The potential benefits of extended rituximab treatment have been investigated in a randomized trial comparing the standard schedule with prolonged treatment in 202 patients with newly diagnosed or refractory/relapsed follicular lymphoma (FL). All patients received standard treatment (rituximab 375 mg/m 2 weekly ؋ 4). In 185 evaluable patients, the overall response rate was 67% in chemotherapynaive patients and 46% in pretreated cases (P < .01). Patients responding or with stable disease at week 12 (n ؍ 151) were randomized to no further treatment
Hematopoietic stem cell transplantation is associated with a severe immune deficiency. As a result, the patient is at high risk of infections. Innate immunity, including epithelial barriers, monocytes, granulocytes, and NK cells recovers within weeks after transplantation. By contrast, adaptive immunity recovers much slower. B- and T-cell counts normalize during the first months after transplantation, but in particular, T-cell immunity may remain impaired for years. During the last decade, much of the underlying mechanisms have been identified. These insights may provide new therapies to accelerate recovery.
Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.
Using quantitative fluorescence in situ hybridization and flow cytometry, the telomere length of telomere repeat sequences after stem cell transplantation (SCT) were measured. The study included the telomeres of peripheral blood monocytes that should reflect the length of telomeres in stem cells and the telomeres of T lymphocytes that could shorten as a result of peripheral expansion. The loss of telomeres in monocytes and in memory T cells, although accelerated initially, became comparable to the loss of telomeres in healthy controls from the second year after transplantation. In addition, the telomere length in the naive T cells that were produced by the thymus was comparable to the telomere length in the naive T cells IntroductionTelomeres are specialized structures at the end of eukaryotic chromosomes that, in vertebrates, consist of hundreds to thousands of tandem repeats of the sequence TTAGGG. 1 Because telomere length decreases with the number of cell divisions in vitro and with aging in vivo, 2 it reflects the mitotic history of the cells. Furthermore, short telomeres might limit the cells' remaining replicative capacity. 3 This may be of special significance after stem cell transplantation (SCT) because the telomere length of leukocytes in the patient may be up to 2000 base pair (bp) shorter than in the donor. [4][5][6][7][8][9] Because the telomerase activity in stem cells does not prevent telomere shortening, 10 the shorter telomeres may be the consequence of the expansion of the transplanted stem cells needed to repopulate the host. In addition, the telomere loss previously observed in peripheral blood mononuclear cells 4,6,9 might be explained by the extensive proliferation of the T lymphocytes cotransfused with the marrow. In this report we show that both phenomena contribute significantly to the accelerated telomere shortening after SCT and that after an initial period of approximately one year, the rate of telomere shortening in patients becomes comparable to that in their donors. Study designThe average length of telomere repeats in individual cells was measured by flow fluorescence in situ hybridization (FISH), as previously described, 11 and expressed as molecules of equivalent soluble fluorochrome (MESF) units 12 after calibration with fluorescein isothiocyanate (FITC)-labeled fluorescent calibration beads (Quantum-24 Premixed; Flow Cytometry Standards Corporation, San Juan, Puerto Rico).Interexperimental variation was monitored by analyzing aliquots of a batch of frozen cells 13 and did not exceed 15%. Fluorescence-activated cell sorter (FACS) analysis of telomere length in monocytes and lymphocytes was performed with gates on single diploid cells with the characteristic light scatter properties. 13 To analyze naive T cells and cells with a memory phenotype, 2-5 ϫ 10 4 cells were fractionated into CD4 ϩ CD45RA ϩ CD45RO Ϫ and CD4 ϩ CD45RA Ϫ CD45RO ϩ by FACS analysis (FACStar Plus; Becton Dickinson, Basel, Switzerland) after staining with anti-CD4-APC (allophycocyanin) (Leu4; Becton Dickinso...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.