Bone marrow transplantation for children with cancer

Bone marrow transplantation is a new, effective method for producing long-term disease-free survival in some cancer patients whose disease cannot be controlled by conventional treatments. The procedure is arduous and costly. The major problems which limit the usefulness of bone marrow transplantation are the effectiveness with which malignant disease can be eradicated and the control of graft-vs-host disease. As approaches to these problems are developed, it is likely that bone marrow transplantation will be more widely employed in the treatment of children with cancer. Careful followup of patients will be necessary in order to define the long-term effects of bone marrow transplantation, particularly as they are expressed in disorders of growth, development, learning, and psychosocial adaptation.     

Unrelated umbilical cord blood transplantation and unrelated bone marrow transplantation in children with hematological disease: A meta-analysis

Abstract:  UCB has been used as an alternative source of HSC. Both unrelated donor BM and UCB are available as potential options for transplantation. However, there have been limited comparisons of the outcomes of unrelated donor UCBT vs. UBMT in the unrelated setting. Our aim is to observe the therapeutic efficacy of UCBT and UBMT for treatment of pediatric hematological diseases. We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and critically appraised all relevant articles (1989.1–2008.5). Comparative studies were carried out on clinical therapeutic effect of UCBT and UBMT with research on stem cells engraftment, complications, earlier mortality, and survival rate. We performed a meta-analysis using review manager 5.0 software (RevMan, The Nordic Cochrane Center, The Cochrane Collaboration) and adopted funnel plot regression to assess the publication bias. We obtained 324 records. Seven trials totaling 1453 patients have been assessed. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of engraftment failure and earlier transplantation-related mortality were higher with UCBT because of its delay of hematological recovery [OR = 4.96, 95% CI (3.25, 7.59), p < 0.00001 and OR = 2.36, 95% CI (1.79, 3.11), p < 0.00001 respectively], but CMV infection didn't increase obviously. There was no difference in long disease-free survival rate [OR = 0.85, 95% CI (0.65, 1.01), p = 0.06] between UCBT and UBMT due to the decrease of GVHD in UCBT [OR = 0.45, 95% CI (0.34, 0.60), p < 0.0001]. Our meta-analysis confirmed that UCBT in children is also an effective way to treat children with hematological disease and has equivalent survival outcomes compared with UBMT.     

Bone marrow transplantation for treatment of leukemia in children

BMT is a well-established treatment for children with ALL in second remission, ANLL in first and second remission and children with JCML and CML. Improvements in transplantation technology and supportive care have resulted in significant increases in the percentage of long-term survivors of allogeneic marrow transplantation. Newer strategies, such as partially matched donor, unrelated matched donor, and autologous transplants, are bineg pursued to overcome the histocompatability barrier. The development of more effective antileukemic cytoreductive chemotherapy and radiation therapy regimens and better methods of preventing GVHD are areas in which further improvements are necessary. Newer methods of marrow purging, such as the use of monoclonal antibodies linked to immunotoxins, already are being tested. In addition, the recent development of molecularly cloned hematopoietic growth factors, such as CSFGM, may make it possible to improve marrow recovery and hasten return of normal immunologic function, thereby increasing the overall safety of the transplant procedure. It is hoped that these innovations eventually will increase the overall applicability of BMT and its role in the treatment of leukemia.     

Unrelated cord blood and bone marrow transplantation in pediatric leukemia

To investigate the role of cord blood as an alternative stem cell source for hematopoietic stem cell transplantation for pediatric acute leukemia, we retrospectively analyzed the outcomes of 35 unrelated cord blood transplantations (UCBT) and 56 unrelated bone marrow transplantations (UBMT) with myeloablative conditioning. The 5 year overall survival (OS) probability was 49.8% (95% confidence interval [95%CI]: 35.6–62.4%) for UBMT and 53.8% (95%CI: 34.0–70.1%) for UCBT (P = 0.92). The 5 year event‐free survival (EFS) probability was 47.3% (33.6–59.8%) for UBMT and 33.0% (15.9–51.2%) for UCBT (P = 0.38). OS and EFS were not significantly different between the groups. On multivariate analysis there was no significant difference between the groups. In conclusion, UCBT can have a role as important as that of UBMT in pediatric acute leukemia.     

Bone marrow transplantation for severe aplastic anemia in children

For young adults and children who have a bone marrow donor who is a genotypic or phenotypic sibling match, bone marrow transplantation is now the preferred treatment for severe aplastic anemia. For those who lack such a matched donor, use of matched unrelated donors and family member donors who are mismatched for a single HLA antigen have been successful and appear to be the treatment of choice. Patients lacking either of these alternatives should receive antilymphocyte globulin, either alone or combined with cyclosporine as a first step. Although the success rate of marrow transplants in our series using mismatched family donors is similar to that following treatment with antilymphocyte globulin, several caveats must be kept in mind. First, the results reported with use of alternative donors must be confirmed with study of larger numbers of patients and longer follow-up. Second, the preparative regimen given prior to bone marrow transplantation destroys the patient's residual bone marrow, whereas antilymphocyte globulin cyclosporine A and androgens do not. The sequence of immunosuppression followed by transplantation with alternative donor marrow should produce greater long-term hematopoietic improvement. Unfortunately, when marrow transplant follows one or more courses of immunosuppressive therapy, nonengraftment is then a problem because of sensitization to blood cell antigens. It should also be kept in mind that studies done in children, especially in those younger than 6 years old, show that these patients respond better to transplantation than to treatment regimens not including marrow transplantation. Therefore, for the child with severe aplastic anemia, every effort should be made to identify a suitable bone marrow donor. Finally, we need to determine the specific components of the conditioning regimen and the constitution of the donor marrow necessary for engraftment and to minimize potential long-term complications, and there should be only a tolerable degree of graft-versus-host disease. Many of the transplant-related problems that plagued us in the 1970s have still not been fully resolved, but many have shown improvement. As we enter the 1990s, increasing the pool of marrow donors for patients with severe aplastic anemia who lack an HLA-matched sibling will continue to be a top priority for research.     

Bone marrow transplantation

Summary Bone marrow transplantations have a definite role in treatment of leukemias and lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an HLA identical donor certainly provides a far superior survival than chemotherapy. Patients with Ph’ chromosome need to be transplanted in first remission if a suitable donor is available. In recurrent lymphomas the best results are chieved if the patient is transplanted in complete remission. Transplantation done using minor mismatched family donors or unrelated donors are still considered experimental and more data is needed before final recomendations can be made. Availability of supportive services is an absolute must prior to establishing transplant program. Selection of patients for transplantation should be done after carefully reviewing the indications and discussing with the family the emotional, financial and physical burden of the procedure. For selected indications in leukemias and lymphomas, BMT may be the only viable treatment option and therefore must be considered.     

Bone marrow transplantation experience for children with aplastic anemia

From May 1971 through December 1981, 81 children (22 months to 17 years of age) received allogeneic bone marrow grafts for severe aplastic anemia. All donors were HLA-identical family members. Fifty-seven of the 81 (70%) are still alive. Twenty-three untransfused patients were conditioned with cyclophosphamide, 50 mg/kg/d, for four days, and 19 (83%) have survived from 5 to 12 years. All 58 transfused patients were conditioned with cyclophosphamide, 50 mg/kg/d, for four days, 11 received additional immunosuppression, and 19 received posttransplantation donor buffy coat cells. Thirty-eight (65%) have survived from 3 to 13 years (P = .1). In a multivariate analysis, the only factor significantly associated with increased survival among patients with sustained grafts was the absence of significant graft v host disease (P less than .0001). The factors significantly related to increased rejection were low bone marrow cell dose (P less than .05) and positive relative response in mixed leukocyte culture (P less than .0001), but the addition of buffy coat cells did not significantly influence graft rejection. The development of grades II to IV acute graft v host disease was associated with random donor platelet refractoriness (P less than .05) and donor/recipient sex differences (P less than .05). Patients at highest risk for chronic graft v host disease were those patients who developed significant acute graft v host disease (P less than .01) and who received buffy coat infusions (P less than .025). All patients who were untransfused had a negative relative response and were not refractory to random donor platelets.     

非血缘脐血及骨髓移植治疗儿童血液病的meta分析

目的 观察非血缘脐血移植(UCBT)和非血缘骨髓移植(UBMT)对儿童血液病的治疗效果.方法 计算机检索Cochrane、Medline、CNKI、CBM在1999-2007年期间发表的关于儿童脐血移植和非血缘骨髓移植的研究文献.从干细胞植入、移植并发症、早期死亡、生存率等方面对比分析了UCBT和UBMT的临床疗效.采用Review Manager 4.2软件进行meta分析,发表性偏倚采用倒漏斗图(funnel plot)显示.结果 检索出292篇文献,最终纳入6个试验共668例患儿.UCBT与UBMT相比,因植入延迟使植入失败率增高、早期移植相关死亡率增加,但巨细胞病毒(CMV)感染并未明显增加,而慢性移植物抗宿主病(GVHD)减少使两者的长期生存率相似.结论 儿童UCBT和UBMT移植后的长期生存率无明显区别,目前文献表明,UCBT也是儿童血液病的有效治疗方法.     

儿童脐血移植后血型及血型抗体的转变

目的脐带血移植是治疗儿童高危白血病最有效的方法之一。脐血与患儿的血型不同可能对脐血移植有影响 ,了解脐血移植后ABO血型抗体的转变 ,对选择成分输血具有重要指导意义。方法4例白血病患儿行ABO血型不合的脐血移植 ,次要不合2例 ,4例均存在主要不合。1例同胞脐血移植 ,3例非血缘脐血移植。移植前后动态观察ABO血型及血型抗体的转变。结果4例患儿均成功植入 ,移植后受者的血清凝集素1个月左右消失 ,植入后没有出现针对受者原有血型抗原的抗体。输血过程中未发生临床溶血情况。结论供受者脐血ABO血型不合可以进行移植 ,按患儿当时的情况进行输血是安全的。     

Bone marrow transplantation in children using unrelated donors at Huddinge Hospital

Twenty-eight out of 31 children that underwent bone marrow transplantation (BMT) from unrelated donors between 1984 and 1995 received HLA-A, HLA-B and HLA-DR matched unrelated donor (MUD) marrows as defined by serologic HLA class I and genomic HLA class II typing. Compared with 28 case-matched controls transplanted with HLA identical sibling donors, MUD patients received a more intensive conditioning. Twenty-six patients (93%) engrafted while two died of septicaemia during the aplastic phase. Two patients rejected their grafts and four developed Evans syndrome. All controls engrafted without incidents of rejection or Evans syndrome. The probability of acute graft-versus-host disease (GVHD) of grade II or above was 27% after MUD-BMT and 7% in the controls. The 5-year probability of survival was 60% in MUD patients and 89% after sibling BMT ( p = 0.03). Leukaemia-free survival was 60% with one relapse in the MUD patients, and 59% with five relapses in the sibling group. Three children who received a mismatched donor marrow died, two of severe GVHD and one after graft rejection. In conclusion, today, a matched unrelated donor BMT is an acceptable alternative for many children who need a BMT but lack a suitable related donor.     

Umbilical cord blood transplantation in Chinese children with beta-thalassemia

To evaluate factors affecting outcome of sibling umbilical cord blood transplantation in Chinese children with thalassemia. The authors conducted a retrospective review of all patients undergoing such transplants in a single institution. Nine children with thalassemia major were diagnosed at a median age of 12 months. They received irregular blood transfusions and suboptimal iron chelation therapy before transplant. Sibling cord blood transplant was performed at a median of 5.5 years (range 3.5-10 years). Six donors were HLA-identical; three were one- to three-antigen mismatched. The mean number of nucleated cells infused was 6.6 x 10(7)/kg (range 3.4-12.7); the mean number of CD34+ cells infused was 3.8 x 10(5)kg (range 0.6-11.7). Seven patients had engraftment of donor cells. The median number of days to achieve a neutrophil count of > 0.5 x 10(9)/L was 19 days (range 10-25); the median number of days to achieve a platelet count of > 20 x 10(9)/L was 33 days (range 19-63). Of the six patients who received HLA-identical transplants, one developed grade 2 and two developed grade 1 acute graft-versus-host disease. Two of the three patients receiving mismatched cord blood did not achieve engraftment, and the other one engrafted but developed grade 4 acute graft-versus-host disease. Two patients subsequently developed secondary graft rejection and had autologous marrow regeneration before day 60 posttransplantation. With a median follow-up of 49 months (range 38-64), eight patients survived but only four were transfusion-independent. Umbilical cord blood transplant appears to have a higher chance of nonengraftment and secondary rejection. A more intensive immunosuppressive conditioning regimen may be required.     

儿童脐血移植后的巨细胞病毒感染

脐带血移植(cord blood transplantation,CBT)是治疗儿童高危白血病的有效方法之一,脐血移植由于造血植入延迟,免疫重建慢,各种感染的机会增加,影响了长期生存率。巨细胞病毒(cytomegalovirus,CMV)感染是异基因干细胞移植严重的合并症之一,CMV活动性感染常常可以致命,导致移植失败;CMV的预防、早期诊断及时治疗,是降低移植患者死亡的关键。我们采用PCR技术对6例脐血移植患者的血液进行了检测,旨在了解脐血移植患者CMV感染情况。     

Bone marrow transplantation in DiGeorge syndrome

A Hispanic infant girl with DiGeorge syndrome underwent successful bone marrow transplantation (BMT) at age 28 1/2 weeks. She had typical facies, a cardiac defect, hypoparathyroidism, severe T and B cell immunodeficiency, and low levels of facteur thymique serique (FTS). In vitro incubation of the peripheral blood lymphocytes with thymosin alpha 1 showed no increase in the number of T cells on two occasions. A fetal thymus for transplantation was not available, and further review of past experience with thymic cells or factors revealed inconsistent and incomplete responses. Because of the patient's worsening clinical and immunologic status, BMT was performed, with her histocompatible brother as donor. The patient has had a good clinical and immunologic response to BMT, with evidence of T cell engraftment, improved B cell function, and increased levels of serum FTS. This experience indicates that minimal thymic influence is necessary for successful BMT and that patients with DiGeorge syndrome with significant T cell deficiency may benefit from this treatment.     

Bone marrow features in children with HIV infection and peripheral blood cytopenias

HIV infection is associated with numerous abnormalities affecting both the myeloid and lymphoid lineages. We studied the features associated with peripheral cytopenias as the first sign of HIV infection in children. Peripheral blood (PB) counts, PB and bone marrow (BM) lymphocyte subsets, as well as viral load and serum levels of ferritin, vitamin B12, and folic acid were determined. Five children were naive of treatment (Group 1) and three were under HAART (Group 2). In Group 1 all patients had anemia of chronic disease. One had a bone marrow culture positive for Mycobacterium avium intracellulare and pancytopenia. Besides this, neutropenia and thrombocytopenia were seen in one patient each. In Group 2 anemia was found in all, neutropenia in one, and thrombocytopenia in two patients. Peripheral blood cytopenias were due to HAART toxicity in one patient. In the other two they were due to iron or folate deficiency. Bone marrow cytology showed cell abnormalities mainly in granulocytic precursors and megakaryocytes. All except two (taking HAART) patients had a high viral load. There was a straight correlation between viral load in PB and bone marrow. Viral load was correlated with peripheral CD4 but not with CD8 lymphocytes. A decrease in bone marrow B lymphocytes was seen in all patients. The introduction of HAART improved peripheral cytopenias. Bone marrow examination was useful for determining the etiology of the cytopenias and for detection of opportunistic infection. Hemopoietic cell abnormalities were similar to those seen in adults and indicative of HIV infection.