Bone Marrow

Nothdurft, Wilhelm

doi:10.1007/978-3-642-83416-5_4

Cited by 9 publications

(7 citation statements)

References 234 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2) can be explained as follows. Complete recovery of initial blood lymphocyte concentration takes at least 1 year, even after a single nonlethal dose of cytotoxic therapy [9]. Thus, the inverse relationship between relative short-term lymphocytopenia within the first month of treatment and the long-term mortality rate during the subsequent 5-year period (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The total fraction of lymphocytes in the blood includes minor mononuclear species, such as angiogenic hematopoietic stem cells and angiogenic T-lymphocytes, which support the development of microvessels in normal, quasi-embryonic, and malignant tissues [20,21,22]. Even "therapeutic" myelosuppression reduces temporarily the number of hematopoietic stem cells, and some cells are redirected from the tumor to regenerate bone marrow and other normal tissues [9,23,24]. These findings clarify the crucial question of why myelo-immunosuppression is inseparable from the benefits of cytotoxic therapy [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Group A included two subgroups of patients with primary cancer who received systemic chemotherapy with cisplatinum and cyclophosphanum (subgroup A CP ) or paclitaxel, carboplatinum, and dexamethasone as a premedication (subgroup A TP ). Patients in Group B received systemic therapy in the form of LHBI according to technology developed in the 1990s as consolidation therapy for patients with gastrointestinal tumors, Ewing's sarcoma, breast cancer, carcinoma of the lung, and others [9]. Group B comprised four subgroups treated with fractionated LHBI: patients with primary cancer were irradiated with 3 Gy daily up to a total dose of 9 Gy (subgroup B 9Gy ); those irradiated with 0.1 Gy daily up to a total dose of 1 Gy (subgroup B 1Gy ); patients with relapse treated with 0.1 Gy daily up to a total dose of 1 Gy (subgroup Br 1Gy ); and those irradiated with 0.1 Gy daily up to a total dose of 1 Gy, followed by conventional local radiotherapy of 2 Gy daily up to a total dose of 30 Gy (subgroup Br 1Gy+LRT ) without a rest interval.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer

Shoutko¹,

Yurkova²,

Borodulya³

et al. 2015

CRJ

View full text Add to dashboard Cite

Abstract:The relationship between 5-year survival and the mean number of circulating lymphocytes during 1 month after beginning a combined therapy was investigated in 175 patients with advanced epithelial ovarian cancer to understand why myelosuppression caused by a cytotoxic treatment is almost inseparable from its benefit. Patients received a combined therapy consisting of primary cytoreductive surgery followed by different systemic treatments according to three schemes: conventional chemotherapy with cisplatinum and cyclophosphanum (CP), conventional chemotherapy with paclitaxel and carboplatinum (TP), or lower-half body irradiation (LHBI). The TP scheme included premedication with dexamethasone. The LHBI involve irradiation with a total dose of 9 Gy (3 Gy daily) in patients with primary disease. LHBI with a total dose of 1 Gy (0.1 Gy daily) was used for patients with primary disease or relapse. The LHBI treatment included five final courses of thiophosphamide/5-fluorouracil for patients with primary cancer or conventional local radiotherapy up to a total dose of 30 Gy (2 Gy daily) for relapsed patients. Survival curves were analyzed by exponential approximation, and 5-year exponential mortality rates were calculated. The mortality rates were compared with the relative decline in the mean number of circulating lymphocytes after 1 month of therapy. If pretreatment lymphocytopenia did not exceed 0.7 10 9 cells /L, a linear dependency of the exponential death rate from the relative deviation of cells in the range of 1.16 to 0.7 (p < 0.001) was observed. The inevitable side effect of cytotoxic cancer therapy in the form of lymphocytopenia sheds doubt on the actual existence of effective antineoplastic immunity; however, it provides a logical background of the morphogenic function of some circulating mononuclear cells in relation to proliferating tissues, including malignant tissues.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer

Shoutko¹,

Yurkova²,

Borodulya³

et al. 2015

CRJ

View full text Add to dashboard Cite

show abstract

“…In cases of BM failure (due to high-dose chemotherapy and total-body irradiation, or myelodysplastic syndromes) hematopoiesis is established in extramedullar sites, most prominently in the spleen. This process is mediated by stem cells of BM and splenic origin [14,15]. Extramedullary hematopoiesis is also affected in conditions in which a mechanism or signaling pathway that concerns hematopoietic cell functions is disturbed; Fas-, integrin-, tumor necrosis factor alpha converting enzyme (TACE-), and STAT5-deficient mice display a markedly increased splenic hematopoiesis [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Extramedullary hematopoiesis is dysregulated in histamine-free histidine decarboxylase knockout (HDC−/−) mice

et al. 2009

View full text Add to dashboard Cite

show abstract

“…The haematopoietic system is quite sensitive to ionizing radiation. Considerable irradiation damage, requiring intensive clinical interventions and support, is often associated with radiotherapeutic treatment of various malignant diseases or can be caused by accidental radiation exposure (Nothdurft, 1991; Mauch et al , 1995). The recovery of haematopoiesis and its support by cytokine therapy is essentially dependent on the number of surviving stem and progenitor cells.…”

mentioning

confidence: 99%

Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis in vitro

Klingler¹,

Kreja²,

Nothdurft³

et al. 2002

Br J Haematol

View full text Add to dashboard Cite

Summary. Ficoll‐separated mononuclear cells (MNC) of cryopreserved human bone marrow were incubated with isotoxic doses of diltiazem, N‐acetylcysteine (NAC), glycopolysaccharide extract of spirulina platensis (SPE), tempol, thiopental, WR2721 and WR1065. After irradiation with a single dose of 0·73 Gy, survival of granulocyte/macrophage colony‐forming cells (GM‐CFC) was determined at d 10–14, using an agar culture system. Diltiazem, NAC, tempol and WR1065 significantly improved radiotolerance with protection factors (PF) between 1·21 and 1·36 (n = 5, P < 0·05) at 0·73 Gy (PF‐0·73 Gy). The survival curves of diltiazem (D0 = 0·88 Gy, n = 1·00), NAC (D0 = 0·92 Gy, n = 1·10), tempol (D0 = 0·99 Gy, n = 1·10), WR1065 (D0 = 0·89 Gy, n = 1·16) and control (D0 = 0·78 Gy, n = 1·00) over 0·36–2·91 Gy showed a significant radioprotective effect for D0 only for tempol (P = 0·018) and for the extrapolation number ‘n’ only in the case of NAC (P = 0·023). Cell cycle analysis of the CD34+ cell subpopulation (control‐0 h: G1 = 82·7%, S = 13·7%, G2/M = 3·6%) revealed that all compounds with a significant PF‐0·73 Gy also caused a significant increase in CD34+ cells in S phase up to 48 h. Within the first 24 h, only NAC (26·7 ± 4·1%), tempol (14·3 ± 1·0%) and possibly WR1065 (15·5 ± 1·6%) had higher fractions of CD34+ S‐phase cells compared with controls. This observation and the improvement of GM‐CFC cloning efficiency indicated that only NAC was able to recruit progenitor cells in the cell cycle, whereas tempol and WR1065 possibly inhibited cell cycle progression by S and G2/M arrest. Of the radioprotectors tested, NAC, tempol and WR1065 may be suitable to support, alone or combined with cytokine therapy, accelerated haematopoietic recovery after irradiation.

show abstract

Bone Marrow

Cited by 9 publications

References 234 publications

Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer

Lymphocytopenia and Cytotoxic Therapy in Patients with Advanced Ovarian Cancer

Extramedullary hematopoiesis is dysregulated in histamine-free histidine decarboxylase knockout (HDC−/−) mice

Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis in vitro

Contact Info

Product

Resources

About