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Biomedical subjects

B Lowenberg

Publications and source records attributed to B Lowenberg.

13 recordsLinked to original sources
PubMed1995

Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy.

PURPOSE AND METHODS: A prospective, randomized, multicenter phase III trial was performed to investigate the feasibility of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in elderly patients ( > or = 60 years) with advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy, and to compare the tolerance and efficacy of doxorubicin versus mitoxantrone (CHOP v CNOP). RESULTS: Of 157 enrolled patients, 148 were eligible and 145 were assessable for response. Thirty-one percent of CNOP and 45% of CHOP patients completed six cycles without dose reduction. The cumulative normalized dose-intensity (NDI) was 92% with CHOP and 90% with CNOP after six cycles. The overall complete response (CR) rates were 49% and 31% in CHOP- and CNOP-treated patients, respectively (P = .03). Survival with CNOP was significantly worse as compared with CHOP (P = .03). Lymphoma-specific survival was significantly better in CHOP-treated patients (P = .034) At 3 years, 42% of CHOP and 26% of CNOP patients were alive. Additional unfavorable prognostic factors at diagnosis were high serum lactate dehydrogenase (LDH) level, bulky mass, and low performance status, but not age. The median disease-free intervals of complete responders were 27 (CHOP) and 15 (CNOP) months, respectively. Considering the complete group of patients, at 3 years 17% of CHOP and 13% of CNOP patients were alive and disease-free (P = .12). Common toxicity criteria (CTC) grade > or = 2 with CNOP and CHOP was not different. CONCLUSION: CHOP is well tolerated in elderly patients with advanced intermediate- or high-grade NHL and its NDI is not seriously impaired. Treatment with CHOP (doxorubicin) results in better CR and survival rates than CNOP (mitoxantrone). CHOP should be recommended for elderly patients with high-risk NHL.

Aged↗
PubMed1995

Impact of cytogenetic abnormalities on outcome of bone marrow transplants in acute myelogenous leukemia in first remission.

This study analyzed the impact of cytogenetic abnormalities on outcome of 1516 HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission reported to the International Bone Marrow Transplant Registry by 188 centers. 708 patients (47%) had cytogenetic studies performed. Transplant outcome in these subjects was similar to the 808 in whom cytogenetic studies were not performed. One or more cytogenetic abnormalities were detected in 284 (40%) of subjects studied. Relapse rates were higher and leukemia-free survival lower in patients with poor prognosis abnormalities vs those with no abnormality or with good or intermediate prognosis abnormalities (relative risk of relapse 2.40, P < 0.01; relative risk of treatment failure 1.68, P < 0.03). We conclude that cytogenetic abnormalities correlated with increased relapse in patients treated with chemotherapy. HLA-identical sibling transplants are similar.

Adolescent↗
PubMed1991

Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion.

Results of 470 bone marrow transplants from related donors other than genotypically HLA-identical siblings (alternative related donors) were analysed to identify factors associated with transplant outcome and to determine whether T cell depletion improved results. As compared to 3648 transplant from HLA-identical siblings, alternative related donor transplants were associated with increased graft failure, increased acute graft-versus-host disease (GVHD), and lower disease-free survival. The likelihood of adverse outcome correlated with increasing donor-recipient HLA-disparity. In multivariate analysis of alternative related donor transplants, donor age greater than or equal to 30 years, (relative risk [RR] 1.7, p less than 0.006), intermediate and advanced leukemia (RR 1.5 and 1.6, p less than 0.01 and p less than 0.003), infection pretransplant (RR 1.7, p less than 0.005) and 2- and 3-locus donor-recipient HLA-disparity (RR 1.3, p less than 0.04) were associated with increased risks of treatment failure. The 2-year probability of leukemia-free survival after alternative related donor transplants (n = 43) with none of these adverse prognostic features was 44% (95% confidence interval 28-59%) compared to 56% (95% confidence interval 52-59%) for similar patients receiving HLA-identical sibling transplants (n = 868, univariate p less than 0.03). T cell depletion increased graft failure and decreased acute GVHD after alternative related donor transplants but did not improve leukemia-free survival.

Bone Marrow Transplantation↗
PubMed1990

The bone-titanium interface in vitro.

Commercially pure 5-mm-diameter titanium (cpTi) discs received droplet inoculations of cells derived from rat bone marrow and were maintained in supplemented culture medium for 2-3 weeks. The cells and extracellular matrix (ECM) were processed for observation by light (LM), scanning (SEM), and transmission electron (TEM) microscopy. The latter was achieved by freeze-fracturing the solid metal from the resin-embedded tissue using a method which preserved the interface. Surface staining of whole discs revealed cells separated from the metal substratum by areas of ECM which stained positively using von Kossa's method to identify mineralization. At SEM, the ECM comprised dense interwoven collagen fiber networks which were partially obscured by globular masses (GMs). Individual GMs were associated with collagen fibers, especially at fiber intersections. EDAX line scan analysis confirmed the presence of Ca and P in these areas which were assumed to be spheritic foci of calcification since the Ca and P peaks diminished in areas which demonstrated only collagen fibers or the underlying cpTi. TEM examination confirmed the presence of globular mineralization and also revealed the presence of an interfacial zone between the metal substratum and the mineralized ECM elaborated by osteoblasts during the culture period. The interfacial zone comprised two layers, a bonding zone containing few collagen fragments and a ruthenium red positive layer containing more densely packed collagen fibers. We believe that this is the first report of both the formation of bonelike tissue on solid titanium substrata in vitro and demonstration of an interface which bears close morphological similarities to that known to develop in vivo.

Animals↗
PubMed1987

Paravascular cells in endosteal spaces of alveolar bone contribute to periodontal ligament cell populations.

Endosteal spaces of alveolar bone communicate with the periodontal ligament and may contribute to its cell populations. We examined cell proliferation and migration in endosteal spaces and in the periodontal ligament contiguous with these spaces. Radioautographs of mouse mandibular molar were prepared from animals pulse-injected with 3H-Tdr and sacrificed in groups of 22 mice each at 1 h, 1, 3, and 7 d after labeling. Cell counts, labeling indices, grain counts, and progenitor cell ratios were determined. The data indicate that endosteal spaces are enriched with 3H-Tdr-labeled progenitor cells whose progeny rapidly migrate out of the compartment. The periodontal ligament contiguous with the endosteal spaces exhibited 5 times as many labeled cells as other sites in this tissue. Thickened areas of cementum were coincident with the openings of endosteal spaces in over 64% of observations. The data are consistent with the hypothesis that cells migrate from endosteal spaces into the periodontal ligament and there express the phenotype for osteoblasts or cementoblasts.

Alveolar Process↗
PubMed1986

A randomized comparison of maintenance treatment with androgens, immunotherapy, and chemotherapy in adult acute myelogenous leukemia. A Leukemia-Lymphoma Group Trial of the EORTC.

Twenty-three European centers participated in a randomized clinical trial (AML-5) to study the effect of androgens and immunotherapy during maintenance in adult acute myelogenous leukemia. Induction treatment consisted of Adriamycin (doxorubicin) 50 mg/m2 day 1, vincristine VCR 1 mg/m2 day 2, and cytosine arabinoside 80 mg/m2 every 12 hours by push injection days 3-9. Patients in complete remission were randomized into four groups: (1) 6-mercaptopurine 70 mg/m2 days 1-14, methotrexate 15 mg/m2 twice weekly days 15-28, and reinduction with daunorubicin 35 mg/m2 and vincristine 1 mg/m2 day 29; (2) chemotherapy as in group 1 plus stanozolol 0.15 mg/kg/day; (3) 6-thioguanine 70 mg/m2 orally on 4 consecutive days and cytosine arabinoside 80 mg/m2 subcutaneously day 5 every week; and (4) chemotherapy as in Group 3 plus irradiated blast cells treated with neuraminidase. Three hundred forty-eight patients were eligible and 295 were evaluable. The median age was 45 yrs. A complete remission was achieved in 64% of the patients, with 158 complete remissions randomized. Patients not randomized and patients receiving bone marrow transplantation (BMT) were analyzed separately. There was no difference in disease-free survival (DFS) or survival in the four maintenance arms. For patients reaching complete remission, the median DFS was 40 weeks, and median survival was 22 months with 30% surviving at 4 years. The overall survival was 18% at 4 years. There was no beneficial effect for DFS or survival by adding either immunotherapy or androgens to chemotherapy during maintenance. However, patients receiving immunotherapy seemed to have a higher rate of responses to reinduction after relapse than those in the other treatment arms.

Adolescent↗
PubMed1986

The influence of chemically-induced modifications of root surfaces on cell migration, attachment, and orientation.

Surface demineralization of tooth root surfaces has been shown to improve re-attachment of cells and to promote tissue reconstruction following periodontal surgery. Exposure of collagen fibers has been thought to facilitate migration, attachment, and orientation of fibroblasts on the root surface. However, using an in vitro assay, we have found that both attachment and orientation of human gingival fibroblasts on demineralized dentin surfaces are further improved following digestion of the exposed collagen with bacterial collagenase. In contrast, pronase and trypsin digestion of the surface collagen had no significant effect, whereas heat denaturation had an inhibitory effect. Dissociative extraction of the demineralized dentin slices with 4 mol/L guanidine hydrochloride (GuHCl) also improved attachment and orientation, and when undemineralized dentin was subjected to dissociative extraction, cell attachment was comparable and orientation superior to that on demineralized surfaces. These studies indicate that demineralization is not a prerequisite for facilitating attachment, and that enhanced attachment and orientation of cells are not dependent upon a collagenous substratum.

Animals↗
PubMed1979

Autologous bone marrow transplantation in patients with cancer.

Ten patients with non-leukemic neoplasms received intensive, marrow-lethal doses of drugs and radiation followed by rescue with autologous cryopreserved bone marrow (nine) or marrow from an identical twin as part of a phase 1-2 study. Nine patients had extensive disease that was unresponsive to conventional therapy. Marrow engraftment was documented in all evaluable cases and most patients had a substantial anti-tumor response. Three patients are alive from 4 to 10 months following transplantation without evidence of disease.

Bone Marrow Transplantation↗
PubMed1977

Nature of the delayed graft-versus-host reactivity of fetal liver cell transplants in mice.

Experiments were designed to determine which actual differences in the cellular composition between fetal liver and bone marrow account for the distinct types of graft-versus-host (GvH) disease. The assay of reactive lymphocytes (by in vitro mitogenic stimulation) in fetal liver transplants in mice, the purification of hemopoietic stem cells (HSC) of the transplants, and the quantitation of HSC numbers in the grafts traced the basis for the distinctly weak type of GvH disease after fetal liver cell grafts. It was found that transplantation of purified HSC concentrates did not modify the severity of GvH mortality. The moderate character of the delayed GvH disease was shown to depend on the presence of an HSC population in fetal liver with different qualities and not on numerical differences between the HSC in fetal liver and bone marrow. Data collected also demonstrated that when GvH disease occurred in the recipients of transplants of fetal liver, it shared the characteristic histologic features of the bone marrow GvH syndrome. The recovery of mitogen responsiveness of spleen cells may have been delayed in fetal liver allotransplantation as compared to syngeneic grafting. By supportive infusion of lymphoid cells, it was suggested that the immunodeficiency coinciding with GvH disease represented a secondary manifestation of the disease rather than a primary impairment in lymphoid differentiation.

Animals↗