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Biomedical subjects

R M Wong

Publications and source records attributed to R M Wong.

At least 19 recordsLinked to original sources
PubMed2001

The DeltauvrB mutations in the Ames strains of Salmonella span 15 to 119 genes.

The DeltauvrB mutations present in strains of Salmonella enterica Typhimurium used commonly in the Salmonella (Ames) mutagenicity assay were isolated independently for at least five different his mutants. These deletions all involved the galactose operon, biotin operon, nucleotide-excision-repair uvrB gene, and chlorate-resistance genes. Beyond this, the size of the deletions and the number and type of genes deleted have remained unknown for nearly 30 years. Here, we have used genomic hybridization to a Typhimurium microarray to characterize these five DeltauvrB deletions. The number of genes (and amount of DNA) deleted due to the DeltauvrB mutations are 15 (16kb) each in TA97 and TA104, 47 (50kb) in TA100, 87 (96kb) in TA1537, and 119 (125kb) in TA98, accounting for 0.3, 0.3, 1.0, 1.9, and 2.6% of the genome, respectively. In addition, TA97 and TA104 contain an identical three-gene deletion elsewhere in their genomes, and, most remarkably, TA104 contains a 282-gene amplification, representing 7% of the genome. Missing genes include mfdA and mdaA, encoding a multi-drug translocase and a major nitroreductase, respectively, both absent in TA98; dps, encoding a DNA-binding protein absent in TA1537 and TA98; and dinG, encoding a lexA-regulated repair enzyme, absent in three DeltauvrB lineages. Genes involved in molybdenum cofactor biosynthesis and a number of ORFs of unknown functions are missing in all DeltauvrB strains investigated. Studies in DeltauvrB strains of Escherichia coli have found that the enhanced mutagenesis of some base analogues was due to the deletion of genes involved in molybdenum cofactor biosynthesis rather than to deletion of uvrB. These discoveries do not diminish the value of the data generated in the Ames strains. However, absence of genes other than uvrB may account for the enhanced mutagenicity of some compounds in DeltauvrB Ames strains. In general, microarrays will be useful for characterizing the extent and nature of deletion and amplification mutations.

DNA Helicases↗
PubMed2001

Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease.

High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.

Adolescent↗
PubMed2001

High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: atopy predicts idiopathic diffuse lung injury syndromes.

The use of high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for children and adolescents with primary refractory and relapsed Hodgkin's disease is increasing. The purpose of this retrospective analysis was to: (1) evaluate the outcome of HDT and AHCT in pediatric patients with Hodgkin's disease, and (2) identify factors that predispose patients to the development of transplantation-related complications. We describe the experiences of 34 pediatric patients from a single institution with primary refractory or relapsed Hodgkin's disease. HDT regimens consisted of cyclophosphamide and etoposide combined with either carmustine, chloroethylcyclohexylnitrosurea, or fractionated total body irradiation. Kaplan-Meier survival predicts that 67% (95% confidence interval [CI] 47%-87%) of patients will be alive and disease-free at 5 years. Nine patients had disease recurrence, of whom 5 relapsed after 1 year (1.5-6.3 years). Five patients succumbed to treatment-related toxicities, of whom 4 died of pulmonary failure. Fifteen patients (44%) developed post-AHCT idiopathic diffuse lung injury syndrome: acute alveolitis (n = 2); diffuse alveolar hemorrhage (n = 2); acute respiratory distress syndrome (n = 2); delayed interstitial pneumonitis (n = 8); and bronchiolitis obliterans (n = 1). The following factors did not predict for the development of a diffuse lung injury syndrome in univariate analysis: prior treatment with bleomycin, pre-HDT pulmonary function tests, and prior thoracic irradiation. Of the patients in our cohort, 44% had a history of atopy (allergic rhinitis and/or asthma). Multivariate logistic analysis revealed that a preexisting history of atopy was highly predictive of idiopathic pulmonary complications (P = .0001, odds ratio = 21, CI 3.6-125). Our experience shows that HDT followed by AHCT results in durable remissions in two thirds of pediatric patients with refractory and relapsed Hodgkin's disease, and a history of atopy is associated with post-AHCT pulmonary complications.

Adolescent↗
PubMed2001

Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome.

OBJECTIVE: To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene. METHODS: Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23-32, where the mutational hotspots for severe forms of Marfan syndrome are located. RESULTS: Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation. CONCLUSION: Taking advantage of the clustering phenomenon of mutations in severe forms of marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots, thus reducing the effort that would otherwise be much greater because of the size of the gene.

Child, Preschool↗
PubMed2000

Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial.

We have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.

Acute Disease↗
PubMed2000

Pulmonary toxicity syndrome in breast cancer patients undergoing BCNU-containing high-dose chemotherapy and autologous hematopoietic cell transplantation.

We performed a retrospective review to investigate pulmonary toxicity syndrome (PTS) in a cohort of breast cancer patients undergoing BCNU-containing high-dose chemotherapy (HDC). Our aim was to characterize presentation, identify risk factors, determine outcome following therapy, and find any association with differences in survival. We reviewed the data of 152 patients with stage II or III or metastatic breast cancer treated with cyclophosphamide 5625 mg/m2, cisplatin 165 mg/m2, and BCNU 600 mg/m2 followed by autologous peripheral blood hematopoietic cell transplantation. During follow-up, PTS was diagnosed when the following criteria were met: (1) presentation with typical clinical symptoms of PTS, (2) an absolute carbon monoxide diffusion capacity (DLCO) decline of 10% compared with pre-HDC DLCO, and (3) no clinical evidence of active pulmonary infection. Patients were then treated with a course of corticosteroid therapy. The incidence of PTS for all 152 patients was 59%, with a median onset at 45 days (range, 21-149 days) post-HDC. The median absolute DLCO decrement was 26% (range, 10%-73%) at diagnosis of PTS. There was no significant correlation between patient age, stage of breast cancer, pre-HDC chemotherapy regimen, pre-HDC chest wall radiotherapy, tobacco use, prior lung disease, or baseline pulmonary function test results and the development of PTS. We did observe an interesting association between PTS and the development of a noncholestatic elevation of transaminases. Of PTS patients treated with prednisone therapy for a median of 105.5 days (range, 44-300 days), 91% achieved resolution of their PTS without pulmonary sequelae. At 3 years, the overall survival (OS) of stage II or III patients who developed PTS was 84% (95% confidence interval [CI], 73%-95%); of metastatic breast cancer patients with PTS, the OS was 58% (95% CI, 38%-78%). These values were not significantly different from those of patients who did not develop PTS (91% [95% confidence interval [CI], 81%-100%] and 53% [95% CI, 32%-74%], respectively). No significant differences in disease-free or event-free survival were observed between patients with and without PTS. The incidence of PTS in breast cancer patients treated with a BCNU-containing HDC regimen can be remarkably high. Treatment with a course of corticosteroid therapy is successful in the vast majority.

Adult↗
PubMed2000

Favorable treatment outcome in non-Hodgkin's lymphoma patients with "poor" mobilization of peripheral blood progenitor cells.

Our purpose was to evaluate the outcome and costs of high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation in patients with the inability to mobilize sufficient numbers of PBPCs to allow rapid engraftment after PBPC transplantation. We treated 172 consecutive non-Hodgkin's lymphoma (NHL) patients with cyclophosphamide and granulocyte colony-stimulating factor followed by apheresis to collect PBPCs. The cells were separated on a Percoll gradient and purged with monoclonal antibodies and complement. The patients were categorized as "good" mobilizers if a collection of > or =2 x 10(6) CD34+ cells/kg was obtained (n = 138, 80%) or "poor" mobilizers if <2 x 10(6) CD34+ cells/kg were obtained (n = 34, 20%). With a median follow-up of 3.5 years, there is no statistically significant difference in actuarial event-free survival, overall survival, or relapse for good mobilizers compared with poor mobilizers. However, there was a trend toward increasing nonrelapse, transplantation-related mortality of 11.8% for poor mobilizers versus 3.6% for good mobilizers (P = .08) and early death from all causes including relapse within 120 days (poor 20.6% versus good 8.7%, P = .06). The total cost for bone marrow transplantation-related care was significantly higher, at $140,264 for poor mobilizers versus $80,833 for good mobilizers (P = .0001). The population of patients with NHL who mobilize PBPCs poorly into the circulation have a higher cost for posttransplant support. However, there is no significant difference in relapse, event-free survival, or overall survival for such patients compared with those who mobilize PBPCs easily.

Adult↗
PubMed2000

Four-cycle high-dose therapy with hematopoietic support for metastatic breast cancer: no improvement in outcomes compared with single-course high-dose therapy.

Multiple-cycle high-dose therapy with autologous hematopoietic progenitor cell (AHPC) support has been used to deliver dose-intensive therapy. We have used this approach as well as single-cycle high-dose therapy in treating patients with metastatic breast cancer. We present the outcomes of multiple-cycle high-dose therapies and compare them with those resulting from single-course high-dose therapies performed at a single institution. Fifty-five patients received 4 cycles of intensive chemotherapy with AHPC support. Three multicycle regimens were sequentially applied. Twenty patients were enrolled to receive 4 cycles of high-dose mitoxantrone, thiotepa, and cyclophosphamide. Nineteen subsequent patients received this regimen modified by the incorporation of paclitaxel. Sixteen patients received 2 cycles of high-dose melphalan, thiotepa, and paclitaxel and 2 cycles of mitoxantrone, thiotepa, and paclitaxel. The results of all 3 multiple-cycle therapies are compared with those of 55 contemporaneous patients with metastatic breast cancer who received a single course of high-dose cyclophosphamide and thiotepa or cyclophosphamide, cisplatin, and BCNU (carmustine) with hematopoietic cell rescue. Multiple-cycle therapy was associated with more infectious complications, increased transfusion requirements, and increased hospital admissions. However, there were no significant differences in outcomes between the groups. For 55 patients who received multiple-cycle therapy, the actuarial 3-year overall survival rate was 36% (95% confidence interval [CI] 23%-49%); freedom from progression and event-free survival were both 15% (CI 5%-25%). The median time to disease progression and median survival were 1.0 and 1.6 years, respectively. For the 55 patients who underwent a single course of high-dose therapy, the 3-year overall survival was also 36% (CI 18%-54%), whereas freedom from progression and event-free survival were both 19% (CI 7%-31%). The median time to progression and median survival were 0.8 and 2.2 years, respectively. Within the constraints of this patient population, the outcomes of 4 cycles of high-dose therapy with AHPC support were not superior to those resulting from single courses of high-dose therapy in the treatment of patients with metastatic breast cancer.

Adjuvants, Pharmaceutic↗
PubMed2000

Analysis of the SOS response in Salmonella enterica serovar typhimurium using RNA fingerprinting by arbitrarily primed PCR.

We report an analysis of a sample of the SOS response of Salmonella enterica serovar Typhimurium using the differential display of RNA fingerprinting gels of arbitrarily primed PCR products. The SOS response was induced by the addition of mitomycin C to an exponentially growing culture of serovar Typhimurium, and the RNA population was sampled during the following 2 h. These experiments revealed 21 differentially expressed PCR fragments representing mRNA transcripts. These 21 fragments correspond to 20 distinct genes. All of these transcripts were positively regulated, with the observed induction starting 10 to 120 min after addition of mitomycin C. Fifteen of the 21 transcripts have no homologue in the public sequence data banks and are therefore classified as novel. The remaining six transcripts corresponded to the recE, stpA, sulA, and umuC genes, and to a gene encoding a hypothetical protein in the Escherichia coli lysU-cadA intergenic region; the recE gene was represented twice by nonoverlapping fragments. In order to determine if the induction of these 20 transcripts constitutes part of a classical SOS regulon, we assessed the induction of these genes in a recA mutant. With one exception, the increased expression of these genes in response to mitomycin C was dependent on the presence of a functional recA allele. The exception was fivefold induced in the absence of a functional RecA protein, suggesting another layer of regulation in response to mitomycin C, in addition to the RecA-LexA pathway of SOS induction. Our data reveal several genes belonging to operons known to be directly involved in pathogenesis. In addition, we have found several phage-like sequences, some of which may be landmarks of pathogenicity determinants. On the basis of these observations, we propose that the general use of DNA-damaging agents coupled with differential gene expression analysis may be a useful and easy method for identifying pathogenicity determinants in diverse organisms.

Bacterial Proteins↗
PubMed1999

Sample sequencing of a Salmonella typhimurium LT2 lambda library: comparison to the Escherichia coli K12 genome.

As part of the ongoing sequencing of the complete Salmonella typhimurium LT2 genome, a partly ordered set of 416 lambda clones has been developed, representing over 90% of the genome. The average insert size is 17 kb. Sequences were obtained from both ends of each clone in this set. A total of over 600 kb of sequence has been deposited in the genome survey sequence section of GenBank. This resource of clones is available from the Salmonella Genome Stock Center. A preliminary comparison with the Escherichia coli K12 genome indicates that there are likely to be many hundred insertion deletion events, encompassing more than one gene, that distinguish these genomes. Fully 30% of the S. typhimurium sequences have no close homologs in the GenBank database.

Adult↗
PubMed1999

Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: effect on chronic graft-vs.-host disease and long-term survival.

Graft-vs.-host disease (GVHD) is a major predictor of outcome following allogeneic bone marrow transplantation (BMT). For patients alive at day 100 after BMT, the presence or absence of chronic GVHD is one of the most important determinants of survival and quality of life. We wished to determine the effects on chronic GVHD of two regimens used for the prophylaxis of acute GVHD: cyclosporine, methotrexate, and prednisone (CSA/MTX/PSE) and cyclosporine and prednisone (CSA/PSE). One hundred forty-nine evaluable patients were entered into the acute GVHD study. As of 31 March 1997, 63 months after the last patient underwent BMT, the median survival time was 4.5 years (range 0.09-9.9). The incidence of chronic GVHD was independent of the prophylactic regimen (55 vs. 54%), and extensive chronic GVHD occurred in 25 and 24% of patients receiving CSA/MTX/PSE and CSA/PSE, respectively. Of note, the median Karnofsky performance status of both groups was 100% (range 70-100%), reflecting the low incidence of extensive chronic GVHD. Survival rates free of chronic GVHD were 52 vs. 42% (p = 0.29) for patients receiving CSA/MTX/PSE vs. CSA/PSE. The incidence of relapse was also similar in both groups of patients. These data suggest that the combinations of CSA/MTX/PSE and CSA/PSE result in comparable chronic GVHD-free survival without an increase in leukemic relapse.

Acute Disease↗
PubMed1999

Impact of admission body weight and chemotherapy dose adjustment on the outcome of autologous bone marrow transplantation.

We performed a retrospective analysis of 473 consecutive adult patients undergoing autologous bone marrow transplantation for hematologic malignancies between 1988 and 1995. The analysis examined whether significant deviation from ideal body mass index is associated with a decrease in event-free survival (EFS), an increase in nonrelapse mortality (NRM) including late toxicities and second malignancies, or relapse. Chemotherapy dosing in underweight and overweight patients is administered based on the relationship of admission body weight (ABW) to ideal body weight (IBW). Doses were adjusted for obesity; however, the adjustment did not obviate increased risk for NRM. Patients were categorized into five groups according to the relationship of ABW to age-adjusted body mass index (aBMI) as a percent of actual BMI, as follows: group I, 70-79%; group II, 80-99%; group III, 100-119%; group IV, 120-139%; and group V, 140-199% aBMI. When body weight was expressed as percent BMI adjusted for age, there was a significantly increased risk for NRM in groups I and IV (p = 0.03 and 0.02, respectively). A trend toward greater NRM in group V (p = 0.10) was also noted. Multivariate analysis confirmed that the risk of NRM for extremely underweight and overweight patients is almost three times that of patients close to ideal body weight. Age-adjusted BMI was an independent predictive factor for NRM but not associated with increased relapse. We determined that dose adjustment could be safely used without significant increase of relapse. In patients with significant deviation of BMI from aBMI, dose adjustment and possible weight normalization should be considered.

Adolescent↗
PubMed1999

Pulmonary infections after bone marrow transplantation: clinical and radiographic findings.

PURPOSE: To assess the clinical and radiographic findings of pulmonary infections diagnosed by using invasive means. MATERIALS AND METHODS: Fifty-nine episodes of pulmonary infection were diagnosed in 52 (7.2%) of a consecutive series of 725 adult bone marrow transplant recipients. Causative organisms, time of diagnoses, radiographic patterns, and mortality rates were reviewed. RESULTS: Cytomegalovirus and Aspergillus species were the two most common pathogens, accounting for 22 and 17 episodes, respectively. During the first 30 days after bone marrow transplantation, fungi caused the majority (nine [82%] of 11 episodes) of pulmonary infections; from days 31 to 100, viruses predominated (21 [62%] of 34 episodes). Recipients of allogeneic transplants had a higher probability of developing Cytomegalovirus pneumonitis than did the recipients of autologous and syngeneic transplants (P < .001). Radiographic findings of Cytomegalovirus pneumonia consisted of parenchymal opacification (90%) and innumerable nodules smaller than 5 mm (29%); in two patients, radiographs were normal. Nodules, masses, or nodules and masses, present in nine (69%) of the 13 patients with Aspergillus infection, were the most common radiographic findings in invasive aspergillosis. Bone marrow transplant recipients with a documented pulmonary infection were found to have a lower event-free survival than recipients without infection (P < .001). CONCLUSION: Opportunistic pathogens account for the majority of pulmonary infections requiring invasive diagnosis and tend to manifest at predictable times in the course of events following recovery from bone marrow transplantation. Cytomegalovirus, the most common pathogen, causes a spectrum of radiographic findings that includes normal findings. Occurrence of a pulmonary infection is associated with an increased mortality rate.

Adolescent↗
PubMed1998

Regulation of cyclin D-dependent kinase activity in rat liver regeneration.

The regulation of cyclin D-dependent kinase activity in tissue regeneration in vivo has not been fully described. In young adult rat liver after 70% partial hepatectomy, the association of cyclin D1 with cdk4 was significantly promoted during G1 phase and was maximal at 18 hr, corresponding mainly to late G1. Cyclin D1-dependent kinase activity also strongly increased during G1 phase. The timing of the induction of cyclin D1 / cdk4 complex assembly correlated well with that of cyclin D1-dependent kinase activity. At 18 hr after partial hepatectomy, the amounts of CDK inhibitors p21(CIP1) and p27(KIP1) were also maximal, while only one-tenth of p21(CIP1) and of p27(KIP1) was associated with cyclin D1. These findings suggest that cyclin D1, cdk4 and their association act as promoting factors, and that both p21(CIP1) and p27(KIP1) may have physiological functions as adaptor proteins in additions to their roles as CDK inhibitors in rat liver regeneration.

Animals↗
PubMed1998

Endoscopic ligation for non-esophageal variceal upper gastrointestinal hemorrhage.

BACKGROUND: Endoscopic ligation can be used for bleeding lesions in non-fibrotic tissue; however, only small numbers of patients with non-esophageal variceal upper gastrointestinal hemorrhage have been treated in this way. To evaluate the utility of the technique, we performed the procedure to treat hemorrhage not from esophageal varices during emergency endoscopy. PATIENTS AND METHODS: Bleeding was identified from gastric Dieulafoy's ulcers (n=4), duodenal ulcers (n=3), gastric angiodysplasia (n=2) and Mallory-Weiss tears (n=3). The bleeding points were aspirated and controlled by endoscopic ligation and complete hemostasis was achieved in all cases. RESULTS: Although these lesions were located in difficult areas where endoscopic injection therapy and clipping sometimes fail, endoscopic ligation was performed easily and effectively without complications. Six of the patients had severe underlying disease, including acute and chronic myelogenous leukemia, liver cirrhosis and chronic renal failure; none suffered deterioration in their general condition after endoscopic ligation. CONCLUSIONS: Our findings suggest that endoscopic ligation is an easy and effective method of treatment for patients with gastrointestinal hemorrhage not from esophageal varices, and is safe even in patients with poor general health.

Adult↗
PubMed1997

High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices.

One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.

Adolescent↗
PubMed1997

Early reconstitution of immunity and decreased severity of herpes zoster in bone marrow transplant recipients immunized with inactivated varicella vaccine.

Varicella-zoster virus (VZV) causes herpes zoster after bone marrow transplantation (BMT). The immunogenicity of heat-inactivated varicella vaccine and effects on VZV pathogenesis were evaluated in 75 BMT patients randomized to receive vaccine or no intervention. Among 14 patients given a single dose at 1 month after transplantation, the mean (+/-SE) stimulation index (SI) was 12.20 +/- 3.13 compared with 4.83 +/- 2.74 (P = .036) in 14 unvaccinated patients, but clinical disease was not altered. Among 24 patients vaccinated at 1, 2, and 3 months, mean SI was 8.43 +/- 3.89 versus 2.00 +/- 0.33 (P = .014) in 23 unvaccinated patients at 4 months and 8.56 +/- 2.81 versus 5.30 +/- 2.47 (P = .043) at 5 months. Disease severity associated with VZV reactivation was decreased dramatically in vaccinees given three doses; severity scores were 6.4 +/- 1.0 versus 11.8 +/- 1.1 (P = .007). This experience with varicella vaccine in BMT patients is the first evidence that active immunization can reduce morbidity due to herpesvirus reactivation in high-risk populations.

Adolescent↗