Degree Of Bone Marrow Suppression Research Articles

Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients.

Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

The influence of various myelosuppression degrees during neoadjuvant chemotherapy on the curative effect and prognosis of triple-negative breast cancer

Objective: To investigate the effect of the degrees of myelosuppression on the curative effect and prognosis of triple-negative breast cancer with neoadjuvant chemotherapy. Methods: The clinical, pathological and follow-up data of 206 patients with triple negative breast cancer who received neoadjuvant chemotherapy with docetaxel combined with epirubicin combined with cyclophosphamide regimen in the Department of Breast Surgery in the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2018 were collected retrospectively. All were female, aged 28-71 (47.8±10.7) years. According to the WHO classification standard of acute and subacute toxicity of anticancer drugs, the patients were divided into 98 cases in the mild group (0-Ⅱ degree) and 108 cases in the severe group (Ⅲ-Ⅳ degree) according to the degree of bone marrow suppression after chemotherapy. The baseline clinicopathological features, pathological complete remission rate (PCR) and objective remission rate (ORR) of the two groups were compared. The survival curve was drawn by Kaplan Meier method, and the differences of disease-free survival (DFS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and overall survival (OS) between the two groups were analyzed by log rank test. Cox regression risk model was used to analyze the related factors affecting the survival of the patients. Results: There were no significant differences in baseline clinicopathological characteristics of patients between the two groups, such as age, physical status score, menopausal status, body mass index, histological grade, clinical T stage, clinical N stage and Ki-67 index (all P>0.05). The severe group had higher PCR, longer median DFS and median DMFS than the mild group [50.9%(55/108) vs 36.7%(36/98); not reached vs 72 months; not reached vs 84 months] (all P<0.05). There was no significant difference in ORR, LRFS and OS between the two groups [89.8%(97/108) vs 81.6%(80/98); both not reached; both not reached] (all P>0.05). The degree of bone marrow suppression after neoadjuvant chemotherapy was an influential factor of DFS in TNBC patients (P=0.025). Compared with mild myelosuppression group, severe myelosuppression group had better disease-free survival prognosis (HR=0.571, 95%CI: 0.349-0.934). Conclusion: The prognosis of grade Ⅲ/Ⅳ myelosuppression is better than grade 0/Ⅰ/Ⅱ myelosuppression in patients with triple-negative breast cancer during neoadjuvant chemotherapy with TEC regimen, which is helpful for judging efficacy.

Anemia and Bone Marrow Suppression After Intra-Arterial Chemotherapy in Children With Retinoblastoma: A Retrospective Analysis.

BackgroundRetinoblastoma (Rb) is a common ocular malignant tumor in children. Intra-arterial chemotherapy (IAC) has been widely used in children with Rb and has achieved an ideal therapeutic effect. However, IAC has side effects, including anemia and bone marrow suppression, for which explicit evidence on the risk factors is lacking. This study aimed to evaluate the covariates that may affect the occurrence of anemia and bone marrow suppression in children with Rb after IAC.MethodsChildren with Rb admitted between May 2019 and January 2021 were included into the study. The differences in the number of children with anemia and bone marrow suppression before and after IAC according to different covariates were recorded. All potential impact factors were included into the univariate and multivariate regression models to identify the related covariates of post-IAC anemia and bone marrow suppression.ResultsData of 282 children with Rb were retrospectively collected. After IAC, children with Rb had increased severities of anemia (p <0.0001, chi-square test) and bone marrow suppression (p = 0.001, chi-square test). Moreover, the number of children with Rb who had an increased cross-level change in the severity of anemia and degree of bone marrow suppression was 80 (41.24%) and 64 (32.49%), respectively. The univariate regression analysis showed that numerous factors (such as pre-IAC intravenous chemotherapy, results of pre-IAC routine blood tests, and some serological indicators for liver and kidney function) affected the anemia severity and degree of bone marrow suppression in children with Rb after IAC. Additionally, the predictive model of the multivariate regression could predict anemia and bone marrow suppression.ConclusionChildren with Rb may have an increased risk of anemia and bone marrow suppression after IAC, but this is temporary and can be influenced by several factors. Therefore, IAC should be maintained as the standard of care. We generated predictive equations for predicting anemia severity and degree of bone marrow suppression, which can guide the prediction and timely control of anemia and bone marrow suppression after IAC.

Common Myeloid Progenitors As Biomarkers of Hbf Response to Hydroxyurea in Sickle Cell Disease

Background Hydroxyurea (HU) is used to treat sickle cell disease (SCD) in part because of its ability to increase hemoglobin F (HbF) concentration, but the mechanism by which HU induces HbF, and the low or lack of HbF response in a fraction of the patient remains unclear. HU causes myelo-suppression and induces stress hematopoiesis, which is associated with increase production of HbF. Earlier research has shown that HbF levels in SCD patients are inversely correlated with reticulocytes, which can be secondary to: 1) HbF-induced decreased hemolysis with less needs for red blood cell (RBC) production, and 2) Myelo-suppression. It has also been shown that the number of CD34+ cells is generally lower in HU treated patients, but the overall response of the hematopoietic system in relationship to HbF has not been characterized. Here, we prospectively isolated hematopoietic stem and progenitor cells (HSPCs) from HU-treated SCD patients and characterize their hematopoietic and HbF responses. Methods Peripheral blood (PB) was collected from 19 HbSS who had been HU for &gt;3 years and from 12 healthy controls. Frozen mono-nuclear cells were analyzed by flow cytometry using CD49f, 90 45Ra, 123, 235a, 38, 34, 33 and lineage antibodies. The number of 49f+ long-term Hematopoietic Stem Cells (LT-HSC), Multipotent Progenitors (MPPs), Common Myeloid Progenitors (CMPs), Megakaryocyte-Erythroid Progenitors (MEPs), and Granulocyte-Monocyte Progenitors (GMPs) per uL of blood or per CD34+ cells was then quantified. Results The percentages of reticulocytes per uL of blood were found to correlate positively with the concentration per uL of blood of all stem and progenitor cell populations tested (CD34 (R2 = 0.6583), LT-HSC (R2 = 0.3532), MPP (R2 = 0.2603), CMP (R2 = 0.5889), MEP (R2 = 0.2411), and GMP (R2 = 0.6911)). Statistically significant (p&lt;0.05) inverse correlations were also observed between HbF levels and the number of CD34+/uL ( R2 = 0.2931), and the number of CMP/uL (R2 = 0.3732). Normalization of the data to the number of circulating CD34+ cells revealed that there was a strong inverse correlation between HbF levels and the percentage of circulating CMPs (R2 = 0.5424), and importantly, that this correlation was specific to the CMP population since Hb F did not correlates with any of the other HSPC populations analyzed . Analysis of the PB of 12 healthy individuals revealed that, as in SCD patients, the percentage of CMPs varied between &lt; 10% and &gt;60% of the total circulating CD34+ cells. Further analysis revealed that the CMP percentages in both SCD and healthy controls appeared characteristics of each individual tested since the measurements were remarkably correlated (R2 &gt;0.7) when they were repeated on blood samples collected at intervals of two-weeks or one-year. Discussion The positive correlation between the reticulocyte and HSPC populations that we observed was previously unreported and suggests that, in first approximation, the reticulocytes could serve as a proxy for the levels of circulating HSPCs which could help assess the degree of bone marrow suppression in compliant non-responding HU-treated patients. We identified an inverse correlation between percentages of HbF and circulating CMPs in HU-treated SCD patients that is specific to these progenitors. The specificity of the correlation suggests that the major mechanism for the correlation is unlikely to be differential mobilization of CMPs to the PB since inducing mobilization generally affect all HSPCs. A depletion of the CMPs in the bone marrow of high Hb F responders is therefore a more likely mechanism. A possible mechanism for the correlation is that HU acts directly on CMPs by accelerating their differentiation leading to the relative depletion of these progenitors in high F individuals, and initiating the reprogramming of gene expression that ultimately results in high level of gamma-globin expression. Alternatively, the similar range of variability in the percentage of CMPs in HU-treated SCD patients and in healthy individuals never exposed to HU, and the observation that the percentage of circulating CMP seem to be an intrinsic characteristic of each individual suggest that the percentage of circulating CMPs might be a genetically determined marker associated with the ability to produce HbF in response to HU therapy, rather than being a consequence of the treatment. Figure Disclosures Minniti: Doris Duke Foundation: Research Funding. Manwani:Novartis: Consultancy; Pfizer: Consultancy; GBT: Consultancy, Research Funding.

Value of dual-input perfusion of 320 row CT on the efficacy evaluation of small cell lung cancer

Objective To discuss the value of dual-input perfusion of 320 row CT on the efficacy evaluation of small cell lung cancer (SCLC). Methods A total of 18 patients with SCLC confirmed by pathology who received cisplatin plus etoposide chemotherapy between June 2016 and June 2018 in the 8th Medical Center of Chinese PLA General Hospital were collected. All patients received 320 row CT perfusion scan at 3 time points before chemotherapy, after 2 cycles and 4 cycles of chemotherapy. Tumor size, perfusion pseudo color map and bronchial arterial blood flow (BF), pulmonary flow (PF) and perfusion index (PI) were obtained. The efficacy and adverse reactions were evaluated. The single factor analysis was used to make the group comparison. Pearson test was used to make correlation analysis. Results Two patients after 2 cycles of chemotherapy had complete remission (CR), another 2 patients after 4 cycles of chemotherapy had CR, and 3 patients of the above 4 cases with CR had abundant BF; after 4 cycles of chemotherapy, 7 cases had partial remission (PR), 6 cases had stable disease (SD), 1 patient had progression of disease (PD). Dual-input perfusion of 320 row CT showed that 10 cases had the tumor area 15 cm2 before the treatment. There was a negative correlation between PI and the tumor area (r=-0.694, P = 0.026) on patients with the tumor area 15 cm2 (P > 0.05). One case had Ⅳ degree of bone marrow suppression, and obvious adverse reactions were not seen in the rest of the patients. Conclusion Dual-input perfusion of 320 row CT based on the simple imaging can make an accurate quantitative judgement of the effect of SCLC according to perfusion parameter, which provides a new basis for curative effect evaluation on SCLC. Key words: Small cell lung carcinoma; Pulmonary perfusion imaging; Dual-input perfusion CT; Treatment outcome

Dasatinib for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia：report of ten cases and review of literature

Objective To observe the clinical response and safety of second-generation tyrosine kinase inhibitor dasatinib in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph + ALL). Methods The clinical data of 10 adult Ph + ALL patients treated with dasatinib were analyzed with review of literatures. Results All the 10 Ph + ALL patients treated with dasatinib achieved remission in 7 weeks, including 9 cases of complete remission[7 cases achieved complete molecular remission(CRm)in 13 weeks]. The median overall survival time(OS)was 13.8 months(5-33), and the median disease-free survival(DFS)time was 10.8 months(4-25). There were 3 cases of pleural effusion, 4 cases of Ⅳ degree of bone marrow suppression and 6 cases of extremely low blood platelet, which could be that was improved via by symptomatic treatment and, with no case of the death occurred during the treatment of dasatinib, the safety was high. Conclusion Dasatinib can deepen molecular biological reaction and prolonged the survival time of patients in the treatment of adult Ph+ ALL, with high remission rate and safety, and which can be considered as first-line treatment. Key words: Dasatinib; Philadelphia chromosome; Leukemia, lymphoblastic, acute

Bone marrow response as a potential biomarker of outcomes in glioblastoma patients.

OBJECTIVE Glioblastoma (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]). METHODS Complete 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. RESULTS Using 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. CONCLUSIONS Decreases 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.

Application effect of the acupoint injection of dexamethasone at Zusanli on improving the tolerance of ;chemotherapy in the patients with breast cancer

Objective To explore the effect of the preventive acupoint injection of dexamethasone at Zusanli on the degree of bone marrow suppression and a series of unwell symptoms in the patients with breast cancer after chemotherapy .Methods Eighty patients who met the inclusion criteria of the breast cancerafter chemotherapy were randomly divided into the control group and the observation group according to the random number table, each with 40 cases.The control group was taken oral medicine as Berbamine Hydrochloride Tablets and Leucogenum , and the observation group received the preventive acupoint injection of dexamethasone at Zusanli on the fifth days after chemotherapy , 5mg/d for 3d, on the basis of the control group .The degree of bone marrow suppression was compared , and the fatigue and appetite of patients were also evaluated by the brief fatigue scale（BFI） and visual analogue scale（VAS） in two groups.Results The levels of WBC, NE and HB in the observation group were respectively （4.73 ±2.11）×10^9/L, （2.13 ±0.61） ×10^9/L, （112.20 ±5.76）g/L on the seventh day after chemotherapy , and better than （3.21 ±0.85） ×10^9/L, （1.66 ±0.42） ×10^9/L, （107.90 ±5.72）g/L in the control group, and the differences were statistically significant （t=4.212, 4.026, 3.349, respectively;P＆lt;0.01）.The count of WBC was on the increase in the observation group on the seventh day after chemotherapy , and then decreased slowly , and the degree of decrease in the observation group was lower than that of control group , and the difference was found in the development trend between two groups （ F=53.19, P〈0.05）.The degree of fatigue and bone marrow suppression in the observation group on the seventh day after chemotherapy were better than those in the control group , and the differences were statistically significant （Z=-2.795, -3.307, respectively;P＆lt;0.01）.The appetite of patients in two groups gradually＆amp;nbsp;returned to normal , and there was a positive correlation the degree of fatigue and bone marrow suppression after chemotherapy （r =0.656, 0.682, respectively; P＆lt;0.05）.The cases of the more than Ⅲdegree of bone marrow suppression was 6 cases in the observation group , and 15 cases in the control groups , and these patients received the Recombinant human granulocyte colony-stimulating factor （rhG-CSF） treatment, and the difference was statistically significant （χ2 =5.230, P 〈0.05 ）.Conclusions The preventive acupoint injection of dexamethasone at Zusanli can reduce the degree of bone marrow suppression and the fatigue symptoms caused by bone marrow suppression after chemotherapy in the patients with breast cancer so as to improve their tolerance of chemotherapy . Key words: Dexamethasone; Acupoint,zusanli; Acupoint injection; Chemotherapy; Tolerance

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Soluble transferrin receptor and depth of bone marrow suppression following high dose chemotherapy

Soluble transferrin receptor (sTfR) reflects erythropoietic activity in the bone marrow. We have sought to identify whether serial measurement of sTfR may predict depth or duration of myelosuppression in patients receiving high dose chemotherapy. We prospectively measured serial sTfR in nine consecutive patients with haematologic malignancy admitted for various high dose regimens. The sTfR nadir was associated with white cell nadir, and sTfR nadir and day 5 sTfR were inversely associated with the number of red cell transfusions required. Our data suggest that sTfR may be helpful in predicting the degree of bone marrow suppression in patients receiving intensive chemotherapy.

Short report: soluble transferrin receptor and depth of bone marrow suppression following high dose chemotherapy

Aim The transferrin receptor (TFR) mediates the transport of iron into cells. Circulating TFR can be measured as soluble transferrin receptor (sTfR) which has been shown to reflect erythropoietic activity in the bone marrow (Beguin 1992, Huebers et al 1990). We have sought to identify whether serial measurement of sTfR may predict depth or duration of bone marrow suppression in patients receiving high dose chemotherapy. We prospectively measured serial sTfR in nine consecutive patients with haematological malignancy admitted for various high dose regimens. Methods Samples for sTfR were collected from surplus patient specimens, centrifuged at 1000×g and frozen at -70°C, thawed and assayed as a batch following patient recovery. sTfR was measured by an automated turbidimetric method on an Abbott Architect ci8200 (Tina quant, Roche) that has been previously evaluated (Pfeiffer et al 2007). Haemoglobin and WCC were measured on Abbott Cell-Dyne 4000 analysers (Abbott Diagnostics). Results The sTfR nadir was associated with white cell nadir, and sTfR nadir and Day 5 sTfR were inversely associated with the number of red cell transfusions required. Conclusion Our preliminary data suggest that sTfR may be helpful in predicting the degree of bone marrow suppression in patients receiving intensive chemotherapy.

Reduced gastrointestinal toxicity following inhibition of the biliary excretion of irinotecan and its metabolites by probenecid in rats.

To ameliorate the late-onset of severe gastrointestinal toxicity provoked by irinotecan (CPT-11), which may be related to the biliary excretion of CPT-11 and/or its metabolites. Effects of probenecid, an inhibitor of MRP2/ABCC2, on the biliary excretion and mucosal intestinal tissue concentration of CPT-11 and its metabolites were examined in rats. CPT-11-induced late-onset gastrointestinal toxicity was also evaluated. Coadministration of probenecid reduced the biliary excretion of CPT-11, an active metabolite (SN-38) and its glucuronide by half with a concomitant increase in their plasma concentration. When the dose of CPT-11, in the presence of probenecid, was set at half that in its absence, the plasma SN-38 concentration was maintained at the same level as the control, whereas the mucosal intestinal tissue concentration of SN-38 was reduced. Under this condition, CPT-11-induced watery diarrhea, changes in intestinal marker enzymes and body weight reduction were much less in the probenecid-treated group, although the degree of bone marrow suppression was almost the same as that in the control. Coadministration of probenecid with a reduced dose of CPT-11 potently reduces both SN-38 exposure and CPT-11-induced late-onset toxicity in gastrointestinal tissues, possibly by inhibiting the biliary excretion of CPT-11 and/or its metabolites.

Care of the heavily irradiated casualty

Patients receiving whole body doses of radiation of more than 4 Gy are unlikely to survive unless haematological support and isolation facilities are available. Bone marrow recovery may occur spontaneously or may be promoted in a number of ways including bone marrow transplantation. Nursing care must include facilities for isolation, provision of sterile supplies, drug administration and control of symptoms relating to the conditioning used for BMT. Infection is the major hazard and is reduced by gut decontamination and prompt treatment of fever with intravenous antibiotics, antiviral and antifungal agents. Industrial accidents involving this degree of bone marrow suppression are uncommon.

Azathioprine-Induced Pancytopenia Occurrence in Two Patients With Connective-Tissue Diseases

Two patients became severely pancytopenic while receiving azathioprine in low dosages for treatment of connective-tissue diseases. While mild hematologic complications are common with this drug, we believe that the degree of bone marrow suppression exhibited in these two patients is unusual, especially at the dosages (0.75 and 1.25 mg/kg/day) of azathioprine being used.