ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeWe reviewed the results of transplanting allogeneic marrow from HLA-identical donors in patients with β-thalassemia. Among the 484 consecutive patients who have received transplants since 1981, survival and disease-free survival rates leveled off at ∼1 year after transplantation, at 82 and 75%, respectively.Patients and MethodsClinical characteristics of patients before transplant have been studied to determine their impact on survival, disease-free survival, and graft rejection. By multivariate analysis, portal fibrosis, hepatomegaly, and a history of inadequate chelation therapy were identified as risk factors. The patients were then divided into three classes of risk.ResultsThe rate of prolonged disease-free survival was 98% and 87% for class 1 and class 2 patients. This rate of disease-free survival is 70% with the use of our last conditioning protocol for class 3 patients. Older patients (17–32 years) have a 79% probability of prolonged diseasefree survival.ConclusionsWe conclude that for patients with thalassemia major, transplantation of bone marrow from a human leukocyte antigen-identical donor offers a high probability of disease-free survival, particularly for those patients in early stages of their disease.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeWe have reviewed the results of bone marrow transplantation in 30 patients with thalassemia major who were treated in the United States.Patients and MethodsTen patients who underwent transplantation in Seattle and 20 patients from five other U.S. centers were identified through a survey of the International Bone Marrow Transplant Registry. These transplants were performed between November 1981 and April 1992 in patients with diverse ethnic backgrounds and ranged in age from 6 months to 14 years (median 4.0 years). Twenty-seven of the 30 patients received marrow from a human leukocyte antigen (HLA)-identical sibling or other family member, one patient received HLA-matched marrow from an unrelated donor, and two patients were given haploidentical but HLA-mismatched marrow from a related donor. Cytoreductive (preparative) therapy varied among institutions and pretransplant risk categories. In general, patients were given busulfan (12–24 mg/kg) or dimethylmyleran (5 mg/kg) in combination with cyclophosphamide (120–240 mg/kg). A subset of patients were given total body irradiation (TBI) at a dose of 720 cGy followed by cyclophosphamide (120 mg/kg).ResultsSixteen of 27 patients (59%) who received marrow from an HLA-identical family member are event-free survivors, with a duration of follow-up ranging from 2 months to >10 years after transplantation. Six of these 27 patients (22%) had recurrence of thalassemia and five (19%) died. The estimated actuarial rate of thalassemia recurrence was 24% and the rate of event-free survival was 57%. Only one of the three patients who received marrow from HLA-nonidentical or unrelated donors survives event-free. Liver biopsies were not routinely performed before transplant. Thus, classification of patients into Lucarelli risk groups was not possible. A modified risk classification was devised by using liver size and iron status assessed by the regularity of chelation and the serum ferritin level. With use of this classification, there was no significant difference in event-free survival between transplant risk groups.ConclusionsThe findings observed in this small series of patients confirms that thalassemia can be cured with bone marrow transplantation. Although most patients are event-free survivors, a significant number experienced recurrence of their disease. A cooperative multicenter trial of U.S. transplant centers may be necessary to evaluate the use of marrow transplantation for thalassemia and to determine optimal treatment.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeIn Belgium and France, 42 patients underwent bone marrow transplantation (BMT) for treatment of sickle cell disease.Patients and MethodsThe patients were young and symptomatic, but without chronic organ damage. Engraftment occurred in all patients and was sustained in 36. These 36 patients became free of symptoms and had a change in electrophoresis of their hemoglobin toward the donor's pattern.ResultsIn five patients, engraftment was followed by bone marrow rejection. Two of these five patients underwent a second transplant, one at 62 days and the other at 21 months after the first transplant, and they are both doing well. The other three patients had autologous recovery of their own bone marrow. One patient died 3 months after marrow transplant of complications of graftversus-host disease (GVHD). All the other patients are alive, with follow-up ranging from 1 to 75 months.ConclusionsConcerning the long-term side effects, six patients had chronic GVHD disease. So far, eight patients returned to Africa where they are continuing to do well.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeAs of June 1992, five patients with sickle cell disease had been treated by matched sibling bone marrow transplantation in the United States.Patients and MethodsThree patients underwent transplantations for complications related to sickle cell disease, two with previous cerebrovascular accidents (CVAs) and one who had had multiple severe vasoocclusive crises. Two patients had other indications for allogeneic bone marrow transplantation: one had acute myeloid leukemia and the other had Morquio's disease. The patients' ages ranged from 3 to 10 years, and four were girls. Ages of the donors ranged from 4 to 13 years; four of the donors were boys and three carried the sickle cell trait. For four patients, the preparative regimen consisted of busulfan and cyclophosphamide given either alone or combined with antithymocyte globulin (ATG). The patient with leukemia was prepared with cyclophosphamide and total body irradiation (TBI). The regimens for prophylaxis of graft-versus-host disease (GVHD) included various combinations of cyclosporine A, methotrexate, and prednisone.ResultsThe patient with Morquio's disease failed to engraft but underwent a successful retransplantation from the same donor. All patients eventually demonstrated donor engraftment and the donor's hemoglobin electrophoretic pattern posttransplant. Two patients had moderately severe GVHD of the skin and gastrointestinal tract, which resolved with prednisone therapy. One of these patients developed transient chronic GVHD involving the skin. Other acute complications included mild venoocclusive disease of the liver, central line infection with bacteremias, uterine hemorrhage in one patient, and pseudomonas sepsis in another.ConclusionsBoth patients who underwent transplantation after CVAs have experienced subsequent neurological events. However, with a median follow-up of 16 months (range 8 months to 9.3 years), all patients are surviving in good to excellent clinical condition and appear to have benefitted from treatment by bone marrow transplantation.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Purpose: To determine who might qualify for allogeneic bone marrow transplantation (BMT), we reviewed the medical records of all 143 patients with sickle cell anemia under the age of 16 years who were registered at our center.Patients and MethodsA total of 135 records were complete and were used to estimate donor availability and disease severity. The mean number of siblings per patient was two, but this number decreased to 0.73 if half-siblings and siblings who had sickle cell anemia were excluded. Probability calculations indicated that a human leukocyte antigen (HLA)-matched sibling donor would be available for only 18% of patients with sickle cell disease.ResultsWith regard to clinical severity, if only stroke and chronic debilitating pain are considered criteria for bone marrow transplantation, only 16% of sickle cell patients would qualify, but with use of the broader criteria of the National Collaborative Study, 38% of patients would qualify. However, not all parents will consent to have bone marrow transplantation for their child, and only a minority of patients (18%) will have an HLA-matched sibling donor. Thus, as few as 1–2% of the total population of children with sickle cell anemia will ultimately qualify for marrow transplantation. Increasing the number who can undergo transplantation will require increasing the size of the donor pool.ConclusionsSearch for other therapies not based on marrow transplantation should continue. For the majority of patients with sickle cell disease, these nontransplant treatments offer the best chance for enabling patients to achieve greater longevity and a better quality of life.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeThe National Marrow Donor Program (NMDP) of the United States has nearly 650,000 unrelated potential marrow donors in its registry and >1,225 marrow transplants have been performed.Patient and MethodsIn 1991, 43% of patients who requested a search found at least one HLA-A-, -B-, -DR- identical donor in the files. The chance of finding a donor match is much better within one's own ethnic group. The individuals enrolled in the donor file are 67.0% white, 3.8% black, 3.0% Asian, 3.9% Hispanic, and 0.8% Native American. Therefore, patients who belong to ethnic minorities are at an obvious disadvantage in obtaining marrow donors. Because of this deficiency, the program has embarked on an aggressive campaign of recruitment of minority donors.ResultsReciprocal search agreements with other countries have made another 200,000 potential donors available, but it is not likely that black patients will find help by this route.ConclusionsSeveral efforts are being made to speed up the search process and to ensure more accurate definition of identities. These efforts include prospective HLA-DR typing of donors in the file, storage of a sample of frozen blood from each donor to permit class II typing (HLA-DR, -DQ) by DNA techniques, and eliminating the mixed lymphocyte culture test as a requirement for designating a given donor as HLA identical.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeThe treatment of choice for many inherited diseases is bone marrow transplantation (BMT). Limitations to using marrow transplants for inherited diseases include (a) the toxicity associated with high doses of chemotherapy necessary to obtain engraftment; (b) the complications associated with graft-versus-host disease (GVHD); (c) the fact that only 20–25% of children will have a human leukocyte antigen (HLA)-matched donor; and (d) the concern that, at least for some inherited diseases, significant organ damage, especially to the nervous system, has occurred by the time the child is diagnosed and evaluated for possible BMT. In utero transplantation of hematopoietic stem cells (HSCs) offers the possibility of overcoming many of these limitations.Patients and MethodsOne of the biggest hurdles to a successful transplant is the ability of the recipient to reject the donor marrow. Except in patients with severe combined immunodeficiency disease (SCID), overcoming this hurdle requires high doses of chemotherapy. Early in gestation, the fetus is significantly immunoincompetent. Before 14–15 weeks of gestation, the human fetus appears to be similar to a child with SCID in its inability to reject allogeneic cells. Potential sources for HSCs are HLA-matched sibling marrow, fetal liver, parental bone marrow, and cord blood.ResultsWith fetal liver, only cells from fetuses <10–12 weeks are acceptable because of the high risk of GVHD. With parental marrow, the cells must be T cell depleted in order to minimize the risk for GVHD. Problems in using fetal liver include the inability to obtain sufficient numbers of cells and inadequate supplies of donor tissue. The source and supply of parental bone marrow is almost unlimited, but, because of the need for T-cell depletion, bone marrow from a parent may have a lower engraftment rate in the child.ConclusionsStudies in fetal murine and Rhesus models using fetal liver or T cell-depleted bone marrow from adult animals suggest that engraftment can be successfully obtained, providing the transplant is performed sufficiently early in gestation. To date, at least a dozen in utero human transplants have been attempted worldwide in fetuses diagnosed with a variety of inherited diseases. Because of the small number of transplanted fetuses and the variety of diseases and differing transplant conditions, it is difficult to draw any firm conclusions regarding ultimate efficacy of the procedure and its risks. However, it does appear that the age of gestation of the recipient, the dose of cells infused, and possibly the route of administration of the HSCs will be critical factors in determining success rates for this approach. The successful application of in utero transplantation would allow treatment of a variety of inherited diseases early in gestation while eliminating many of the risks associated with conventional BMT.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

PurposeThe two major factors associated with lack of survival after allogeneic marrow transplant for severe aplastic anemia have been graft rejection and acute graft versus host disease (GVHD). As a result, survival for patients transplanted in the 1970s was ∼68%. Improved survival during the 1980s was primarily related to the decrease in the incidence of acute GVHD with the use of combination methotrexate and cyclosporine for GVHD prophylaxis. Although the incidence of graft rejection has not changed, the time to graft rejection has been delayed.Patients and MethodsOne hundred forty children <18 years of age received a marrow transplant for severe aplastic anemia at the Fred Hutchinson Cancer Research Center between May, 1971 and June, 1991. Four recipients of syngeneic marrow received a simple marrow infusion, 119 recipients of HLA-identical family member marrow received cyclophosphamide (CY), 200 mg/kg; most recipients of alternative donor marrow received CY plus 12.0 Gy fractionated total body irradiation. GVHD prophylaxis was MTX only for 91 recipients of HLA-identical family member marrow, and was MTX plus CSP for all other allogeneic marrow patients. Estimates of graft rejection, acute and chronic GVHD, survival and event-free survival (EFS) were determined by the Kaplan-Meier method.ResultsTwo recipients of syngeneic marrow achieved engraftment with donor marrow infusion only and two required immunosuppression with CY. Among the 119 recipients of HLA-identical family member marrow the type of GVHD prophylaxis did not influence graft rejection but non-transfused patients had 10% incidence of rejection compared to 22% for transfused patients (p = 0.1). All patients with late graft rejection survive whereas those with early rejection usually do not. The incidence of acute GVHD was 27% and 11% for MTX recipients and MTX plus CSP recipients, respectively (p = 0.11), and the probability of chronic GVHD was 30% and 26%, respectively. Survival is 64% for recipients of MTX and 96% for recipients of MTX plus CSP (p = 0.007), but EFS was 60% and 71%, respectively (p = 0.48). Recipients of partially matched family member or unrelated marrow donor grafts have transplants complicated by infections and GVHD. Growth and development of CY only recipients is normal and several children have been born to these former patients.ConclusionsHigh dose CY is usually an effective preparative regimen for children with severe aplastic anemia and an HLA-identical family member marrow donor. Additional immunosuppression with anti-thymocyte globulin may result in a further decrease in graft rejection and improved EFS. Identification of a group of children who are unlikely to respond to immunosuppressive treatment could permit earlier transplantation for patients without HLA-identical family member donors available. Children who receive CY only have normal growth and development.

ISSN:0192-8562    

出版商:OVID    

年代:1994

数据来源: OVID