Disparities in the Occurrence of Long-Term Effects of Bone Marrow Suppression after Treatment in Adolescent Young Adult Breast Cancer Survivors.

BACKGROUND: Many adolescent and young adult (AYA) patients with breast cancer (BC) receive adjuvant therapy as initial treatment, with long-term bone marrow suppression as a potential complication, but no studies have evaluated the impact of race/ethnicity on the development of bone marrow suppression in AYA BC survivors. PATIENTS AND METHODS: Female patients ages 15-39 years diagnosed with BC (2006-2018) and surviving ≥ 2 years were identified from the California Cancer Registry and linked to statewide hospitalization data. We estimated the cumulative incidence of developing late effects of bone marrow suppression, such as leukopenia, anemia, thrombocytopenia, bleeding, and infection/sepsis, during hospital discharge diagnoses present ≥ 2 years after diagnosis. We examined the impact of sociodemographic and clinical factors on late effects using multivariate Cox proportional hazards regression. RESULTS: Of 11,293 patients, 42.8% were non-Hispanic (nH) White, 28.8% Hispanic, 19.5% nH Asian/Pacific Islander, and 7.5% nH Black. In multivariable analyses, nH Blacks had the highest risk (versus nH Whites) of anemia [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.47-2.02], leukopenia (HR 1.56, CI 1.14-2.13), thrombocytopenia (HR 1.46, CI 1.08-1.99), major infection/sepsis (HR 1.64, CI 1.4-1.92), and bleeding (HR 1.89, CI 1.39-2.58). Hispanics had a higher risk of developing anemia (HR 1.17, CI 1.04-1.32), bleeding (HR 1.4, CI 1.12-1.76), and major infections/sepsis (HR 1.36, CI 1.21-1.52). Asian/Pacific Islanders had only a higher risk of developing bleeding (HR 1.33, CI 1.03-1.72). Patients from a low neighborhood socioeconomic status had a 20% higher risk of infection/sepsis (HR 1.21, CI 1.1-1.34), but there were no associations for the other late effects. CONCLUSIONS: We identified that AYAs of nH Black, Hispanic, and Asian/Pacific Islander race/ethnicity are at an increased risk of several late effects after adjuvant therapy compared with nH White patients. From these data, providers can implement early/frequent screening of hematologic late effects in these high-risk survivors.

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.

Chimeric flavivirus causes vascular leakage and bone marrow suppression in a mouse model.

Previously, we demonstrated the utility of a recombinant chimeric flavivirus (DV2ChimV), which carries the premembrane (prM) and envelope (E) genes of a type 2 DENV clinical (Thai) isolate on a backbone of Japanese encephalitis virus, for evaluating the protective efficacy of antidengue envelope antibodies both in vitro and in vivo. Here, to assess the potential use of this model for pathological studies, we aimed to characterize interferon-α/ß-γ-receptor double-knockout mice (IFN-α/ß/γR dKO mice) infected with DV2ChimV. Vascular leakage and bone marrow suppression are unique features of severe dengue. In the current model, DV2ChimV caused vascular leakage in the liver and intestine at the moribund stage. High levels of virus were detected in the bone marrow, and strong bone marrow suppression (i.e., disappearance of megakaryocytes and erythroblastic islets) was observed. These observations suggest that the DV2ChimV-infected mouse model mimics the vascular leakage and bone marrow suppression observed in human cases.

Genomic methylation variations predict the susceptibility of six chemotherapy related adverse effects and cancer development for Chinese colorectal cancer patients.

Colorectal cancer (CRC) remains a major concern with high morbidity and mortality worldwide. Despite the positive influence of chemotherapy on the decline in CRC mortality, the negative influence of chemotherapy-related adverse effects (CRAEs) caused by capecitabine (Cap) remains a challenging problem. DNA methylation alteration plays a pivotal role in gene expression regulation. Here, we aimed to screen reliable and novel biomarkers for CRC diagnosis and CRAE prediction using the advanced Illumina Infinium MethylationEPIC (850 K) BeadChip. Paired tumor and normal tissues from 21 Chinese CRC patients who received Cap-based adjuvant chemotherapy were analyzed. CRC-related methylation was characterized by hypermethylated promoter islands and hypomethylated intragenic openseas; CRAE-related methylation was characterized by hyper- (or hypo-) methylated intragenic (or intergenic) regions. Based on three types of methylation profiles (differentially methylated probes, differentially methylated regions, and gene-function-differentially methylated regions), pathway enrichment analyses revealed that CRC-related genes were significantly enriched in the neuronal system, metabolism of RNA, and extracellular matrix organization; CRAE-related genes were abundantly enriched in pathways controlling regeneration functions and immune response. Finally, based on genes within the mostly related pathways and LASSO logistic regression selection, the integrated-methylation-marker systems developed here demonstrated high discriminative accuracy in both CRC diagnosis (AUROC = 1) and CRAE prediction (AUROC = 0.817-1). In conclusion, we conducted a comprehensive DNA methylation analysis of CRC patients with chemotherapy, which provided new insights into the formation of CRC and CRAEs. Most importantly, our findings identified potentially CRAE-related metabolic pathways and markers, providing a valuable reference for personalized medicine promising better safety. Trail registration:ClinicalTrials.gov,NCT03030508, Registered 25 January 2017,https://www.clinicaltrials.gov/ct2/show/NCT03030508?term=NCT03030508&draw=2&rank=1.

TPMT and NUDT15 polymorphisms in thiopurine induced leucopenia in inflammatory bowel disease: a prospective study from India.

BACKGROUND: Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. METHODS: We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. RESULTS: Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn's disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). CONCLUSION: NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.

Risk prediction models based on hematological/body parameters for chemotherapy-induced adverse effects in Chinese colorectal cancer patients.

PURPOSE: To determine risk factors and develop novel prediction models for chemotherapy-induced adverse effects (CIAEs) in Chinese colorectal cancer (CRC) patients receiving capecitabine. METHODS: A total of 233 Chinese CRC patients receiving post-operative chemotherapy with capecitabine were randomly divided into a training set (70%) and a validation set (30%). CIAE-related hematological/body parameters were screened by univariate logistic regression. Based on a set of factors selected from LASSO (least absolute shrinkage and selection operator) logistic regression, stepwise multivariate logistic regression was applied to develop prediction models. Area under the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow (HL) test were used to evaluate the discriminatory ability and the goodness of fit of each model. RESULTS: In total, 35 variables were identified to be associated with CIAEs in univariate analysis. Developed multivariable models had AUCs (area under curve) ranging from 0.625 to 0.888 and 0.428 to 0.760 in the training and validation set, respectively. The grade ≥ 1 anemia multivariable model achieved the best discriminatory ability with AUC of 0.760 (95%CI: 0.609-0.912) and good calibration with HL P value of 0.450. Then, a nomogram was constructed to predict grade ≥ 1 anemia, which included variables of age, pre-operative hemoglobin count, and pre-operative albumin count, with C-indexes of 0.775 and 0.806 in the training and validation set, respectively. CONCLUSIONS: This study identified valuable hematological/body parameters related to CIAEs. A nomogram based on the multivariable model including three hematological/body predictors can accurately predict grade ≥ 1 anemia, facilitating clinicians to implement personalized medicine early for Chinese CRC patients receiving post-operative chemotherapy for better safety treatment. Trial registration This study was registered as a clinical trial at www.clinicaltrials.gov (NCT03030508).

Genoprotective effects of Origanum vulgare ethanolic extract against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.

CONTEXT: Cyclophosphamide (CP), an alkylating chemotherapeutic agent, can bind DNA, causing chromosome breaks, micronucleus (Mn) formation, and cell death. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against DNA damage. OBJECTIVE: The genoprotective effect of O. vulgare ethanolic extract against CP-induced genotoxicity in mouse bone marrow cells was evaluated using a Mn assay. MATERIALS AND METHODS: Mice were pre-treated with aerial parts of O. vulgare ethanolic extract at different doses (50, 100, 200, or 400 mg/kg) for 7 d. One hour after the last administration of O. vulgare, animals were injected with CP at 200 mg/kg. After 24 h, the bone marrow cells of both femurs were flushed and the frequency of MnPCEs was evaluated to measure the chromosomal damages. In addition, the number of PCEs per 1000 NCEs in each animal was recorded to evaluate the bone-marrow suppression; mitotic activity was calculated as [PCE/(PCE + NCE)] × 100 to assess the cell division. RESULTS: At 400 mg/kg, O. vulgare displayed its maximum protective effect, reduced the number of MnPCEs from 10.52 ± 1.07 for CP group to 2.17 ± 0.26 and completely normalized the mitotic activity (p < 0.001). Origanum vulgare also led to significant proliferation and hypercellularity of immature myeloid elements after the mice were treated with CP, mitigating the bone marrow suppression. DISCUSSION AND CONCLUSION: Origanum vulgare ethanolic extract exerts a potent genoprotective effect against CP-induced genotoxicity in mice bone marrow, which might be possibly due to the scavenging of free radicals during oxidative stress conditions.

The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

[Intradermal needling and acupuncture in prevention and treatment of leukopenia after chemotherapy with spleen-kidney deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of intradermal needling and acupuncture in prevention and treatment of leukopenia after chemotherapy with spleen-kidney deficiency. METHODS: A total of 90 patients with malignant tumor who received chemotherapy were randomly divided into a intradermal needling group (30 cases, 1 case dropped out), an acupuncture group (30 cases, 2 cases dropped out, 1 case was eliminated) and a control group (30 cases). The control group received conventional symptomatic treatment after chemotherapy. On the basis of the treatment in the control group, the intradermal needling group received intradermal needling at Guanyuan (CV 4), Dazhui (GV 14) and bilateral Geshu (BL 17), Zusanli (ST 36)，Shenshu (BL 23), the needles were retained for 48 h, once every other day. On the basis of the treatment in the control group, the acupuncture group received conventional acupuncture at the same acupoints as the intradermal needling group, once every other day. The treatment started from the first day of chemotherapy, for a total of 2 weeks in the three groups. The white blood cell count, neutrophil count, hemoglobin content, platelet count and Karnofsky performance status (KPS) score before treatment and on 3rd, 7th, 14th, and 21st days after treatment were compared among the three groups. The incidence and grading of leukopenia and the usage of leukocyte-boosting drug during chemotherapy cycle was recorded. RESULTS: On 7th day after treatment, the white blood cell count in the intradermal needling group and the acupuncture group was higher than that in the control group (P<0.01, P<0.05). On the 14th day after treatment, the hemoglobin content in the intradermal needling group and the acupuncture group was higher than that in the control group (P<0.01). On the 7th, 14th, and 21st days after treatment, the platelet count in the acupuncture group was higher than that in the control group (P<0.01), on the 14th and 21st days after treatment, the platelet count in the intradermal needling group was higher than that in the control group (P<0.01). There was no statistically significant difference among the three groups after treatment in terms of neutrophil count, KPS score, incidence and grading of leukopenia, and the usage of leukocyte-boosting drug (P>0.05). CONCLUSION: Both intradermal needling and acupuncture can effectively increase peripheral blood white blood cell count, hemoglobin content and platelet count during chemotherapy cycle, reduce the toxicity of chemotherapy drug to bone marrow hematopoietic function, and alleviate bone marrow suppression after chemotherapy. The two treatments are equally effective.

Treatment Continuity and Bone Marrow Suppression in Whole-Brain and Whole-Spinal Cord Radiotherapy for Medulloblastoma Patients.

Background: This study investigated the factors influencing treatment continuity and bone marrow suppression in whole-brain and whole-spinal cord radiotherapy for medulloblastoma, providing a clinical reference for mitigating the impact of hematological suppression on radiotherapy continuity. Methods: A retrospective analysis was conducted on patients with medulloblastoma who underwent craniospinal irradiation (CSI) radiotherapy at our hospital between August 2019 and December 2023. According to the inclusion and exclusion criteria, a total of 87 patients were enrolled. The bone marrow suppression status, clinical data, and radiotherapy dose data of the enrolled patients were recorded, and correlation analyses were performed. Based on the correlation results, further group comparisons were subsequently conducted. Results: Overall, 22.99% (20 out of 87) of the patients experienced treatment interruption (median duration, 6.5 [5, 8] days), typically during the 12th (7.5, 14.75) radiotherapy session. Treatment continuity was weakly correlated with age and treatment modality, and the timing of interruptions was weakly correlated with dosage and treatment modality. Bone marrow suppression severity was weakly correlated with age, body mass index (BMI), and treatment modality. Treatment modality and age were found to be independent predictors of treatment continuity and the degree of bone marrow suppression, respectively. Subgroup comparisons revealed differences in the severity of bone marrow suppression, grade of hematological toxicity, and timing of interruption depending on the treatment modality, dosage, and sex (P < .05). Conclusions: Timely monitoring of hematological changes, especially in the middle and posterior segments after radiotherapy, is crucial. Treatment with helical tomotherapy, male sex, younger age, and lower BMI during radiotherapy are indicators of greater clinical attention.

Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.

Introduction: Severe dengue is thought to be caused by an excessive host immune response. Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre+Ifnarflox/flox mice carrying depleted Ifnar expression only in subsets of murine myeloid cells. Results: Although dengue virus (DENV) clinical isolates were not virulent in LysM Cre+Ifnarflox/flox mice, mouse-adapted DV1-5P7Sp and DV3P12/08P4Bm, which were obtained by passaging the spleen or bone marrow of mice, demonstrated 100% lethality with severe vascular leakage in the liver and small intestine. DV1-5P7Sp and DV3P12/08P4Bm harbored five and seven amino acid substitutions, respectively. Infection also induced neutrophil infiltration in the small intestine, and increased expression of IL-6 and MMP-8 and blockade of TNF-α signaling protected the mice, as demonstrated in a previous severe dengue mouse model using C57/BL6 mice lacking both IFN-α/ß and IFN-γ receptors. Notably, the new models with DV1-5P7Sp and DV3P12/08P4Bm showed an increased proliferative capacity of the adapted viruses in the thymus and bone marrow. Discussion: These observations suggest that myeloid cell infection is sufficient to trigger cytokine storm-induced vascular leakage. This model can refine the factors involved in the pathology of severe dengue leading to vascular leakage.

The influence of lentinan on the capacity of repair of DNA damage and apoptosis induced by paclitaxel in mouse bone marrow cells.

The ability of the flavonoid lentinan (LAN) to enhance the repair of paclitaxel (PAC)-induced DNA damage and apoptosis in mouse bone marrow cells was investigated. Moreover, the possible mechanism underlying this modulation was determined. LAN was neither genotoxic nor apoptogenic at doses equivalent to 1 or 2 mg/kg/day. Pretreatment of mice with LAN significantly enhances the repair of PAC-induced DNA damage and bone marrow suppression in a dose dependent manner. Moreover, LAN affords significant protection against PAC-induced apoptosis. A significant increase of reactive oxygen species and a decrease in reduced glutathione levels were observed after PAC treatment and prior administration of LAN before PAC challenge ameliorated these oxidative stress markers. Conclusively, our study provides, for the first time, that LAN enhances the repair of PAC-induced DNA damage and apoptosis that resides, at least in part, on its ability to modulate the cellular antioxidant levels and consequently protect bone marrow cells from PAC genotoxicity.

Application of immunomodulatory therapy in a human brucellosis patient with pancytopenia: A case report.

Brucellosis is a common zoonotic infectious disease with diverse and non-specific clinical manifestations caused by Brucella. Although Brucella can cause damage to multiple systems in the human body, hematological complications are relatively rare. We present a case of a 47-year-old male brucellosis patient with pancytopenia. In May 2018, the patient was diagnosed with brucellosis and recovered after receiving antibiotic treatment (rifampicin 600 mg/day and doxycycline 200 mg/day) for six weeks. However, after three years, the patient experienced a recurring high fever. Brucellosis relapse was confirmed based on the patient's clinical history, Rose Bengal plate agglutination test and standard tube agglutination test results. Routine blood examination revealed a decrease in the whole blood cell count, suggesting bone marrow suppression. Bone marrow aspiration and bacterial culture confirmed the diagnosis of brucellosis with pancytopenia. Antibiotic treatment failed to effectively improve the patient's condition. Therefore, a combination of immunomodulatory and antibiotic treatments was used. The antibiotic regimen included oral rifampicin 600 mg/day, intravenous doxycycline hydrochloride 200 mg/day, and subcutaneous injection of human granulocyte-stimulating factor (0.2 mg/day). Immunomodulatory therapy consisted of 20,000 mg/day intravenous human immunoglobulin (pH 4) for five days and 800 mg/day oral pidotimod liquid for 20 days. As the treatment progressed, the count gradually recovered to normal levels, and the symptoms of bone marrow suppression were alleviated. PCR testing revealed the absence of Brucella DNA in both monocyte and serum samples. Furthermore, negative standard tube agglutination test results were obtained. These findings indicate that the immunomodulatory therapy resulted in a complete clearance of Brucella. Therefore, immunomodulatory therapy could be an effective option in cases of brucellosis with pancytopenia that are unresponsive to conventional antibiotic treatment. Further research and clinical evidence are required to confirm and optimize the use of immunomodulatory therapies in patients with brucellosis.

Effectiveness of Acupuncture for Relieving Chemotherapy-Induced Bone Marrow Suppression: A Systematic Review with a Meta-analysis and Trial Sequential Analysis.

Objective: Bone marrow suppression is the most common side effect of chemotherapy that may lead to discontinuation for treatment pertaining to patients during the therapy course. Acupuncture may relieve bone marrow suppression with regulation hematopoietic function during chemotherapy. The purpose of this study is to evaluate the effectiveness of acupuncture in relieving chemotherapy-induced bone marrow suppression and determine the effects of acupuncture on bone marrow function. Design: PubMed, Embase, Cochrane Library, Medline OVID, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure databases were searched up to February 2023. Publications in both English and Chinese were eligible for inclusion without any limitations on the publication date. Only randomized controlled trials investigating the impact of acupuncture on chemotherapy-induced bone marrow suppression were considered. In addition, a trial sequential analysis was performed to assess the adequacy of the current sample size. Results: A total of 25 studies met the inclusion criteria. Acupuncture was found to increase the levels of hematopoietic cytokine granulocyte colony-stimulating factor (G-CSF) (Hedges' g = 0.79, p < 0.001), as well as stimulate the production of white blood cells (Hedges' g = 0.69, p < 0.001), red blood cells (Hedges' g = 0.37, p = 0.01), neutrophils (Hedges' g = 0.66, p < 0.001), absolute neutrophil count (Hedges' g = 0.89, p = 0.01), hemoglobin (Hb) (Hedges' g = 0.37, p = 0.02), platelets (Hedges' g = 0.50, p < 0.001), and natural killer (NK) cells (Hedges' g = 1.30, p = 0.02). Further, the levels of platelets and NK cells were observed to increase cumulatively over time. Conclusions: Acupuncture may improve chemotherapy-induced bone marrow suppression due to increasing levels of the hematopoietic cytokine, G-CSF and further relieving chemotherapy-induced bone marrow suppression. PROSPERO Registration: This review was registered with PROSPERO (International Prospective Register of Systematic Reviews: CRD42020185813).

Analysis of adverse drug reactions/events of cancer chemotherapy and the potential mechanism of Danggui Buxue decoction against bone marrow suppression induced by chemotherapy.

Objective: To analyze the clinical characteristics of adverse reactions/events based on chemotherapy in cancer patients, and then explore the potential mechanism of Danggui Buxue Decoction (DBD) against chemotherapy-induced bone marrow suppression (BMS). Methods: Retrospectively collected and evaluated were the clinical data of patients in a hospital who experienced adverse reactions/events brought on by chemotherapeutic medications between 2015 and 2022. We explored the potential mechanism of DBD against BMS using network pharmacology based on the findings of the adverse reactions/events analysis. Results: 151 instances (72.25%) experienced adverse reactions/events from a single chemotherapy medication. Besides, platinum-based medications produced the most unfavorable effects. The study also found that chemotherapy caused the highest number of cases of BMS, including platinum drugs. Consequently, BMS is the most prevalent adverse reaction disease caused by chemotherapy found in this part. According to network pharmacology findings, DBD can prevent BMS primarily involving 1,510 primary targets and 19 key active ingredients. Based on the enrichment analysis, PI3K-AKT, TNF, MAPK, and IL-17 signaling pathways made up the majority of the DBD-resisting BMS pathways. Molecular docking displayed that kaempferol, the major active ingredient of DBD, had the highest binding energy (-10.08 kJ mol-1) with PTGS2 (a key target of BMS). Conclusion: Cancer patients who received chemotherapy had a risk to develop BMS. Regular blood tests should be performed while taking medicine; early discovery and treatment can reduce a patient's risk of experiencing adverse reactions/events. Additionally, this study demonstrated that DBD, through a variety of targets and pathways, may be crucial in avoiding BMS.

Travesty of Undetected Hypoparathyroidism: A Series of Missed Opportunities.

We describe a 20-year-old male with childhood-onset seizures and a prolonged history of anti-epileptic use. The cause of his seizures remained undetected until he reached the second decade of his life. Extensive intracranial calcifications on brain imaging helped us identify hypocalcemia as a cause of seizures. He had low calcium due to primary hypoparathyroidism. He also had severe aplastic anemia at this time. There were a series of missed opportunities in his history that could have prevented prolonged anti-epileptic use and probably preserved his marrow. This is an educational case for all physicians on how parathyroid abnormalities may get missed.

Bone Marrow Suppression Secondary to the COVID-19 Booster Vaccine: A Case Report.

As of September 2021, SARS-CoV-2 booster shots became widely available in the US to ensure continued protection against the virus. A temporal relationship has been previously reported between the first or second dose of the COVID-19 vaccine and the development of thrombocytopenia. However, adverse events related to the third COVID-19 vaccine are still being reported and studied. We report a 74-year-old male who developed bone marrow suppression and pancytopenia recorded seven days after receiving the Pfizer SARS-CoV-2 vaccine. During his hospital stay, the patient's hemoglobin, white blood cell, and platelet levels continued to trend downwards. However, all three levels showed improvement one week after discharge without robust intervention. Global vaccination is of utmost importance, as is understanding and documenting post-vaccination reactions including bone marrow suppression. Prompt evaluation and patient education are imperative to improve patient outcomes and combat hesitancy against vaccine administration.

Bone Marrow Suppression during Postoperative Radiation for Bladder Cancer and Comparative Benefit of Proton Therapy-Phase 2 Trial Secondary Analysis.

PURPOSE: For patients with high-risk bladder cancer (pT3+ or N+), local regional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase 2 trial (NCT01954173) is examining the role of postoperative photon radiation therapy for high-risk patients using volumetric modulated arc therapy. Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiation therapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose. MATERIALS AND METHODS: All enrolled patients were retrospectively analyzed after pelvic radiation per protocol with 50.4 to 55.8 Gy in 28 to 31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multifield optimization technique. Changes in hematologic nadirs were assessed using paired t test. Correlation of mean nadirs and relative PBM dose levels were assessed using the Pearson correlation coefficient (CC). RESULTS: Eighteen patients with a median age of 70 were analyzed. Mean cell count values after radiation therapy decreased compared with preradiation therapy values for white blood cells (WBCs), absolute neutrophil count (ANC), absolute lymphocyte count (all P < .001), and platelets (P = .03). Increased mean PBM dose was associated with lower nadirs in WBC (Pearson CC -0.593, P = .02), ANC (Pearson CC -0.597, P = .02), and hemoglobin (Pearson CC -0.506, P = .046), whereas the PBM V30 to V40 correlated with lower WBC (Pearson CC -0.512 to -0.618, P < .05), and V20 to V30 correlated with lower ANC (Pearson CC -0.569 to -0.598, P < .04). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (P < .001) and had significant reductions in the volume of PBM receiving doses from 5 to 40 Gy (P < .001). CONCLUSION: Increased PBM mean dose and V20 to V40 were associated with lower hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.

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

Background: Retinoblastoma (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. Methods: Children 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. Results: Data 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. Conclusion: Children 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.

Acute and delayed cytopenias following CAR T-cell therapy: an investigation of risk factors and mechanisms.

Prolonged myelosuppression after chimeric antigen receptor (CAR) T-cell therapy is common and poorly understood. A retrospective analysis of 43 patients was conducted to investigate factors contributing to CAR T-cell-related cytopenias. Thirty-five patients were evaluable for analysis of delayed cytopenias occurring after initial hematologic recovery. Time to hematologic recovery (TTHR) was defined as number of days after CAR T-cell infusion for recovery to hemoglobin ≥8.0 g/dL, platelets ≥50.0 k/µL, and neutrophil count ≥1.0 k/µL without transfusions or growth factors for 7 days. Baseline percent bone marrow (BM) malignancy involvement correlated with TTHR (p = .0047). Patients with grades 3-4 cytokine-release syndrome (CRS) had longer TTHR than those with grades 0-2 CRS (p = .0479). Patients who developed prolonged or delayed cytopenias after anti-BCMA CAR T cells had a higher percentage of BM aspirate CAR+ cells at 2 months (n = 10; p = .0159).