Decision letter for "Red and white blood cell counts are associated with bone marrow adipose tissue, bone density and bone microarchitecture in premenopausal women"

2017 ◽  
Vol 127 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Eugene J. Vaios ◽  
Brian V. Nahed ◽  
Alona Muzikansky ◽  
Amir T. Fathi ◽  
Jorg Dietrich

OBJECTIVEGlioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remains unclear whether the degree of bone-marrow suppression might serve as a biomarker for treatment outcome. The aim of the current study was to investigate whether the degree of bone-marrow toxicity in patients treated with TMZ correlates with overall survival (OS) and MRI-based time to progression (progression-free survival [PFS]).METHODSComplete blood counts and clinical and imaging information were collected retrospectively from 86 cases involving GBM patients who had completed both radiation therapy and at least 6 monthly cycles of chemotherapy with TMZ.RESULTSUsing a multivariate Cox proportional hazard model, it was observed that MGMT promoter methylation, wild-type EGFR, younger patient age at diagnosis, and treatment-induced decreases in white blood cell counts were associated with improved OS. The 2-year survival rate was 25% and 58% for patients with increases and decreases, respectively, in white blood cell counts from baseline over 6 months of TMZ treatment. Consistent with the literature, IDH mutation and MGMT promoter methylation were associated with better PFS and OS. IDH mutation and MGMT promoter methylation were not correlated with changes in peripheral red blood cell or white blood cell counts.CONCLUSIONSDecreases in white blood cell counts might serve as a potential biomarker for OS and PFS in malignant glioma patients treated with radiation therapy and TMZ. It remains unclear whether treatment-induced changes in white blood cell counts correlate with drug-induced antitumor activity or represent an independent factor of the altered local and systemic tumor environment. Additional studies will be needed to determine dose dependence for chemotherapy based upon peripheral blood counts.


2008 ◽  
Vol 27 (5) ◽  
pp. 401-407 ◽  
Author(s):  
YM Lee ◽  
WH Choi ◽  
YB Kim ◽  
CS Ha ◽  
CW Song ◽  
...  

We made gene therapeutics for X-chronic granulomatous disease (CGD) by transducing murine bone marrow-derived stem cells with MT-gp91 retrovirus and evaluated possible toxicity in mice as a prerequisite for human clinical trials. Male C57BL/6 mice were injected intravenously with gene therapeutics for X-CGD twice at an interval of two weeks at 5 × 107 cells/kg and sacrificed 2 weeks after the last administration. Significant changes noted in gene therapeutics for X-CGD-treated animals were an increase in white blood cell counts and a slight decrease in albumin/globulin ratio. The red pulp hyperplasia in the spleen accompanied with an increase in organ weight was considered to result from the accumulation of gene therapeutics for X-CGD, bone marrow-derived stem cells, in the spleen. No anti-gp91 antibody was detected in the sera collected from the animals treated with gene therapeutics for X-CGD. No integration of gp91 DNA from retroviral vector was detected in chromosomal DNA of gonads in animals dosed with the test substance, indicating no potential of genomic integration. In conclusion, the repeated dose of gene therapeutics for X-CGD exerted no toxicity. The splenic red pulp hyperplasia and the increase observed in white blood cell counts and in spleen weights were considered as pharmacological changes induced by the treatment.


1960 ◽  
Vol 199 (5) ◽  
pp. 824-828 ◽  
Author(s):  
D. O. Anderson ◽  
D. M. Whitelaw

Lymphocytes from the thoracic duct of rats were injected intraperitoneally into homologous rats previously exposed to 900 rads of total body radiation. Repeated white blood cell counts, platelet counts and polychromatophilia and reticulocyte counts provided no evidence that the transplanted cells were able to repopulate the bone marrow.


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