Showing papers by "Keith M. Sullivan published in 1994"

Marrow transplant experience for children with severe aplastic anemia.

Abstract: PURPOSE The 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 approximately 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 METHODS One 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. RESULTS Two 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. CONCLUSIONS High 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.

Bone marrow transplantation for sickle cell disease. The United States experience.

Abstract: Purpose As of June 1992, five patients with sickle cell disease had been treated by matched sibling bone marrow transplantation in the United States. Patients and methods Three 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. Results The 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. Conclusions Both 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.

Bone marrow transplantation for thalassemia. The USA experience.

Abstract: Purpose We have reviewed the results of bone marrow transplantation in 30 patients with thalassemia major who were treated in the United States. Patients and methods Ten 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). Results Sixteen 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. Conclusions The 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.

Reduction in transplant-related complications in patients given intravenous immuno globulin after allogeneic marrow transplantation.

Abstract: Bone marrow transplantation renders patients immunocompetent due to the need for supralethal doses of chemoradiotherapy prior to infusion of the donor stem cells. Multiple immunological deficiencies are seen and patients are at high risk of developing a variety of infections. This period of immunological incompetence usually lasts from 6 to 12 months. In some subsets of patients [those with chronic graft-versus-host disease (GVHD); recipients of unrelated transplants; increasing patient age] persistent T and B cell abnormalities may be seen for years, despite normal serum immunoglobulin levels. This review summarizes a number of trials of intravenous immune globulin (IVIG) therapy to prevent infection following bone marrow transplantation. IVIG has shown benefit in reducing septicaemia, interstitial pneumonia, fatal cytomegalovirus (CMV) disease, acute GVHD and transplant-related mortality in adult recipients of related marrow transplants. Further investigation into dose, schedule and duration of IVIG prophylaxis needs to be conducted.

Spontaneous factor VIII inhibitor occurring in association with chronic graft‐versus‐host disease

Abstract: The development of spontaneously acquired Factor VIII inhibitors is rare and may lead to serious hemorrhagic sequelae. We report here the case of a patient who acquired a Factor VIII inhibitor two years after an allogeneic bone marrow transplant for CML. This occurred in association with a flare of chronic graft versus host disease (GVDH). He responded to corticosteroid therapy. A review of autoimmune phenomena associated with chronic GVDH and the treatment of Factor VIII inhibitors is discussed.

Complications of allogeneic bone marrow transplantation.

Abstract: Recent research has increased our understanding of the pathogenesis and prevention of the immediate and delayed complications of allogeneic bone marrow transplantation. Cytokines appear to play a major role in the pathogenesis of acute graft-versus-host disease and new therapies are being developed to modulate these effects. Risk factors for fatal venoocclusive disease of the liver such as elevated serum transaminase levels and fever prior to transplantation can be used in mathematical models to predict the outcome of venoocclusive disease. Use of total-body irradiation in pretransplantation conditioning regimens increases the risk of secondary cancers and is being used less commonly in patients with nonmalignant hematologic conditions. For patients with malignant diseases, fractionation of total-body irradiation have been shown to delay the onset and reduce the severity of radiation-induced cataracts. These and other late effects such as the development of chronic graft-versus-host disease and associated infections are major determinants of the quality of life following allogeneic marrow transplantation. Increased understanding of these complications assists the hematologist in long-term follow-up care of the marrow graft recipient.