Biomedical subjects

J E Sanders

Publications and source records attributed to J E Sanders.

At least 91 records · Page 5Linked to original sources

PubMed1996

Barriers to bone marrow transplantation for sickle cell anemia.

While allogeneic marrow transplantation is curative therapy for patients with sickle cell anemia, only a small fraction of patients in the United States receive this treatment. We surveyed participants in our multicenter study of marrow transplantation for sickle cell anemia to determine reasons for not proceeding to transplantation. Among the 4848 patients less than 16 years of age with sickle cell anemia that were followed in 22 collaborating centers, 315 (6.5%) patients were reported to meet protocol entry criteria for transplantation, although there was wide variation among the institutions (0.9-36%). Among the 315 patients eligible for transplantation, 128 (41%) had human leukocyte antigen (HLA) typing performed, and of these 44 (14% of those meeting entry criteria) had an HLA-identical sibling. Common reasons for not proceeding with HLA typing in the remaining 187 patients included lack of a candidate sibling donor (76 patients, 24% of those meeting criteria) and lack of financial or psychosocial support (33, 10.5%). Parental refusal (30, 9.5%), physician refusal (13, 4%), history of medical noncompliance (2, < 1%), and other reasons (33, 10.5%) were less frequently cited. To date, 25 patients have been transplanted. Of the remaining 19 patients with HLA-matched donors, seven did not proceed to transplantation because of parental refusal, while the others anticipate a future transplantation (6), have experienced symptomatic improvement (4), or have relocated abroad (2). We conclude that the major barrier to marrow transplantation for sickle cell anemia is lack of an HLA-identical donor. But since only 6.5% of all children with sickle cell disease were considered eligible for transplantation, it is possible that other significant obstacles remain to be identified. For patients reported to meet eligibility criteria, parental refusal and limited financial or psychosocial support were infrequent barriers to transplantation.

Anemia, Sickle Cell↗

PubMed1996

Marrow transplantation for hepatitis-associated aplastic anemia: a follow-up of long-term survivors.

Between 1971 and 1989 we have treated 19 patients with hepatitis-associated aplastic anemia by marrow transplantation from their HLA-identical siblings following conditioning with 200 mg/kg cyclophosphamide (Cy) administered over a period of 4 days. One patient failed to engraft by day 34 and was given a second transplantation. He died from infection 15 days after the second transplantation. Eighteen patients had sustained engraftment. Six patients developed acute graft-vs.-host disease (GVHD) and two of these patients died 2.8 and 3.3 months after transplantation. Fifteen patients are surviving 4 to 24 (median 13) years after transplantation, while one patient died in a car accident 17 years after successful transplantation. Six of the surviving patients developed chronic GVHD. Two of the patients with chronic GVHD had preceding acute GVHD and four did not. Five of the six patients with chronic GVHD received donor buffy coat cells in addition to the marrow inoculum to prevent graft rejection. Twelve of the 15 surviving patients have Karnofsky performance scores of 100%. One patient, living more than 4 years after transplantation, has a Karnofsky score of 40% because of persistent cognitive deficits following non-A, non-B hepatitis with hepatic coma. Two patients developed hepatitis C infection 12 and 18 years after transplantation, respectively. Except for mild fatigue and mildly elevated liver function tests, these patients are doing well with Karnofsky performance scores between 95 and 100%. One patient developed severe coronary artery disease 10 years after transplantation, decreasing his Karnofsky performance score to 80%. Serum samples before and after transplantation from 13 patients were tested for hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA by polymerase chain reaction (PCR). Only one patient tested positive for HCV RNA before transplantation. Seven of 15 sera were hepatitis C RNA-positive posttransplantation, but only one of these patients has developed active hepatitis C. All 13 patients were were negative for hepatitis B surface antigen and HBV DNA. Only one patient had IgM antibodies against hepatitis A virus (HAV) before transplantation, which suggested HAV infection. Hepatitis-associated aplastic anemia apparently was caused in most patients by a non-A, non-B, non-C agent. HLA-identical marrow transplantation for hepatitis-associated aplastic anemia with Cy as conditioning regimen is well-tolerated and has a long-term event-free survival in excess of 80%, not different from results of marrow transplantations for aplastic anemia of other etiologies.

Adolescent↗

PubMed1995

Unrelated donor marrow transplantation in children.

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.

Adolescent↗

PubMed1995

Cataractogenesis in rats induced by in utero exposure to RG 12915, a 5-HT3 antagonist.

RG 12915, a selective 5-HT3 antagonist developed for the treatment of emesis and nausea associated with cancer chemotherapy, was administered by gavage to four groups of pregnant rats from Gestation Day 6 to 17 at doses of 0, 1, 10, and 100 mg/kg/day, as part of a Segment II (developmental toxicity) study. The 100 mg/kg/day dose was maternally toxic as indicated by decreased body weight gain and food consumption during the treatment period. A portion of the rats were allowed to deliver and rear their litters and three pups from two litters in the 100 mg/kg/day group were observed to have lens opacities (visible to the naked eye) at weaning. At a later examination, when the offspring were approximately 4 months old, four additional animals from the same two litters had cataracts. A slight growth retardation was also observed postweaning in the offspring of the 100 mg/kg/day group. To confirm the lens findings and more precisely define the no-effect dose, another study was conducted in which pregnant rats were administered daily RG 12915 doses of 0, 10, 30, 60, or 100 mg/kg/day from Gestation Day 6 to 17. There was a dose-related decrement in maternal body weight gain during the treatment period in the 30, 60, and 100 mg/kg/day groups (12, 28, and 47%, respectively) compared to the control group. A treatment-related incidence of nuclear cataract was observed in the offspring of the 60 and 100 mg/kg/day groups (litter incidence 6 and 45%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Subchronic toxicity studies with the leukotriene D4 antagonist RG 12525.

Preclinical safety studies with the leukotriene D4 antagonist RG 12525 were conducted by the oral route in mice, rats, and monkeys. Oral administration of RG 12525 was repeated daily in studies up to 6 months in duration. RG 12525 was shown to have limited high-dose toxicity after repeated oral administration. The effects of RG 12525 were strongly dependent upon the species considered. High doses of RG 12525 caused significant increases in liver weight in mice, rats, and monkeys that were associated with diffuse hepatocellular hypertrophy in mice and rats but not in monkeys. No related clinical chemistry changes were observed in any of the species and hepatic activities of peroxisomal enzymes or cytochrome P450 were increased only slightly. Proliferation of brown adipose tissue (BAT) was observed in rats and mice but not in monkeys. The BAT reaction was more pronounced in the interscapular area but it was also observed in other subcutaneous locations as well as in mediastinal and bone marrow fat. In all locations, the RG 12525-induced BAT had some morphological similarities with cold-adapted BAT. Repeated administration of RG 12525 at high doses to female rats resulted in a lack of progression to the luteal phase of the estrous cycle that was reversible after discontinuation of treatment. Finally, RG 12525 was nephrotoxic in mice with males being more sensitive than females.

Animals↗

PubMed1995

Interface mechanics in external prosthetics: review of interface stress measurement techniques.

Instrumentation to measure accurately the stresses at the interface of a residual limb and prosthetic socket has a strong potential for use in prosthetic treatment. As a tool in the clinical setting, the device would allow a clinician to identify sites of excessive loading, information which could then be combined with clinical assessment of skin quality to determine regions of potential skin breakdown. Stress distributions for different prosthetic designs could be compared, facilitating a clinician's judgement to determine the optimal design for a patient. The instrumentation would have additional use in research as an evaluation tool for computer-based finite-element (FE) models. Stump-socket FE models predict stress distributions for proposed socket designs, thus offering advantages over interface stress measurement because evaluation can be conducted before a prosthesis is fabricated or put on an amputee patient. However, FE models must first be proven valid against experimental measurements before they can be considered accurate predictors of interface stresses. Current interface stress measurement techniques are described, with a concentration on a physical explanation of the advantages and limitations with each technique. New emerging technologies are discussed which are instruments that have been described but for which no data collected on amputees have been reported in the literature. The important new features of those technologies are also discussed.

Amputation Stumps↗

PubMed1995

Use of patient-controlled analgesia for pain control for children receiving bone marrow transplant.

We report 2 years' experience managing 39 preteen (ages 4-12 years) children with patient-controlled analgesia (PCA) for pain associated with bone marrow transplantation (BMT). We prescribed morphine or hydromorphone PCA (starting bolus 20 micrograms/kg morphine or 2 micrograms/kg hydromorphone) with or without continuous infusion (CI), for a period of 6-74 days. The duration of PCA use (median 19 days) depended upon severity of mucositis or other painful conditions. The peak morphine use was on the 11th day after BMT. We prescribed CI opioids in addition to PCA, either at night or around the clock, in 52% of patients. Ninety-five percent of children successfully mastered PCA to control pain associated with BMT. We observed no instances of drug misuse, parental tampering, accidental overdose, or difficulty weaning from opioids. We conclude that opioid PCA, with or without CI, over several days or weeks is safe and effective for preteen children suffering BMT-related pain.

Analgesia, Patient-Controlled↗

PubMed1995

Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics.

We have determined the relationships between busulfan average concentration at steady-state and (1) rejection of graft, and (2) regimen-related toxicity, and have evaluated the dependence of busulfan clearance/F on body size and age. Patients received 16-30 mg/kg of busulfan followed by cyclophosphamide in doses of 120, 150, 174, or 200 mg/kg or 8 g/m2 in preparation for autologous, syngeneic or allogeneic grafts varying in compatibility from HLA-matched siblings to HLA-partially-matched unrelated donors. In a multivariate Cox time-to-rejection analysis, only busulfan concentration remained a significant determinant of rejection, P = 0.0154. An average concentration of busulfan at steady-state of at least 200 ng/ml was needed to avoid rejection of a matched-sibling graft, while 600 ng/ml was needed to avoid rejection of HLA-partially-matched related or HLA-matched unrelated donor grafts. The toxicity of the cytoreductive regimen correlated with busulfan average concentration at steady-state (rs = 0.717). Busulfan clearance/F expressed relative to body weight, ideal body weight or surface area declined with age during the first decade of life. Over the entire span of age, the coefficient of variation in clearance/F for all ages was similar when clearance/F was expressed in absolute terms (ml/min) and when adjusted for body surface area; the coefficient of variation was greater for clearance/F when expressed relative to total or ideal body weight. We conclude that busulfan concentration in plasma is an important determinant of graft survival and regimen-related toxicity, and that the variability of busulfan pharmacokinetics with age precludes the use of a fixed dose for all ages and indications.

Adolescent↗

PubMed1995

Phase II study of busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for allogeneic bone marrow transplantation in patients with advanced myeloid malignancies.

A previous phase I dose escalation study determined that the maximum tolerated doses of busulfan and cyclophosphamide that could be combined with 12.0 Gy of total body irradiation were 7 mg/kg and 50 mg/kg, respectively. A phase II study of these three agents was carried out in 56 patients with advanced myeloid malignancies receiving allogeneic bone marrow transplants from HLA-identical donors. Cyclosporine with methotrexate or with prednisone was administered for prophylaxis against graft-versus-host disease. Grade 3 (n = 8) and 4 (n = 3) regimen-related toxicity occurred in 20% of patients, which was the maximum predicted from the phase I study. The 2-year actuarial probabilities of non-relapse mortality and relapse were 0.52 and 0.55, respectively. Fourteen patients survive, 12 in remission, 581-1761 days post-transplant. The actuarial probabilities of disease-free survival for patients with recurrent acute myeloid leukemia and advanced chronic myeloid leukemia at 2 years were 20% and 23%, respectively. When compared with our historical experience in patients receiving other treatment regimens, there was no apparent improvement in disease-free survival.

Adolescent↗

PubMed1995

A small and lightweight three-channel signal-conditioning unit for strain-gage transducers: a technical note.

A small and lightweight signal conditioning unit for use with strain-gage transducers is described. The unit provides bridge-balancing, amplification, and filtering for three channels of Wheatstone bridge circuits. The electronics are housed with a 4.5 cm x 3.0 cm x 2.5 cm box that allows connection to a transducer and to a cable that extends to power supplies and a data storage facility. Evaluation tests showed the signal conditioning unit had low noise (0.356 microV, peak-to-peak, referenced to input) with crosstalk between channels of less than 0.02% of the peak-to-peak input signal. The signal conditioning unit has application in biomechanics where a small and lightweight unit is needed; for example, skin/support interface stress measurements in prosthetics and orthotics research.

Biomechanical Phenomena↗

PubMed1995

Skin response to mechanical stress: adaptation rather than breakdown--a review of the literature.

The abnormal loading of skin and other surface tissues unaccustomed to bearing large mechanical forces occurs under many circumstances of chronic disease or disability. A result of abnormal loading is breakdown of the body wall tissues. An effective rehabilitation program avoids the pathological processes that result in skin trauma and breakdown and encourages load-tolerance and adaptation, changes in the body wall so that the tissues do not enter an irreversible degenerative pathological process. In the past, prevention has been the principal approach to the challenge of maintaining healthy skin and avoiding breakdown; therefore, relatively little is described in the rehabilitation literature about skin adaptation. However, adaptation has been investigated in other fields, particularly biomechanics and comparative anatomy. The purpose of this paper is to assemble the research to date to present the current understanding of skin response to mechanical stress, specifically addressing load cases applicable to rehabilitation. Factors important to tissue response are considered and their effects on adaptation and breakdown are discussed.

Adaptation, Physiological↗

PubMed1994

Unrelated donor or autologous marrow transplantation for treatment of acute leukemia.

High-dose chemoradiotherapy followed by marrow transplantation from an HLA-matched sibling donor is curative for patients with acute leukemia. Autologous marrow transplantation has been used with success for some patients without such a sibling. Alternatively, the option of performing a transplant from an HLA-matched unrelated donor has been made possible by the recent development of large registries of HLA-typed volunteers. The purpose of this study was to compare the outcomes for patients with advanced leukemia treated by unrelated or autologous marrow transplantation. Forty-three patients with acute myeloid or lymphoid leukemia were transplanted from a closely HLA-matched unrelated donor. Results were compared with those of a disease-, disease-stage-, and age-matched cohort of 77 patients treated with autologous marrow transplantation at the same institution during the same period. Myeloid reconstitution with peripheral granulocyte counts greater than 10(9)/L was achieved in 93% of unrelated recipients and 70% of autologous recipients at a median of 24 and 36 days after transplantation, respectively (P = .0001). The cumulative proportions of patients discharged alive (79% v 77%) and times from transplant to first hospital discharge (35 v 34 days) were not different between unrelated and autologous recipients (P = .65). For patients transplanted in complete remission, relapse occurred after transplantation in 27% of the unrelated and in 55% of the autologous recipients (P = .08). For patients transplanted in relapse, the corresponding posttransplant relapse rates were 48% and 63%, respectively (P = .72). Forty percent of unrelated recipients and 28% of autologous recipients died in remission. Leukemia-free survivals were 33% for unrelated and 25% for autologous recipients transplanted in remission (P = .45), and 12% for unrelated and 5% for autologous recipients transplanted in relapse (P = .75). Unrelated donor transplants appear no less effective than autologous transplants to achieve long-term survival and may be more effective in eradicating leukemia in patients who have failed conventional chemotherapy. Further studies are warranted to assess the relative effectiveness of unrelated and autologous transplantation performed earlier in the course of the disease.

Adolescent↗

PubMed1994

How does vacuum forming affect Pelite mechanical properties?

Pelite is a polyethylene closed cell foam commonly used as an interface material in prosthetics. Both normal and vacuum-formed Pelite were tested under compression and under shear loading. For shear testing, the results were not significantly different for normal and vacuum-formed Pelite. For normal Pelite, the slope of the stress-strain curve was 1.17MPa (+/- 0.14) while for vacuum-formed Pelite it was 1.24MPa (+/- 0.22). Compressive results, however, were significantly different. Below 80kPa of applied compression, the slope of the stress-strain curve for normal Pelite was 0.99MPa (+/- 0.11) while for vacuum formed Pelite it was 0.72MPa (+/- 0.12). Between 80kPa and 200kPa of applied compression, the slope of the stress-strain curve for normal Pelite was 0.45MPa (+/- 0.03) while for vacuum formed Pelite it was 0.55MPa (+/- 0.05). Reasons for the differences and their significance to interface mechanics and computer-aided prosthesis design are discussed.

Artificial Limbs↗

PubMed1994

Comparison of morbidity and mortality after marrow transplantation from HLA-genotypically identical siblings and HLA-phenotypically identical unrelated donors.

The nature and incidence of life-threatening or fatal toxicity after marrow transplantation were analyzed in 52 patients who received HLA-A, B, DR, Dw-phenotypically identical marrow transplants from unrelated volunteer donors (URD). An age and disease-matched cohort of 104 patients transplanted from HLA-genotypically identical siblings was used as a comparative group. The actuarial probability of grade 3 or 4 regimen-related toxicity was 31% after URD transplants and 21% after matched sibling transplants (log-rank p = 0.1041). The median duration of first hospitalization was 33 days for recipients of genotypically-identical marrow and 36 days for recipients of URD marrow (p = 0.0244). Sixty percent of genotypically identical marrow recipients and 51% of unrelated volunteer donor marrow recipients were discharged home from Seattle free of disease at a median of 99 days post-transplant (p = 0.5095). The percentage of patients requiring readmission to hospital and the actuarial probability of requiring either hemodialysis or mechanical ventilation were not statistically different between the two groups. We conclude that matched URD marrow transplantation is not associated with significantly greater regimen-related toxicity or mortality than transplantation from HLA-genotypical siblings.

Adolescent↗

PubMed1994

Marrow transplant experience for children with severe aplastic anemia.

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.

Anemia, Aplastic↗

PubMed1993

Marrow transplantation from unrelated donors for treatment of hematologic malignancies: effect of mismatching for one HLA locus.

One hundred twelve patients less than 36 years old received marrow grafts from unrelated donors as treatment for hematologic malignancy. Seventy donor/recipient pairs were phenotypically identical for HLA-A, -B, and -D, while 42 had a "minor" disparity at one HLA locus. There was an increase in the risk of acute graft-versus-host disease (GVHD) in patients receiving HLA-partially matched grafts compared with those receiving HLA-matched grafts (51% v 36% probability of grades III-IV acute GVHD). However, in this cohort of patients, there was no significant difference in survival (at 1.5 years, 46% v 51% for good-risk patients, 44% v 30% for poor-risk patients). This finding suggests that some degree of HLA disparity can be tolerated in young patients transplanted from unrelated donors for malignant disease, thus making transplantation an option available to larger numbers of patients.

Acute Disease↗

PubMed1993

Long-term survival and cure after marrow transplantation for congenital hypoplastic anaemia (Diamond-Blackfan syndrome).

Four patients with Diamond-Blackfan syndrome (congenital hypoplastic anaemia) whose disease was resistant to corticosteroid treatment and who were red blood cell transfusion-dependent, were given marrow grafts from allogeneic human-leucocyte-antigen (HLA)-identical siblings. The patients were conditioned with regimens including cyclophosphamide and busulfan. Three of four patients had sustained and complete marrow engraftment. One patient showed early signs of haematopoietic recovery but died on day 35 of pulmonary toxicity. The three surviving patients are well with normal haematopoiesis and Karnofsky performance scores of 100%, 3.0, 7.4 and 10.6 years after transplantation. Congenital hypoplastic anaemia can be treated successfully by allogeneic marrow grafts.

Acute Disease↗

PubMed1993

Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.

PURPOSE: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow.

Actuarial Analysis↗