51 results on '"Patricia S. Stewart"'
Search Results
2. Data from Occupational Trichloroethylene Exposure and Renal Carcinoma Risk: Evidence of Genetic Susceptibility by Reductive Metabolism Gene Variants
- Author
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Nathaniel Rothman, Wong-Ho Chow, Stephen Chanock, Maria Merino, Ivana Holcatova, Jan Gromiec, Dana Mates, Neonila Szeszenia-Dabrowska, Marie Navratilova, Vladimir Bencko, Helena Kollarova, Vladimir Janout, Vsevolod Matveev, David Zaridze, Rayjean Hung, Patricia S. Stewart, Paul Brennan, Sara Karami, Paolo Boffetta, and Lee E. Moore
- Abstract
Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine β-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04–2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81–2.35; OR = 2.34; 95% CI, 1.05–5.21; Ptrend = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06–3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35–2.44; Pinteraction = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79–3.10; OR = 2.77; 95% CI, 1.01–7.58; Ptrend = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27–5.04; Ptrend = 1.00; Pinteraction = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with ≥1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans. Cancer Res; 70(16); 6527–36. ©2010 AACR.
- Published
- 2023
3. Supplementary Figure 1 from Occupational Trichloroethylene Exposure and Renal Carcinoma Risk: Evidence of Genetic Susceptibility by Reductive Metabolism Gene Variants
- Author
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Nathaniel Rothman, Wong-Ho Chow, Stephen Chanock, Maria Merino, Ivana Holcatova, Jan Gromiec, Dana Mates, Neonila Szeszenia-Dabrowska, Marie Navratilova, Vladimir Bencko, Helena Kollarova, Vladimir Janout, Vsevolod Matveev, David Zaridze, Rayjean Hung, Patricia S. Stewart, Paul Brennan, Sara Karami, Paolo Boffetta, and Lee E. Moore
- Abstract
Supplementary Figure 1 from Occupational Trichloroethylene Exposure and Renal Carcinoma Risk: Evidence of Genetic Susceptibility by Reductive Metabolism Gene Variants
- Published
- 2023
4. Borealis-1: a randomized, first-line, placebo-controlled, phase II study evaluating apatorsen and chemotherapy for patients with advanced urothelial cancer
- Author
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Sumanta K. Pal, B.J. Eigl, Cora N. Sternberg, Daniel P. Petrylak, Normand Blais, Daniel Castellano, Joaquim Bellmunt, Margitta Retz, Cindy Jacobs, Yohann Loriot, Elżbieta Senkus, B.A. Blumenstein, Srikala S. Sridhar, Patricia S. Stewart, and Przemyslaw Twardowski
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Urologic Neoplasms ,medicine.medical_treatment ,HSP27 Heat-Shock Proteins ,Phases of clinical research ,Kaplan-Meier Estimate ,Placebo ,Deoxycytidine ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Heat-Shock Proteins ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Hazard ratio ,Area under the curve ,Hematology ,Middle Aged ,Oligonucleotides, Antisense ,Chemotherapy regimen ,Gemcitabine ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Cisplatin ,business ,medicine.drug ,Molecular Chaperones - Abstract
Background Five-year survival of patients with inoperable, advanced urothelial carcinoma treated with the first-line chemotherapy is 5%–15%. We assessed whether the Hsp27 inhibitor apatorsen combined with gemcitabine plus cisplatin (GC) could improve overall survival (OS) in these patients. Patients and methods This placebo-controlled, double-blind, phase II trial randomized 183 untreated urothelial carcinoma patients (North America and Europe) to receive GC plus either placebo (N=62), 600 mg apatorsen (N = 60), or 1000 mg apatorsen (N=61). In the experimental arm, treatment included loading doses of apatorsen followed by up to six cycles of apatorsen plus GC. Patients receiving at least four cycles could continue apatorsen monotherapy as maintenance until progression or unacceptable toxicity. The primary end point was OS. Results OS was not significantly improved in the single or combined 600- or 1000-mg apatorsen arms versus placebo [hazard ratio (HR), 0.86 and 0.90, respectively]. Exploratory study of specific statistical modeling showed a trend for improved survival in patients with baseline poor prognostic features treated with 600 mg apatorsen compared with placebo (HR = 0.72). Landmark analysis of serum Hsp27 (sHsp27) levels showed a trend toward survival benefit for poor-prognosis patients in 600- and 1000-mg apatorsen arms who achieved lower area under the curve sHsp27 levels, compared with the placebo arm (HR = 0.45 and 0.62, respectively). Higher baseline circulating tumor cells (≥5 cells/7.5 ml) was observed in patients with poor prognosis in correlation with poor survival. Treatment-emergent adverse events were manageable and more common in both apatorsen-treatment arms. Conclusions Even though apatorsen combined with standard chemotherapy did not demonstrate a survival benefit in the overall study population, patients with poor prognostic features might benefit from this combination. Serum Hsp27 levels may act as a biomarker to predict treatment outcome. Further exploration of apatorsen in poor-risk patients is warranted.
- Published
- 2017
5. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial
- Author
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Fred Saad, Karim Fizazi, Florence Joly, Brent A. Blumenstein, Kim N. Chi, Vsevolod Matveev, Boris Alekseev, Gwenaelle Gravis, Cindy Jacobs, Sebastien J. Hotte, Patricia S. Stewart, Tomasz M. Beer, Aude Flechon, and Zafar Malik
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Internationality ,Maximum Tolerated Dose ,Urology ,Docetaxel ,Kaplan-Meier Estimate ,Disease-Free Survival ,Drug Administration Schedule ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Prednisone ,Median follow-up ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Enzalutamide ,Humans ,Neoplasm Invasiveness ,Prospective Studies ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Mitoxantrone ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,Thionucleotides ,medicine.disease ,Prognosis ,Survival Analysis ,Surgery ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,Treatment Outcome ,Oncology ,chemistry ,Cabazitaxel ,030220 oncology & carcinogenesis ,Taxoids ,business ,Tomography, X-Ray Computed ,Febrile neutropenia ,medicine.drug - Abstract
Summary Background Docetaxel and cabazitaxel improve overall survival compared with mitoxantrone in patients with metastatic castration-resistant prostate cancer. Custirsen (OGX011) is a second generation highly specific antisense oligonucleotide that inhibits the production of clusterin, an antiapoptotic protein that is upregulated in response to chemotherapy and that confers treatment resistance. We aimed to assess whether custirsen in combination with cabazitaxel and prednisone increases overall survival in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. Methods In this randomised, open-label, international, phase 3 trial, men with radiographically documented metastatic castration-resistant prostate cancer that had progressed after docetaxel treatment with a Karnofsky performance status of more than 70% and who were fit for chemotherapy, were recruited from 95 cancer treatment centres in eight countries. Patients were randomly assigned (1:1) centrally using permuted blocks (block size 8) to receive cabazitaxel plus prednisone (cabazitaxel 25 mg/m 2 intravenously every 21 days plus oral prednisone 10 mg daily) with or without custirsen (640 mg intravenously on days 1, 8, and 15, plus three previous loading doses) until disease progression, unacceptable toxicity, or the completion of ten treatment cycles. Randomisation was stratified by use of opioids for prostate cancer-related pain at screening, disease progression following first-line docetaxel treatment established by radiographic evidence, and previous treatment with abiraterone or enzalutamide. The co-primary endpoints were overall survival in all randomly assigned patients and in a poor-prognosis subgroup. All analyses were intention to treat with the exception of safety, which was reported for patients who received any assigned treatment. The trial has been completed and the results presented here are the final analysis. This trial is registered with Clinicaltrials.gov, number NCT01578655. Findings Between Sept 9, 2012, and Sept 29, 2014, 795 patients were screened for enrolment. 635 men were eligible for inclusion and were randomly assigned (n=317 in the cabazitaxel and prednisone plus custirsen group and n=318 in the cabazitaxel and prednisone group). Median follow up was 28·3 months (IQR 24·4–34·5) for the custirsen group and 29·8 months (IQR 25·3–35·2) for the control group. Median overall survival in all randomly assigned patients did not differ between the two groups (14·1 months [95% CI 12·7–15·9] in the curtisen group vs 13·4 months [12·1–14·9] in the control group; hazard ratio [HR] 0·95 [95% CI 0·80–1·12]; log-rank p=0·53). In the poor prognosis subgroup, median overall survival also did not differ between the two treatment groups (11·0 months [95% CI 9·3–13·3] in the custursin group vs 10·9 months [8·2–12·4] in the control group; HR 0·97 [95% CI 0·80–1·21]; two-sided p=0·80). The most frequently reported grade 3 or worse adverse events in the custirsen versus control groups were neutropenia (70 [22%] of 315 vs 61 [20%] of 312), anaemia (68 [22%] vs 49 [16%]), fatigue (23 [7%] vs 18 [6%]), asthenia (16 [5%] vs 8 [3%]), bone pain (16 [5%] vs 5 [2%]), and febrile neutropenia (16 [5%] vs 9 [3%]). Serious adverse events were reported in 155 (49%) versus 132 (42%). 27 patients died within 30 days of treatment in the cabazitaxel and prednisone plus custirsen group, seven of which were deemed to be treatment related, versus 17 in the cabazitaxel and prednisone group, eight of which were deemed to be treatment related. Of the 21 deaths reported, 15 were reported as complications related to study treatment, either chemotherapy (eight and three, respectively) or study drug (none and four, respectively). Interpretation We noted no survival benefit in men with metastatic castration-resistant prostate cancer with the addition of custirsen to cabazitaxel and prednisone treatment. Cabazitaxel and prednisone remains the standard of care for patients with metastatic castration-resistant prostate cancer progressing after docetaxel chemotherapy. Funding OncoGenex Pharmaceuticals.
- Published
- 2017
6. A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers
- Author
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Celestia S. Higano, J. Bazov, Sebastien J. Hotte, Patricia S. Stewart, Cindy Jacobs, C.K. Kollmannsberger, Evan Y. Yu, Martin E. Gleave, Kim N. Chi, and Som D. Mukherjee
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Cmax ,HSP27 Heat-Shock Proteins ,Loading dose ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Circulating tumor cell ,Internal medicine ,Medicine ,Humans ,Heat-Shock Proteins ,Tumor marker ,Aged ,Aged, 80 and over ,Bladder cancer ,Diazepam ,Dose-Response Relationship, Drug ,business.industry ,Cancer ,Hematology ,Middle Aged ,Oligonucleotides, Antisense ,medicine.disease ,Neoplastic Cells, Circulating ,Gene Expression Regulation, Neoplastic ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,Endocrinology ,Tumor progression ,030220 oncology & carcinogenesis ,business ,Molecular Chaperones - Abstract
BACKGROUND Heat shock protein 27 (Hsp27) is a chaperone protein that regulates cell survival via androgen receptor and other signaling pathways, thereby mediating cancer progression. Apatorsen (OGX-427) is a 2'-methoxyethyl-modified antisense oligonucleotide that inhibits Hsp27 expression. This study evaluated the safety profile and recommended phase II dosing of apatorsen in patients with advanced cancer. PATIENTS AND METHODS Patients with castration-resistant prostate (CRPC), breast, ovary, lung, or bladder cancer were enrolled to this phase I dose-escalation study. Apatorsen was administered i.v. weekly in 21-day cycles following 3 loading doses and over 5 dose levels (200-1000 mg). Apatorsen plasma concentrations, circulating tumor cells (CTCs) and CTC Hsp27 expression, and serum Hsp27 levels were evaluated. RESULTS Forty-two patients were accrued, of which 52% had CRPC. Patients were heavily pretreated, with 57% having had ≥3 prior chemotherapy regimens. During the loading dose/cycle 1 and overall study period, 93% and 100% of patients (N = 42) experienced treatment-related adverse events, respectively; most were grade 1-2 and included chills, pruritus, flushing, prolonged aPTT, lymphopenia, and anemia. One patient experienced a dose-limiting toxicity at the 600 mg dose level (intracranial hemorrhage in a previously undiagnosed brain metastasis). A maximum tolerated dose was not defined. Apatorsen Cmax increased proportionally with dose. Decreases in tumor markers and declines in CTCs were observed, with a prostate-specific antigen decline >%50% occurring in 10% of patients with CRPC; 29/39 assessable patients (74%) had reductions from ≥5 CTC/7.5 ml at baseline to
- Published
- 2015
7. Comparison of Two Culture Methods for Detection of Tobramycin-Resistant Gram-Negative Organisms in the Sputum of Patients with Cystic Fibrosis
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Jenny R. Stapp, Patricia S. Stewart, Jane L. Burns, Jill M. Van Dalfsen, and Charles Phelps
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Adult ,Male ,Microbiology (medical) ,food.ingredient ,Adolescent ,Cystic Fibrosis ,Colony Count, Microbial ,Microbial Sensitivity Tests ,medicine.disease_cause ,Microbiology ,Sputum culture ,chemistry.chemical_compound ,food ,Drug Resistance, Bacterial ,Gram-Negative Bacteria ,Tobramycin ,medicine ,Humans ,Agar ,False Positive Reactions ,Child ,Bacteriological Techniques ,biology ,medicine.diagnostic_test ,Pseudomonas aeruginosa ,Broth microdilution ,Sputum ,Bacteriology ,Achromobacter xylosoxidans ,Middle Aged ,biology.organism_classification ,Anti-Bacterial Agents ,Culture Media ,Stenotrophomonas maltophilia ,chemistry ,Female ,Gram-Negative Bacterial Infections ,MacConkey agar ,medicine.drug - Abstract
A culture method utilizing quantitative plating on antibiotic-containing media has been proposed as a technique for the detection of tobramycin-resistant organisms that is more sensitive than standard methods. Typical sputum culture methods quantitate the relative amounts of each distinct morphotype, followed by antibiotic susceptibility testing of a single colony of each morphotype. Sputum specimens from 240 cystic fibrosis patients were homogenized, serially diluted, and processed in parallel by the standard method (MacConkey agar and OF basal medium with agar, polymyxin, bacitracin, and lactose) and by plating on antibiotic-containing media (MacConkey agar with tobramycin added at 25 μg/ml [MAC-25] and 100 μg/ml [MAC-100]). MICs of tobramycin were determined for all Pseudomonas aeruginosa isolates by broth microdilution. Growth of P. aeruginosa on MAC-25 was considered to be equivalent to a tobramycin MIC of ≥16 μg/ml, and growth on MAC-100 was considered to be equivalent to a tobramycin MIC of ≥128 μg/ml. Analysis of method-specific detection rates showed that tobramycin-containing medium was more sensitive than the standard method for the detection of tobramycin-resistant P. aeruginosa, Stenotrophomonas maltophilia , and Achromobacter xylosoxidans but was less sensitive for the detection of Burkholderia cepacia than the standard method. When MICs for P. aeruginosa that grew on tobramycin-containing medium were tested by broth microdilution, the MICs for 28 of 121 strains (23%) growing on MAC-25 and 22 of 56 strains (39%) growing on MAC-100 were MICs
- Published
- 2002
8. genitourinary tumours, prostate Final overall survival (OS) from the AFFINITY phase 3 trial of custirsen and cabazitaxel/prednisone in men with previously treated metastatic castration-resistant prostate cancer (mCRPC)
- Author
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Vsevolod Matveev, Fred Saad, G. Gravis, Aude Flechon, Florence Joly, Zafar Malik, Patricia S. Stewart, Karim Fizazi, Cindy Jacobs, Boris Alekseev, Tomasz M. Beer, S.J. Hotte, and Kim N. Chi
- Subjects
Oncology ,medicine.medical_specialty ,Genitourinary system ,business.industry ,Hematology ,Castration resistant ,medicine.disease ,Prostate cancer ,Cabazitaxel ,Prednisone ,Internal medicine ,medicine ,Overall survival ,Previously treated ,business ,medicine.drug - Published
- 2016
9. Occupational trichloroethylene exposure and renal carcinoma risk: evidence of genetic susceptibility by reductive metabolism gene variants
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Ivana Holcatova, Nathaniel Rothman, Stephen J. Chanock, Jan P. Gromiec, Helena Kollárová, Paolo Boffetta, Paul Brennan, Vsevolod Matveev, Sara Karami, Vladimir Janout, Rayjean Hung, Maria J. Merino, Patricia S. Stewart, Lee E. Moore, Neonila Szeszenia-Dabrowska, Marie Navratilova, Dana Mates, Wong Ho Chow, David Zaridze, Vladimir Bencko, Moore, L.E., Boffetta, P., Karami, S., Brennan, P., Stewart, P.S., Hung, R., Zaridze, D., Matveev, V., Janout, V., Kollarova, H., Bencko, V., Navratilova, M., Szeszenia-Dabrowska, N., Mates, D., Gromiec, J., Holcatova, I., Merino, M., Chanock, S., Chow, W.-H., and Rothman, N.
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Physiology ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Internal medicine ,Occupational Exposure ,Genotype ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,trichloroethylene exposure ,Risk factor ,Glutathione Transferase ,Cocarcinogenesis ,Case-control study ,Odds ratio ,Confidence interval ,Kidney Neoplasms ,Trichloroethylene ,Minor allele frequency ,Carbon-Sulfur Lyases ,Endocrinology ,Oncology ,Case-Control Studies ,Female ,renal carcinoma risk: genetic susceptibility - Abstract
Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine β-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04–2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81–2.35; OR = 2.34; 95% CI, 1.05–5.21; Ptrend = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06–3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35–2.44; Pinteraction = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79–3.10; OR = 2.77; 95% CI, 1.01–7.58; Ptrend = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27–5.04; Ptrend = 1.00; Pinteraction = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with ≥1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans. Cancer Res; 70(16); 6527–36. ©2010 AACR.
- Published
- 2010
10. MARROW TRANSPLANTATION FROM HLA-MATCHED UNRELATED DONORS FOR TREATMENT OF HEMATOLOGIC MALIGNANCIES
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Jean E. Sanders, Scott I. Bearman, Rainer Storb, Effie W. Petersdorf, Eric Mickelson, C. D. Buckner, Claudio Anasetti, F R Appelbaum, Reginald A. Clift, Patrick G. Beatty, Thomas Ed, Keith M. Sullivan, Margaret S. Pepe, Gary Longton, Paul J. Martin, Finn Bo Petersen, J. D. Hansen, Robert P. Witherspoon, Michele Tesler, and Patricia S. Stewart
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Adult ,medicine.medical_specialty ,Graft vs Host Disease ,HLA Antigens ,Internal medicine ,Humans ,Medicine ,Sibling ,Survival analysis ,Bone Marrow Transplantation ,Retrospective Studies ,Transplantation ,business.industry ,Incidence (epidemiology) ,Retrospective cohort study ,Hematologic Diseases ,Survival Analysis ,Tissue Donors ,Surgery ,Histocompatibility ,surgical procedures, operative ,medicine.anatomical_structure ,Acute Disease ,Chronic Disease ,Cohort ,Bone marrow ,business - Abstract
Less than 40% of the patients who could benefit from marrow transplantation have an HLA-matched relative who can serve as a donor. For this reason, several centers have explored marrow transplantation from other categories of donors. This retrospective study analyzes the results of marrow transplantation for 52 patients receiving grafts from HLA-A,B,DR,Dw-phenotypically matched, MLC-compatible, unrelated volunteer donors compared to a disease, disease-stage, and age-matched cohort of 104 patients transplanted from HLA-genotypically identical sibling donors. The patients transplanted from unrelated donors had an increased incidence of grade II-IV acute graft-versus-host disease compared to patients transplanted from related donors (79% vs. 36%, P much less than 0.001). However, the probability of relapse-free survival appears similar in the two groups (P = 0.39 over all, with estimates of 41% vs. 46% at 1 year). We conclude from this preliminary data that marrow transplantation from HLA-matched unrelated donors should be considered in most, if not all, circumstances where transplantation from an HLA-matched sibling would be indicated if such a donor were available.
- Published
- 1991
11. What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?
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Patricia S. Stewart, Rainer Storb, FR Appelbaum, Kristine Doney, Robert P. Witherspoon, Keith M. Sullivan, P.J. Martin, Patrick G. Beatty, Claudio Anasetti, and Margaret S. Pepe
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Lymphocyte proliferation ,Cell Biology ,Hematology ,medicine.disease ,Gastroenterology ,Biochemistry ,Surgery ,Transplantation ,Leukemia ,medicine.anatomical_structure ,Prednisone ,Internal medicine ,medicine ,Methotrexate ,Bone marrow ,Aplastic anemia ,business ,medicine.drug - Abstract
One hundred forty-seven consecutive patients with leukemia, myelodysplastic syndrome, or aplastic anemia were treated by marrow grafts from genotypically HLA-identical siblings (n = 122) or HLA- haploidentical family members (n = 25). Haploidentical recipients differed from their donors for no more than one HLA locus on the nonshared haplotype. All were given postgrafting immunosuppression with a combination of methotrexate and cyclosporine. In a randomized study we explored whether prednisone administered from day 0 through 35 along with methotrexate/cyclosporine could improve prevention of acute graft- versus-host disease (GVHD). The GVHD incidence in patients not given prednisone was comparable with that previously reported with methotrexate/cyclosporine. Unexpectedly, significant increases in acute and also chronic GVHD were seen in HLA-identical recipients administered prednisone, but not in the small number of patients administered HLA-nonidentical grafts. However, the resultant increase in transplant-related mortality in patients administered prednisone was offset by an increase in leukemic relapse in patients not administered prednisone, presumably related to the absence of a graft-versus- leukemia effect. Therefore, overall disease-free survival of the two groups of patients was comparable, with slightly more than 50% of the patients being alive at more than 2 years after transplantation. We speculated that prednisone adversely affected GVHD prophylaxis, interfering with methotrexate's cell cycle-dependent suppression of donor lymphocyte proliferation in response to host antigens. In a pilot study we explored whether beginning prednisone on day 15, after completion of methotrexate administration, would avoid this adverse effect. The GVHD incidence in patients administered methotrexate/cyclosporine along with “late” prednisone was comparable with that in patients not administered prednisone. We conclude that methotrexate/cyclosporine is effective in decreasing the incidence of grade II through IV GVHD, and that the addition of prednisone to this regimen is not beneficial in recipients of HLA-identical marrow grafts.
- Published
- 1990
12. 2637 Baseline circulating tumor cells (CTC) and serum heat shock protein 27 (Hsp27) levels are increased in advanced bladder cancer (BC) patients with poor prognostic factors: Results from the randomized phase 2 Borealis-1™ trial of first-line gemcitabine/cisplatin plus apatorsen or placebo
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Przemyslaw Twardowski, Cindy Jacobs, Brent A. Blumenstein, Elżbieta Senkus, Joaquim Bellmunt, Margitta Retz, Cora N. Sternberg, Daniel P. Petrylak, Patricia S. Stewart, Y. Loriot, Normand Blais, B.J. Eigl, Srikala S. Sridhar, and Daniel Castellano
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,First line ,Gemcitabine/cisplatin ,Placebo ,Circulating tumor cell ,Hsp27 ,Heat shock protein ,Internal medicine ,medicine ,Advanced bladder cancer ,biology.protein ,business - Published
- 2015
13. First-line randomized phase II study of gemcitabine/cisplatin plus apatorsen or placebo in patients with advanced bladder cancer: The International Borealis-1 trial
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Normand Blais, Brent A. Blumenstein, Cindy Jacobs, Daniel Castellano, Patricia S. Stewart, Yohann Loriot, Joaquim Bellmunt, Margitta Retz, Daniel P. Petrylak, Bernhard J. Eigl, Elżbieta Senkus-Konefka, Cora N. Sternberg, Przemyslaw Twardowski, and Srikala S. Sridhar
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Bladder cancer ,biology ,business.industry ,Phases of clinical research ,Pharmacology ,urologic and male genital diseases ,Placebo ,medicine.disease ,Metastasis ,Hsp27 ,Heat shock protein ,Internal medicine ,Advanced bladder cancer ,medicine ,biology.protein ,In patient ,business - Abstract
4503 Background: Heat shock protein 27 (Hsp27) is over-expressed in bladder cancer (BC) and postulated to increase tumor growth, metastasis, and chemotherapy resistance. Apatorsen (A; OGX-427), a n...
- Published
- 2015
14. The Borealis-2 clinical trial: A randomized phase 2 study of OGX-427 (Apatorsen) plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer
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Toni K. Choueiri, Noah M. Hahn, Ajjai Shivaram Alva, Richard C. Lauer, Robert Dreicer, Joel Picus, Roberto Pili, Arjun Vasant Balar, Guru Sonpavde, Jean H. Hoffman-Censits, Elizabeth A. Guancial, Robert Alter, Meredith M. Regan, Cindy Jacobs, Patricia S. Stewart, Sumanta Kumar Pal, and Jonathan E. Rosenberg
- Subjects
Cancer Research ,Oncology - Published
- 2015
15. The Borealis-2 clinical trial: A randomized phase 2 study of OGX-427 (apatorsen) plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer
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Toni K. Choueiri, Noah M. Hahn, Sumanta Kumar Pal, Ajjai Shivaram Alva, Robert Dreicer, Alexander Starodub, Guru Sonpavde, Jean H. Hoffman-Censits, Joel Picus, Arjun Vasant Balar, Elizabeth A. Guancial, Meredith M. Regan, Cindy Jacobs, Patricia S. Stewart, and Jonathan E. Rosenberg
- Subjects
Cancer Research ,Oncology - Published
- 2014
16. Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC)
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Sebastien J. Hotte, Patricia S. Stewart, Karim Fizazi, Cindy Jacobs, Tomasz M. Beer, and Brent A. Blumenstein
- Subjects
Cancer Research ,medicine.medical_specialty ,Clusterin ,biology ,business.industry ,Castration resistant ,medicine.disease ,Second line chemotherapy ,Prostate cancer ,Endocrinology ,Oncology ,Downregulation and upregulation ,Prednisone ,Cabazitaxel ,Internal medicine ,medicine ,Cancer research ,biology.protein ,business ,medicine.drug - Abstract
TPS5103 Background: Custirsen enhances chemotherapeutic activity via inhibition of clusterin expression. Clusterin is a cytoprotective, antiapoptotic chaperone upregulated by anticancer therapies that confers treatment resistance. In a phase 2 study, mCRPC patients who had progressed within 6 mos of completing first-line docetaxel (DOC)/prednisone (P) and who were retreated with DOC/P and custirsen had a median overall survival of 15.8 mos. Lowering of serum clusterin level during second-line treatment was associated with significantly longer survival. CbzP has recently shown a survival advantage in patients with prostate cancer that has progressed after DOC therapy. The AFFINITY study was designed to evaluate in a larger study whether adding custirsen to CbzP will further improve survival in this patient population. Methods: AFFINITY was initiated in August 2012. Eligible patients in this phase 3, international, multicenter, open-label trial must have received ≥225 mg/m2 of DOC; have progressive disease as defined by RECIST 1.1, bone scan progression, and/or serum prostate-specific antigen level; have metastatic disease of the chest/abdomen/pelvis/bone; have adequate renal and liver function; and have a Karnofsky score ≥70%. Patients may have received up to 1 DOC regimen as well as abiraterone and/or enzalutamide. Approximately 630 patients will receive 21d cycles of Cbz (25 mg/m2IV q21d) + P (10 mg PO/d), either alone or with custirsen 640 mg IV given for 3 loading doses and then weekly until disease progression, unacceptable toxicity, or 10 cycles. The primary efficacy measure is overall survival. The secondary measure is proportion of patients alive without disease progression at Day 140 post-randomization. All efficacy analyses are intent to treat. Adverse events of all patients who receive ≥1 dose of custirsen or Cbz will be included in the safety analysis. This study is sponsored by Teva BPP R&D, Inc., in collaboration with OncoGenex Pharmaceuticals, Inc. Clinical trial information: NCT01578655.
- Published
- 2013
17. The Borealis-2 clinical trial: A randomized phase II study of OGX-427 plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer
- Author
-
Jonathan E. Rosenberg, Cindy Jacobs, Toni K. Choueiri, Noah M. Hahn, Meredith M. Regan, and Patricia S. Stewart
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Lung ,biology ,business.industry ,Phases of clinical research ,Clinical trial ,medicine.anatomical_structure ,Hsp27 ,Docetaxel ,Prostate ,Heat shock protein ,Internal medicine ,Relapsed refractory ,medicine ,biology.protein ,business ,medicine.drug - Abstract
TPS4588^ Background: Heat shock protein 27 (Hsp27) is over-expressed in many cancers including bladder, lung, prostate, and breast. Increased Hsp27 has been associated with inhibition of chemotherapy-induced apoptosis, increased tumor cytoprotection, and development of treatment resistance. OGX-427 is an antisense oligonucleotide designed to bind Hsp27 mRNA, inhibiting production of the Hsp27 protein. Inhibition of Hsp27 has been shown to increase apoptosis, inhibit tumor growth, and sensitize tumor cells to chemotherapy in a variety of malignancies, including urothelial cancer. Results of preclinical and phase 1 studies suggest that addition of OGX-427 to chemotherapy is well tolerated and may improve treatment efficacy. BOREALIS-2 is a randomized, multicenter, phase 2 study of OGX-427 in combination with docetaxel (DOC) vs. DOC alone in locally advanced/metastatic bladder cancer patients who received at least one line of prior platinum-based therapy. The primary objective is to evaluate overall survival. Secondary objectives include comparisons of safety and tolerability, disease response, and serum levels of Hsp27 and other pathway-related proteins. Associations between clinical outcomes, levels of Hsp27 and other proteins, and circulating tumor cells will be evaluated. Methods: Patients (N=200) are randomized in a 1:1 ratio following stratification (time from prior systemic chemotherapy; Bellmunt criteria). Up to 2 prior systemic therapies are allowed. Treatment-arm patients receive three loading doses of OGX-427 (600 mg) followed by up to ten 21-day treatment cycles (OGX-427 1000 mg on Days 1, 8, and 15 and DOC 75 mg/M2 IV on Day 1). Control-arm patients receive DOC 75 mg/M2 IV on Day 1 of each cycle. Treatment may continue until disease progression, unacceptable toxicity, completion of 10 cycles, or patient withdrawal. Patients who discontinue DOC due to toxicity after ≥2 cycles and do not have disease progression may receive maintenance therapy with OGX-427. One interim futility analysis will be performed. The trial will not be stopped early based on efficacy. Clinical trial information: NCT01780545.
- Published
- 2013
18. The Pacific trial: A randomized phase II study of OGX-427 in men with metastatic castration-resistant prostate cancer (mCRPC) and PSA progression while receiving abiraterone acetate (AA)
- Author
-
Christopher Sweeney, Noah M. Hahn, Cindy Jacobs, Patricia S. Stewart, and Kim N. Chi
- Subjects
Oncology ,Cancer Research ,Cell signaling ,medicine.medical_specialty ,biology ,business.industry ,Abiraterone acetate ,Phases of clinical research ,Cancer ,Castration resistant ,medicine.disease ,Prostate cancer ,chemistry.chemical_compound ,Hsp27 ,chemistry ,Internal medicine ,Heat shock protein ,medicine ,biology.protein ,business - Abstract
TPS5101 Background: Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone protein that regulates cell signaling and survival pathways implicated in cancer progression and over-expressed in many cancers including prostate, bladder, lung, and breast. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a second-generation antisense oligonucleotide designed to inhibit Hsp27 expression with in vitro and in vivo efficacy that increases apoptosis, inhibits tumor growth, sensitizes cells to chemotherapy and inhibits AR activity (Cancer Res 2007;67(21):10455). A phase 2 study of OGX-427 in patients with mCRPC reported preliminary activity with 50% of patients having a ≥50% PSA decline during treatment (J Clin Oncol 30, 2012 (suppl; abstr 4514)). The purpose of this study was to evaluate the clinical activity of OGX-427 in patients with mCRPC progressing on AA. Methods: In this randomized, phase 2 study, 74 evaluable patients with mCRPC who are currently receiving AA and have PSA progression despite a prior response are randomized 1:1 to receive either OGX-427 (600 mg IV x 3 loading doses in week 1 followed by 1000 mg IV weekly) with AA or continuing AA alone. Additional eligibility criteria include: ECOG performance status ≤1, no evidence of radiographic progression, adequate liver/kidney/bone marrow function, and ≤1 prior chemotherapy for CRPC. Protocol therapy is continued until disease progression, unacceptable toxicity, or patient withdrawal. Eligible control arm patients may cross over to receive OGX-427 following disease progression. The primary objective of the study is to evaluate the proportion of patients progression-free at Day 60 post randomization. Secondary objectives include comparisons between arms of PSA and disease response, progression free survival, time to disease progression, serial serum levels of Hsp27, and circulating tumor cell enumeration. The study is designed to detect a 25% improvement in the primary endpoint (α = 0.2, β = 0.1). The study was initiated December, 2012. Clinical trial information: NCT01681433.
- Published
- 2013
19. Long-Term Comparison of Immunosuppressive Therapy with Antithymocyte Globulin to Bone Marrow Transplantation in Aplastic Anemia
- Author
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Keith M. Sullivan, John A. Hansen, H. Joachim Deeg, Fred Appelbaum, Reginald A. Clift, Kristine Doney, Tom Loughran, Rainer Storb, Claudio Anasetti, Kenneth J. Kopecky, Roger Hill, Jean E. Sanders, Finn Bo Petersen, Robert P. Witherspoon, George E. Sale, Jack W. Singer, C. Dean Buckner, Paul L. Weiden, William Bensinger, Paul J. Martin, Ronald J. Berenson, Patricia S. Stewart, E. Donnall Thomas, and Patrick G. Beatty
- Subjects
Globulin ,biology ,Bone marrow transplantation ,business.industry ,Lymphoblast ,Aplasia ,medicine.disease ,Age limit ,Patient age ,Immunology ,Paroxysmal nocturnal hemoglobinuria ,medicine ,biology.protein ,Aplastic anemia ,business - Abstract
Treatment recommendations for aplastic anemia are based on long-term survival data for recipients of syngeneic or allogeneic bone marrow transplants (BMT) and the more recent results of “immunosuppressive therapy” (1ST), which usually includes antihuman thymocyte globulin (ATG) or antihuman lymphoblast globulin (ALG). Patient age and availability of a suitable marrow donor limit the number of patients who are potential candidates for marrow grafting. Many centers will not recommend an allogeneic BMT for patients with aplasia who are over 40 years of age, although some extend the upper age limit to 50 years. Suitable marrow donors include identical twins, genotypically HLA-identical siblings, or phenotypically HLA-identical family members. Transplants using HLA-mismatched family members or phenotypically identical, unrelated donors are usually reserved for “salvage” therapy after failure of a nontransplant treatment regimen.
- Published
- 1990
20. Supportive Care of the Marrow Transplant Recipient: The Seattle Experience
- Author
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C. D. Buckner, Keith M. Sullivan, William I. Bensinger, Joel D. Meyers, G. C. Counts, Clift Ra, Thomas Ed, F R Appelbaum, John I. Clark, Finn Bo Petersen, R Storb, Patricia S. Stewart, Mark M. Schubert, Raleigh A. Bowden, and Banaji M
- Subjects
Resuscitation ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Total body irradiation ,medicine.disease ,Surgery ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,medicine ,Bone marrow ,Stem cell ,Aplastic anemia ,business - Abstract
Bone marrow transplantation is a worldwide activity involving more than 250 transplant centers in over 40 countries [5]. Since its clinical introduction almost 20 years ago, the indications for transplantation have increased as the long-term results have improved [33]. Following marrow ablation with supralethal doses of total body irradiation and/or chemotherapy, hematopoietic and immunologic reconstitution is achieved via proliferation of engrafted marrow donor stem cells [36]. The ultimate success of the procedure depends, in large measure, upon supportive care of the transplant recipient. The following report reviews aspects of this special care.
- Published
- 1990
21. Long-term follow-up of three controlled trials comparing cyclosporine versus methotrexate for graft-versus-host disease prevention in patients given marrow grafts for leukemia [letter]
- Author
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Deeg Hj, F R Appelbaum, R Storb, Patricia S. Stewart, Jean E. Sanders, Paul J. Martin, Jack W. Singer, Claudio Anasetti, Margaret S. Pepe, and KM Sullivan
- Subjects
medicine.medical_specialty ,business.industry ,Long term follow up ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Leukemia ,Graft-versus-host disease ,Medicine ,In patient ,Methotrexate ,business ,medicine.drug - Published
- 1992
22. Bone Marrow Transplantation for Patients with Myelodysplasia
- Author
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Keith M. Sullivan, C. Dean Buckner, J. W. Singer, Patrick G. Beatty, Finn Bo Petersen, Patricia S. Stewart, Reginald A. Clift, John A. Hansen, Gary Schoch, Claudio Anasetti, Paul J. Martin, R E Ramberg, Frederick R. Appelbaum, Scott I. Bearman, Janet Barrall, Howard M. Shulman, Jean E. Sanders, Robert P. Witherspoon, Rainer Storb, William I. Bensinger, LD Fisher, and E. Donnall Thomas
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,Bone marrow transplantation ,Preleukemia ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Autogenous bone ,Child ,Busulfan ,Cyclophosphamide ,Bone Marrow Transplantation ,Marrow transplantation ,business.industry ,Dysmyelopoietic Syndromes ,Age Factors ,General Medicine ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Child, Preschool ,Karyotyping ,Myelodysplastic Syndromes ,Multivariate Analysis ,Female ,business ,Whole-Body Irradiation ,Follow-Up Studies ,Case series - Abstract
To determine the efficacy of allogeneic bone marrow transplantation for severe myelodysplasia, and to identify variables predictive of outcome.Case series study.A referral-based bone marrow transplant center.Consecutive series of 59 patients with myelodysplasia or closely related disorders and either life-threatening cytopenia or a progressive increase in marrow blast percentage.Patients were treated with high-dose cyclophosphamide and total body irradiation followed by allogeneic bone marrow transplantation from either an HLA-identical (n = 45) or HLA-partially matched (n = 14) donor.The product-limit estimate for disease-free survival 3 years after transplant is 45% (95% CI, 32% to 59%). The commonest causes of death after transplant were disease recurrence, interstitial pneumonia, and graft-versus-host disease, accounting for eight deaths each. In a univariate analysis, younger patients, those with shorter disease duration, and those whose disease was characterized by an abnormal cytogenetic karyotype had better survival and disease-free survival than the group as a whole. In a multivariate analysis, younger age and abnormal karyotype were independent predictors of improved disease-free survival and overall survival. Patients who received transplants when they had fewer blasts in their bone marrow had a decreased chance for disease recurrence when compared with patients with excess blasts.Bone marrow transplantation offers a potential cure for many patients with myelodysplasia. Best results can be expected in younger patients who receive transplants relatively early in their disease course.
- Published
- 1990
23. Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?
- Author
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M Banaji, Thomas Ed, C. D. Buckner, Joachim Deeg, Robert P. Witherspoon, Kristine Doney, Ross L. Prentice, Patricia S. Stewart, Keith M. Sullivan, F R Appelbaum, Rainer Storb, Clift Ra, Jean E. Sanders, and Mark Mason
- Subjects
Cyclophosphamide ,business.industry ,Marrow transplantation ,Incidence (epidemiology) ,Immunology ,Cell Biology ,Hematology ,Human leukocyte antigen ,medicine.disease ,Biochemistry ,Transplantation ,Antigen ,High dose cyclophosphamide ,medicine ,Aplastic anemia ,business ,medicine.drug - Abstract
The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One- hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment.
- Published
- 1983
24. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts
- Author
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H. J. Deeg, FR Appelbaum, A Fefer, Patricia S. Stewart, C. D. Buckner, Robert P. Witherspoon, Paul J. Martin, J.A. Hansen, Reginald A. Clift, and Jean E. Sanders
- Subjects
medicine.medical_specialty ,Cyclophosphamide ,business.industry ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Cell Biology ,Hematology ,Human leukocyte antigen ,Total body irradiation ,Monoclonal antibody ,Biochemistry ,Gastroenterology ,Surgery ,Transplantation ,Chimera (genetics) ,surgical procedures, operative ,Internal medicine ,medicine ,Stem cell ,business ,medicine.drug - Abstract
We report results of a pilot study designed to evaluate the effects of in vitro depletion of T lymphocytes from donor marrow in patients receiving HLA-identical marrow grafts for treatment of hematologic malignancies. Twenty patients aged 31 to 50 years were prepared for transplantation with cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12.0 or 15.75 Gy). All received cyclosporine after grafting. The donor marrows were treated with a mixture of eight murine monoclonal antibodies and rabbit serum complement in a manner that achieved a 2- to 3-log depletion of T cells in most patients. Initial engraftment occurred promptly in 19 of the patients, and only three had clinically significant acute graft-versus-host disease. Depletion of donor T cells, however, was associated with an increased incidence of graft failure, which occurred as late as 244 days after transplantation. Graft failure was transient in one patient but apparently was irreversible in seven others. Three of the seven patients had cytogenetic but not morphological evidence of leukemic relapse at the time of graft failure. All seven patients with irreversible graft failure have died, six after receiving second bone marrow transplants. Seven of the eight cases of graft failure occurred among the 11 patients prepared for transplantation with 12.0 Gy of total-body irradiation, and only one occurred among the nine patients with advanced malignancies who received 15.75 Gy of total-body irradiation. This association with irradiation dose suggests that host factors were partly responsible for the graft failures. Because graft failure seldom occurs in irradiated recipients of unmodified HLA- identical allogeneic marrow transplants, it appears that T cells in the donor marrow may serve a beneficial function in helping to maintain sustained engraftment possibly by eliminating host cells that can cause graft failure. Optimal application of in vitro manipulation of donor marrow as a method for preventing graft-versus-host disease will require more effective immunosuppression of the recipient in order to assure sustained engraftment and function of donor stem cells.
- Published
- 1985
25. Marrow harvesting from normal donors
- Author
-
H. J. Deeg, Jean E. Sanders, Reginald A. Clift, Buckner Cd, FR Appelbaum, Robert P. Witherspoon, William I. Bensinger, Kristine Doney, Patricia S. Stewart, and Keith M. Sullivan
- Subjects
medicine.medical_specialty ,Allogeneic transplantation ,medicine.diagnostic_test ,business.industry ,Cerebral infarction ,Immunology ,Cell Biology ,Hematology ,Aspiration pneumonia ,medicine.disease ,Biochemistry ,Surgery ,Pneumonia ,Postoperative fever ,Biopsy ,medicine ,Very low risk ,business ,Complication - Abstract
The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.
- Published
- 1984
26. Bone marrow transplantation in patients aged 45 years and older
- Author
-
A Fefer, Phil Greenberg, Deeg Hj, Martin A. Cheever, C. D. Buckner, Keith M. Sullivan, Hans G. Klingemann, Rainer Storb, F R Appelbaum, and Patricia S. Stewart
- Subjects
medicine.medical_specialty ,Anemia ,business.industry ,Incidence (epidemiology) ,Immunology ,Preleukemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,Leukemia ,Internal medicine ,medicine ,business ,Idiopathic interstitial pneumonia ,Survival rate ,Chronic myelogenous leukemia - Abstract
Increasing age has been reported to be a poor prognostic factor for survival after bone marrow transplantation. We evaluated causes of death and frequency and type of complications after marrow grafting in 24 syngeneic and 39 allogeneic recipients who were 45 to 68 years old at the time of transplant. Most patients were in an advanced stage of hematologic malignancy. Among patients given syngeneic transplants, actuarial disease-free survival at 7 years is 20%. The major causes of death were relapse of leukemia and idiopathic interstitial pneumonia. Among allogeneic recipients, 9 (23%) are currently alive, and actuarial disease-free survival at 7 years is 11%. Cytomegalovirus pneumonia and septicemia were the most frequent causes of death. Patients over 50 years of age had the poorest survival rate (1/13), but many of these were transplanted in an advanced stage of their disease. However, among 12 patients transplanted while in remission or at an early stage of their disease, 5 are surviving 65 to 1,160 days after transplantation, with an actuarial survival rate of 22% at 3 years. This is in contrast to those who received their transplant in relapse: 2 out of 20 patients (10%) became long-term survivors, with a probability of survival of 15% at 3 years. The actuarial incidence of grade II through IV acute graft- v-host disease (GVHD) was 30% for allogeneic recipients 45 to 50 years of age. This was not significantly different from the incidence in younger patients. In patients 51 to 62 years of age, the actuarial incidence of acute GVHD was 79%; however, this group included three partially HLA-mismatched transplants. Ten of 15 patients surviving at least 3 months developed chronic GVHD. These results suggest that marrow transplantation is feasible and should be considered in patients over 45 years, especially if recipients are in good clinical condition and are at an early stage of their disease, such as the chronic phase of chronic myelogenous leukemia and preleukemia. For patients more than 50 years of age, allogeneic marrow grafting cannot presently be considered first-line therapy.
- Published
- 1986
27. Early infectious complications in allogeneic marrow transplant recipients with acute leukemia: Effects of prophylactic measures
- Author
-
Patricia S. Stewart, Thomas Ed, John Hersman, James C. Wade, Joel D. Meyers, Clift Ra, M. Murphy, Jean E. Sanders, C. D. Buckner, and George W. Counts
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Blood transfusion ,Pulmonary Fibrosis ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Graft vs Host Disease ,Infections ,Sepsis ,Internal medicine ,Humans ,Medicine ,Blood Transfusion ,Bone Marrow Transplantation ,Cause of death ,Infection Control ,Acute leukemia ,Leukemia ,business.industry ,General Medicine ,Environment, Controlled ,medicine.disease ,Anti-Bacterial Agents ,Leukemia, Lymphoid ,Surgery ,Infectious Diseases ,Evaluation Studies as Topic ,Bacteremia ,Acute Disease ,business ,Complication ,Granulocytes - Abstract
One hundred eighty-two patients with acute leukemia underwent allogeneic marrow transplantation and received one of two forms of infection prophylaxis: isolation and decontamination procedures in laminar air flow rooms (90 patients) or prophylactic granulocyte transfusion from a single family member (92 patients). Infection acquisition and survival were analyzed from the time of admission to 100 days posttransplant. There were 20 major local infections in the laminar air flow group and 16 in the prophylactic granulocyte group. Of the patients in the laminar air flow group, 24 (27%) had 27 episodes of bacteremia, while 23 (25%) of the prophylactic granulocyte group had 25 episodes of bacteremia. There were no significant differences in infection acquisition between the two groups during the period of granulocytopenia or after engraftment. The mortality during the first 100 days was 28% for the laminar air flow group and 35% for the prophylactic granulocyte group. Thirteen patients (14%) in the laminar air flow group and five (5%) in the prophylactic granulocyte group died with bacterial or fungal infections. There were no statistically significant differences between the two groups in overall incidence of or mortality from interstitial pneumonitis which was the predominant cause of death. However, the subset of patients who were seronegative for cytomegalovirus antibody at the time of transplant and received granulocytes from seropositive donors had a significantly higher incidence of and mortality from cytomegalovirus interstitial pneumonitis.
- Published
- 1983
28. Graft-versus-host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: long-term follow-up of a controlled trial
- Author
-
Robert P. Witherspoon, Jack W. Singer, Frederick R. Appelbaum, William I. Bensinger, Roger Hill, Rainer Storb, Thomas P. Loughran, Gary Longton, Jean E. Sanders, C. Dean Buckner, Patricia S. Stewart, Paul J. Martin, Reginald A. Clift, Keith M. Sullivan, Claudio Anasetti, E. Donnall Thomas, Kris Doney, Margaret S. Pepe, J. D. Hansen, Patrick G. Beatty, and H. Joachim Deeg
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Cyclophosphamide ,Graft vs Host Disease ,Cyclosporins ,Disease ,Gastroenterology ,law.invention ,Random Allocation ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,In patient ,Child ,Bone Marrow Transplantation ,Clinical Trials as Topic ,business.industry ,Incidence (epidemiology) ,Anemia, Aplastic ,Hematology ,medicine.disease ,Surgery ,Regimen ,Methotrexate ,surgical procedures, operative ,Graft-versus-host disease ,Child, Preschool ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Summary Forty-six patients with aplastic anaemia (median age 23 years) were given cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-versus-host disease (GVHD), the patients were entered into a randomized prospective trial comparing a combination of methotrexate and cyclosporin (n= 22) to methotrexate alone (n= 24). Methotrexate/cyclosporin significantly reduced the incidence and severity of acute GVHD and improved early survival. This report updates the results of the randomized trial with follow-up ranging from 3 to more than 6 years. The methotrexate/cyclosporin regimen did not interfere with sustained engraftment, and there were no significant differences in the incidence of early or late graft rejection among the two treatment groups (10%v 4%). The incidence of chronic GVHD was higher among methotrexate/cyclosporin-treated patients (58%v 36%; P=0·18). Two patients in each treatment group still require treatment for chronic GVHD, while treatment is no longer needed in the other patients. Projected 4-year survival is 73% in patients given methotrexate/cyclosporin compared to 58% in patients given methotrexate alone (P=0·16). Having achieved a reduction in the incidence of acute GVHD and associated early mortality without impairing engraftment, it is clear that future progress in marrow grafting for aplastic anaemia must come in the area of chronic GVHD.
- Published
- 1989
29. Fanconi's anemia treated by allogeneic marrow transplantation
- Author
-
Jean E. Sanders, FR Appelbaum, Keith M. Sullivan, H. J. Deeg, Patricia S. Stewart, Kristine Doney, Thomas Ed, Reginald A. Clift, Buckner Cd, Linda K. Johnson, Rainer Storb, and Robert P. Witherspoon
- Subjects
Intracerebral hemorrhage ,medicine.medical_specialty ,Cyclophosphamide ,Anemia ,Marrow transplantation ,business.industry ,Immunology ,Cell Biology ,Hematology ,Disease ,medicine.disease ,Procarbazine ,Biochemistry ,Surgery ,surgical procedures, operative ,Fanconi's anemia ,medicine ,Chronic gvhd ,business ,medicine.drug - Abstract
Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.
- Published
- 1983
30. MYCOBACTERIAL INFECTIONS IN MARROW TRANSPLANT PATIENTS
- Author
-
RUDOLPH M. NAVARI, KEITH M. SULLIVAN, STEVEN C. SPRINGMEYER, MARTIN S. SIEGEL, JOEL D. MEYERS, C. DEAN BUCKNER, JEAN E. SANDERS, PATRICIA S. STEWART, R. A. CLIFT, ALEXANDER FEFER, RAINER STORB, and E. DONNALL THOMAS
- Subjects
Adult ,Male ,Tuberculosis ,Adolescent ,Mycobacterium Infections, Nontuberculous ,Mycobacterium tuberculosis ,Humans ,Medicine ,Tuberculoma ,Pulmonary pathology ,Tuberculosis, Pulmonary ,Bone Marrow Transplantation ,Immunosuppression Therapy ,Mycobacterium kansasii ,Transplantation ,Leukemia ,biology ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,Immunology ,Female ,Mycobacterium fortuitum ,Bone marrow ,business ,Chest radiograph - Abstract
Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.
- Published
- 1983
31. Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse
- Author
-
Thomas Ed, C. D. Buckner, F R Appelbaum, R Storb, Keith M. Sullivan, Clift Ra, and Patricia S. Stewart
- Subjects
medicine.medical_specialty ,business.industry ,Marrow transplantation ,Immunology ,Early Relapse ,Cell Biology ,Hematology ,Time optimal ,medicine.disease ,Biochemistry ,Surgery ,Transplantation ,First relapse ,Leukemia ,Acute nonlymphoblastic leukemia ,Medicine ,In patient ,business - Abstract
Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2–6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.
- Published
- 1983
32. Autologous bone marrow transplantation in metastatic breast cancer
- Author
-
Patricia S. Stewart
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,Antineoplastic Agents ,Breast Neoplasms ,Disease ,Transplantation, Autologous ,Breast cancer ,Bone Marrow ,Internal medicine ,Freezing ,Methods ,medicine ,Adjuvant therapy ,Humans ,Neoplasm Metastasis ,Bone Marrow Transplantation ,business.industry ,Total body irradiation ,medicine.disease ,Metastatic breast cancer ,medicine.anatomical_structure ,Toxicity ,Female ,Tissue Preservation ,Bone marrow ,business ,medicine.drug - Abstract
The use of adjuvant chemotherapy following the primary treatment of breast cancer has led to an increased disease-free survival. The outlook for patients who present with metastatic disease however remains dismal, with little improvement in survival in the last decade. A recent analysis by Bonadonna and his colleagues has demonstrated a strong influence of the dose of drugs administered on relapse-free survival in patients with breast cancer receiving adjuvant therapy and those with metastatic disease. The utilization of cryopreserved autologous bone marrow permits the use of more aggressive therapy without regard to marrow toxicity, the dose-limiting feature of many antineoplastic agents. Some of the questions and potential problems with the use of autologous marrow rescue in solid tumors is discussed. Preliminary data on a protocol to evaluate the role of high-dose cyclophosphamide and total body irradiation with autologous marrow transplantation in patients with metastatic breast carcinoma are presented.
- Published
- 1982
33. The effects of splenectomy on engraftment and platelet transfusion requirements in patients with chronic myelogenous leukemia undergoing marrow transplantation
- Author
-
H. Joachim Deeg, Banaji M, Patricia S. Stewart, Rainer Storb, Robert W. McGuffin, Sherrill J. Slichter, C. Dean Buckner, Reginald A. Clift, Roger Hill, Jean E. Sanders, Scott I. Bearman, Finn Bo Petersen, William I. Bensinger, and E. Donnall Thomas
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Pulmonary Fibrosis ,medicine.medical_treatment ,Splenectomy ,Graft vs Host Disease ,Platelet Transfusion ,Granulocyte ,Leukocyte Count ,Refractory ,Humans ,Transplantation, Homologous ,Medicine ,Blood Transfusion ,Platelet ,Bone Marrow Transplantation ,Platelet Count ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Transplantation ,Platelet transfusion ,medicine.anatomical_structure ,Leukemia, Myeloid ,Female ,Bone marrow ,business ,Granulocytes ,Chronic myelogenous leukemia - Abstract
Granulocyte and platelet recovery as well as platelet transfusion requirements following allogeneic marrow transplantation were analyzed in 67 patients with chronic myelogenous leukemia in the chronic phase. Twenty patients had splenectomy prior to transplantation. Forty-seven patients were transplanted without splenectomy, 21 of whom had splenic enlargement by physical examination. There were no differences in the proportion of patients with granulocyte recovery, but the recovery of peripheral granulocytes to levels of 200, 500 and 1,000/mm3 occurred more rapidly in the splenectomy group than in the no-splenectomy group. Patients with splenectomy received platelet transfusions for a mean of 10 (2–36) days as compared to 20 (3–82) days for patients without splenectomy (p < .001). Eighteen (90%) patients with splenectomy became platelet transfusion independent at a median of 16 (2–32) days after transplantation as compared to 40 (85%) patients without splenectomy who became transfusion independent at a median of 28 (15–86) days (p < .001). The proportion of patients achieving platelet levels of 50 and 100 × 103/mm3 did not differ between the two groups (p = .07), but patients in the splenectomy group achieved these levels more rapidly following transplant (p < .001). One of 17 evaluable patients in the splenectomy group and 31 of 46 in the no-splenectomy group became refractory to random platelets (p < .001) and required platelets from family members or unrelated completely or partially HLA matched donors. In the no-splenectomy group, splenic size did not affect the speed of granulocyte or platelet recovery or platelet transfusion requirements. There was no difference in the post-transplant survival of patients with or without splenectomy.
- Published
- 1986
34. Marrow transplantation for leukemia following fractionated total body irradiation. A comparative trial of methotrexate and cyclosporine
- Author
-
Frederick R. Appelbaum, Michael S. Kennedy, William I. Bensinger, Martin A. Cheever, Philip D. Greenberg, Robert W. McGuffin, Rainer Storb, Patrick G. Beatty, C. Dean Buckner, H. Joachim Deeg, Roger Hill, Robert P. Witherspoon, Jean E. Sanders, Paul J. Martin, Reginald A. Clift, Alexander Fefer, Kristine Doney, E. Donnall Thomas, Keith M. Sullivan, Claude Irle, and Patricia S. Stewart
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Graft vs Host Disease ,Cyclosporins ,Gastroenterology ,Recurrence ,Internal medicine ,Acute lymphocytic leukemia ,Humans ,Medicine ,Vascular Diseases ,Bone Marrow Transplantation ,Chemotherapy ,Leukemia ,business.industry ,Liver Diseases ,Hematology ,Middle Aged ,Total body irradiation ,medicine.disease ,Surgery ,Transplantation ,Methotrexate ,Graft-versus-host disease ,Oncology ,Kidney Diseases ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Fifty-six patients, 30-47 yr of age, with leukemia in relapse received allogeneic marrow transplants from HLA-identical siblings. All patients were treated with cyclophosphamide (120 mg/kg) and 7 daily fractions of 2.25 Gy of total body irradiation (TBI) for seven consecutive days. Nine patients (16%) are currently alive and free of disease 324-845 days from transplantation. The actuarial relapse and survival rates at 2 yr were 56% and 9.5% respectively. These data were not remarkably different from those in previous studies using 10 Gy of TBI administered as a single dose. Thirty patients were randomized to receive methotrexate (MTX) and 26 to receive cyclosporine (CSP) as postgrafting prophylaxis for acute graft-versus-host disease (GVHD). The probability of developing significant acute GVHD by day 100 post-transplant was 71% for patients in the MTX group and 45% for patients in the CSP group (p less than 0.05). The probability of relapse was 37% for patients in the MTX group and 70% for patients in the CSP group (p less than 0.05). Transplant-related deaths were more frequent in the MTX group and leukemic deaths were more frequent in the CSP group although this may have been related to an uneven distribution of high-risk patients. Long-term disease-free survival was comparable. Patients in the MTX group had more severe mucositis, more alveolar pneumonias and possibly more deaths due to complications of acute and chronic GVHD. Patients in the CSP group had a higher incidence of hypertension, neurological complications and renal dysfunction.
- Published
- 1985
35. Marrow transplantation for acute nonlymphoblastic leukemia in first remission using fractionated or single-dose irradiation
- Author
-
Robert W. McGuffin, J.W. Smith, Clift Ra, Jean E. Sanders, Thomas Ed, Alexander Fefer, R Storb, Patricia S. Stewart, John Hersman, and C. D. Buckner
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Child ,Bone Marrow Transplantation ,Leukemia ,Radiation ,business.industry ,Radiotherapy Dosage ,Immunosuppression ,Middle Aged ,Total body irradiation ,medicine.disease ,Radiation therapy ,Regimen ,Haematopoiesis ,medicine.anatomical_structure ,Oncology ,Child, Preschool ,Acute Disease ,Bone marrow ,Nuclear medicine ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Fifty-three patients with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, total body irradiation and marrow transplantation. Twenty-seven patients received 1000 rad in one exposure and 12 are living in remission 6–29 months later. Twenty-six received 200 rad on each of 6 days and 18 are living in remission after 4–27 months. Kaplan-Meier analysis shows a survival advantage for the fractionated regimen (p = 0.05).
- Published
- 1982
36. Bone Marrow Transplantation Experience for Children With Aplastic Anemia
- Author
-
Jean E. Sanders, John Whitehead, Rainer Storb, C. Dean Buckner, Reginald A. Clift, Eric Mickelson, Frederick R. Appelbaum, William I. Bensinger, Patricia S. Stewart, Kristine Doney, Keith Sullivan, H. Joachim Deeg, Robert P. Witherspoon, and E. Donnall Thomas
- Subjects
Pediatrics, Perinatology and Child Health - Abstract
From May 1971 through December 1981, 81 children (22 months to 17 years of age) received allogeneic bone marrow grafts for severe aplastic anemia. All donors were HLA-identical family members. Fifty-seven of the 81 (70%) are still alive. Twenty-three untransfused patients were conditioned with cyclophosphamide, 50 mg/kg/d, for four days, and 19 (83%) have survived from 5 to 12 years. All 58 transfused patients were conditioned with cyclophosphamide, 50 mg/kg/d, for four days, 11 received additional immunosuppression, and 19 received posttransplantation donor buffy coat cells. Thirty-eight (65%) have survived from 3 to 13 years (P = .1). In a multivariate analysis, the only factor significantly associated with increased survival among patients with sustained grafts was the absence of significant graft v host disease (P < .0001). The factors significantly related to increased rejection were low bone marrow cell dose (P < .05) and positive relative response in mixed leukocyte culture (P < .0001), but the addition of buffy coat cells did not significantly influence graft rejection. The development of grades II to IV acute graft v host disease was associated with random donor platelet refractoriness (P < .05) and donor/recipient sex differences (P < .05). Patients at highest risk for chronic graft v host disease were those patients who developed significant acute graft v host disease (P < .01) and who received buffy coat infusions (P < .025). All patients who were untransfused had a negative relative response and were not refractory to random donor platelets.
- Published
- 1986
37. Granulocyte collection by continuous-flow centrifugation using arteriovenous shunts
- Author
-
Banaji M, William I. Bensinger, Robert O. Hickman, Buckner Cd, Patricia S. Stewart, Thomas Ed, Reginald A. Clift, Jean E. Sanders, and B. M. Williams
- Subjects
medicine.medical_specialty ,business.industry ,Blood Donors ,Centrifugation ,Hematology ,General Medicine ,Granulocyte ,Hydroxyethyl starch ,Surgery ,Severe anemia ,Transplantation ,medicine.anatomical_structure ,Arteriovenous Shunt, Surgical ,Continuous flow centrifugation ,medicine ,Humans ,Leukapheresis ,business ,Shunt (electrical) ,IBM 2997 ,Whole blood ,medicine.drug ,Granulocytes - Abstract
Two thousand nine hundred twenty-seven granulocyte collections were made using continuous-flow centrifugation with the Aminco Celltrifuge I, the Fenwal Celltrifuge II, and the IBM 2997. There were 231 recipients and 246 donors. In 32 patients attempts to provide daily granulocyte transfusions from a single donor were unsuccessful owing to clotting of the silastic-Teflon arteriovenous shunt. Repeated granulocyte donations produced severe anemia requiring red cell transfusions in all the females and most of the males who had previously donated marrow for transplantation. Granulocyte collections were similar when collected with the Celltrifuge I or the IBM 2997, but collections with the Celltrifuge II were smaller. Infusion of hydroxyethyl starch directly into whole blood as it entered the centrifuge increased granulocyte collections. Granulocyte collections decreased with increasing number of daily collections.
- Published
- 1984
38. Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation
- Author
-
Jean E. Sanders, Kristine Doney, C. D. Buckner, Paul E. Neiman, Keith M. Sullivan, Alexander Fefer, Patricia S. Stewart, Clift Ra, Joachim Deeg, R Storb, Thomas Ed, and Jack W. Singer
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pulmonary Fibrosis ,Graft vs Host Disease ,Antineoplastic Agents ,Disease ,Human leukocyte antigen ,Philadelphia chromosome ,Postoperative Complications ,HLA Antigens ,Pulmonary fibrosis ,medicine ,Chromosomes, Human, 21-22 and Y ,Humans ,Child ,Bone Marrow Transplantation ,business.industry ,Chronic granulocytic leukaemia ,Age Factors ,General Medicine ,medicine.disease ,Surgery ,Transplantation ,Transplantation, Isogeneic ,surgical procedures, operative ,medicine.anatomical_structure ,Leukemia, Myeloid ,Drug Therapy, Combination ,Female ,Bone marrow ,business ,Chemoradiotherapy ,Follow-Up Studies - Abstract
Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).
- Published
- 1982
39. Allogeneic and Syngeneic Marrow Transplantation for Aplastic Anemia: Overview of Seattle
- Author
-
Alexander Fefer, Reginald A. Clift, Robert W. McGuffin, Jean E. Sanders, C. Dean Buckner, Kristine Doney, E. Donnall Thomas, Roger Hill, Robert P. Witherspoon, Frederick R. Appelbaum, Claudio Anasetti, Keith M. Sullivan, William Bensinger, Paul J. Martin, Rainer Storb, Jack W. Singer, Patrick G. Beatty, Patricia S. Stewart, and John A. Hansen
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Marrow transplantation ,Context (language use) ,Newly diagnosed ,Disease ,medicine.disease ,Severe Aplastic Anemia ,Supportive psychotherapy ,Immunology ,Cohort ,medicine ,Aplastic anemia ,business - Abstract
Marrow transplantation for the treatment of severe aplastic anemia has to be viewed in the context of alternate therapies for this disease. An earlier study of the International Aplastic Anemia Study Group showed that newly diagnosed patients with severe aplastic anemia treated by supportive therapy with or without androgens had a survival of only 20% at 5 years, with most patients dying within the first 6 months of diagnosis [1]. Most surviving patients had partial or complete spontaneous hematologic recoveries sufficient to live without the need for transfusions. These results were subsequently confirmed by the study group in another cohort of patients [2].
- Published
- 1988
40. Treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Randomized study comparing corticosteroids and cyclosporine
- Author
-
Michael S. Kennedy, Patricia S. Stewart, C. Dean Buckner, Paul J. Martin, Paul L. Weiden, Rainer Storb, Frederick R. Appelbaum, Kristine Doney, E. Donnall Thomas, Robert P. Witherspoon, H. Joachim Deeg, Keith M. Sullivan, and Jean E. Sanders
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Graft vs Host Disease ,Cyclosporins ,Gastroenterology ,Injections, Intramuscular ,Methylprednisolone ,law.invention ,Random Allocation ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Prospective Studies ,Aplastic anemia ,Child ,Bone Marrow Transplantation ,Clinical Trials as Topic ,business.industry ,Incidence (epidemiology) ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Transplantation ,medicine.anatomical_structure ,Pancreatitis ,Acute Disease ,Injections, Intravenous ,Corticosteroid ,Methotrexate ,Female ,Kidney Diseases ,Bone marrow ,business ,medicine.drug - Abstract
Seventy-seven patients (age 12 to 46 years) who underwent allogeneic marrow transplantation for hematologic malignancy or aplastic anemia and who had grade II to IV acute graft-versus-host disease despite methotrexate prophylaxis were randomly assigned to receive methylprednisolone 2 mg/kg per day intravenously (n = 39) or cyclosporine (n = 38) either 12 to 15 mg/kg per day orally or 3 to 5 mg/kg per day intravenously. In both groups, clinical and histologic evidence of graft-versus-host disease was detected at medians of 16 and 25 days, respectively. Drugs were given for a minimum of 14 days unless significant deterioration occurred. If graft-versus-host disease did not improve with this therapy, treatment with a second agent was Initiated. Treatment responses were scored after reviewing clinical and laboratory data collected before, during, and after the 14-day treatment period. Possible scores were as follows: −1, worse; 0, no change; +1, improvement in one organ system (skin, liver, gut) with no deterioration in the other two; +2, complete resolution of all Involved systems. The median response score among 39 methylprednisolone-treated patients was 0. Sixteen patients (41 percent) showed response to treatment, 11 with partial and five with complete response. The median response score among 38 cyclosporine-treated patients was +1. Twenty-three patients (61 percent) showed response to treatment, 15 with partial and eight with complete response (p = 0.039). Twenty patients receiving methylprednisolone and 18 receiving cyclosporine required additional therapy. The incidence of chronic graft-versus-host disease was similar In both groups. It developed in all nonresponding patients at risk who had received secondary therapy. Among responding patients (scores +1 or +2) who were not given additional treatment, chronic graft-versus-host disease developed in eight of 11 (72 percent) receiving methylprednisolone and five of ten (50 percent) receiving cyclosporine. Survival beyond 17 months was similar In the two groups (28 percent and 24 percent, respectively). These data suggest that cyclosporine is a useful agent for the treatment of acute graft-versus-host disease, comparable in its efficacy to methylprednisolone.
- Published
- 1985
41. Allogeneic marrow transplantation using fractionated total body irradiation in patients with acute lymphoblastic leukemia in relapse
- Author
-
Reginald A. Clift, Robert W. McGuffin, C. Dean Buckner, Keith M. Sullivan, Jean E. Sanders, Rainer Storb, George E. Sale, E. Donnall Thomas, Patricia S. Stewart, and John Hersman
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Lymphoblastic Leukemia ,Gastroenterology ,Interstitial pneumonitis ,Graft vs Host Reaction ,Recurrence ,Internal medicine ,Medicine ,Humans ,In patient ,Child ,Bone Marrow Transplantation ,business.industry ,Marrow transplantation ,Hematology ,Pneumonia ,Total body irradiation ,Middle Aged ,Surgery ,Leukemia, Lymphoid ,Regimen ,Oncology ,Child, Preschool ,Methotrexate ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Six fractionated total body irradiation (TBI) regimens given over 2–7 days to a total midline dose of between 1200 and 1750 rads were evaluated in 41 patients with acute lymphoblastic leukemia in relapse. Cyclophosphamide 120 mg/kg was given prior to TBI in all cases, and dimethylbusulphan was added to cyclophosphamide and 1500 rad TBI in one regimen. Relapses occurred in all regimens. The overall disease-free survival of three of 41 patients was not different from previous studies with 1000 rad TBI given in a single dose. Graft-vs-host disease occurred in only 12 of 41 patients. Two of three disease-free survivors had significant graft-vs-host disease.
- Published
- 1982
42. Autologous Marrow Transplantation for Malignant Lymphoma
- Author
-
C. Dean Buckner, Keith M. Sullivan, Alexander Fefer, E. Donnall Thomas, Patricia S. Stewart, Frederick R. Appelbaum, Reginald A. Clift, H. Joachim Deeg, Roger Hill, Jean E. Sanders, Rainer Storb, and Nancy Flournoy
- Subjects
Oncology ,Chemotherapy ,medicine.medical_specialty ,Allogeneic transplantation ,business.industry ,medicine.medical_treatment ,Total body irradiation ,medicine.disease ,Radiation therapy ,Malignant lymphoma ,Leukemia ,Internal medicine ,medicine ,business ,Chemoradiotherapy ,Autologous Marrow Transplantation - Abstract
Patients with disseminated malignant lymphoma who have failed first line chemotherapy are unlikely to be cured with additional chemotherapy or radiotherapy delivered at conventional doses. Based on the success of high dose chemoradiotherapy and marrow transplantation as treatment for relapsed leukemia, a number of studies have been performed using a similar approach in patients with relapsed malignant lymphoma (1–14). This report details the initial Seattle experience with autologous marrow transplantation as treatment for patients with relapsed or resistant malignant lymphoma and compares this approach with our previously published experience using syngeneic and allogeneic transplantation in a similar group of patients (3–5).
- Published
- 1986
43. Acute renal failure following bone marrow transplantation: a retrospective study of 272 patients
- Author
-
Richard A. Zager, Howard M. Shulman, J. O'Quigley, B.K. Zager, Thomas Ed, Charles E. Alpers, L.M. Gamelin, and Patricia S. Stewart
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Renal function ,Jaundice ,Gastroenterology ,chemistry.chemical_compound ,Postoperative Complications ,Hepatorenal syndrome ,Renal Dialysis ,Risk Factors ,Internal medicine ,Amphotericin B ,Sepsis ,medicine ,Humans ,Dialysis ,Bone Marrow Transplantation ,Retrospective Studies ,Kidney ,Creatinine ,business.industry ,Histocompatibility Testing ,Body Weight ,Acute Kidney Injury ,medicine.disease ,Prognosis ,Surgery ,medicine.anatomical_structure ,chemistry ,Nephrology ,Hemodialysis ,medicine.symptom ,business ,Complication - Abstract
To assess the incidence, risk factors, and course of acute renal failure (ARF) following bone marrow transplantation (BMT), a retrospective analysis of 272 patients receiving transplants at the Fred Hutchinson Cancer Research Center during 1986 was undertaken. The patients were divided into three groups: group 1, hemodialysis requiring ARF; group 2, mild renal insufficiency (doubling of serum creatinine, S cr but no dialysis); group 3, relatively normal post-BMT renal function (no doubling of S cr ). Fifty-three percent of patients at least doubled their S cr (Groups 1 and 2), and 24% required dialysis. The degree of renal functional impairment had a dramatic impact on patient mortality rates (84%, 37%, and 17% in groups 1, 2, and 3, respectively). Jaundice (bilirubin ≥ 2.0 mg/dL), weight gain (≥ 2.0 kg), amphotericin B use, and a pretransplant S cr ≥ 0.7 mg/dL were independently associated with the subseqent development of dialysis-requiring ARF ( P v host disease correlated with the development of ARF. A mismatched graft was a significant risk factor for ARF by univariate but not by multivariate analysis. Within 48 hours before doubling the S cr , 63% of group 1 patients had positive blood cultures and 39% developed hypotension. Of the 26 group 1 patients who had urine Na concentrations measured, 85% had values ≤ 40 mEq/L. Autopsy kidney specimens provided no clear explanation for ARF in the vast majority of patients in group 1. We conclude that ARF is an extremely common complication following BMT; its development is frequently preceded by hepatic dysfunction, weight gain, amphotericin B use, septicemia, and hypotension; and it augers a grave prognosis. We speculate, based on the data, that the renal functional impairment is usually hemodynamic, rather than structural, in nature.
- Published
- 1989
44. Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings
- Author
-
H. Joachim Deeg, Howard M. Shulman, Kristine Doney, Reginald A. Clift, Patricia S. Stewart, C. Dean Buckner, Appelbaum Fa, Jean E. Sanders, Robert P. Witherspoon, Keith M. Sullivan, E. Donnall Thomas, Ross L. Prentice, and Rainer Storb
- Subjects
Adult ,Male ,Risk ,Cyclophosphamide ,Adolescent ,Human leukocyte antigen ,Sustained Engraftment ,Graft vs Host Reaction ,Postoperative Complications ,HLA Antigens ,Internal Medicine ,medicine ,Humans ,Predictor variable ,In patient ,Aplastic anemia ,Child ,Bone Marrow Transplantation ,Marrow transplantation ,business.industry ,Age Factors ,Anemia, Aplastic ,Infant ,General Medicine ,medicine.disease ,Graft-versus-host disease ,Child, Preschool ,Immunology ,Female ,business ,medicine.drug ,Follow-Up Studies - Abstract
One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.
- Published
- 1983
45. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia
- Author
-
Robert W. McGuffin, John Whitehead, C. Dean Buckner, William I. Bensinger, Lawrence G. Lum, Kristine Doney, Vernon T. Farewell, Patricia S. Stewart, Reginald A. Clift, Gary Yee, J. D. Hansen, H. Joachim Deeg, Robert P. Witherspoon, Roger Hill, Jean E. Sanders, Paul J. Martin, Patrick G. Beatty, Keith M. Sullivan, Rainer Storb, E. Donnall Thomas, and Frederick R. Appelbaum
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Graft vs Host Disease ,Cyclosporins ,Gastroenterology ,Random Allocation ,Pharmacotherapy ,Internal medicine ,Medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Bone Marrow Transplantation ,Leukemia ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Graft-versus-host disease ,medicine.anatomical_structure ,Methotrexate ,Leukemia, Myeloid ,Acute Disease ,Drug Therapy, Combination ,Female ,Bone marrow ,business ,medicine.drug - Abstract
We treated 93 patients who had acute nonlymphoblastic leukemia in the first remission or chronic myelocytic leukemia in the chronic phase (median age, 30 years) with high-dose cyclophosphamide and fractionated total-body irradiation, followed by infusion of marrow from an HLA-identical sibling. To evaluate postgrafting prophylaxis for graft versus host disease, we studied these patients in a sequential, prospective, randomized trial that compared the effect of a combination of methotrexate and cyclosporine (n = 43) with that of cyclosporine alone (n = 50). All patients had evidence of sustained engraftment. A significant reduction in the cumulative incidence of grades II to IV acute graft versus host disease was observed in the patients who received both methotrexate and cyclosporine (33 percent), as compared with those who were given cyclosporine alone (54 percent) (P = 0.014). Seven patients who received cyclosporine alone acquired grade IV acute graft versus host disease, as compared with none who received both methotrexate and cyclosporine. Thirty-five of the 43 patients given both methotrexate and cyclosporine and 31 of the 50 patients given cyclosporine are alive as of this writing, at 4 months to 2 years (median, 15 months); the actuarial survival rates in the two groups at 1.5 years were 80 percent and 55 percent, respectively (P = 0.042). We conclude that the combination of methotrexate and cyclosporine is superior to cyclosporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival.
- Published
- 1986
46. Allogeneic marrow transplantation for acute leukemia in relapse
- Author
-
Christopher C. Badger, Keith M. Sullivan, E. Donnall Thomas, Nancy Flournoy, Jean E. Sanders, C. Dean Buckner, Reginald A. Clift, Rainer Storb, Patricia S. Stewart, and Howard M. Shulman
- Subjects
Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Daunorubicin ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Child ,Bone Marrow Transplantation ,Acute leukemia ,Leukemia ,business.industry ,Infant ,Hematology ,Total body irradiation ,Middle Aged ,medicine.disease ,Surgery ,Leukemia, Lymphoid ,Transplantation ,Regimen ,Child, Preschool ,Methotrexate ,business ,Whole-Body Irradiation ,medicine.drug ,Follow-Up Studies - Abstract
The results of allogeneic marrow transplantation in 75 patients with acute lymphoblastic leukemia and 63 patients with acute non-lymphoblastic leukemia in relapse are reviewed. The effects of various chemotherapeutic regimens added to the basic regimen of cyclophosphamide (Cy) 60 mg/kg given on each of two successive days followed by 1000 rad of total body irradiation (TBI) were evaluated. The regimens tested were dimethylbusulphan (DMB), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and daunorubicin. Seventeen of 138 patients are alive between three and nine and a half years from transplantation. The addition of other chemotherapeutic agents to th basic Cy and TBI regimen did not decrease relapse frequency or prolong survival.
- Published
- 1982
47. Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation
- Author
-
Patricia S. Stewart, Keith M. Sullivan, C. Dean Buckner, Reginald A. Clift, E. Donnall Thomas, Rainer Storb, Jean E. Sanders, and Robert C. Hackman
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Lymphoblastic Leukemia ,Interstitial pneumonitis ,Graft vs Host Reaction ,Recurrence ,medicine ,Humans ,Child ,Bone Marrow Transplantation ,Probability ,Single exposure ,Leukemia ,Marrow transplantation ,business.industry ,Hematology ,Total body irradiation ,Middle Aged ,Prognosis ,Surgery ,Transplantation ,Oncology ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
Twelve patients with acute lymphoblastic leukemia in second to fourth remission received allogeneic marrow transplants following preparation with cyclophosphamide, 120 mg/kg and 1400 rad of fractionated total body irradiation. Two patients died of interstitial pneumonitis 32 and 62 days post-transplantation. Six patients relapsed between days 59 and 659 and four died of leukemia-related problems. Two patients who relapsed are currently alive, one in remission and one in relapse. Four patients are alive and free of disease 657 to 991 days following transplantation. This disease-free survival was not significantly better than the six of 22 disease-free survivors previously observed following cyclophosphamide and 1000 rad of total body irradiation given in a single exposure.
- Published
- 1982
48. High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia
- Author
-
FR Appelbaum, Rainer Storb, S.R. Riddell, Keith M. Sullivan, Patricia S. Stewart, Jean E. Sanders, Buckner Cd, Reginald A. Clift, and Thomas Ed
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Gastroenterology ,Acute lymphocytic leukemia ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Child ,Preparative Regimen ,Bone Marrow Transplantation ,Immunosuppression Therapy ,Acute leukemia ,Clinical Trials as Topic ,Leukemia ,business.industry ,Cytarabine ,Infant ,Total body irradiation ,medicine.disease ,Surgery ,Leukemia, Lymphoid ,Oncology ,Leukemia, Myeloid ,Acute Disease ,business ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.
- Published
- 1988
49. Treatment of non-Hodgkin's lymphoma with chemoradiotherapy and allogenic marrow transplantation
- Author
-
Patricia S. Stewart, Alexander Fefer, C. D. Buckner, Keith M. Sullivan, Clift Ra, Jean E. Sanders, Thomas Ed, Deeg Hj, F R Appelbaum, Paul E. Neiman, and R Storb
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Lymphoma ,Pulmonary Fibrosis ,Graft vs Host Disease ,Disease ,medicine ,Humans ,Transplantation, Homologous ,Child ,Bone Marrow Transplantation ,Acute leukemia ,business.industry ,Combination chemotherapy ,Hematology ,General Medicine ,Bacterial Infections ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Surgery ,Non-Hodgkin's lymphoma ,Transplantation ,surgical procedures, operative ,Oncology ,Child, Preschool ,Chronic Disease ,Female ,Neoplasm Recurrence, Local ,business ,Complication ,Chemoradiotherapy - Abstract
Twenty patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Four patients remain alive in complete remission from 153 to 784 days after transplant. The reason for failure in eight cases was persistence or relapse of lymphoma. In the other eight cases, death was due to a complication of the transplant procedure including interstitial pneumonia, veno-occlusive disease of the liver, graft-versus-host disease, or infection. These results appear similar to those previously observed in patients with acute leukemia in relapse in that a small but significant proportion of patients with otherwise end-stage disease may achieve prolonged complete remission after intensive chemoradiotherapy and allogeneic marrow transplantation.
- Published
- 1983
50. Simulated aortic or pulmonary stenosis in the rat
- Author
-
Patricia S. Stewart and Hugh A. Lindsay
- Subjects
Male ,Food intake ,medicine.medical_specialty ,Weanling ,Appetite ,Growth ,General Biochemistry, Genetics and Molecular Biology ,Text mining ,Internal medicine ,medicine ,Animals ,business.industry ,Appetite Regulation ,Body Weight ,Aortic Valve Stenosis ,medicine.disease ,Rats ,Pulmonary Valve Stenosis ,Stenosis ,Cardiac hypertrophy ,cardiovascular system ,Cardiology ,Body Composition ,Body Constitution ,business ,Vascular obstruction - Abstract
SummaryWe have demonstrated the feasibility of banding intrathoracic vessels in the weanling rat, with survival of an acceptable proportion of the animals for 9 weeks. The vascular obstruction resulted in reduced food intake, growth failure, cardiac hypertrophy, and other changes indicative of cardiac failure.
- Published
- 1967
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