Incidence Of Bone Marrow Suppression Research Articles

Aplastic anemia in a lung adenocarcinoma patient receiving pemetrexed

Pemetrexed (PEM) is an antimetabolite drug that interferes with enzymes involved in DNA synthesis and also the folate-dependent metabolic processes necessary for DNA replication and homocysteine homeostasis. Continuation maintenance with PEM after induction therapy with PEM plus cisplatin has been the standard form of first-line chemotherapy for advanced non-squamous non-small cell lung cancer. The regimen has a low incidence of bone marrow suppression, and the incidences of anemia, leukopenia, neutropenia and thrombocytopenia exceeding grade 3 are less than 5%. Here we report a 68-year-old Japanese man with stage IIIB (cT4N3M0) lung adenocarcinoma who received 4 cycles of chemotherapy with PEM 500 mg/m2 and cisplatin 75 mg/m2 every three weeks, which resulted in a partial response, and then continued to receive maintenance PEM monotherapy. After 11 cycles of PEM maintenance therapy, the patient's platelet count decreased, and progressed to pancytopenia within two months. A bone marrow puncture revealed replacement with fatty marrow. As other diseases possibly responsible for pancytopenia were ruled out, we diagnosed the patient as having aplastic anemia. This is the first reported case of aplastic anemia to have occurred during PEM therapy. Clinicians should bear in mind that PEM can potentially trigger severe pancytopenia, including aplastic anemia.

The effect and clinical efficacy of lienal polypeptide injection combined with FOLFOX chemotherapy regimen in colon cancer patients.

The aim was to investigate the clinical efficacy and immunomodulatory effect of lienal polypeptide injection combined with postoperative FOLFOX chemotherapy regimen in colon cancer patients. A total of 84 colon cancer patients were selected between January, 2014 and December, 2015. The selected patients were randomly divided into the observation (42 patients) and control (42 patients) groups. The observation group patients were treated with FOLFOX chemotherapy regimen combined with lienal polypeptide, whereas, the control group patients were treated with FOLFOX chemotherapeutic regimen only. After two cycles of treatment, Karnofsky performance scale (KPS) index, side effects or toxicity and the peripheral blood T-cell subset analyses in the two groups of patients were evaluated. The patients who received FOLFOX chemotherapeutic regimen combined with lienal polypeptide in the observation group showed significantly higher score of KPS than patients of the control group (P<0.05). No significant difference in the spectrum of side effects such as nausea, vomiting, neurotoxicity, liver and kidney dysfunction, oral mucosal inflammation were observed in the treatment groups. However, the incidence of bone marrow suppression was significantly lower in the observation group in comparison with the control group (P<0.05). Additionally, the CD8+ T cells were decreased in the observation group patients compared to the control group, while the ratio of CD4+ T/CD8+ T (TH/TC) cells and the number of natural killer cells were higher in the observation group patients than the control group (P<0.05). In conclusion, the results suggest that, when the standard FOLFOX chemotheraputic regimen is combined with lienal polypeptide to treat colon cancer, it enhances the general well being of patients and strengthens the immune system in the combat against cancer.

Relationship between sternum protection and bone marrow suppression in postoperative radiotherapy for esophageal carcinoma

Objective To evaluate the relationship between sternum protection and bone marrow suppression in postoperative radiotherapy for esophageal carcinoma. Methods Total of 98 postoperative patients with thoracic esophageal carcinoma were randomly divided into experimental group (52 cases) and control group (46 cases). All patients were given intensity-modulated radiotherapy (IMRT), with the dose of 50-50.4 Gy. The patients in experimental group were irradiated by 6 fields (4-fields in front, 2-fields behind) which were crossed to avoid direct exposure to the sternum. The patients in control group were irradiated by 5 fields (3-fields in front, 2-fields behind) with front-middle of the field passing through the sternum. Concurrently all patients received 2 cycles of cisplatin chemotherapy. Results Dmean, V20 and V30 of the sternum in the experimental group were (20.21±3.60) Gy, (40.78±7.19) % and (33.78±9.44) %, which were lower than those in the control group [(30.91±5.21) Gy, (81.01±4.81) %, (51.60±6.84) %], respectively (P 0.05). Both the incidence rates of bone marrow suppression at 14th day and 35th day after radiotherapy were significantly higher in the control group (52.2 %, 73.9 %) than those in the experimental group (28.8 %, 50.0 %) (P< 0.05), and the incidence rate of bone marrow suppression at 7th day after radiotherapy was similar between the two groups. Conclusion Protecting and sketching for sternum in postoperative radiotherapy for esophageal carcinoma can reduce the incidence of bone marrow suppression effectively, which would not increase the radiation dose in the lung, heart and spinal cord. Key words: Esophageal neoplasms; Surgical procedures, operative; Sternum protection; Radiotherapy, computer-assisted; Bone marrow suppression

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review.

To evaluate the incidence of bone marrow suppression and consequences of MMF dose adjustment in patients within the first year after heart transplantation. Group I (n=47) was treated with a regimen currently used in patients after heart transplantation (mycophenolatemofetil - MMF, valganciclovir - VGC and trimethoprim/sulfamethoxazole - TMP-SMX). Group II (n=47) received only MMF of potentially myelotoxic medications. The myelotoxic effect and need for dose modification were assessed. The incidence of rejections and infectious episodes associated with MMF adjustment were analyzed during the first 12 months in Group I. There was a significantly greater proportion of patients with leukopenia (leukocyte count < 4 x 10^9/L) at 3 months after orthotopic heart transplantation in Group I compared with Group II (19.1% vs 2.1%; P = 0.02). The difference in lymphopenia (lymphocyte count < 0.8 x 10^9/L) at 3 months follow-up was highly significant (38.3 % vs 6.4 %; P = 0.0002). MMF was modified due to bone marrow suppression or severe infection in 63.8% patients in Group I and in only 8.5% of patients in Group II (P < 0.001). Reducing or stopping MMF was not associated with increased rejections. In Group I, at least 1 episode of higher degree cellular or humoral rejection occurred in 35% of patients with the standard MMF dosage compared with only 26% in patients with modified MMF (P = 0.0534). Addition of VGC+TMP-SMX to current immunosuppressive medication regimen in patients after heart transplantation is associated with significant lymphocytopenia and leukopenia. Importantly, modification of immunosuppressive prophylaxis (reducing or stopping MMF) leads to normalization of blood count without increased incidence of rejections.

The impact of 5-aminosalicylic acid on bone marrow suppression caused by thiopurines

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.Methods The clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.Conclusions The incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression. Key words: Aminosalicylic acids; Azathioprine; 6-mercaptopuzine; Bonemarrow diseases; Dose-response relationship, drug

Intraoperative versus interstitial radiotherapy: A comparison of morbidity in the head and neck

Intraoperative radiation therapy (IORT) and interstitial radiotherapy (brachytherapy) are highly effective adjunctive treatments for head and neck cancer. The radiotolerance of the carotid artery, pharynx, and mandible to therapeutic doses of these modalities, however, has not been clearly established. To investigate the effects of IORT and interstitial iridium 192 (192Ir) on these structures in the canine, both sides of the neck of 12 mongrel dogs were operated on to expose 4-cm segments of the common carotid artery, pharynx, and mandible. One side of the neck was irradiated in each animal with the opposite side serving as the unirradiated control. The animals were divided into 3 groups of 4 dogs each. The first group received 40-Gy IORT and the second, 60-Gy IORT. In the third group of animals, afterloading catheters were implanted followed by placement of 60-Gy 192Ir. At 2 and 4 months after irradiation, 2 dogs in each treatment group were killed and histopathologic examination of the carotid artery, pharynx, and mandible was performed using hematoxylin-eosin staining. No statistically significant difference between treatment groups was found for carotid artery injury, but a trend for the proportion of fibrosis of the carotid on the irradiated side to increase with dose (P = .125) and time (P = .250) was noted. No apparent or statistically significant difference was found between treatment groups for pharyngeal injury. The greatest histologic changes noted following IORT and 192Ir brachytherapy were found in mandible specimens. The incidence of bone marrow suppression in irradiated mandible specimens versus controls approached statistical significance (P = .062). Osteoradionecrosis (ORN) was noted in the irradiated mandible specimens of two dogs, one of which received 60-Gy IORT and the other 60-Gy interstitial 192Ir. This manuscript reviews animal and clinical investigations relevant to the use of IORT and interstitial radiotherapy to the head and neck. Recommendations are made regarding further animal and clinical research as well as methods of treatment.