, 4 patients had refractory anemia (RA) , 2 RA with ringed sideroblasts (RARS) , 7 RA with excess blasts(RAEB) , 14 RAEB in transformation (RAEB-t) , 3 already progressed to secondary AML. For IPSS system, 6 patients were in intermediate- I risk group, 11 in intermediate- li risk group, and 13 in high risk group. The modified BU/CY conditioning regimen was used. Four patients received bone marrow transplantation (BMT), 8 received peripheral blood stem cell transplantation (PBSCT) , and 18 received BMT + PBSCT., Results: The 3-year expected overall survival (OS) was 63.61%, 3-year expected disease-free survival ( DFS) 61.41%, and relapse rate 5.26%; OS for RA/ RAS, RAEB and RAEB-t/AML subgroup was 83.33%, 34.29% and 66.67% , respectively, and all had no statistic difference among them. OS for IPSS-intermediate and high risk subgroup was 64.7% , and 69.0% respectively, also had no statistic difference. 3-year expected OS in no aGVHD,grade I - II aGVHD and grade III - IV aGVHD group was 57.75% , 100% and 0% , respectively (P = 0.009). Pre-HSCT chemotherapy, disease subtype and cGVHD all had no correlation with LFS or OS (P > 0.05)., Conclusion: For young MDS patients having HLA-identical sibling donors, HSCT should be the first line therapy and performed as soon as possible.

The study was aimed to investigate the pp65 antigen of human cytomegalovirus (CMV) and its clinical significance in patients revived allogeneic hematopoietic stem cell transplantation (HSCT). 104 patients received allogeneic HSCT were studied. Anticoagulant blood samples were obtained from the recipients before and after transplantation and in the convalescence. CMV pp65 antigen in leukocytes was detected by indirect immunofluorescence assay using CMV Brite Kit weekly. The results showed that among the 104 patients, 29 cases were CMV pp65 positive (27.88%). Out of 29 cases 16 were CMV antigenemia and 13 cases were CMV disease. There were 25 cases who positively responded to antiviral therapy (effective ratio 86.21%) and 4 cases died (case-fatality ratio 13.79%). The detection revealed a significant difference in the incidence of CMV infection between the patients received unrelated or haploidentical family donor HSCT (39.29%) and HLA-identical sibling donor HSCT (14.58%) (P < 0.05). The incidence rate of CMV infection in patients with 0-I grade aGVHD and patients with II-IV grade aGVHD were 19.44% and 46.88% respectively, which had significant difference (P < 0.05). There was significant difference in the occurrence of aGVHD between the patients with and without positive CMV pp65 (P < 0.05). It is concluded that infection of CMV can be detected by the CMV pp65 monoclonal fluorescence immunohistochemistry, The detection of CMV pp65 antigen in peripheral blood leukocytes as a indicator for CMV disease surveillance after HSCT, which may be used to early diagnose the CMV infection, to guide the antiviral treatment and evaluate its efficacy.

Objective: To evaluate the value of real time quantitative RT-PCR (Q-PCR) for monitoring bcr-abl mRNA levels in chronic myeloid leukemia (CML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: Quantification of bcr-abl mRNA was performed on 316 bone marrow samples from 112 patients with CML after HSCT by Q-PCR using the TaqMan probe system. The bcr-abl mRNA level was normalized by control gene abl. Cytogenetic response was evaluated with fluorescent in-situ hybridization (FISH)., Results: The reproducible sensitivity of Q-PCR was 5 copies. The coefficients C(T) of interassay and intraassay variation for abl and bcr-abl were all below 2.0%. 289 bone marrow samples were collected from 101 CML patients who achieved a sustained complete cytogenetic response (CCyR) one month post allo-HSCT in a period of 6 - 60 months (median 12 months) at different intervals. In general, the median bcr-abl levels gradually decreased with the prolongation of time after HSCT: the median bcr-abl levels were 0.035% (0 - 0.406%) at 1 month post allo-HSCT (+ 1 month), 0.006% (0 - 0.683%) at +3 month, 0% (0 - 0.225%) at +6 month and remained 0% till +24 months. The highest level in CCyR patients detected at + 6 month was 0.068%. The bcr-abl mRNA level was decreased by 3 log in sustained CCyR patients at + 1 month compared with the newly diagnosed CML-CP patients (33.0%, data unpublished). On the contrary, Q-PCR results ranged from 0.12% to 13.45% in 8 cytogenetic non-responders or relapsed patients post allo-HSCT. Among them, 5 patients' samples were collected 1 - 2 months before cytogenetic relapse, the results were ranged from 0.09% to 3.42%. If 0.09% was assumed 0.09% as a threshold, 9 sustained CCyR patients (8.9%) were tested once higher than that within 6 month after HSCT but decreased to 0% eventually. 2 blast crisis patients achieved CCyR within 1.6 and 3 months after HSCT, but hematological relapse occurred after 1 and 1.5 months, and their bcr-abl mRNA levels increased dramatically from 0% and 0.14% to 46.9% and 75.9% respectively., Conclusions: Q- PCR is a sensitive, precise and reliable technique, and can be used to monitor CML patients post allo-HSCT regularly. Patients in blast phase of CML should be monitored more frequently.

Objective: To compare the outcomes in hematological patients receiving unrelated peripheral blood stem cell transplants (UPBSCT) with those receiving unrelated bone marrow transplants (UBMT) in a retrospective analysis., Methods: Sixty-three patients with hematological diseases with HLA-matched (65%) or mismatched (35%) unrelated donors were receiving UPBSCT (n = 33) or UBMT (n = 30) between May 2001 and June 2005 in our institute. They all received standard conditioning regimens with Bu/Cy (n = 53) or TBI/Cy (n = 10) with the addition of ATG for 3 - 4 days (n = 58) or CD3 antibody (n = 5). There were more patients receiving rabbit ATG in the UPBSCT group than UBMT (21/33 vs 8/25, P = 0.02) and the remaining patients received pig ATG. Graft versus host disease (GVHD) prophylaxis consisting of cyclosporine, methotrexate and mycophenolate mofetil were the same., Results: The two groups were matched for the following factors: gender, diagnosis, HLA-compatibility and conditioning regimens. The median age in the UPBSCT group was 29.5 (10 - 47) years and in the UBMT 21.5 (7 - 42) years (P < 0.05). The UPBSCT group consisted of 10 females and 23 males and the UBMT group 7 females and 23 males. Eleven patients in the UPBSCT and 8 patients in the UBMT group were diagnosed with as chronic myeloid leukemia (CML); 9 and 12 as acute myelocytic leukemia (AML); 11 and 10 as acute lymphatic leukemia (ALL); 2 and 0 as severe aplastic anemia (SAA). There were more patients in aggressive stage (>CR1) in the UBMT group than in the UPBSCT group (9/30 vs 3/33, P = 0.06). Median follow-up was 12 months after UPBSCT and 20 months after UBMT (P < 0.05). UPBSCT group had a higher number of infused MNC as comparison with UBMT group (6.16 x 10(8)/kg vs 2.80 x 10(8)/kg, P < 0.05). Both neutrophil and platelet recovery were faster after UPBSCT (11 days vs 17 days, 14 days vs 27.5 days, P < 0.01). Although the cumulative incidence of grades II - IV acute GVHD and severe aGVHD in the UPBSCT group were less than in the UBMT group (33.04% vs 66.69%, 7.26% vs 34.52%, P < 0.05), there was no difference after the source of ATG was counted. The incidence of chronic GVHD did not differ between the two groups (18/25 vs 14/22). Relapse including molecular relapse occurred in 6 of the 31 patients after UPBSCT and in 4 of the 30 patients after UBMT (P > 0.05). Finally, fifteen of the 30 patients died after UBMT, as compared with 8 of the 33 patients after UPBSCT. The cumulative overall survival was 62.45% after UPBSCT and 47.22% after UBMT (P = 0.114)., Conclusion: Our results indicate that UPBSCT led to significantly faster leukocyte and platelet engraftment without increasing the incidence of aGVHD and the overall survival was comparable between the two methods of therapy.

The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n = 158) or related HLA-mismatched (n = 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 + ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P = .13), respectively, with the relative risk (RR) = 0.64 (95% CI, 0.43-0.94), P = .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P = .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P = .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P = .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P = .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P = .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes.

Objective: To study the effect of growth factor-primed donor hematopoietic stem cells infusion (GPBSCI) as an early adoptive immunotherapy., Methods: Twelve patients with high-risk leukemia received prophylactic GPBSCI after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Out of the 12 patients, two were Ph(+) ALL in CR(1), one ALL in CR(2), one refractory ALL, three AML (one in relapse, one refractory disease, one in CR(3)), four CML in advanced stage and one myelodysplastic syndrome-refractory anemia with excess blast (MDS-RAEB)., Results: Sixteen infusions were performed in the 12 patients, including 5 infusions were performed within +90 days post-SCT. The median mononuclear cells (MNC) and CD3(+) cells infused for GPBSCI before +90 d were 1.00 (0.95 - 1.24) x 10(8)/kg and 0.53 (0.39 - 0.63) x 10(8)/kg, and after +90 d were 2.27 (1.00 - 4.30) x 10(8)/kg and 1.15 (0.55 - 2.10) x 10(8)/kg, respectively. Four patients developed grade I - II acute GVHD, and one grade III acute GVHD. Seven patients developed chronic GVHD, of which four cases were extensive. Two patients had no transfusion related GVHD. No transfusion related pancytopenia was observed. Ten patients survived disease-freely at 563 (415 - 728) days of follow-up. Two patients died of leukemia relapse after GPBSCI., Conclusion: Allo-HSCT with prophylactic GPBSCI could maximize graft-versus-leukemia effect with few fatal complications and might be a potentially curative strategy for hematological malignancy patients with high risk of relapse.

Objective: To investigate the pathologic and clinical characteristics of patients with liver dysfunction after allogeneic hemopoietic stem cell transplantation (Allo-HSCT), and evaluate the role of liver biopsy in diagnosis and management of liver dysfunction post Allo-HSCT., Methods: Ten patients with hematological diseases, 5 males and 5 females, aged 34.5 (15-56), underwent Allo-HSCT, 6 receiving Allo-HSCT from their HLA-matched siblings, one receiving haploidentical transplant, two receiving cord blood transplantation from sibling, and one receiving unrelated BMT. The conditioning regimens included Cy/TBI (in 2 cases), and non-TBI regimen (in 8 cases). All the patients received cyclosporine A, short term MTX and MMF for the prophylaxis of graft-versus-host disease (GVHD). Test of liver function and examination of HBV and HCV related serologic markers were performed for the patients and recipients before transplantation and for those who had liver dysfunction after transplantation. Percutaneous liver biopsy was performed for these 10 patients. Biopsy specimens were examined histologically by hematoxylin-eosin staining, Masson staining and immunohistochemical stating of related viruses., Results: All 10 patients showed liver dysfunction on average 3.5 months (2-5 months) after the transplantation. Seven patients positive in HBV and HCV serologic markers before HSCT remained positive after the transplantation. Three patients negative in HBV/HCV markers before and after Allo-HSCT were diagnosed as with GVHD clinically. Eight patients had other manifestations of chronic GVHD. Eight patients received liver biopsy 5.5 months (4-12 months) because of poor improvement in the initial treatment stage. The result of biopsy showed hepatic GVHD in 3 patients and hepatic GVHD concomitant with HBV or HCV hepatitis reactivation in 7 patients. The liver function of 3 patients diagnosed as with hepatic GVHD returned to normal after the use of the second-line anti-GVHD therapy. The other 7 patients used anti-virus agents combined with immunosuppressive agents with the result that 2 patients remained alive with normal liver function and 5 patients died due to pulmonary complication (2 cases) or hepatic failure and hepatic coma (3 cases)., Conclusion: Liver biopsy is of distinguished diagnostic value for patients with refractory hepatic GVHD after Allo-HSCT. The prognosis is poor for patients having hepatic GVHD concomitant with active hepatic virus infection. At this time the role of liver biopsy is limited and management should be made according to the clinical features and liver pathology.

Objective: To improve the outcome of hematopoietic stem cell transplantation from unrelated donors., Methods: Sixty-six patients with hematological diseases (40 cases of acute leukemia, 24 chronic myeloid leukemia, and one each severe aplastic anemia and beta-thalassemia) received bone marrow (BMT, n = 48) or peripheral blood stem cell transplantation (PBSCT, n = 18) from HLA-compatible unrelated donors after BUCY or TBI conditioning. Forty patients received longer and intensive GVHD prophylaxis (cyclosporin A from day -10 combined with mycophenolate mofetil)., Results: Sixty-four patients achieved sustained donor engraftment. The median time of leukocyte engraftment was 15 days, being significantly earlier in PBSCT group compared with BMT group (12 vs 16 days, P = 0.002). The cumulative incidence rates of grades I-II and III-IV acute GVHD at day 100 were 57.15% and 32.25%, respectively. Chronic GVHD was seen in 21 of the 36 evaluable cases and ten of them were extensive type. Six patients relapsed and 27 dead, the overall survival at 5 years was 52.91%. The COX method analysis showed that HLA-compatible level and source of graft affected the incidence of aGVHD. The patients transplanted from HLA-matched donor with high resolution and PBSCT had the less probability for aGVHD. Patients without GVHD or with longer and intensive GVHD prophylaxis had significantly improved OS., Conclusion: The key to improvement the outcome of HCT from unrelated donor is to reduce the incidence and severity of aGVHD by selecting the HLA-matched donor, intensifying the immunosuppression at the early stage of transplantation.

Objectives: To study clinical characteristics and outcome of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: Variables including sex, age, stem cell source, granulocyte engraftment time, blood transfusion and isoagglutinin type against donor RBC were analyzed to identify risk factors for the development of PRCA., Results: Twelve of 100 patients received major ABO-incompatible allo-HSCT developed PRCA, with out any effect on incidence of aGVHD and CMV infection. ABO blood groups of recipient/donor pairs of these twelve PRCA patients were O/A in nine, B/A in one and O/B in two. Patients with anti-A isoagglutinins against donor RBC developed PRCA more frequently than those with anti-B (10/49 vs 2/49). Median duration to the recovery of erythropoiesis tended to be longer in patients with PRCA (PRCA vs non-PRCA, 203.5 vs. 76 days, P < 0.05 ). Median durations to the disappearance of incompatible isoagglutinins tended to be longer in patients with PRCA (PRCA vs. non-PRCA, 150.5 vs. 60 days,P <0.05) and in those with anti-A isoagglutinins (anti-A vs anti-B, 90 vs 55 days, P < 0.05)., Conclusion: ABO blood group of O/A in recipient/donor pair was the only high risk factor for PRCA after major ABO-incompatible allo-HSCT.

Objective: To explore the optimal time of allogeneic hematopoietic stem cell transplantation (allo-HSCT) applied in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and the optimum order of donor selection., Methods: From Mar 2000 to Jul 2004, 32 patients with Ph+ ALL were treated by Allo-HSCT, and the follow up ended at Dec 30.2004 with medium of 13 months. Of whom, 24 were male, and 8 were female. Twenty-three patients have been transplanted in CR1, 9 patients beyond CR1 (1 in CR2, 8 in refractory or relapse status). Twelve cases received HSCT from identical sibling donor, 4 unrelated Cord Blood Transplantation (CBT), 3 HSCT from matched unrelated donor (MUD), and 13 HSCT from mismatched related donor (MMRD), of which, 6 cases were M(BCR/ABL) subtype, and 20 m(BCR/ABL) subtype. The Kaplan-Meier method was used to estimate the probabilities of leukemia-free survival (LFS), overall survival (OS) and relapse incidence (RI), and the factors were compared by means of the Log-rank test. Simultaneous effect of multiple covariates were estimated with Cox model., Results: Of all the 32 cases engrafted, 4-year OS was 57.19%, LFS 37.09%, and RI 56.36%. In univariate prognostic analysis model, the OS was higher in CR1 group pre-HSCT than that in non-CR1 group (74.50% vs 22.22%, P=0.0046), LFS was higher (49.06% vs 11.11%, P=0.0057), RI was lower (44.80% vs 84.76%, P=0.0157); the OS was higher in M(BCR/ABL) group than that in m(BCR/ABL) group (100% vs 40.91%, P=0.0318), LFS was higher (75% vs 17.72%, P=0.0057), RI was lower (25% vs 77.88, P=0.0116); OS was similar in HLA MM RD group to that in HLA identical group (52.65% vs 55.56%, P=0.6247), LFS was similar (45.12% vs 30.00%, P=0.8315), and RI was also similar (50.77% vs 60.62%, P=0.8217). In multiple covariate analysis model, the BCR/ABL type was the risk factor of LFS [P=0.005, Exp(B)=9.971] and RI (P=0.006, Exp(B)=9.488), the status of disease pre-HSCT and BCR/ABL subtype was the risk factor of OS [P was 0.010 and 0.038, Exp(B) was 4.532 and 37.537 respectively]., Conclusion: We had better do HSCT in CR1 to treat Ph+ ALL, if patient is refractory to chemotherapy, we can try STI571, and HSCT should be done as soon as possible if the patients get CR. Mismatched related donor is considered as regular donor for Ph+ ALL patients without identical donors. We should pay more attention to monitoring and prophylaxis of relapse in m(BCR/ABL) patients after HSCT.

Objective: To investigate the efficacy of intravenous administration of itraconazole on fungal infections in immunocompromised patients with hematological diseases according to stratified diagnoses., Methods: Twenty-five patients with hematological diseases who were diagnosed according to the criteria of European Organization for Research and Treatment of Cancer (EORTC), including 6 cases with confirmed diagnosis diagnosis, 12 cases with clinical diagnosis, and 7 cases with recommended diagnosis, underwent intravenous injection of itraconazole 125 approximately 200 mg bid for 2 days and then qd for at most 2 weeks and then oral administration of itraconazole 0.4 g/day for at most 2 weeks, and then the repeated regimen with a course of treatment of 1 approximately 3 months from 2002 to 2004. Eighteen cases were diagnosed with lung infection, 1 case with sinuses and trachea infection, and the infection sites were not documented for other 7 cases. The clinical results were analyzed., Results: The effective rates of the patients with confirmed diagnosis, with clinical diagnosis, and with recommended diagnosis were 66.7% (4/6), 83.3% (10/12), and 14.3% (1/7) respectively. The effective rates of the patients with major imaging signs and those with secondary imaging signs were 90.0% (9/10) and 97.1% (4/7). There was a significant difference between the curative effects of the patients with confirmed diagnosis and those with recommended diagnosis (P = 0.006)., Conclusion: Fungal infections in immunocompromised patients with hematological diseases can be successfully treated with intravenous administration of itraconazole.

Objective: To analyze the features, causes, treatments and outcomes of severe gastrointestinal (GI) bleeding after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: Fifteen patients suffered from massive GI bleeding (blood loss leading to hemorrhagic shock) or subacute GI bleeding (at least 1 or more units of red blood cell transfusion on each of two consecutive days) were observed and analyzed after allo-HSCT., Results: Seventeen severe GI bleeding episodes occurred in 15 patients. The severe bleeding occurred in three periods of time: within 1 week, 1 to 2 months and 4 to 7 months after transplantation. The main manifestation was hematemesis and hematochezia in the first period, and hematochezia alone in the second and third periods. Platelet counts at the onset of severe bleeding were < or = 50 x 10(9)/L in the majority of patients. Causes of bleeding were conditioning regimen-related toxicity in 2 patients/episodes, graft versus host disease (GVHD) or/and intestinal cytomegalovirus (CMV) or fungal infections in 11 patients/12 episodes, intestinal CMV infections in 1 patient/episode, acid-peptic ulcer in 2 patients/episodes, and cause unknown in 1 patient/episode. Supportive care such as transfusions of platelet, red blood cell and fresh frozen plasma, H2 receptor blockers and omeprazole were given to all patients, immunosuppressive drugs to patients developed GVHD and antiviral drugs to patients with complicated CMV infection. Eight patients/9 episodes of bleeding were controlled. Eight patients continued severe GI bleeding and died of acute GVHD or related serious complications., Conclusions: Severe GI bleeding after allo-HSCT are mainly caused by regimen-related toxicity, GVHD or/and intestinal CMV infection. Bleeding caused by conditioning regimen-related toxicity is self-limited and has a better prognosis. However, treatment failure and mortality are high if the patient's bleeding resulted from GVHD and intestinal CMV infection.

Objective: To evaluate the use of a new reduced intensity of BuCy conditioning regimen for the treatment of malignant hematologic diseases in aged or intolerable patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the siblings., Methods: Twelve patients with acute lymphoblastic leukemia (ALL, n = 4), acute myelogenous leukemia (AML-M(2), n = 2), chronic myelogenous leukemia (CML, n = 4), and myelodysplastic syndromes-refractory anemia with excess blasts (MDS-RAEB, n = 2) were intolerant of conventional myeloablative therapy because of age (older than 50 years) or having severe concurrent diseases. The median age was 49 years (range 42-64 years). Seven were males and five females. Two of the 12 patients were HLA one antigen-mismatched and the rest HLA identical with their donors. The low dosage conditioning regimen consisted of busulfan (2 mg.kg(-1).d(-1) for 3 days), Ara-C (2 g.m(-2).d(-1) for 1 or 2 times), cyclophosphamide (1.0 g.m(-2).d(-1) for 2 days) and anti-T-lymphocyte globulin (ATG 2.5 mg.kg(-1).d(-1) for 4 days, -5 - -2 day). Granulocyte colony-stimulating factor mobilized bone marrow and peripheral blood stem cells (PBSC) were harvested (1 patient using PBSC alone). All patients received cyclosporin A, short-term MTX and mycophenolate mofetil (MMF) for prophylaxis of acute graft-versus-host disease (aGVHD). DNA short tandem repeat (STR) sequence analysis, cytogenetics and molecular-biologic technique were used to analyze chimerism., Results: All the patients were well tolerated the regimen, with no severe regimen related toxicity. In all the 12 patients, absolute neutrophil count > or = 0.5 x10(9)/L was achieved in 11 to 17 (median 15) days and platelet count > 20 x 10(9)/L in 10 to 23 (median 15) days after transplantation. Complete chimerism was achieved in 11 patients and 1 patient was in mixed chimerism at one month after HSCT. With a median follow-up of 14.5 (4.0-24.0) months, 7 of the 12 patients (58.0%) were alive and 5 (42.0%) of the 7 were disease-free. The probabilities of OS and DFS at 12 months were 75.0% and 48.1%. Five patients (41.6%) had aGVHD and four had local chronic GVHD with a cumulative probability of chronic GVHD of 41.5%., Conclusion: This reduced intensity conditioning regimen is well tolerated and safe for HSCT in the older patients or patients with severe concurrent medical conditions and can achieve full chimerism and long-term disease-free survival.

Objective: To evaluate the efficacy and safety of low-dose methotrexate in patients with graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT)., Methods: Thirty-one patients with minor or moderate grade acute GVHD (aGVHD), chronic GVHD (cGVHD) or GVHD post donor lymphocyte infusion (post-DLI GVHD) after Allo-HSCT received intravenously administrated methotrexate at a dose of 5 or 10mg every 5 to 7 days until achieving complete or partial responses, treatment failure or intolerable side effects., Results: The overall response rate was 93.8% (15/16 patients) in patients with aGVHD, 75% (12/16 patients) in patients with cGVHD and 100% (2/2 in patients) with post-DLI GVHD. The response rate for GVHD involving organs was 100% in skin, 60% in gut, 71% in liver, 75% in mouth and 100% in eyes. Side effects were minor. During the therapy, the other immunosuppressive agents were reduced., Conclusion: Short-term low-dose methotrexate is a tolerable and effective regimen for patients with minor or moderate grade aGVHD, cGVHD or post-DLI GVHD after Allo-HSCT.

Objective: To analyse the clinical features and pathogenesis of pneumonia post allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: Analysis was made of 255 patients of recipients of allo-HSCT from 1998 to 2001., Results: Seventy-two episodes of pneumonia occurred in 66 patients with the morbidity of 25.9%; 50 (75%) patients were cured. Twelve episodes (16.7%) were caused by mixed infection of bacteria and fungi; 22 episodes (30.6%) were caused by cytomegalovirus infection and 36 episodes (50.0%) were classified as idiopathic pneumonia syndrome. The total mortility of pneumonia post allo-HSCT in our institute was 22.7%. The occurrence of chronic graft-versus-host disease was significantly high in idiopathic pneumonia syndrome, in which good response to immune suppressive therapy was observed., Conclusion: Pneumonia post allo-HSCT is a common complication, of which pathogenesis includes infection and non-infection. Its clinical outcome could be improved by specific therapy.

Objective: To investigate the incidence and risk factors of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: The clinical data of 151 cases of allo-HSCT in 150 patients from Nov 2001 to Jan 2004 was analyzed., Results: aGVHD was developed in 60 cases (40.2%), including 43 cases with grade I - II and 17 with grade III - IV aGVHD, the mean time of aGVHD development was 21 days (range 1 - 85 days) after allo-HSCT, 35 out of 55 cases achieved complete response (CR) (63.6%). The early survival rate for grade I - II aGVHD was more than 90%, while that for grade III - IV aGVHD was 46%. Nineteen factors possibly correlated with the development of aGVHD were analyzed. The univariate analysis showed that recipient age, donor's sex, recipient's sex, sex and ABO blood group disparity between donor and recipient, diagnosis, the status of disease, the stage of disease, stem cell source, conditioning regimen (TBI/without TBI), CD34(+) cell number, CD3(+) cell number, early engraftment and neutropenic infection were not closely associated with the occurrence of aGVHD (P > 0.05). On the Cox regression model, 2 independent factors for grade I - IV aGVHD were identified:HLA mismatch (RR = 1.681, P < 0.05) and positive surface antigen (HBsAg) (RR = 1.907, P < 0.05). In addition, the univariate analysis showed aGVHD was strongly associated with CMV infection (P < 0.01)., Conclusion: aGVHD is a common complication after HSCT, HLA mismatch and HBsAg positivity are independent risk factors for aGVHD.

The objective was to use STI571, a kind of tyrosine kinase inhibitor, to treat acute myeloid leukemia (AML) with Philadelphia chromosome. 2 AML cases with Philadelphia chromosome, were collected to observe effect of STI571. One of them was given STI571 after routine chemotherapy failed to respond to treatment, other case received routine chemotherapy only. Both of them underwent HLA-matched/mismatched sibling hematopoietic stem cell transplantation (HSCT). The results showed that cytogenetic and hematologic CR was acquired in case 1 with STI571 while another one gained hematologic CR by accepting routine chemotherapy. Recovery of hemopoiesis was found at 18 and 11 days after HSCT respectively without serious graft-versus-host-disease. The case 1 has been surviving in disease-free state for 5 months since HSCT. The case 2 died from interstitial pneumonia at 8 months after HSCT. In conclusion, STI571 is one of choice for the treatment of Philadelphia chromosome positive AML.

Background: Many patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) do not have an human leukocyte antigen (HLA)-matched donor. Alternative donors, such as HLA mismatched family donors, are associated with higher rates of graft rejection and acute graft versus host disease (aGVHD) if T cells are not first depleted. We developed a new technique for HLA mismatched allogeneic HSCT using G-CSF primed bone marrow plus G-CSF-mobilized peripheral blood stem cells without ex vivo T cell depletion., Methods: In this study, 58 patients, including 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with 1 - 3 mismatched loci. After conditioning, patients received G-CSF-primed bone marrow grafts that had not been depleted ex vivo of T cells, in combination with G-CSF-mobilized peripheral blood stem cells, as well as GVHD prophylaxis., Result: All patients achieved sustained, full donor-type engraftment. The incidence of grade II-IV aGVHD was 37.9%, including 3 patients with grade III-IV aGVHD. The development of aGVHD was not associated with the extent of HLA disparity. Chronic GVHD was observed in 30 of 51 evaluable patients (65.4%). Fourteen patients died among whom 7 died of recurrent disease and 7 of transplant-related complications. Forty-four of the 58 patients survived, and 42 remained disease free at the time of a median follow-up of 12 months (3.5 to 39.5 months). The 2-year probabilities of disease-free survival were 74.8% and 69.3% for standard- and high-risk patients, respectively., Conclusion: We developed a new method to use bone marrow from haploidentical family donors without ex vivo T cell depletion, in combination with G-PBSCs, as a source of stem cells even in cases of HLA mismatched transplantation.

This study was aimed to investigate various factors influening erythrocyte recovery following ABO-incompatible allogeneic HSCT. 157 patients following ABO-incompatible allogeneic HSCT were selected for the investigation. Cox regression analysis were used to identify the statistically significant factors including sex, age, schemes of transplantation, HLA-matched, mismathed, conditioning regimens, preventive measures for GVHD, occurrence of grade I-II GVHD, CMV infections and types of incompatible blood group. The results showed that minor ABO-incompatible, number of mononuclear cells infused, age of patients and unrelated BMT were four important main factors influening the erythrocyte recovery. In conclusion, the erythrocyte recovery is more quick in patients with minor ABO-incompatible and more number of mononuclear cells infused, while it is slow in patents with old age and unrelated BMT.

Objective: To explore the clinical application of human leukocyte antigen (HLA) mismatched hematopoietic stem cell transplantation (HSCT) for malignant hematological diseases using a new GIAC protocol., Methods: One hundred patients with malignant hematological disease received G-CSF mobilization, intensive immunosuppression, ATG and combination of bone marrow and peripheral blood stem cell transplantation at least 1 locus mis-matched hematopoietic stem cell transplant performed with GIAC protocol. The conditioning regimen was intensified and prolonged with combined use of CsA, MMF and ATG for GVHD prophylaxis., Results: All patients achieved sustained, full donor-type engraftment. The cumulative incidence of grade II approximately IV aGVHD was 48.39%, and grade III approximately IV aGVHD was 12.90%. Thirty-eight patients had cGVHDs which were of extensive type in 11 patients. Twelve patients relapsed, 11 of them were high-risk patients, and 3 returned to CR after donor lymphocyte infusion. Twenty-two patients died, owing to recurrent diseases in 6 and transplant-related complications in 16 cases. Seventy-two patients were alive and disease free, with 1 year disease-free survival probabilities for standard and high risk patients of (83.52 +/- 7.41)% and (47.63 +/- 8.49)%, respectively., Conclusion: The GIAC protocol for at least 1 locus mismatched hematopoietic stem cell transplantation is relatively safe and efficient for patients with hematological malignancies.

Objective: To investigate the new methods of human leukocyte antigen (HLA) mismatched transplantation in patients with hematologic malignancies., Methods: In this pilot study, 58 patients, 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with at least 1 of 6 loci mismatched. After conditioning, patients received non ex vivo, T cell-depleted grafts of G-CSF-primed bone marrow plus G-CSF-mobilized peripheral blood stem cells, as well as graft-versus-host-disease (GVHD) prophylaxis., Results: All patients achieved sustained, full donor type engraftment. The incidence of grades II-IV acute GVHD was 37.9% (22 of 58), and grades III and IV aGVHD developed in only 2 and 1 patients, respectively. Furthermore, there was no statistically significant association between the extents of HLA mismatching and the degree of aGVHD. Twenty six of 42 (61.9%) evaluable patients had developed chronic GVHD (cGVHD) with limited cGVHD in 15. Nine patients relapsed, all but one with advanced or refractory leukemia. Fourteen patients died (24.1%), of whom 7 died of recurrent diseases and 7 of transplant-related complications (TRM): main causes of TRM were infection(2), intestinal pneumonia(2), CMV encephalitis(1), hepatitis(1) and aGVHD (1). Forty-four of the 58 patients (75.9%) survived and 42 (72.4%) were disease free with a median follow-up of 10 months (range, 2 to 37.5 months). The 2-year probabilities of disease-free survival for patients with standard and high risks were 77.6% and 63.2% respectively, which showed that high-risk disease status at transplantation was associated with worse disease-free survival (P=0.04). The degree of HLA mismatching between the donor and the recipient was not related to event-free survival (P=0.57), nor was cell number infused and aGVHD (P=0.78, 0.94 respectively)., Conclusion: (1)HLA mismatched transplantation can be per formed without ex vivo T cell depletion. (2)Using G CSF mobilized PBSCs as a source of stem cells may be possible and safe even in HLA mismatched transplantation.

Objective: To retrospectively analyze the results of a consecutive series of 100 ALL patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our center., Methods: Of the 100 ALL patients, 69 were male and 31 female, with a median age of 29.5 (4 - 47) years. Sixty-nine cases were in the first complete remission (CR(1)), 13 in more than CR(1) and 18 in relapse before transplant. Allo-HSCT from HLA identical siblings was performed for 86 patients, of whom 64 received bone marrow transplantation (BMT) and 22 peripheral blood stem cell transplantation (PBSCT). HLA matched unrelated BMT was performed for 8 patients, cord-blood transplantation from unrelated donor for 6 patients. Forty-five patients underwent allo-HSCT with conditioning regimen of Cy/TBI, 55 with BUCY. Prophylaxis of graft-versus-host disease (GVHD) included long-term MTX regimen (4 cases) and CsA + MTX regimen (96 cases). The average follow-up was 38.1 months., Results: The 5-year overall survival (OS) and disease-free survival (DFS) of the 100 cases of ALL was 53.4% and 50.5%. The 5-year OS and DFS were significantly longer for patients in CR(1) than in >CR(1) and relapse patients before allo-HSCT (P < 0.001). The outcome of PBSCT seemed superior to that of BMT, but there was no difference between them. Multivariate analysis showed the most significant factor associated with long post allo-HSCT survival was that the patient underwent transplantation in CR(1). There was no significant difference in 5-year OS, DFS, cumulative incidences of relapse rate and treatment related mortality between the two cohorts prepared with TBI or BUCY., Conclusions: Allo-HSCT can cure a significant proportion of ALL patients, especially for those in CR(1). There was no significant difference in OS, DFS between the two different conditioning regimens and the different transplant choices.