Deep myelosuppression, an officially sanctioned effect of non-selective cytotoxic cancer therapy, would be expected to be incompatible with mounting of a powerful host defense against spontaneous malignancy. To explore this theoretical difficulty, we used middle age as a natural model of a temporary decline in lymphocytopoiesis, caused by physiological thymus involution. The impact of middle age on the levels of death from nonmalignant and malignant diseases was analyzed retrospectively, using population health data from

Data extracted from the γ Beagle Dog Tissue Archive hosted by the Woloschak Laboratory (Chicago, IL, USA) were used in a retrospective comparative study of the influence of associated morbidities on the ability of organisms to regenerate hematopoietic cells. There were 209 dogs that had been subjected to whole-body irradiation from a cobalt 60 source from 1.1 years of age until death, with dose rates of 0.003-0.038 Gy/day. One hundred fifty-six nonirradiated dogs served as controls. The presence of neoplasms clinically recorded during each dog's lifetime (uncertain benign or malignant nature) was used to assign experimental subjects and controls to one of two groups: W (with) and WO (without) lesions. Differences between the two groups were noted, mainly a longer average life span and a prevalence of solid malignancy over malignant hematopoiesis in both irradiated and nonirradiated W dogs. We propose an interpretation of these data as showing variability of the activity of tissue-committed hematopoietic stem cells, reflected not only by an increased incidence of solid benign and malignant tumors, but also by greater marrow radioresistance and a stronger viability of W cohorts.

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.

To prevent potential overtreatment of metastatic non-small cell lung cancer, the individual parameters of circulating hematopoietic stem cells (HSCs) (percentage of CD133 + HSCs, CD34 + HSCs, and mitotic activity in the circulating lymphocyte fraction) were measured before conventional cytotoxic therapy in 35 patients by flow cytometry and then compared retrospectively with their individual survival periods. The plot of dependence of the CD133 + HSC × mitotic activity product versus CD34 + HSC revealed the prognostic properties during the survival period (range 0.3-124 months). Discrimination of patients with an expected survival shorter than 12 months was possible based on the positions of individual points on the plot, with a sensitivity and specificity of ~100 each and a diagnostic odds ratio of 1250. The evaluation of individual lymphoproliferative resources before cytotoxic treatment may be useful for the optimal therapeutic compromise between the desired inhibition of malignant target cells and the life-threatening depression of lymphocytopoiesis.

We've reported earlier about spontaneous regular fluctuations of concentration of the CD34 + -cells recorded in the blood of Chernobyl cleanup workers (CUWs) in remote period of time and about an opportunity of artificial growth of the previously mentioned parameter by transcutaneous vibrational impact on awake medullary hemopoiesis zones. The current research aims at studying interfacing of CUWs' exercise performance indices and of the amount of haemopoietic stem cells in their peripheral blood after vibroacoustic influence. Materials: A random sampling of CUWs under long-term dispensary observation (40 male patients, aged 50 on average) have been examined under dispensary conditions. Methods: A course of vibroacoustic mobilization of autologous haemopoietic stem cells into the bloodstream from the bone marrow haemopoietic zones has been conducted with the purpose of correction of CUWs' psychosomatic condition. The CUWs' exercise performance has been examined via veloergometric exercise ECG testing before the modulation course and 3 to 6 months later on. CD34+ -cell subpopulation in peripheral blood was estimated by laser cross flow-cytometry method (FACScan, Beckton-Dickinson) with monoclones (DAKO, BD) before and right after the end of the modulation course. Results: For a cluster of patients examined, certain increase in the number of CD34 + -cells in the blood right after the end of the modulation course has been discovered. Dynamic tracking (3 to 6 months) of this cluster has revealed certain increase in the number of patients capable of fulfilling the exercise ECG test; maximal oxygen uptake for all the patients of this cluster has also shown certain increase in the same period of time. On the contrary, increase of the reviewed indices were uncertain for those patients, who did not demonstrate any growth of the amount of CD34 + -cells right after the modulation course. Conclusions: For a distinct cluster of examined patients, interfacing has been discovered in between growth of the amount of CD34 + -cells into their peripheral bloodstream right after the course of noninvasive vibroacoustic modulation and increase of the showings of their exercise performance in 3 to 6 months.