ABSTRACT
Objective@#To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) .@*Methods@#Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively.@*Results@#With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95%CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95%CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95%CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT (P=0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS (P=0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor.@*Conclusions@#Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.
ABSTRACT
Objective@#To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR1-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR1-AML.@*Methods@#Between April 2012 and March 2015, consecutive 186 patients with CR1-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive.@*Results@#①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR1-AML.@*Conclusion@#MRD positive pre-conditioning was the only negative impact factor for patients with CR1-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR1-AML after allo-HSCT.
ABSTRACT
Objective@#To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#Retrospective analysis of 258 patients with AML in CR (186 cases in CR1, 72 cases in CR2) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk.@*Results@#①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34+ cell number and transfused CD3+ cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR2 compared to that in CR1 (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM.@*Conclusion@#Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR1 and CR2 patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of HLA- haploidentical donor hematopoietic transplantation (Haplo- HSCT)for severe aplastic anemia (SAA)by compared with the same period of unrelated donor transplantation (UD- HSCT).</p><p><b>METHODS</b>Of a cohort of 50 SAA patients between September 2012 and July 2014, 26 patients underwent UD- HSCT and 24 patients Haplo- HSCT.</p><p><b>RESULTS</b>OS rate was 91.3% with a median follow-up of 9 (2-26)months. According to transplant type, there was no significant difference between UD- and Haplo-HSCT (96.1%vs 86.0%,P=0.30). 3 of 50 (6%)patients had primary engraft failure. Haplo- HSCT developed higher significantly incidence of Ⅱ- Ⅳ aGVHD (37.5%vs 3.83%,P=0.003)and cGVHD (37.5%vs 15.3%,P=0.030)than UD-HSCT. Haplo-HSCT also had significantly higher incidences of CMV viremia (78.2%vs 46.1%,P=0.005)and EBV viremia (43.1%vs 16.0%,P=0.040), respectively than UD-HSCT. But the incidences of hemorrhagic cystitis were similar between two transplant types (39.1%vs 23.0%,P=0.120).</p><p><b>CONCLUSION</b>This study showed favorable outcome of Haplo-HSCT for SAA, which was comparable with UD-HSCT.</p>
Subject(s)
Humans , Anemia, Aplastic , Therapeutics , Hematopoietic Stem Cell Transplantation , Incidence , Treatment Outcome , Unrelated DonorsABSTRACT
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.
ABSTRACT
Objective To investigate early Epstein-Barr virus (EBV) reactivation and the outcome of preemptive therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods From January 2007 to January 2009, totally 277 patients after allo-HSCT were studied (haploidentical 116,unrelated 75, matched sibling 86). Conditioning regimens were mainly busulfan (BU) + cyclophosphamide ( CY)/fludarabine(Flu) or total body irradiation (TBI) + CY/Flu. Antihuman thymocyte globulin (ATG)was added in haploidentical and unrelated transplants. Plasma EBV DNA was monitored once to twice weekly in the first 3 months after allo-HSCT with real time quantitative polymerase chain reaction (RQ-PCR). EBV viremia was diagnosed when EBV DNA was more than 5 × 102 copies/ml but without symptoms. Acyclovir (10 mg/kg, intravenous drip, 8 h) was used for preemptive therapy and immnuo-suppressants were decreased if possible. Results Totally 33 patients ( 11.9% ) developed EBV viremia with a median time at day 44 (day 19 to day 84). The incidences of EBV viremia in the transplants from matched sibling,haploidentical, unrelated donors were 0, 15.5%, 20. 0%, respectively. There was no significant difference between haploidentical and unrelated transplants ( P = 0. 09 ), but much less EBV viremia was seen in matched sibling transplant ( P = 0. 001 ). Twenty of 33 patients ( 60. 6% ) had complete response to preemptive therapy. The median time to reach EBV DNA negative in plasma was 11 (4-56) d. The median duration of preemptive therapy was 21 (14-60) d. Both univariate and multivariate analysis indicated that haploidentical and unrelated transplants, acute graft versus host disease (GVHD) were the risk factors for EBV viremia. Two-year overall survival in the patients with EBV viremia was significantly lower than that without EBV viremia (54. 2% vs 72. 1%, P = 0. 006 ). Conclusions Our large clinical study has demonstrated that preemptive therapy with acyclovir that is guided by EBV viremia is effective in majority of the patients with high-risk for EBV reactivation after allo-HSCT, which may further decrease the risk for developing life-threatening EBV disease or post-transplantation lymphoproliferative disorder. Haploidentical and unrelated transplants, acute GVHD are the risk factors for EBV viremia which has negative impact on survival.
ABSTRACT
Objective To study the incidence, risk factors and prognosis of central nervous system (CNS) complications after hematopoietic stem cell transplantation ( HSCT) in order to prevent or reduce its occurrence, provide better diagnosis and treatment and improve the survival of the patients.Methods A total of 640 patients who consecutively underwent HSCT in our hospital between May 2001 and December 2007 were included.The clinical outcomes of the patients who developed CNS complications were analyzed.Results The patients received stem cells from haploidentical family members ( Haplo, n = 289 ) , identical siblings (IS, n = 237) , unrelated donors ( URD, n = 83) , unrelated cord blood (n = 14) , syngeneic siblings (n = 9 ) or autologous peripheral blood ( n = 8 ).Fifty-seven of 640 patients (8.9% ) developed CNS complications.The incidences were 12.0%, 13.5% and 3.4% in URD-HSCT, Haplo-HSCT and IS-HSCT respectively ( P <0.001).The incidences of CNS complications were 19.4% and 8.3% in cases who received or did not receive conditioning with TBI ( P = 0.047 ).There was no significant difference in the incidences of CNS complications between children (15.3% ) and adults(8.3% ) (P = 0.072).Similar incidences of CNS complications were seen in patients with hematological malignancies (8.9%) and non-malignant hematological disorders (7.7%)(P = 1.000).Five of the 57 patients developed two kinds of CNS complications.The patterns of CNS complications included relapse (17 cases) , infections (15 cases) , cyclosporine or FK506 encephalopathy (9 cases) , cerebral hemorrhage ( 8 cases) , cerebral infarction (2 cases), Wernicke's encephalopathy (1 case), skull fracture (1 case), drug-related meningitis (1 case), hepatic encephalopathy (3 cases), post-transplant lymphoproliferative disorder (1 case) and undetermined causes (4 cases).The overall mortality in the patients who developed CNS complications was 57.9% and 66.7% of them died of CNS complications.Conclusions CNS complications are not uncommon after HSCT and they have high mortality and poor prognosis.Our data suggest that haplo-HSCT,URD-HSCT and conditioning with TBI, but not the age and types of hematological diseases are the risk factors for development of CNS complications.Relapse and infections are the most common CNS complications in HSCT recipients.Early diagnosis and appropriate management are crucial to the improvement of clinical outcomes in these patients.
ABSTRACT
Objectives To establish culture system for unilineage differentiation of umbilical cord blood CD 34 + cells into granulocytes, erythrocytes or platelets. Methods After CD 34 + cells were separated by midiMACS using micro beads conjugated with anti-CD 34 monoclonal antibody, these cells were induced to specifically differentiate along granulocyte, erythrocyte or platelet by adding appropriate hematopoietic growth factors including SCF plus G-CSF, EPO or TPO. Then morphology, immunological phenotype and function analysis were performed to identify these induced cells. Results After induced unilineage differentiation, the percentages of CD 15 +, GPA + and CD 41 + cells were 81 17%, 95 35% and 77 82%, respectively. These induced cells acquired terminal cell's morphologies. The cells from the granulocytic culture had the ability to phagocytose Chinese ink and plate-like particles could aggregate under the action of thrombin. Conclusion The culture system for unilineage differentiation of CD 34 + cells into erythrocytes, granulocytes, or platelets was established, which was a basis for the research about cell treatment, gene regulation and exogenous gene expression in hemopoiesis.