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Biomedical subjects

E D Thomas

Publications and source records attributed to E D Thomas.

At least 91 records · Page 5Linked to original sources
PubMed1989

Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy.

Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.

Adult↗
PubMed1989

Analysis of prognostic factors for the outcome of marrow transplantation or further chemotherapy for patients with acute nonlymphocytic leukemia in first remission.

To test whether variables at diagnosis can identify patients with acute nonlymphoblastic leukemia (ANL) for whom bone marrow transplantation (BMT) is more likely to be of benefit and those for whom continued chemotherapy is a better approach, the association of 15 clinical and laboratory factors with outcome was investigated among 220 patients (ages 1 to 53 years) treated with cyclophosphamide and total body irradiation (TBI) followed by allogeneic BMT, and among 392 patients (ages 13 to 50) administered intensive chemotherapy. In the BMT group, female sex, younger age, the absence of hepatitis during induction, a larger percentage of circulating blasts, and a shorter duration of symptoms were associated with longer survival, whereas only female sex and younger age favorably influenced disease-free survival (DFS). In the chemotherapy group, younger age, lower WBC at diagnosis, a single successful induction course, and the absence of circulating promyelocytes were associated with longer survival, whereas only a lower WBC and a lower percentage of peripheral neutrophils were associated with longer DFS. Estimated regression coefficients for treatment-by-prognostic-factor interactions were used to characterize subgroups of patients in which one treatment or the other produced better outcomes. BMT and chemotherapy produced similar durations of survival in a subset of patients characterized by many or all of the following: older age, male sex, achievement of complete remission (CR) after one induction, and absence of circulating blast cells at presentation. These data suggest that, using pretreatment variables, subgroups of patients can be identified for whom either BMT or continued chemotherapy is most likely to be beneficial.

Adolescent↗
PubMed1989

Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma.

Ninety-five patients transplanted for malignant lymphoma were retrospectively evaluated for regimen-related toxicity (RRT) and early posttransplant survival. Nineteen patients developed life-threatening (grade 3) or fatal (grade 4) RRT in one or more organs. Grade 3 or 4 RRT was more common in patients with advanced disease versus those transplanted earlier in their course (P = .008), and was more common in patients with advanced disease conditioned with cytarabine (Ara-C)/total body irradiation (TBI) versus those prepared with cyclophosphamide (CY)/TBI (P = .033). There was no significant difference in the incidence of grade 3 or 4 toxicity in autologous, histocompatibility locus antigen (HLA)-identical, or HLA-mismatched marrow recipients. Grade 3 or 4 RRT tended to be more common and 100-day survival worse in patients with a Karnofsky performance status of less than 90 (P = .063 and .0002, respectively). Patients receiving 20 Gy or more of mediastinal irradiation before coming to transplant had more idiopathic or cytomegalovirus (CMV) interstitial pneumonitis than those who received less than 20 Gy (30% v 9%, P = .027). The probability of survival decreased with the number of organs in which toxicity was observed (P = .0001). Severe or fatal toxicities directly related to the preparative regimen are a significant problem in the treatment of patients with advanced malignant lymphoma and can be reduced by carrying out transplantation earlier in the course of the disease.

Actuarial Analysis↗
PubMed1989

Allogeneic marrow transplantation: the Seattle experience.

Allogeneic marrow transplantation from a normal donor provides potential life-saving therapy for a variety of inherited and acquired diseases of the hematopoietic system. Donor selection is a major issue, and most marrow transplants have been done only when an HLA-identical sibling donor has been available. Successful transplants can be done from partially HLA-matched relatives, but graft failure, graft rejection, and GvHD become increasingly serious complications as the number of HLA incompatibilities increase. More recently it has been shown that marrow transplants from HLA-identical unrelated donors can be successful. The recent development of a National Marrow Donor Program to recruit large numbers of HLA-typed volunteers and to facilitate the unrelated donor search process promises to make marrow transplants available to a growing number of patients.

Bone Marrow Transplantation↗
PubMed1989

Engraftment and transfusion requirements after allogeneic marrow transplantation for patients with acute non-lymphocytic leukemia in first complete remission.

This retrospective study analysed factors affecting engraftment and transfusion requirements of platelets and red blood cells in 303 patients transplanted for acute non-lymphocytic leukemia in first remission from HLA-identical or one-antigen mismatched donors. Multivariant analysis showed that the most important factors affecting the speed of engraftment were drugs used for graft-versus-host disease (GVHD) prophylaxis, the development of acute GVHD and HLA matching. Factors affecting only granulocyte recovery included patient age and sex. The radiation regimen used for preparing patients affected the time to platelet independence. Patients transplanted in laminar airflow rooms took longer to achieve red cell independence and required more units of red cells and platelets than patients transplanted in regular rooms. In addition, ABO incompatibility affected red cell transfusion requirements while GVHD prophylaxis and acute GVHD influenced both red blood cells and platelet support.

Adult↗
PubMed1988

Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation.

Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.

Acyclovir↗
PubMed1988

Clonal expansion after bone marrow transplantation in a patient with chronic myelogenous leukemia.

A patient with chronic myelogenous leukemia (CML) having the standard [t(9;22), Ph] translocation is presented where the Philadelphia (Ph) chromosome disappeared following bone marrow transplantation (BMT). The Ph chromosome reappeared in host cells after one year of stable hematologic remission. Three additional cell lines, all possessing the Ph chromosome with other abnormalities were consistently present in her marrow cells. Two years after BMT, ninety percent of her dividing bone marrow cells had become leukemic. The patient's clinical status remains unchanged, despite complex cytogenetic findings. The high incidence of multiple aberrant leukemic clones present in this case remains intriguing. Possible mechanisms for this unique transformation after BMT are discussed.

Adult↗
PubMed1988

Single dose or fractionated total body irradiation and autologous marrow transplantation in dogs: effects of exposure rate, fraction size, and fractionation interval on acute and delayed toxicity.

Dogs were given single dose or fractionated total body irradiation (TBI) and autologous marrow grafts to prevent death from myelosuppression. Acute and delayed non-marrow toxicities were compared. Fifty-six dogs were given single dose TBI at 2.1 (n = 13), 5 (n = 12), 10 (n = 15), or 20 (n = 16) cGy/min. Acute radiation toxicity and mortality was related to the exposure rate; radiation doses resulting in 50% mortality at 7 days (LD 50/7) at 2.1, 5, 10 and 20 cGy/min were 1,692, 1,499, 1,261, and 1,056 cGy respectively. Fifty-three dogs were given fractionated TBI, 200 cGy three times a day with 6-hour intervals at 2.1 (n = 13), 5 (n = 9), 10 (n = 13), or 20 (n = 18) cGy/min. The LD 50/7 at the four exposure rates were 1,628, 1,470, 1,184, and 1,320 respectively. Thus, for exposure rates of 2.1, 5, and 10 cGy/min, the tolerated doses were comparable for single dose and fractionated TBI. At 20 cGy/min dose fractionation appeared to offer some advantage, although this fractionation effect in part may have been due to random variation with small numbers of dog treated. Following recovery from the immediate TBI-related toxicity, eight dogs given single dose and four dogs given fractionated TBI died, generally from infections, 8-30 days following transplantation. There was a striking difference in regards to long-term survival dependent upon the TBI regimen. Among dogs given greater than or equal to 1,000 cGy of TBI and alive 30 days after transplant only 1 of 18 given single dose TBI became a long-term survivor compared to 19 of 22 given fractionated TBI. Causes of death included pancreatic fibrosis, malnutrition, hepatic failure, and a generalized wasting syndrome. All 5 dogs given a single dose of 800 cGy (at 20 cGy/min) became long-term survivors. Fourteen dogs were given increments of 150 cGy at 7 cGy/min every 3 hours for total doses of 1,500-2,400 cGy. The LD 50/7 was approximately 1,900 cGy. All 6 dogs alive at 30 days became healthy long-term survivors. Four dogs were given increments of 600 cGy at 2.1 cGy/min every 48 hours for a total dose of 1,800 cGy. All 4 dogs became long-term survivors. In conclusion, exposure rate and total dose are the most important parameters for acute toxicity associated with TBI. The effect of dose fractionation is minimal at low exposure rates and appears to be dependent also upon increment size and fractionation interval.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies.

A dose-escalation trial was carried out to determine the efficacy and safety of using an IgG2a anti-CD3 monoclonal antibody to treat acute graft-v-host disease (GVHD) in marrow transplant recipients. Two patients received the antibody as the initial treatment of GVHD, and 22 patients received the antibody after failure of initial treatment with corticosteroids, cyclosporine, antithymocyte globulin (ATG), or combined ATG and cyclosporine. Antibody was administered at four dose levels, beginning at approximately 0.015 mg/kg/d and increasing by threefold increments. The initial doses of antibody were nearly always associated with fever and chills, and treatment had to be discontinued in one patient because of intolerable side effects. Improvement in skin disease could be reliably achieved at a dose of 0.15 mg/kg/d, but threefold higher doses appeared to be necessary for improvement in the liver or gut. In no case was there complete resolution of all manifestations of disease, and all patients surviving after antibody treatment required additional immunosuppressive treatment. Four patients developed Epstein-Barr virus (EBV)-associated lymphoproliferative disorders within seven to 18 days after starting antibody therapy. The overall risk of this complication in patients not given anti-CD3 monoclonal antibody is less than 1%. Anti-CD3 antibody represents an effective immunosuppressive agent for treatment of acute GVHD, but this treatment is associated with a substantial risk of EBV-associated lymphoproliferative disorders.

Acute Disease↗
PubMed1988

Interactions of 57Co, 85Sr and 137Cs with peat under acidic precipitation conditions.

Following the burial of low-level wastes in nuclear waste repositories, the interactions of radionuclides with surrounding soil infiltrated by acid precipitation could cause radionuclide migration and transport into nearby wells. To evaluate this migration through organically rich soil in the unsaturated zone, we measured sorption and desorption distribution ratios (Rd) of 57Co, 85Sr and 137Cs onto peat at pH 4. Peat samples rich in organic C showed relatively higher sorption Rd values for 57Co and 85Sr compared to soil samples with less organic C. The sorption and desorption Rd values for these radionuclides are similar, indicating the reversibility of the sorption process. The measurements suggest the importance of organic complexes for the retention of these radionuclides at the pH range (pH 4), where hydrolysis of the metals is not important and sorption is expected to be low. Cesium-137, on the other hand, appears to be associated more strongly with inorganic components of the soil samples, with its Rd value significantly higher in the peat material containing less organic C. The 137Cs desorption Rd on the same peat sample is also comparable to the sorption Rd indicating equilibrium. Both the organic and inorganic components of peat are thus able to retard the migration of radionuclides which may be found in nuclear waste repositories. The design of such a repository may be improved using a peat barrier to restrict radionuclide migration.

Cesium Radioisotopes↗
PubMed1988

The use of ranitidine in bone marrow transplantation. A review of 223 cases.

To determine the incidence of ranitidine-induced myelosuppression in the bone marrow transplant setting, we reviewed the records of all patients at our institution (223) who received ranitidine while undergoing bone marrow transplantation. We identified 37 cases in which a myelosuppressive episode was temporally associated with ranitidine use. In-depth analysis of the 37 cases showed 12 in which no alternative cause could be found and in which strong evidence for a ranitidine effect existed. Three of these cases are included herein as case reports. Based on this series, the overall incidence of ranitidine-induced myelosuppression in bone marrow transplant patients was approximately 5% (12/223).

Bone Marrow↗