骨髓移植早期感染的综合防治

对12例骨髓移植患者采用层流室隔离、无菌护理、肠道净化、移植激活骨髓并联用IL-2和G-CSF等防治感染措施。结果表明：层流室空气细菌数接近零，但要完全消除体表细菌特别是鼻咽部G＋菌十分困难。白细胞下降时间延迟，粒缺期明显缩短。仍发生3例早期和2例可疑的感染，多为呼吸道G＋菌感染，但程度轻，预后好。光霉菌、病毒感染。综合防治骨髓移植早期感染效果满意。     

Cytomegalovirus and marrow function

Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. A proportion of patients with CMV infection also experience neutropenia. To investigate the possible role of CMV in the suppression of hematopoiesis, we have examined the effect of CMV on the growth of isolated myeloid progenitors and on the production of myeloid cells in the longterm bone marrow culture (LTMC) system. In these studies, various isolates of CMV were added either directly to cultures of progenitors or to LTMC established from normal CMV-seronegative donors. In the first system, myelosuppression is manifested by a reduction in the number of colonies that grow. In the second system, myelosuppression is manifested by a reduction in the number of myeloid cells produced and released into the culture supernatant. Analysis of the data observed indicated that myelosuppression could in some cases be attributed to direct infection of myeloid progenitors. In other cases stromal cells were infected. In the latter cases, myelosuppression was then caused by an alteration in cytokines produced by the stromal cells. These observations made in vitro raise the possibility that comparable mechanisms may be responsible for the myelosuppression observed with CMV infection in vivo. To pursue this possibility we proposed to detect the CMV genome in defined subpopulations of marrow cells isolated from infected patients. Given the technical restrictions imposed by the small sample size available from patient marrow aspirations, our initial attempts to develop on appropriate technique involved isolation of cells from CMV-seropositive normal bone marrow donors. Using the polymerase chain reaction we were able to amplify CMV DNA contained within marrow cells of some healthy CMV-seropositive marrow donors.This work was supported in part by grants CA18221, CA 47748, DK 34431, and HL36444 from the National Institutes of Health, Department of Human and Health Services, USA. D. Stachel was supported by the Dr. von Haunersches Kinderspital, Munich, Federal Republic of Germany     

C-反应蛋白在骨髓移植后并发症早期诊断及疗效评估中的应用价值

目的探讨C-反应蛋白(CRP)在骨髓移植后患者临床并发症诊断及疗效评估中的价值。方法选取北京大学人民医院血液病研究所2004—2005年骨髓移植后出现不同并发症的患者66例,在不同时间点进行CRP定量检测,分析不同CRP值与所对应的并发症的关系。结果骨髓移植后不同并发症患者中,其CRP是否升高及升高程度明显不同,在细菌感染、合并细菌感染的混合感染、超急性移植物抗宿主病(GVHD)及抗胸腺细胞球蛋白(ATG)反应中可出现CRP明显升高,细菌感染、真菌感染、细菌合并病毒感染、急慢性GVHD等并发症均可出现CRP轻度升高,而单纯病毒感染CRP不升高。在细菌感染临床症状最明显时,CRP可达最高;治疗有效者CRP逐渐降低;CRP恢复正常后又出现增高者,临床上出现新并发症。结论CRP在骨髓移植后患者并发症的早期鉴别诊断及治疗效果的评估中有一定的应用价值。     

Cytogenetic studies in bone marrow transplant recipients

Summary Chromosome studies were performed in 24 patients who underwent allogeneic bone marrow transplantation (BMT) for severe aplastic anaemia (8), chronic myeloid leukemia (5 in chronic, 2 in accelerated phase and 1 in lymphoid blast crisis), acute myeloid leukemia (6), acute lymphoblastic leukemia in relapse (1) and Hodgkin's disease (1). Donor-cell type engraftment was demonstrated in 21 patients: in all 17 sex-mismatched transplants and — as demonstrated by reconstitution with Ph-negative cell populations — in 4 CML patients with a sex-matched donor. Recipient-type mitoses were seen in the bone marrow of 5 cases (1 SAA, 3 CML, 1 AML) after transplantation. They were only observed on one occasion in patients with SAA (4 of 25 on day 33) and AML (44 of 50 on day 14). Despite the continued demonstration of some Ph-positive mitoses in 3 patients with CML up to day 28, 323 and 451 after BMT, respectively, all surviving CML patients are still in complete haematological and clinical remission. So far the significance of these cytogenetically abnormal persisting host cells remains unknown. Present address: Roswell Park Memorial Institute, Department of Genetics and Endocrinology, 666 Elm Street, Buffalo, NY 14 222, USA     

Hypereosinophilic syndrome with multiple organ dysfunction treated by allogeneic bone marrow transplantation

A 26-year-old man with hypereosinophilic syndrome who had initial neurologic, cardiac, and pulmonary dysfunction, high eosinophil count, thrombocytopenia, and bone marrow fibrosis had only a transient response to conventional treatment with corticosteroids and hydroxyurea. He therefore received human lymphocyte antigen-identical allogeneic bone marrow transplantation (BMT) after conditioning with cytoxan and fractionated total body irradiation. Hematologic recovery was prompt, with normalization of blood counts and bone marrow. The patient died less than 3 months after transplantation from diffuse cytomegalovirus infection. Potential interest of BMT in patients with resistant hypereosinophilic syndrome and features of poor prognosis is discussed.     

Allogeneic bone marrow transplantation for severe aplastic anaemia-the London experience

Using the Seattle protocol with minor modifications, 23 patients with severe aplastic anaemia received allogeneic bone marrow transplants from HLA/ mixed leucocyte culture matched sibs in three London centres between 1973 and 1977. Ten patients (43.5%) are alive 6 months to 5 years after transplantation, and are well with full haemopoietic reconstitution, two with autologous bone marrow recovery following the graft procedure. A failure of the marrow graft to take, or take followed by rejection occurred in 12 patients (52%). Failure of marrow recovery was associated with a high early mortality from bacterial or fungal infection. The only survivors amongst those who rejected the first graft were four patients in whom a subsequent graft from the same donor was successful, and two in whom autologous recovery occurred. Graft versus host disease (GVHD) occurred in seven patients, and was fatal in one case. The most frequent complication after successful engraftment was varicella-zoster infection which occurred in five patients and was fatal in one patient. The overall results compare favourably with those from other transplant centres, but the high rate of graft rejection and low incidence of GVHD differ from other series. The results should encourage further referral of patients with severe AA for bone marrow transplantation.     

Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia

Summary The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneicn=271, autologousn=27, syngeneicn=5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.     

Antigen-independent reactivation of anti-E, years after allogeneic bone marrow transplantation: a case report

Summary. Nine years after allogeneic bone marrow transplantation a strong anti-E was observed in a patient transplanted with bone marrow from his HLA-identical brother. This IgG anti-E, with a titre of 4000, was detected together with autoantibodies to red blood cells and platelets and was not induced by transfusion with E⁺ cells. The hypothesis is proposed that the anti-E represents either antigen-independent desuppression of the donor immune system sensitized at the time of bone marrow transplantation by E antigens in the recipient, or antigen-independent memory B-cell activation by Epstein-Barr virus infection.     

Prevention and treatment of CMV infection after allogeneic bone marrow transplant

CMV infection is the major infectious complication following bone marrow transplantation. It is most often related to reactivation of latent infection in patients who were CMV seropositive before BMT. The incidence and severity have recently been modified by the use of preventive and curative treatments. Prevention of CMV infection with the transfusion of seronegative blood products is useful only when donor and recipient are seronegative. High-dose acyclovir has been shown effective in one randomized study. A multicenter study is currently being performed in Europe to confirm this result. Intravenous gammaglobulins seemed to lower the number of patients who incur interstitial pneumonitis but not the incidence of viremia. They also decreased the incidence of gram-negative sepsis and severe GVH and improved survival. The treatment is based on the use of gancyclovir. Several studies show that gancyclovir is more effective in asymptomatic patients with viral isolation from blood or bronchoalveolar lavage. The addition to gancyclovir of high-dose gammaglobulin improves survival in symptomatic patients with interstitial pneumonitis. This progress in the prevention and treatment of CMV infection has improved the overall results of allogeneic bone marrow transplantation.     

Changes in serum erythropoietin levels during allogeneic bone marrow transplantation

Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.     

Influence of human cytomegalovirus on immune reconstitution after bone marrow transplantation

HCMV infection diagnosed by the highly sensitive polymerase chain reaction (PCR) technology in blood, urine and skin biopsies of patients after bone marrow transplantation (BMT) correlated with the reconstitution of peripheral blood lymphocytes and dermal immunohistological alterations to evaluate the interaction of viral infection with the recovery of the immune system, as well as with the induction or aggravation of graftversus-host disease (GVHD). In a prospective study 73% of 63 patients showed viremia at a median time of 25 days after BMT. Only 44% of these cases that also presented with a higher frequency of acute GVHD symptoms developed HCMB disease later on. In the skin, similar immunohistological alternations, as well as frequent primary local HCMV infection before the development of cutaneous signs of GVHD, was found, suggesting the direct involvement of anti-HCMV immune responses in the induction of GVHD-associated organ lesions.     

Y-body study in bone marrow precursors, peripheral blood cells and alveolar macrophages for demonstration of haemopoietic engraftment in allogeneic bone marrow transplantation

The value of Y-body study for assessment of haemopoietic engraftment was analyzed in 50 consecutive patients submitted to allogeneic bone marrow transplantation (BMT) (sex-matched in 28 cases, sex-mismatched in 22). The study was performed weekly on bone marrow and peripheral blood smears in all cases, and alveolar macrophages were also studied in 15 patients in whom bronchoalveolar lavage was carried out because of concurrent respiratory disturbances. The analysis was performed blindly by 2 independent observers. In both sex-matched and sex-mismatched cases there was an absolute concordance between recipient and donor Y-body results, as well as with the simultaneous cytogenetic study. The engraftment of erythroid and granulopoietic lines was documented at day +14 in all cases of sex-mismatched BMT, whereas megakaryocyte and lymphocyte take was demonstrated at d +21. On the other hand, the results from alveolar macrophages were in accordance with those obtained in the simultaneous study of bone marrow precursors after BMT. The above results indicate that Y-body analysis is a simple and useful tool for the demonstration of bone marrow take in sex-mismatched BMT.     

Unrelated volunteer bone marrow transplantation: initial experience at St Vincent's Hospital, Sydney

Background: Only 30% of patients with leukaemia have an HLA-compatible family member able to act as a marrow donor. The recent development of volunteer bone marrow donor registries has supplied HLA-matched donors for a number of such individuals. Aims: To define the problem and outcome of the first cohort of patients given HLA-matched unrelated volunteer bone marrow transplants at St Vincent's Hospital, Sydney. Methods: Post transplant outcome of patients with advanced leukaemia given HLA-identical unrelated donor marrow transplants was compared to that of patients transplanted concurrently from HLA-identical sibling donors, in terms of survival, leukaemia-free survival, incidence and severity of acute graft-versus-host disease (GVHD), duration of neutropenia, incidence of infection and duration of transplant hospitalisation. Results: Sixteen patients with advanced leukaemia and without a histocompatible family member donor received unrelated donor bone marrow transplants. Actuarial survival at two years post transplant was 30%. Actuarial survival of 23 recipients of HLA-identical sibling bone marrow transplants with advanced leukaemia transplanted during the same time period was 17% (not significant). Actuarial disease free survival at two years was 30% and 13% respectively. Three of five long term survivors of the unrelated transplants had chronic myeloid leukaemia in blastic transformation at the time of transplant; thus blastic transformation should not preclude consideration of unrelated marrow transplantation. Recipients of unrelated allografts had a higher incidence of acute GVHD which occurred earlier and with greater severity than in recipients of sibling allografts, a longer duration of post transplant neutropenia (24 days to reach 0.5 × 10⁹/L versus 19.5, p= 0.07), a higher frequency of infection in the first 100 days post transplant (p= 0.0004) and a longer duration of transplant hospitalisation (p= 0.04). Transplant-related complications were the commonest cause of death in the unrelated donor recipients, while leukaemic recurrence was the commonest single cause of death in the HLA-identical sibling recipients. Improvements are needed in prophylaxis of infection and in prevention and treatment of acute GVHD in recipients of unrelated donor transplants. Nevertheless, this modality provides curative treatment for patients with otherwise incurable haematological malignancies and should no longer be considered experimental. (Aust NZ J Med 1993; 23: 450–457.)     

Bone marrow transplantation in a patient with myelodysplasia associated with diffuse eosinophilic fasciitis

A 34-year-old man with diffuse eosinophilic fasciitis and a hypocellular myelodysplastic syndrome underwent marrow transplantation from an HLA-identical brother. Prompt hematopoietic reconstitution was observed, strongly suggesting that the marrow hypocellularity was caused by neither a serum inhibitory factor nor a microenvironmental disorder. The patient died of disseminated cytomegalovirus infection too early to evaluate the impact of hematopoietic reconstitution on the eosinophilic fasciitis. Nevertheless, marrow transplantation may offer a therapeutic option for those patients with this disorder who develop severe hematopoietic dysfunction and who have a suitable marrow donor.     

Purification of Placenta-Eluted Gamma Globulins and Their Strong Effect against Graft-versus-Host Reactions In Vitro and In Vivo

A retrospective study was performed to determine the prevalence of Helicobacter pylori (H pylori) infection, the effect of H pylori eradication on platelet counts, and the characteristic clinical features of chronic immune or idiopathic thrombocytopenic purpura (ITP) with H pylori infection. H pylori infection was found in 300 patients, a group that was significantly older (P < .005) and had more cases of hyperplastic megakaryocytes in the bone marrow (P = .01) than patients without H pylori infection. H pylori eradication therapy was performed in 207 H pylori-positive ITP cases, and the platelet count response was observed in 63% of the successful eradication group and in 33% of the unsuccessful eradication group (P < .005). In the successful group, the complete remission and partial remission rates were 23% and 42%, respectively, 12 months after eradication. In the majority of responders, the platelet count response occurred 1 month after eradication therapy, and the increased platelet count continued without ITP treatment for more than 12 months. H pylori eradication therapy was effective even in refractory cases, which were unresponsive to splenectomy. In conclusion, H pylori infection was involved in most ITP patients older than 40 years in Japan, and eradication therapy should be the first line of treatment in H pylori-positive ITP patients.     

A novel BMT technique for treatment of various currently intractable diseases

A recently-developed BMT method combines a "Perfusion Method" (PM) for collecting bone marrow cells (BMCs) with the Intra-Bone Marrow (IBM) injection of BMCs (IBM-BMT). As distinct from the conventional aspiration method (AM), the PM allows rapid (within 1?h) collection of BMCs without T cell contamination (T cells?相似文献   

Prevention of primary transfusion-associated cytomegalovirus infection in bone marrow transplant recipients by the removal of white cells from blood components with high-affinity filters

Summary. A prospective study was carried out to determine whether use of cytomegalovirus (CMV) unscreened red blood cells and platelet concentrates, white blood cell (WBC) depleted with high-efficiency filters, would prevent transfusion-associated (TA) CMV infection in CMV seronegative bone marrow transplant recipients. Blood components were filtered in the bloodcentre under quality control and after filtration residual WBC counts were always below 5 × 10⁶ cells/U. Since 1990, 23 consecutive allogeneic and 37 autologous CMV seronegative marrow transplant recipients, have been transfused with filtered blood components and followed for 6 months for evidence of CMV infection by monitoring culture and CMV serology. None of the patients showed clinical symptoms of CMV infection, and CMV cultures during episodes of fever were always negative. IgM anti-CMV antibodies were negative during the study in all patients. Low titres of IgG anti-CMV antibodies (5-12 relative ELISA units) were found in 24/60 patients during the first month after bone marrow transplantation (BMT), probably due to passive transfer of IgG administered with the platelet transfusions. 3 and 6 months after BMT, 56 and 48 patients respectively were still alive; and CMV serology was negative in all patients. The results show that TA-CMV infection is preventable by filtration of blood through high-efficiency filters in patients undergoing autologous and allogeneic BMT.     

Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases

Abstract: Toxoplasma infection following bone marrow transplantation (BMT) is infrequently reported. We report 9 cases of disseminated Toxoplasma gondii infection in BMT recipients documented during an 11‐year period at our institution. The incidence of T. gondii infection in our institution (1.14 per 100 allogeneic BMT) is higher than previously reported. The most frequently affected sites were the brain, lungs, and heart. Findings common to most patients who developed toxoplasmosis were positive pre‐transplant serology, allogeneic transplant and graft‐versus‐host disease and its treatment, as well as BMT from matched unrelated donors. All 9 patients died and 8 were diagnosed only after autopsy. Heightened awareness of the occurrence of toxoplasmosis in marrow recipients, especially in highly endemic areas, and early diagnosis and therapy are needed for a better outcome.     

Successful second allogeneic bone marrow transplantation in a relapsed acute myeloid leukemia patient with fungal liver abscess

Summary Disseminated fungal infection not infrequently complicates the course of allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised patients, and the prognosis of BMT patients who develop systemic fungal infection is very poor. We describe a patient who developed disseminatedCandida albicans infection with liver abscess after the first allo BMT for acute myelogenous leukemia (FAB M2). The infection was successfully eradicated by the administration of miconazole and amphotericin B. However, 1 year after the first allo BMT, the patient suffered a relapse of acute myelogenous leukemia with fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by recombinant human granulocyte colony-stimulating factor (rhG-CSF), was successfully performed and the fungal liver abscess resolved with a combination therapy of fluconazole and amphotericin B. The patient is alive and free of both leukemia and fungal disease more than 37 months after the first allo BMT and 25 months after the second allo BMT.     

自体混合HLA半相合异基因骨髓移植后的移植物抗宿主病

作者在动物实验的基础上,成功地用自体骨髓混合HLA半相合异基因骨髓移植治疗了16例恶性血液病患者。本文报告这些患者混合移植后GVHD的发生情况及其对疗效的影响。结果证实移植过程是安全的,16例中无1例发生aGVHD。但在ABMT后2h内输入异基因骨髓的8例皆有不同程度的cGVHD,主要表现在皮肤、粘膜炎,全血细胞减少,肝功异常,发热、体重减轻及易感冒等,中位随访13.5个月无1例复发,除2例在移植后3和8月分别因爆发肝炎和急性阑尾炎穿孔死亡外,余6例皆存活,最长1例已无病存活19月余,其中供受者性别不同的6例移植后性染色体观察3例皆形成嵌合体,最长者12月余。而ABMT移植后6h输异基因骨髓的8例,未观察到急慢性GVHD,其中5例4～7月后复发,仅1例仍持续缓解,其中5例染色体检查未形成嵌合体,提示ABMT后2h内输入异基因骨髓的混合移植,可诱发早发的cGVHD,部分受体内可形成嵌合体,减少白血病的复发,并发症较少而较轻,可望成为恶性血液病治疗的新的更有效的途径。