Longitudinal assessment of anchored transponder migration following lung stereotactic body radiation therapy.

PURPOSE: To assess the long-term stability of the anchored radiofrequency transponders and compare displacement rates with other commercially available lung fiducial markers. We also sought to describe late toxicity attributable to fiducial implantation or migration. MATERIALS AND METHODS: The transponder cohort was comprised of 17 patients at our institution who enrolled in a multisite prospective clinical trial and underwent bronchoscopic implantation of three anchored transponders into small (2-2.5 mm) airways. We generated a comparison cohort of 34 patients by selecting patients from our institutional lung SBRT database and matching 2:1 based on the lobe containing tumor and proximity to the bronchial tree. Assessment of migration was performed by rigidly registering the most recent follow-up CT scan to the simulation scan, and assessing whether the relative geometry of the fiducial markers had changed by more than 5 mm. Toxicity outcomes of interest were hemoptysis and pneumothorax. RESULTS: The median follow-up of patients in the transponder cohort was 25.3 months and the median follow-up in the comparison cohort was 21.7 months. When assessing the most recent CT, all fiducial markers were within 5 mm of their position at CT simulation in 11 (65%) patients in the transponder group as compared to 23 (68%) in the comparison group (P = 0.28). One case of hemoptysis was identified in the transponder cohort, and bronchoscopy confirmed bleeding from recurrent tumor; no cases of hemoptysis were noted in the comparison cohort. No case of pneumothorax was noted in either group. CONCLUSION: No significant difference in the rates of fiducial marker retention and migration were noted when comparing patients who had anchored transponders placed into small airways and a 2:1 matched cohort of patients who had other commercially available lung fiducial markers placed. In both groups, no late or chronic toxicity appeared to be related to the implanted fiducial markers.

What predicts early volumetric edema increase following stereotactic radiosurgery for brain metastases?

A volumetric analysis of pre- and post-radiosurgery (PreSRS and PostSRS) edema in patients with cerebral metastases was performed to determine factors of a predictive model assessing the risk of developing increased edema relatively early after SRS. One-hundred-fourteen metastases in 55 patients were analyzed. Selection for this analysis required an MRI ≤ 30 days before SRS and an MRI ≤ 100 days after SRS. Tumor volumes were calculated on PreSRS, SRS, and PostSRS T1-weighted postgadolinium images while edema volumes were calculating using PreSRS and PostSRS fluid-attenuated inversion recovery MR images. An increase in edema was defined as an increase in measurable edema of at least 5%. We developed and evaluated a model predicting the relative risk (RR) of increased edema after SRS. Peritumoral edema increased in 18% (21/114) of the analyzed lesions. Melanoma/renal histology, recursive partitioning analysis class III, and prior WBRT carried RRs of developing postSRS edema increase of 2.45, 2.48, and 3.16, respectively (all P values <0.05). The PreSRS edema/tumor ratio predicted for a RR of 1.007/ratio unit, and steroid dose at time of SRS predicted for a RR of 0.89/mg (all P values <0.05). A predictive model for assessing the RR of increased edema after SRS was developed based from these data and may be useful in identifying patients who might benefit from prophylactic anti-edema therapies before, during, or after SRS. This model could be used as the basis of inclusion criteria for prospective trials investigating novel anti-edema therapies.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. METHODS: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). RESULTS: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. CONCLUSIONS: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Analysis of pathological complete response rates with paclitaxel-based regimens in trimodality therapy for esophageal cancer.

The study aimed to examine whether omission of 5-fluorouracil (5-FU)-containing chemotherapy alters pathological complete response rates in patients receiving trimodality therapy for locally advanced esophageal cancer. A total of 159 patients were identified. One hundred twenty-nine patients received platinum/5-FU concurrently with radiotherapy, and 30 received taxane/platinum-containing chemoradiotherapy prior to esophagectomy. Patients were staged using the 2002 American Joint Committee on Cancer staging system. Patients were matched between chemotherapeutic groups, with no significant demographic or clinical differences other than T stage (14% T2 in the 5-FU group; no T2 in the platinum/taxane group) and radiotherapy technique (8.5% received intensity-modulated radiotherapy in the 5-FU group; 60% in the platinum/taxane group). Pathological complete response rates for 5-FU and platinum/taxane-based groups were not significantly different (45% and 30%, respectively; P = 0.1548). Five-year overall survival and progression-free survival were not statistically different between the two groups. Significant predictors of pathological complete response included N stage (56% N0 and 33% N1; P = 0.0083), histology (37% adenocarcinoma and 59% squamous cell; P = 0.0123), tumor location (39% distal and 59% proximal/mid; P = 0.048), gastroesophageal junction involvement (33% involved and 55% uninvolved; P = 0.005), and radiotherapy end-to-surgery interval (50% < 55 days and 34% ≥ 55 days; P = 0.04). Grades 3-4 hematological toxicity was higher in the 5-FU group (36%) than in the paclitaxel-containing therapy group (17%; P = 0.0484). Use of paclitaxel-containing chemoradiotherapy did not result in inferior pathological complete response, overall survival, or progression-free survival rates, and resulted in less hematological toxicity than 5-FU treatment.

Unlocking the adaptive advantage: correlation and machine learning classification to identify optimal online adaptive stereotactic partial breast candidates.

Objective.Online adaptive radiotherapy (OART) is a promising technique for delivering stereotactic accelerated partial breast irradiation (APBI), as lumpectomy cavities vary in location and size between simulation and treatment. However, OART is resource-intensive, increasing planning and treatment times and decreasing machine throughput compared to the standard of care (SOC). Thus, it is pertinent to identify high-yield OART candidates to best allocate resources.Approach.Reference plans (plans based on simulation anatomy), SOC plans (reference plans recalculated onto daily anatomy), and daily adaptive plans were analyzed for 31 sequential APBI targets, resulting in the analysis of 333 treatment plans. Spearman correlations between 22 reference plan metrics and 10 adaptive benefits, defined as the difference between mean SOC and delivered metrics, were analyzed to select a univariate predictor of OART benefit. A multivariate logistic regression model was then trained to stratify high- and low-benefit candidates.Main results.Adaptively delivered plans showed dosimetric benefit as compared to SOC plans for most plan metrics, although the degree of adaptive benefit varied per patient. The univariate model showed high likelihood for dosimetric adaptive benefit when the reference plan ipsilateral breast V15Gy exceeds 23.5%. Recursive feature elimination identified 5 metrics that predict high-dosimetric-benefit adaptive patients. Using leave-one-out cross validation, the univariate and multivariate models classified targets with 74.2% and 83.9% accuracy, resulting in improvement in per-fraction adaptive benefit between targets identified as high- and low-yield for 7/10 and 8/10 plan metrics, respectively.Significance.This retrospective, exploratory study demonstrated that dosimetric benefit can be predicted using only ipsilateral breast V15Gy on the reference treatment plan, allowing for a simple, interpretable model. Using multivariate logistic regression for adaptive benefit prediction led to increased accuracy at the cost of a more complicated model. This work presents a methodology for clinics wishing to triage OART resource allocation.

Improving Communication of Peer-Review Conference Outcomes: A Practical Experience.

Purpose: The aim of this work was to describe the design and implementation of a more robust workflow for communicating outcomes from a peer-review chart rounds conference. We also provide information regarding cycle times, plan revisions, and other key metrics that we have observed since initial implementation. Methods and Materials: A multidisciplinary team of stakeholders including physicians, physicists, and dosimetrists developed a revised peer-review workflow that addressed key needs to improve the prior process. Consensus terminology was developed to reduce ambiguity regarding the priority of peer-review outcomes and to clarify expectations of the treating physician in response to peer-review outcomes. A custom workflow software tool was developed to facilitate both upstream and downstream processes from the chart rounds conference. The peer-review outcomes of the chart rounds conference and resulting plan changes for the first 18 months of implementation were summarized. Results: In the first 18 months after implementation of the revised processes, 2294 plans were reviewed, and feedback priority levels assigned. Across all cases with feedback, the median time for the treating attending physician to acknowledge conference comments was 1 day and was within 7 calendar days for 89.1% of cases. Conference feedback was acknowledged within 1 day for 74 of 115 (64.3%) cases with level 2 comments and for 18 of 21 (85.7%) cases with level 3 comments (P = .054). Contours were modified in 13 of 116 (11%) cases receiving level 2 feedback and 10 of 21 (48%) cases receiving level 3 feedback (P < .001). The treatment plan was revised in 18 of 116 (16%) cases receiving level 2 feedback and 13 of 21 (61%) cases receiving level 3 feedback (P < .001). Conclusions: We successfully implemented a workflow to improve upstream and downstream processes for a chart rounds conference. Standardizing how peer-review outcomes were communicated and recording physician responses allow for improved ability to monitor conference activities.

Predictors of In-Hospital Death in Patients with Lung Cancer Admitted for Acute Radiation Pneumonitis: A Healthcare Cost and Utilization Project (HCUP) Analysis.

BACKGROUND: Radiation pneumonitis (RP) is a dose-limiting and potentially fatal toxicity of thoracic radiotherapy most often seen in patients treated for primary lung cancer. The purpose of this study was to identify predictors of in-hospital death among lung cancer patients admitted for acute RP in the Healthcare Cost and Utilization Project (HCUP) database. MATERIALS AND METHODS: The HCUP National Inpatient Sample database was queried from 2012 through 2016 to capture adult lung cancer patients admitted to the hospital with a principal diagnosis of acute RP. Multivariate logistic regression modeling and χ2 tests were used to determine predictors of in-hospital death. RESULTS: Of the 882 patients with lung cancer admitted for RP, 67 patients (7.6%) died during the hospitalization and 90 patients (10.2%) required mechanical ventilation. Of those requiring mechanical ventilation, 38 patients (42.2%) died. The average age at hospitalization was 70.4 years (range, 35-90). Of those factors associated with death on univariate analysis, interstitial lung disease (odds ratio [OR] = 6.14; 95% confidence interval [CI], 1.9-19.4; P = .002), pulmonary hypertension (OR = 3.1; 95% CI, 1.6-6.2; P = .001), diabetes mellitus (OR = 2.0; 95% CI, 1.1-3.3; P = .013), and more affluent Zip Code (OR = 1.9; 95% CI, 1.1-3.2; P = .021) remained statistically significant on multivariate logistic regression. CONCLUSION: In the largest reported cohort of patients with lung cancer hospitalized with a principal diagnosis of acute RP, the presence of interstitial lung disease, pulmonary hypertension, diabetes mellitus, and more affluent Zip Code were associated with in-hospital death. Comorbid diagnoses may be useful for risk-stratified management of inpatients with RP.

Factors influencing hematopoietic spleen colony formation in irradiated mice. 3. The effect of repetitive irradiation upon proliferative ability of colony-forming cells.

Mice were irradiated repetitively at 6 wk intervals. The proliferative capacity of the hematopoietic stem cell compartment was studied after each irradiation and compared to that of age-matched controls which had been irradiated only once. Hematopoietic proliferation capacity was measured by determining the number of spleen colonies, splenic iron uptake, spleen weight, and volume of packed red cells 10 days after irradiation. 6 wk after the first irradiation, the hematopoietic compartment was apparently supranormal in size for, when such mice were again irradiated, their postirradiation hematopoiesis was in excess of that of the controls. Thereafter, there was a steady decline in regenerative capacity with each sequential irradiation. After the sixth irradiation, the number of spleen colonies and iron uptake were reduced to one-fifth of that of singly irradiated controls. A decline in body weight and an increase in irradiation mortality accompanied the decline in postirradiation hematopoiesis. The degree of measured decline in hematopoietic proliferative ability was less than that observed by other investigators who studied the effect of serial transplantation of cells upon their ability to proliferate. Furthermore, even after the sixth irradiation, a marked stimulation of postirradiation hematopoiesis was induced by bleeding the animals before irradiation.

Factors influencing hematopoietic spleen colony formation in irradiated mice. II. The effect of foreign materials.

Normal dog plasma and serum, human, rat, and Swiss-Webster mouse plasma, phytohemagglutinin, sheep red cells, mumps and influenza vaccine, fibrinogen, and endotoxin injected before irradiation led to an increased number of endogenously derived spleen colonies in irradiated mice. Spleen weight and uptake of radioactive iron and iododeoxyuridine into such spleens were also increased. The relationship between these parameters of splenic hematopoiesis was unchanged by plasma injection suggesting that, while the number of colonies was increased, the composition of individual colonies was unchanged. This conclusion was supported by studies on plethoric mice in which splenic erythropoiesis is abolished. Increased splenic hematopoiesis was accompanied by an increase in the volume of packed red blood cells 10 days after irradiation. The total volume of plasma injected, the number of days of plasma injection preceding irradiation, and the route of administration were all important variables influencing the effect of plasma injections. Crude fractions of human albumin and gamma globulin, cortisol, C57BL (maternal) and DBA (paternal) mouse plasma, and isogeneic plasma were without effect. The ineffectiveness of isogeneic and closely related allogeneic plasma rendered unlikely the hypothesis that this effect represented the presence of homeostatic hematopoietic regulating factors in plasma. The increased hematopoiesis induced with plasma appeared to be limited to the spleen, for increased bone marrow hematopoiesis was not detected. Certain observations suggested that the effect of plasma may not be due to an antigenic or an inflammatory effect. From current observations, it was unclear whether the increased colonies induced by plasma were representative of expansion of the colony-forming cell pool or of increased efficiency of growth of the fraction surviving irradiation.

Factors influencing hematopoietic spleen colony formation in irradiated mice. I. The normal pattern of endogenous colony formation.

Data pertaining to the endogenous mouse spleen colony system, 10 days postirradiation, are presented. The D(o) for visible colonies is 78 R, while that for 6 hr iron uptake over a range of 600-800 R is 50 R. The D(o) for spleen weight is 196 R and that for IUdR uptake is 193 R. These measurements increase with the age of the mouse. Hypertransfusion decreases spleen iron uptake and colony number. DF-(32)P and sodium sulfate-(35)S are not useful indicators of splenic hematopoiesis in this system. Visible hematopoietic colonies in the spleen are not produced by vinblastine, nitrogen mustard, methotrexate, or cyclophosphamide.

Bone marrow colonies: stimulation in vitro by supernatant from incubated human blood cells.

A substance which stimulates growth of granulocytic and mononuclear cell colonies from mouse and human bone marrow was produced by incubated human blood cells. It is resistant to heat and freezing and is not dialyzable. Intact irradiated and unirradiated cells had very little activity, and sonically disrupted cells had no activity. The addition of plasma or sonically disrupted cells to the cell supernatant decreased its activity.

Seasat scatterometer: results of the gulf of alaska workshop.

The Seasat microwave scatterometer was designed to measure, globally and in nearly all weather, wind speed to an accuracy of +/- 2 meters per second and wind direction to +/- 20 degrees in two swaths 500 kilometers wide on either side of the spacecraft. For two operating modes in rain-free conditions, a limited number of comparisons to high-quality surface truth indicates that these specifications may have been met.

Hospice care, cancer-directed therapy, and Medicare expenditures among older patients dying with malignant brain tumors.

Background: End-of-life care for older adults with malignant brain tumors is poorly understood. The purpose of this study is to quantify end-of-life utilization of hospice care, cancer-directed therapy, and associated Medicare expenditures among older adults with malignant brain tumors. Methods: This retrospective cohort study included deceased Medicare beneficiaries age ≥65 with primary malignant brain tumor (PMBT) or secondary MBT (SMBT) receiving care within a southeastern cancer community network including academic and community hospitals from 2012-2015. Utilization of hospice and cancer-directed therapy and total Medicare expenditures in the last 30 days of life were calculated using generalized linear and mixed effect models, respectively. Results: Late (1-3 days prior to death) or no hospice care was received by 24% of PMBT (n = 383) and 32% of SMBT (n = 940) patients. SMBT patients received late hospice care more frequently than PMBT patients (10% vs 5%, P = 0.002). Cancer-directed therapy was administered to 18% of patients with PMBT versus 25% with SMBT (P = 0.003). Nonwhite race, male sex, and receipt of any hospital-based care in the final 30 days of life were associated with increased risk of late or no hospice care. The average decrease in Medicare expenditures associated with hospice utilization for patients with PMBT was $-12,138 (95% CI: $-18,065 to $-6210) and with SMBT was $-1,508 (95% CI: $-3,613 to $598). Conclusions: Receiving late or no hospice care was common among older patients with malignant brain tumors and was significantly associated with increased total Medicare expenditures for patients with PMBT.

Autonomous erythropoiesis during erythroblastic crisis of chronic myelocytic leukemia.

Two patients with chronic myelocytic leukemia who developed an erythroblastic rather than a myeloblastic phase were studied with respect to whether or not the megaloblastic erythropoiesis was subject to normal control mechanisms. After transfusion, no significant reduction was observed in the percentage of nucleated erythroid precursors or of proerythroblasts in marrow or in blood reticulocytes. In one of the two patients, ferrokinetics and urinary erythropoietin levels were studied and were also compatible with the conclusions that erythropoiesis was autonomous in this rare syndrome. Three patients with clinical pictures compatible with Di Guglielmo's syndrome were studied as controls. As has been reported previously, erythropoiesis in this syndrome appeared to be responsive to normal control mechanisms. These data suggest that these two clinically similar syndromes, erythroblastic crisis of chronic myelocytic leukemia and Di Guglielmo's syndrome may represent qualitatively different defects in hematopoietic stem cells.

Neutrophil kinetics in acute infection.

Neutrophil kinetics of acute experimental infection were studied with diisopropylfluorophosphate-(32)P labeling in 31 dogs inoculated intrabronchially with pneumococci. In vitro neutrophil labeling indicated a rapid transit time through the blood in early infections, with an elevated marginal granulocyte pool sometimes preceding an elevation of the circulating granulocyte pool. 13 hr after infection, the circulating and total blood granulocyte pools were increased but the rate of neutrophil transit through the blood was normal. During the recovery from infection there was a marked prolongation of neutrophil blood transit time, suggesting virtually complete cessation of bone marrow release of neutrophils into the blood. Labeling of neutrophils in vivo indicated an increased rate of emptying of the bone marrow storage pool proportional to the severity of infection as measured by the fever index. The change in the blood ratio of nonsegmented to segmented neutrophils was a much more accurate index of the severity of infection than the blood granulocyte concentration, correlating significantly with the fever index.

Leukokinetic studies. 13. A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis.

The mechanism by which adrenocortical steroids induce granulocytosis in man has been investigated using granulocytes labeled with radioactive diisopropylfluorophosphate. After an intravenous injection of 200 mg of cortisol was given to five normal subjects, the mean value for the total blood granulocyte pool increased from 79 to 138 x 10(7) cells per kg of body weight and reflected an increase in the size of both the circulating granulocyte pool and the marginal granulocyte pool. When granulocytes in the circulation were labeled with diisopropylfluorophosphate and granulocytosis was induced later by the intravenous administration of cortisol, the rate of decline of granulocyte specific activity was increased, indicating that the blood pool was being diluted at an accelerated rate by unlabeled cells entering from the bone marrow. The rate of egress of granulocytes from the blood pool to an inflammatory exudate was studied by the "skin window" technique. After the administration of cortisol, there was a mean reduction in the cellularity of induced inflammatory exudates of 75%. However, this reduction in cellularity varied considerably from subject to subject (45-98%). From these studies we can infer that steroids induce an absolute granulocytosis by decreasing the rate of egress of cells from the total blood granulocyte pool as well as by increasing the influx of cells from the bone marrow. By model simulation studies of the non-steady state induced by cortisol injection, it has been possible to quantitate these rate changes. In the present studies cortisol injection resulted in a mean decrease in blood granulocyte egress of 74% (1-99%) and a mean increase in cell inflow of 450% (300-750%).

Hematopoietic stem cells with high proliferative potential. Assay of their concentration in marrow by the frequency and duration of cure of W/Wv mice.

THIS STUDY WAS DESIGNED TO APPROACH TWO PRIMARY QUESTIONS CONCERNING HEMATOPOIETIC STEM CELLS (HSC) IN MICE: what is the concentration of HSC with extensive proliferative potential in marrow, and how long can an HSC continue to function in an intact animal? The assay system was the W/W(v) mouse, a mouse with an inherited HSC defect, reflected in a reduction in all myeloid tissue and most particularly in a macrocytic anemia.A single chromosomally marked HSC will reconstitute the defective hematopoietic system of the W/W(v). The concentration of HSC in normal littermate (+/+) marrow was assayed by limiting dilution calculation using cure of W/W(v) as an end point (correction of anemia and erythrocytes' macrocytosis) and found to be approximately 10/10(5). This is significantly less than spleen colony forming cell (CFU-S) concentration: approximately 220/10(5) in +/+ and ranging from 50 to 270/10(5) in various other studies. Blood values were studied at selected intervals for as long as 26 mo. Of 24 initially cured mice, which were observed for at least 2 yr, 75% remained cured. However, of all cured mice, 17 lost the cure, returning to a macrocytic anemic state. Cured mice had normal numbers of nucleated and granulocytic cells per humerus and a normal concentration of CFU-S. However, cure of secondary W/W(v) recipients by this marrow was inefficient compared with the original +/+ marrow. These studies suggest the CFU-S assay over-estimates extensively proliferating HSC or perhaps does not assay such a cell. A single such HSC can not only cure a W/W(v), but can sustain the cure for 2 yr or more, despite a relative deficit of cells capable of curing other W/W(v). However, the duration of sustained cure may be finite.

Hematopoiesis and aging: IV. Mass and distribution of erythroid marrow in aged mice.

Aged mice are "anemic," i.e., they have a lower hematocrit than young adult mice, but this appears to be a "dilutional" anemia; the red cell mass is normal. Other observations have supported the hypothesis that basal erythropoiesis does not change as mice grow old. In the present study, the percentage of injected 59Fe found in the skeleton and spleen, 59Fe distribution between various bones and bone groups, and the number of nucleated erythroid cells per humerus were studied and the total mass of erythroid precursors was calculated. There was no significant difference in any of these values between mice aged 3-27 months. The variability of 59Fe distribution within various skeletal parts was no greater in aged than in young mice. Thus, these data further strengthen the case for normal basal rates of erythropoiesis in aged mice.

Aging and hematopoiesis. VI. Neutrophilia and other leukocyte changes in aged mice.

The concentration of blood leukocytes rose progressively as mice aged. All blood leukocytes increased, although a greater degree of increase was seen in neutrophils and monocytes than in lymphocytes and eosinophils. The total number of nucleated cells per marrow cavity of the humerus was also higher in aged than in young adult mice, the increase primarily reflecting peroxidase-positive cells. Both blood and marrow neutrophils of aged mice responded to perturbations induced by bleeding or by endotoxin injection in a manner qualitatively similar to that seen in young adults. When hematopoietic chimeras were produced by marrow transplantation, blood and marrow neutrophils were characteristic of the age of the recipient, not the cells; i.e., young mice kept a "young" neutrophil pattern and old mice kept an "old" neutrophil pattern when given marrow from either old or young mice. Colonies of granulocytes and/or monocyte-macrophages were grown from young marrow cells placed in plasma clots in Millipore chambers in the peritoneal cavity. The number of colonies was the same in young and in old mice, suggesting that long-range humoral stimulation of cell growth was similar in young and old. Thus, neutrophilia due to increased neutrophil production appears to be a normal part of the aging process in the mouse. The increase in neutrophil production may be due to a changing hematopoietic microenvironment.

Modulation of hematopoiesis and survival after high-dose chemotherapy or radiotherapy: review and discussion of possible mechanisms.

This paper reviews ways by which growth of transplanted or surviving hematopoietic stem cells might be enhanced to improve survival in the case of autologous marrow transplantation. Most of the treatments known to have such effects have been used in isologous mouse models and improve animal survival by enhancing hematopoietic recovery after high doses of whole body irradiation or chemotherapy. Although some of these were studied 20 years ago, the use of such treatments in man has awaited the realization that some disseminated cancer can only be eliminated by use of various treatments where hematopoietic damage is the limiting factor. Although increasing the number of transplanted pluripotent stem cells is the most certain way to hasten return of needed blood cells in transplant patients, several of the treatments listed in the paper have growth enhancing effects on both surviving host stem cells and transplanted cells. There are recent studies which indicate that such priming treatments may also be effective in other normal tissues such as gut and bladder epithelium. At least one study in man has intentionally applied this approach with the expected benefit and others may have done so inadvertently. Much work remains to find new combinations to select the best priming treatments and intervals in man and to determine whether or not such treatments are effective against tumors.