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Biomedical subjects

A Keating

Publications and source records attributed to A Keating.

At least 37 records · Page 2Linked to original sources
PubMed2001

Male sexual function after autologous blood or marrow transplantation.

Although endocrine dysfunction has been reported in survivors of allogeneic bone marrow transplantation (alloBMT), data for autologous BMT (autoBMT) recipients are lacking. Because information on male potency in particular is scanty, we prospectively assessed male sexual function after autoBMT. We identified 16 men who were < or =50 years of age at the time of evaluation and disease free for at least 6 months after autoBMT. Nine had Hodgkin's disease, 4 had acute myelogenous leukemia, and 3 had non-Hodgkin's lymphoma. Blood samples were assayed for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Patients were surveyed with a modified version of the Pyschosocial Adjustment to Illness Scale regarding erectile dysfunction and loss of interest in sexual activities. Seventy five percent of the men reported normal interest in sexual activities and 87.5% reported normal erectile function; however, 4 of 16 reported a moderate loss of interest in sexual activities, and another 2 of 16 reported frequent loss of erectile function. All 4 men with decreased libido and both men with impaired erectile function had Hodgkin's disease. Fourteen (88%) of 16 patients had an elevated FSH level, 7 (47%) of 15 had elevated LH, and 6 (38%) of 16 had decreased testosterone levels. Decreased testosterone levels correlated with a moderate or total loss of libido (P = .008) and a diagnosis of Hodgkin's disease (P = .01). Thus, after transplantation, most men have abnormal levels of gonadotrophins. Decreased levels of testosterone and symptoms of sexual dysfunction correlated with a diagnosis of Hodgkin's disease and may be related to the induction and salvage therapy received prior to autoBMT.

Adult↗
PubMed2000

E2F1 and p53 are dispensable, whereas p21(Waf1/Cip1) cooperates with Rb to restrict endoreduplication and apoptosis during skeletal myogenesis.

We describe temporal and genetic analyses of partially rescued Rb mutant fetuses, mgRb:Rb-/-, that survive to birth and reveal specific defects in skeletal muscle differentiation. We show that in the absence of Rb, these fetuses exhibit increased apoptosis, bona fide endoreduplication, and incomplete differentiation throughout terminal myogenesis. These defects were further augmented in composite mutant fetuses, mgRb:Rb-/-:p21-/-, lacking both Rb and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Although E2F1 and p53 mediate ectopic DNA synthesis and cell death in several tissues in Rb mutant embryos, both endoreduplication and apoptosis persisted in mgRb:Rb-/-:E2F1-/- and mgRb:Rb-/-:p53-/- compound mutant muscles. Thus, combined inactivation of Rb and p21(Waf1/Cip1) augments endoreduplication and apoptosis, whereas E2F1 and p53 are dispensable during aberrant myogenesis in Rb-deficient fetuses.

Animals↗
PubMed2000

Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial.

PURPOSE: To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia. PATIENTS AND METHODS: A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events. RESULTS: The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic (</= 100 cells/microliter) patients (55% v 43%, respectively), bone marrow transplant patients (73% v 27%, respectively), and patients given antibiotic prophylaxis before study entry (71% v 52%, respectively). Common adverse effects of meropenem and ceftazidime therapy were rash, diarrhea, and nausea and vomiting. CONCLUSION: Monotherapy with meropenem represents a suitable choice for initial empirical antibiotic therapy for febrile episodes in neutropenic cancer patients.

Adolescent↗
PubMed2000

High-dose chemotherapy and autologous stem-cell transplantation for ovarian cancer: an autologous blood and marrow transplant registry report.

BACKGROUND: Autologous transplantation is increasingly used to treat epithelial ovarian cancer. However, it is not clear which patients may benefit. OBJECTIVE: To determine overall and progression-free survival and factors associated with favorable outcome after autotransplantation for ovarian cancer. DESIGN: Observational cohort study. SETTING: 57 centers reporting to the Autologous Blood and Marrow Transplant Registry (ABMTR). PATIENTS: 421 women who received transplants between 1989 and 1996. INTERVENTIONS: High-dose chemotherapy using diverse regimens with hematopoietic stem-cell rescue. MEASUREMENTS: Primary outcomes were progression-free survival and overall survival. Multivariate analyses using Cox proportional hazards regression considered the following factors: age, Karnofsky performance score, initial stage, histologic characteristics, previous therapy, remission status, extent of disease, graft source, transplant regimen, and year of transplantation. RESULTS: Most patients had extensive previous chemotherapy. Forty-one percent had platinum-resistant tumors, and 38% had tumors at least 1 cm in diameter. Only 34 patients (8%) received transplants as part of initial therapy. The probability of death within 100 days was 11% (95% CI, 8% to 14%). Two-year progression-free survival was 12% (CI, 9% to 16%), and 2-year overall survival was 35% (CI, 30% to 41%). Younger age, Karnofsky performance score of at least 90%, non-clear-cell disease, remission at transplantation, and platinum sensitivity were associated with better outcomes. Progression-free and overall survival were 22% (CI, 12% to 33%) and 55% (CI, 42% to 66%), respectively, for women with a high Karnofsky performance score and non-clear-cell, platinum-sensitive tumors. CONCLUSIONS: Some subgroups of patients with ovarian cancer seem to have good outcomes after autotransplantation, although several biases may have affected these observations. Phase III trials are needed to compare such outcomes with outcomes of conventional chemotherapy.

Age Factors↗
PubMed2000

Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission.

Allogeneic bone marrow transplantation is an effective postremission strategy for patients with acute myelogenous leukemia (AML) in first complete remission (CR). The value of administering consolidation chemotherapy before human leukocyte antigen (HLA)-identical sibling transplantation is not established. Outcomes of patients with AML in first CR receiving no consolidation therapy, standard-dose cytarabine consolidation therapy, and high-dose cytarabine consolidation therapy before HLA-identical sibling transplantation were compared. Five-year treatment-related mortality rates were 30% (95% confidence interval [CI], 18% to 42%) in patients receiving no consolidation chemotherapy, 22% (95% CI, 17% to 28%) in those receiving standard-dose cytarabine consolidation, and 24% (95% CI, 17% to 31%) in those receiving high-dose cytarabine (P = NS). Five-year cumulative incidences of relapse were 19% (10% to 30%), 21% (16% to 27%), and 17% (11% to 24%), respectively (P = NS). Five-year probabilities of leukemia-free survival were 50% (36% to 63%), 56% (49% to 63%), and 59% (50% to 66%), respectively (P = NS). Five-year probabilities of overall survival were 60% (46% to 71%), 56% (49% to 63%), and 60% (51% to 67%), respectively (P = NS). The data indicate that postremission consolidation with cytarabine before allogeneic transplantation for AML in first CR is not associated with improved outcome compared to proceeding directly to transplantation after successful induction. (Blood. 2000;96:1254-1258)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Overview of autologous stem cell transplantation.

There has been a dramatic increase in the number of autologous peripheral blood stem cell transplants over the last decade. Faster recovery of cell counts, lesser transplant morbidity, shorter hospital stay and reduced cost compared with marrow autografts have been the main advantages of autologous peripheral blood cell over marrow transplants. In this paper we attempt to review the advances in the biology and mobilization of stem cells, and focus on clinical results of autologous peripheral stem cell and marrow transplants for disease specific sites such as breast cancer, myeloma, autoimmune diseases, germ cell tumors, the acute and chronic leukemias, the non-Hodgkin's lymphomas and Hodgkin's disease. We also discuss transplant related complications, gene therapy and the different methods of purging. This review was intended for autologous peripheral stem cell transplants, however, unavoidably, it also discusses autologous marrow transplantation and aspects common to both procedures.

Bone Marrow Purging↗
PubMed2000

Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada.

In 1986, the bone marrow transplant centers in Ontario agreed to a strategy for the treatment of patients with NHL. Suitable patients would undergo autotransplant but be referred for allotransplant if they had persistent marrow involvement or an inadequate marrow/stem cell harvest. Data of all patients were recorded in a database. We reviewed this database to compare these transplant modalities with respect to overall survival, rate of relapse and treatment-related mortality. Between January 1986 and August 1997, 429 patients underwent BMT for NHL - 385 autotransplants and 44 allotransplants. Sixty-eight percent of patients received their transplant for aggressive NHL, while the others had indolent lymphoma. Three-year actuarial survival did not differ between allogeneic and autologous BMT: 71% vs 62%, respectively (P = 0.5330 by log-rank testing). Three-year actuarial rate of relapse was lower after allotransplant than autotransplant: 6% vs 41%, respectively (P = 0.0006 by log-rank testing). Treatment-related mortality was higher after allotransplant than autotransplant: 23% vs 6%, respectively (P = 0.001 by chi2 analysis). For further comparison, autotransplant patients were randomly matched 2:1 with the allotransplant patients for age +/- 5 years, disease status at BMT, disease histology, and year of BMT. In the matched comparison, survival did not differ (relative risk of death after allotransplant: 0.711 (95% CI: 0.309-1.637)). Relapse rate was significantly lower in the allotransplant group (relative risk of relapse for allotransplant: 0.190 (95% CI: 0.043-0.834)) and treatment-related mortality was not significantly different (relative risk for allotransplant: 1.425 (95% CI: 0.527-3.851)). In conclusion, a review of a provincial strategy for treatment of NHL, shows that survival is not different after allogeneic or autologous BMT, but the rate of relapse is lower after allotransplant. These data support continuing the current provincial strategy.

Adolescent↗
PubMed2000

Quality assurance of progenitor cell content of apheresis products: a comparison of clonogenic assays and CD34+ enumeration. The Canadian Apheresis Group and Canadian Bone Marrow.

The most common methods used for evaluation of the haematopoietic stem cell content of peripheral blood apheresis products are the colony forming cell assay and the enumeration of CD34+ cells by flow cytometry. The Canadian Apheresis Group and the Canadian Bone Marrow Transplant Group established a multicentre study to compare the reproducibility of colony forming cell assays and CD34+ enumeration by flow cytometry in six transplant centres routinely performing haematopoietic stem cell apheresis. Over a 5-month period in 1996, 31 fresh apheresis samples were shipped by overnight courier for testing at six centres to perform CD34+ enumeration by flow cytometry and clonogenic assays. The mean coefficient of variation and range for the following assays were: cell count 36% (2.6-148%), CFU-GM 82% (46-123%), CD34+ absolute/kg 60% (14-174%) and CD34+ per cent 42% (12-84%). The wide variation in cell count in this pilot study highlights the difficulties related to provision of samples for quality assessment programmes. Results showed poor interinstitutional reproducibility even among selected samples with similar cell counts for both CFC and CD34+ assays demonstrating the need for development and implementation of an interinstitutional quality assurance programme for haematopoietic stem cell assessment. Provision of a reliable source of testing material will be a necessary next step.

Antigens, CD34↗
PubMed2000

Analysis of the microenvironment necessary for engraftment: role of the vascular smooth muscle-like stromal cells.

This is a review of recent data concerning the phenotype of human and murine stroma, as grown in long-term cultures. Using data on cytoskeletal and extracellular matrix protein expression, a sequential model of differentiation from mesenchymal (stem) cells to vascular-smooth muscle-like stromal cells is proposed. This model would apply, at least in the mouse, to stromal cells generated from different sites of hematopoiesis (bone marrow, fetal liver, spleen, and yolk sac). The in vivo counterparts of vascular-smooth muscle-like stromal cells in the different sites of definitive hematopoiesis are discussed.

Animals↗
PubMed2000

Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer.

PURPOSE: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m(2)/d and mitoxantrone 16 mg/m(2)/d combined with escalating doses of carboplatin 200 to 500 mg/m(2)/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 microg/d subcutaneously starting on day 1. RESULTS: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with < or = 400 mg/m(2) of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 10(9)/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 10(9)/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). CONCLUSION: The maximum-tolerated dose of carboplatin was 400 mg/m(2)/d in combination with mitoxantrone 16 mg/m(2)/d and cyclophosphamide 1,500 mg/m(2), all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.

Adolescent↗
PubMed2000

Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia.

PURPOSE: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. PATIENTS AND METHODS: We compared outcomes of HLA-identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451) versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. RESULTS: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P =.003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P =.005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P =.1). Treatment-related mortality was higher in the Bu/CY group (RR, 1.68; P =.012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1. 39; P =.017 for death; RR, 1.42; P =.006 for treatment failure). CONCLUSION: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

Adolescent↗
PubMed1999

Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: implications for ex vivo tumor purging and autologous stem cell transplantation.

The ribosome-inactivating protein, Shiga-like toxin-1 (SLT-1), targets cells that express the glycolipid globotriaosylceramide (CD77) on their surface. CD77 and/or SLT-1 binding was detected by flow cytometry and immunocytochemistry on lymphoma and breast cancer cells recovered from biopsies of primary human cancers as well as on B cells or plasma cells present in blood/bone marrow samples of multiple myeloma patients. Breast cancer cell lines also expressed receptors for the toxin and were sensitive to SLT-1. Treatment of primary B lymphoma, B-cell chronic lymphocytic leukemia, and myeloma B or plasma cells with SLT-1-depleted malignant B cells by 3- to 28-fold, as measured by flow cytometry. Depletion of myeloma plasma cells was confirmed using a cellular limiting dilution assay followed by reverse transcriptase-polymerase chain reaction analysis of clonotypic IgH transcripts, which showed a greater than 3 log reduction in clonotypic myeloma cells after SLT-1 treatment. Receptors for the toxin were not detected on human CD34(+) hematopoietic progenitor cells (HPC). HPC were pretreated with a concentration of SLT-1 known to purge primary malignant B cells and cultured for 6 days. The number of HPC was comparable in toxin-treated and untreated cultures. HPC were functionally intact as well. Colony-forming units (CFU) were present at an identical frequency in untreated and SLT-1 pretreated cultures, confirming that CFU escape SLT-1 toxicity. The results suggest the ex vivo use of SLT-1 in purging SLT-1 receptor-expressing malignant cells from autologous stem cell grafts of breast cancer, lymphoma, and myeloma patients.

Antibodies, Monoclonal↗
PubMed1999

Delphi-panel analysis of appropriateness of high-dose therapy and bone marrow transplants in adults with acute myelogenous leukemia in 1st remission.

BACKGROUND: Despite considerable data, there is still controversy over which adults with acute myelogenous leukemia (AML) in 1st remission should receive high-dose therapy and a bone marrow transplant rather than conventional-dose chemotherapy. Analyses of data from randomized trials are complex, conclusions sometimes contradictory and results not sufficiently detailed to allow subject-level decisions. OBJECTIVE: To determine appropriate use of high-dose therapy and bone marrow transplants in persons with AML in 1st remission with specific features. Develop a treatment algorithm. PANELISTS: Nine leukemia experts from diverse geographic sites and practice settings. EVIDENCE: Boolean MEDLINE searches of acute myelogenous leukemia and chemotherapy and/or transplants. CONSENSUS PROCESS: We used a modified Delphi-panel group judgment process. Age, WBC, cytogenetics and FAB-type were permuted to define 72 clinical settings. Each panelist rated appropriateness of high-dose therapy and a transplant versus conventional-dose chemotherapy on a nine-point ordinal scale (1, most inappropriate, 9, most appropriate) considering 3 types of donors: (1) HLA-identical siblings; (2) alternative donors (HLA-matched related or unrelated people other than an HLA-identical sibling); and (3) autotransplants. An appropriateness index was developed based on median rating and amount of disagreement. The relationship of appropriateness indices to the permuted clinical variables was considered by analysis of variance and recursive partitioning. Preference between donor types was analyzed by comparing mean appropriateness indices of comparable settings and a treatment algorithm developed. CONCLUSIONS: In people with an HLA-identical sibling, this type of transplant was rated appropriate in those with unfavorable cytogenetics and uncertain in all other settings. In people without an HLA-identical sibling, an alternative donor transplant was rated appropriate in those < 30 years with unfavorable cytogenetics, uncertain in those > 30 years and unfavorable cytogenetics and inappropriate in all other settings. Autotransplants were rated appropriate in people with unfavorable cytogenetics and uncertain in all other settings. An HLA-identical sibling donor, when available, was always preferred to an alternative donor transplant or autotransplant. In people without an HLA-identical sibling, an autotransplant was almost always favored over an alternative donor transplant with the magnitude of preference inversely correlated with transplant appropriateness.

Adult↗
PubMed1999

Delphi-panel analysis of appropriateness of high-dose therapy and bone marrow transplants in chronic myelogenous leukemia in chronic phase.

BACKGROUND: It is uncertain which people with chronic myelogenous leukemia (CML) in chronic phase should receive conventional treatment (interferon and/or chemotherapy) versus high-dose therapy and a bone marrow transplant. There are no randomized trials comparing these approaches and analyses of data from non-randomized studies are complex, contradictory without sufficient detail to allow subject-level treatment decisions. OBJECTIVE: Determine appropriateness of high-dose therapy and bone marrow transplants in persons with CML in chronic phase with specific features. Develop a treatment algorithm. PANELISTS: nine leukemia experts from diverse geographic sites and practice settings. EVIDENCE: Boolean MEDLINE searches of chronic myelogenous leukemia and chemotherapy and/or transplants. CONSENSUS PROCESS: We used a modified Delphi-panel group judgment process. Age, prognostic score, disease duration, and type of conventional therapy and response were permuted to define 90 clinical settings. Each panelist rated appropriateness of high-dose therapy and a transplant versus conventional therapy on a 9-point ordinal scale (1, most inappropriate, 9, most appropriate) considering three types of donors: (1) HLA-identical siblings; (2) alternative donors (HLA-matched related or unrelated people other than an HLA-identical sibling); and (3) autotransplants. An appropriateness index was developed based on median rating and amount of disagreement. Relationship of appropriateness indices to permuted clinical variables was considered by analysis of variance and recursive partitioning. Preference between donor types was analyzed by comparing mean appropriateness indices of similar settings and a treatment algorithm developed. CONCLUSIONS: In people with CML in chronic phase and an HLA-identical sibling donor and in those with an alternative donor (but no HLA-identical sibling), a transplant was rated appropriate in those with a < or = partial cytogenetic response to interferon and uncertain or inappropriate in all other settings. Autotransplants were rated uncertain or inappropriate in all settings. Most of the variance in appropriateness ratings between different clinical settings was accounted for by response to interferon: complete versus < or = partial response. An HLA-identical sibling donor, when available, was always preferred to an alternative donor or autotransplant. In people without an HLA-identical sibling, an alternative donor was favored over an autotransplant at higher appropriateness indices and the converse at lower appropriateness indices.

Adolescent↗
PubMed1999

Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group.

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.

Adolescent↗