[Severe gastrointestinal bleeding after allogeneic hematopoietic stem cell transplantation--15 case analysis].

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.

[Umbilical cord blood transplantation for patients with beta-thalassemia major].

OBJECTIVE: The beta-thalassemia major is a common hereditary hematology disease in southern China. The combination of blood transfusion and iron chelation is now the reference treatment. The allogeneic hematopoietic stem cell transplantation is the only curative therapy for beta-thalassemia major. In this study the investigators observed and evaluated the effects of umbilical cord blood transplantation (UCBT) for patients with beta-thalassemia major. METHODS: Twelve cases of beta-thalassemia major aged from 1.3 to 8.3 years (8 male and 4 female) received UCBT. Eleven of the twelve donors were siblings and one was unrelative. Eight patients received no antigen and four patients received two antigen disparate grafts. According to the Pesaro's classification for thalassemia, 10 patients were at grade I or II, and 2 were at grade III. The HLA-identical patients accepted the conditioning regimen consisting of busulfan, cyclophosphamide and antithymocyteglobulin. The HLA-mismatched patients accepted the conditioning regimen consisting of hypertransfusions, continuous iv desferrioxamine, hydroxyurea, fludarabine, busulfan, cyclophosphamide and antithymocyteglobulin. The harvest stem cells contained 3.63 - 16.0 x 10(7)/kg of nucleated cells, 0.11 - 1.03 x 10(6)/kg of CD(34)(+) cells and 0.17 - 1.18 x 10(5)/kg of colony-forming-unit-granulocyte macrophages. Cyclosporine alone or in combination with mycophenolate mofetil (MMF) was given for acute graft-versus-host disease (aGVHD) prophylaxis. RESULTS: Of the 12 patients, 10 were engrafted. Ten patients had neutrophil recovery (> 0.5 x 10(9)/L) and seven patients had platelet recovery (> 50 x 10(9)/L). The median time was 18.1 and 57.3 days, respectively. Seven patients had disease-free survival (DFS) at a median follow up of 23 months (range 4 - 63 months). Three patients had rejection and autologous hematopoitic reconstitution. Two patients were not engrafted. One patient acquired severe aplastic anemia, another patient died of severe infection. The incidences of grade I and grade II aGVHD were 60% (6/10) and 40% (4/10), respectively. There were no long-term complications in the disease free survivors. CONCLUSIONS: Grade I-II beta-thalassemia major patients receiving sibling UCBT had high DFS. UCBT is an effective way to treat beta-thalassemia major.

[Analysis of pathogenesis of pneumonia post allogeneic hematopoietic stem cell transplantation].

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.

[Application of ricin-immunotoxin mediated T cell depletion to allogeneic hematopoietic stem cell transplantation].

This study was aimed to investigate the clinical outcome of ricin-immunotoxin mediated T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation. 13 patients with hematological malignancies were treated by ricin-immunotoxin mediated T cell partially depleted allogeneic hematopoietic stem cell transplantations from HLA/MLC mismatched donors, including 6 cases of CML in CP(1), 1 case of ALL in CR(1), 1 case of ALL in CR(2), 1 case of ALL in relapse, 2 cases of AML in CR(1), 1 case of AML in CR(2), 1 case of MDS-RAEBT-AML (M(4)) in CR(1). The results showed that 8 cases were engrafted successfully, 2 cases of them developed grade II acute GVHD and 2 cases developed grade III-IV acute GVHD. Within following-up of 8 - 90 months, 2 patients who experienced grade III-IV acute GVHD died early after transplantation; 1 patient died of late onset of infection; the other 5 patients survived free from diseases. After failure at first infusion, 4 patients were given reinfusion of peripheral blood hematopoietic stem cells from the same donor. 3 out of 4 cases failed to engraft and only one patient got engraftment but died of related complications of transplantation. One patient was performed a second transplantation from a syngeneic donor and survive free of disease until now. In conclusion, T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation by ricin-immunotoxin decreases the occurrence of severe acute GVHD but with high risk of rejection, which clinical outcome still needs further evaluation.

[Allogeneic hematopoietic stem cell transplantation for acute lymphocytic leukemia].

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.

[Detection of cytomegalovirus infection by polymerase chain reaction in hematopoietic stem cell transplantation recipients].

OBJECTIVE: To evaluate the detection of cytomegalovirus (CMV) by polymerase chain reaction (PCR) for predicting the development of CMV disease. METHODS: 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. RESULTS: 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%. CONCLUSIONS: Detected by CMV-PCR, MCV viremia may predict the development of CMV disease, but MCV vireuria cannot.

[Cytomegalovirus diseases after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and related risk factors].

OBJECTIVE: To analyze the incidence of cytomegalovirus (CMV) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and related risk factors. METHODS: The clinical data of 131 patients undergoing allo-HSCT August 1999 to July 2001 were analyzed retrospectively. RESULTS: Twenty-eight of the 131 patients developed CMV interstitial pneumonia (IP) with an incidence rate of 21.35%, 9 patients developed CMV enteritis with an incidence rate of 6.87%; in total 37 of the 131 patients developed CMV disease with the accumulative one-year incidence rate of 32.54%. Thirteen patients (35.14%)died of CMV diseases. Univariate analysis showed that accumulative incidence of CMV disease was associated with unrelated donor, II-IV degrees acute graft versus host disease (aGVHD), additional immunosuppressive therapy for GVHD, chronic graft versus host disease (cGVHD), antilymphocyte globulin (ALG)/monoclonal antibody (MoAb) administration, high dose of methylprednisolone (MP), plasma viramia-PCR (PV-PCR) positivity of patients, blood transfusion and pre-emptive treatment. Multivariate analysis showed that risk factors for CMV disease included plasma CMV-DNA positivity, immense amount of blood transfused, and additional immunosuppressive therapy for aGVHD, and pre-emptive therapy capable of turning PV-PCR positive reduced the incidence of CMV disease (RR: 3.309, 1.046, 2.242, and 0.346). CONCLUSION: CMV disease has a high morbidity and mortality in allo-HSCT patients. Patients with positive plasma CMV-DNA should receive pre-emptive therapy till their plasma CMV-DNA turns to be negative, especially in condition of severe aGVHD, immense amount of blood transfused, or additional immunosuppressive therapy.

[Treatment of severe steroid-refractory graft-versus-host disease with IL-2R alpha chain (CD25) monoclonal antibody].

OBJECTIVE: To investigate the effects of IL-2R alpha chain (CD(25)) monoclonal antibody on severe steroid-refractory graft-versus-host disease (GVHD). METHODS: Seventeen patients (18 times) with severe steroid-refractory GVHD were treated with intravenous drip of humanized CD(25) monoclonal antibody on day 1, 3 or 4, 8, 15 and 22. The cumulative scoring of GVHD and status of infection were observed, and laboratory tests, including blood counting and blood biochemical test were made before and 1, 4, 8, 15, 22, 29, 36, 43 and 50 days after the treatment. RESULTS: (1) Eleven of the eighteen case-times (61.1%) got complete relief, five (27.8%) GVHD got partial relief, and two (11.1%) failed to get relief. (2) Seven case-times (33.3%) had infection. (3) Relapse of GVHD occurred in four of the eleven case-times with complete relief (36.4%). (4) No infusion-related reaction was observed. CONCLUSION: The monoclonal antibody against IL-2 receptor alpha chain (CD(25)) has a marked effect upon severe steroid-refractory GVHD.

[Exploration of acute graft versus host disease and its risk factors after allo-hematopoietic stem cell transplantation].

OBJECTIVE: To explore the incidence, prognosis and risk factors of the acute graft versus host disease (aGVHD) after allo-hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 118 cases undergone 120 times of allo-HSCT were analyzed. RESULT: 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. CONCLUSION: aGVHD is a common complication after allo-HSCT, the earlier it takes place, the poorer the prognosis.

[Middle-high dose of cyclophosphamide or conventional routine chemotherapy with increased dose of cyclophosphamide combined with G-CSF for mobilizing peripheral blood progenitor cells in patients with tumor].

OBJECTIVE: To investigate the clinical value of glycosylated G-CSF combined with middle-high dose cyclophosphamide (Cy) or conventional chemotherapy with increased dose of Cy for mobilizing peripheral blood progenitor cells in patients with tumor. METHODS: Thirty patients from four hospitals in Beijing region were enrolled in this clinical study. Diagnoses of the patients were non-Hodgkin' lymphoma (n = 21), Hodgkin disease (n = 1), breast cancer (n = 7) and ovary cancer (n = 1). Autologous peripheral blood progenitor cells (APBPC) were mobilized by middle-high dose Cy or conventional chemotherapy with increased dose of Cy combined with G-CSF. G-CSF was given subcutaneously from the nadir of the white blood cell (WBC) count to the end of PBPC collection. The dosage of G-CSF was 250 microg/d in 29 patients and 500 microg/d in 1 patient. When WBC count was > 5 x 10(9)/L, APBPC were harvested with CS 3000 plus/COBE Spectra. RESULTS: The average dosage of Cy was 3.95 g (2.3 g/m(2)). The doses of G-CSF were 3.1 approximately 6.4 microg x kg(-1) x d(-1). Thirteen patients (43%) were collected twice, 14 patients (47%) three times and 3 patients (10%) four times. All of the patients could tolerate the treatment regimens. Seven patients had bone pain after G-CSF injection and one was severe, one patient had headache and one had nausea and vomiting. CONCLUSION: 250 microg glycosylated G-CSF combined with middle-high Cy or conventional chemotherapy with increased dose of Cy combined G-CSF is an optimal method for APBPC mobilization in tumor patients.

[Unrelated cord blood transplantation for the treatment of hematological malignancies].

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Follow up Detection of AML/ETO Fushion Transcripts after Chemotherapy or Bone Marrow Transplantation in Leukemia Patients]

Expression of AML1/ETO mRNA was observed in bone marrow cells from 49 untreated leukemic patients, and continuously detected during different periods after chemotherapy (12 cases) or bone marrow transplantation (8 cases). The results showed that AML1/ETO mRNA could be expressed in cells from AML-M(2), AML-M(4) and MDS-RAEB-T patients. The positive expression changed into negative at different duration in patients who achieved complete remission either by chemotherapy (9 cases), allogeneic bone marrow transplantation (5 cases) and autologous peripheral blood stem cell transplantation (1 case), and they were sustained in complete remission status. In chemotherapeutic group, patients whose AML1/ETO expression turning from negative (2 cases) or faint positive (1 case) to positive relapsed later. Two patients treated with Allo-BMT showed continuously positive results and died of GVHD and relapse, respectively. These observations suggest that AML1/ETO chimeric mRNA could disappeared after chemotherapy or bone marrow transplantation. The patients have a great probability to relapse if the results of RT-PCR are continuously positive or change from negative to positive. Regular detection is necessary for leukemic patients.