Flow cytometric monitoring of minimal residual diseases in patients with acute leukemia after allogeneic hemapoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the significance of flow cytometric monitoring minimal residual diseases (MRD) in patients with acute leukemia (AL) after allogeneic hemapoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>From January 2007 and January 2008 MRD were detected by flow cytometry (FCM) in 402 bone marrow (BM) in 102 AL patients without leukemic gene and chromosomal changes at first diagnosis after HSCT (1, 2, 3, 6,12 months after HSCT; adding detection frequency in part of high risk patients), The relationship between the MRD results and clinical prognosis were observed. Patients with significantly higher MRD were treated and the effectiveness was monitored by FCM (MRD > 0.01% considered as positive).</p><p><b>RESULTS</b>(1) 71 cases were persistently negative for MRD after HSCT and all them were in hematologic complete remission (CR). Only 3 cases had extramedullary relapse. The disease free survival (DFS) and overall survival (OS) were 66.2% and 90.1%, respectively. (2) Of 27 MRD(+) cases 11 converted to MRD negativity after chemotherapy plus donor lymphocyte infusion (DLI), CIK, NK cells. The DFS and OS were 63.6% and 72.7%, respectively. Other 16 cases had hematologic relapse. The DFS and OS were 11.1% and 25.0%, respectively. The median time from MRD increasing to hematologic relapse was 48 days (7-69 day). (3) Four cases had hematologic relapse after HSCT and died in the end.</p><p><b>CONCLUSIONS</b>(1) The DFS and the OS in MRD(-) cases are significantly higher than those of MRD(+) cases. (2)MRD(+) patients after HSCT coveted to MRD(-) after intervention. Therapy, whose DFS and the OS are still significantly higher than those of MRD(+) cases. (3) Patients with hematologic relapse after HSCT have the worst prognosis and the DFS and OS are significantly low. FCM monitoring of MRD in patients after HSCT is a sensitive, specific, quick and simple method. It can indicate recurrent state in time, facilitates early intervention, reduces the hematologic relapse risk and improves DFS.</p>

Efficacy of allogeneic hematopoietic stem cell transplantation in treatment of childhood myelogenous leukemia: the observation of 24 cases / 中华儿科杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on childhood chronic myelogenous leukemia (CML).</p><p><b>METHOD</b>Of the 24 consecutive cases, 16 were boys and 8 were girls. The median age of patients was 12 (3 - 16) years old; 16 cases were in chronic phase (CP) of CML, 1 case in accelerated phase (AP) and 5 cases in blastic phase (BP). Allo-HSCT from HLA identical siblings were performed for 5 cases, HLA haplotype was performed for 14 cases and unrelated allo-HSCT for 5 cases. Twenty-four cases underwent allo-HSCT with conditioning regimen of BUCY. Prophylaxis of graft versus host disease (GVHD) included CsA + MTX plus MMF. The average follow-up was 36 months.</p><p><b>RESULT</b>All of patients were successfully engrafted. The 5-year overall survival (OS) of the 24 cases was 81%. Four patients died after allo-HSCT including 3 cases in BP from haploidentical donors and 1 case in CP from HLA identical sibling. The 5 cases who received unrelated allo-HSCT have been alive. Among the 10 cases who survived over 5 years, 3 had chronic GVHD.</p><p><b>CONCLUSION</b>Children with CML could be treated effectively with allo-HSCT. There were no significant differences among different donors. Transplantation to children with CML should be performed as early as possible. Preparative regimen adjustment before transplantation, the transplantation of associated comorbidities and effective prevention and treatment for CML patients after prolonged graft survival of high quality have important significance.</p>

Hemorrhagic cystitis following hematopoietic stem cell transplantation: incidence, risk factors and association with CMV reactivation and graft-versus-host disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The definite pathogenesis of hemorrhagic cystitis (HC) after allogenic hematopoietic stem cell transplantation (allo-HSCT) has not been well elucidated. The role of cytomegalovirus (CMV) reactivation and graft-versus-host disease (GVHD) in the development of HC remains obscure. This study determined the incidence and risk factors for HC after allo-HSCT and analyzed its association with CMV reactivation and GVHD.</p><p><b>METHODS</b>We retrospectively studied 250 patients at high risk for CMV disease who underwent allo-HSCT all based on busulfan/cyclophosphamide (BU/CY) myloablative regimens. The incidence, etiology, risk factors and clinical management of HC were investigated.</p><p><b>RESULTS</b>HC developed within 180 days of transplant in 72 patients, with an overall incidence of 28.8% and an incidence of 12.6% in patients with HLA-matched related donors (MRD), 34.38% in those with HLA-matched unrelated donors (MUD), 49.45% in those with mismatched related donors (MMRD). CMV-viremia significantly increased the incidence of later onset HC (LOHC); however, only 9 out of 15 patients with CMV viruria actually developed LOHC. Multiple regression analysis identified grade II - IV acute GVHD (RR = 2.75; 95% CI 1.63 +/- 4.66; P < 0.01) and grafts from MUD or MMRD (RR = 2.60; 95% CI 1.52 +/- 5.20; P < 0.01) as independent risk factors for HC. Event sequence analysis indicated a majority of HC episodes began around GVHD initiation.</p><p><b>CONCLUSIONS</b>CMV-viremia is a high risk factor for LOHC. Our data also showed a correlation between acute GVHD and HC, which suggested that alloimmunity may be involved in the pathogenesis of HC.</p>

Surveillance of cytomegalovirus for antiviral efficacy and risk factors in allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

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.

Severe gastrointestinal bleeding after allogeneic hematopoietic stem cell transplantation--15 case analysis / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the features, causes, treatments and outcomes of severe gastrointestinal (GI) bleeding after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVES</b>To study clinical characteristics and outcome of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>ABO blood group of O/A in recipient/donor pair was the only high risk factor for PRCA after major ABO-incompatible allo-HSCT.</p>

Analysis of 66 cases received hematopoietic stem cell transplantation from unrelated donors / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the outcome of hematopoietic stem cell transplantation from unrelated donors.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Analysis of risk factors for the development of acute graft-versus-host disease in 151 cases of allo-hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence and risk factors of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>The clinical data of 151 cases of allo-HSCT in 150 patients from Nov 2001 to Jan 2004 was analyzed.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>aGVHD is a common complication after HSCT, HLA mismatch and HBsAg positivity are independent risk factors for aGVHD.</p>

A novel approach to human leukocyte antigen-mismatched transplantation in patients with malignant hematological disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

Multiple factors in erythrocytic recovery following ABO-incompatible allogeneic HSCT / 中国实验血液学杂志

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.

Allogeneic hematopoietic stem cell transplantation for acute lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the results of a consecutive series of 100 ALL patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our center.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Detection of cytomegalovirus infection by polymerase chain reaction in hematopoietic stem cell transplantation recipients / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the detection of cytomegalovirus (CMV) by polymerase chain reaction (PCR) for predicting the development of CMV disease.</p><p><b>METHODS</b>One hundred and thirty one allo-HSCT patients performed in the past 2 years were analyzed retrospectively. PCR-CMV was used to monitor CMV viremia and vireuria once a week after transplantation.</p><p><b>RESULTS</b>In the dynamic detection, CMV viremia was positive for at least one chance in 89 patients, vireuria did in 99 patients. Thirty-seven patients developed CMV disease with an accumulative incidence of 32.5%. The incidence of CMV disease was 15.6% in plasma CMV-PCR negative group, 31.3% in positive once group, and 47.3% in positive over twice group. There was significant difference among the three groups (P = 0.0126). The incidence of CMV disease was 24.8% in urine CMV-PCR negative group, 43.5% in positive once group, and 33.0% in positive over twice group, being no significant difference among them (P = 0.845). On analysis, viremia could predict the development of CMV disease: the PPV (positive predictive value) is 40.5%, NPV (negative predictive value) is 84.4%, sensitivity is 75.0%, and specificity is 69.2%.</p><p><b>CONCLUSIONS</b>Detected by CMV-PCR, MCV viremia may predict the development of CMV disease, but MCV vireuria cannot.</p>

Exploration of acute graft versus host disease and its risk factors after allo-hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the incidence, prognosis and risk factors of the acute graft versus host disease (aGVHD) after allo-hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of 118 cases undergone 120 times of allo-HSCT were analyzed.</p><p><b>RESULT</b>aGVHD was observed in 63 cases (52.57%) including 17 severe cases (14.17%). The patients with aGVHD had a poor outcome, the 2-year overall survival rates were 61.40%, 64.08% and 17.65% for the non aGVHD, mild (degree I-II) and severe (degree III-IV) aGVHD groups respectively (P < 0.01). However, the relapse rates were 12.48%, 20.53% and 0% with no statistic significance. Unrelated transplantation and HLA-mismatch were the risk factors for aGVHD.</p><p><b>CONCLUSION</b>aGVHD is a common complication after allo-HSCT, the earlier it takes place, the poorer the prognosis.</p>

Unrelated cord blood transplantation for the treatment of hematological malignancies / 中华血液学杂志

<p><b>OBJECTIVES</b>To investigate the engraftment, survival and graft-versus host disease (GVHD) after transplantation of unrelated cord blood for the treatment of childhood and adult hematological malignancies.</p><p><b>METHODS</b>Seventeen patients (13 children and 4 adults) with hematological malignancies were enrolled in this study. Twelve patients were transplanted with one unit and 5 with 2 units of cord blood. There were HLA-matched in 6 and HLA-mismatched at 1 approximately 2 loci in 11 patients. Ten patients were transplanted at stable status, 7 at advanced stage of leukemia. Conditioning regimens were BU/CY for 13 and CY/TBI for 3 patients. Most patients received additional ATG at a dose of 15 approximately 20 mg x kg(-1) x d(-1) for 3 days. CsA, mycophenolate mofetil (MMF) and methylprednisolone were used for GVHD prophylaxis.</p><p><b>RESULTS</b>Fourteen patients survived more than 40 days after transplantation were evaluated for engraftment. At day 60 after UCBT, 86% and 71% of the patients showed neutrophil and platelet engraftment, respectively. The time for an absolute neutrophil count > or = 0.5 x 10(9)/L was (21.0 +/- 1.3) days and platelet > or = 20 x 10(9)/L was (39.0 +/- 10.3) days. Four patients developed grade II acute GVHD and 2 chronic GVHD. Of the 17 patients, 11 were still alive and 8 of them were in event-free status. For the 10 patients transplanted at stable status, 2 year overall survival is 90%, and event-free survival (EFS) 70%. However, for the 7 patients transplanted at advanced stage of leukemia, only 2 survived without relapse. Of the 4 adult patients, 2 had sustained engraftment and survived for 18 and 14 months, respectively.</p><p><b>CONCLUSIONS</b>HLA-matched or 1 approximately 2 loci-mismatched UCBT is a feasible procedure to cure a significant proportion of children or adults with leukemia, especially if performed in a favourable phase of disease. Two units of CBT can be used for adult patients if the cell number of one unit is not enough.</p>