Search

Therapeutic response and drug-induced toxicity have been reported to be associated with genetic variants of drug-metabolizing enzymes and transporters. Recently, new causative variants associated with drug response have been reported by genome-wide association studies (GWASs). Additionally, therapeutic response has been predicted using a model of multiple single-nucleotide polymorphisms. In acute lymphoblastic leukemia (ALL), the genetic variants of NUDT15 associated with therapeutic response to 6-mercaptopurine (6-MP) have been reported by GWASs, and the frequency of NUDT15 variants was higher in Asians. Then, several reports on NUDT15 genetic variants associated with 6-MP-induced toxicities and the tolerable doses and outcomes of 6-MP therapy for ALL have been published in Asian countries. The drugs used in treating hematological malignancies have reported new genetic variants associated with its therapeutic response. However, the association between these genetic variants has not been validated in other populations. Here, we reviewed recent reports on the association between the genetic variants and response to drugs used in treating hematological malignancies, such as 6-MP, cytarabine, methotrexate, and vincristine.

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. A second course of CAG therapy was started 15 days postoperatively. However, he was then diagnosed with exacerbation of the AML; remission induction therapy (daunorubicin, cytarabine)was started in November. In December, he developed a fever and abdominal pain, and on CT scan, it was discovered that an abscess had formed around the rectal resection site. Myelosuppression from AML led to prolonged sepsis; and by January 2020, the sepsis was systemic. His actual cause of death was given as circulatory failure. We report this, because only a few cases on the treatment of overlapping AML and colorectal cancers can be found in the literature.

Development of acute myeloid leukemia (AML) during pregnancy is rare, and the available data are limited to small retrospective reports. Currently, no guidelines exist for the management of AML during pregnancy in Japan. A 26-year-old female was diagnosed with AML at 19 weeks of gestation, received chemotherapy with daunorubicin and cytarabine, and achieved complete remission. Following the first consolidation therapy, she gave birth to a 1964-g female infant by cesarean section at 33 weeks of gestation. One week later, she was initiated on the second consolidation therapy; however, she developed a pelvic abscess during neutropenia. She underwent urgent surgery for open drainage and recovered soon after surgery. She has been in complete remission for eight months, and the daughter is healthy. Chemotherapy delivered after the second trimester rarely causes congenital malformations and may not require the termination of pregnancy. The clinical course of the present case suggests that chemotherapy can be performed safely and effectively in pregnant patients with AML after the trimester and babies.

A 43-year-old man was diagnosed with gastric cancer with diaphragm invasion and multiple lymph node metastases and underwent total gastrectomy. The histological diagnosis was por2>tub2, ypT4b(diaphragm), int, INF c, ly1, v1, ypN3, yp Stage ⅢC. Three months postoperatively, computed tomography showed recurrence in the peritoneum and multiple lymph nodes, and he received chemotherapy(RAM plus PTX). After initiating the third course of chemotherapy, he was hospitalized due to loss of appetite and fatigue. On the third day of hospitalization, he lost consciousness and had a temporary convulsion seizure. Thereafter, he complained of headache and nausea. Brain magnetic resonance imaging and cerebrospinal fluid examination lead to a diagnosis of carcinomatous meningitis due to gastric cancer. An Ommaya reservoir was placed, and intrathecal infusion with methotrexate(MTX)and cytarabine(Ara-C)was planned; however, intrathecal infusion could not be administered because of hepatic injury due to acute obstructive cholangitis. He died 6 months postoperatively. Carcinomatous meningitis has a rapidly progressive course with very poor prognosis. Early diagnosis is important, and the treatment should be initiated as soon as possible. Moreover, an effective standard treatment for carcinomatous meningitis needs to be established.

Therapeutic modalities for acute myeloid leukemia (AML) in elderly include intensive chemotherapy, less-intensive chemotherapy, and best supportive care. The choice of treatment is based on patients' general physical condition, leukemic prognostic factors, preference of the patient/family, and the available social support. Findings of comprehensive geriatric assessment and comorbidities are considered while selecting therapeutic modalities. AML score may suggest the appropriateness of the use of intensive chemotherapy. When intensive chemotherapy is tolerable, enocitabine or cytarabine + daunorubicin is used as remission induction chemotherapy. Consolidation chemotherapy comprising three courses of cytarabine-based regimens is administered after complete remission. When intensive chemotherapy is not tolerable, low-dose cytarabine is used. CPX351, a novel antileukemic agent, is a liposomal formulation of asynergistic 5 : 1 molar ratio of cytarabine and daunorubicin. In a randomized phase 2 trial in older patients with AML, CPX351 showed better response rate and survival than cyarabine + daunorubicin regimen.

Here, we report a case of a 67-year-old man who had septic shock due to Citrobacter braakii infection during the course of chemotherapy with high-dose cytosine arabinoside for acute myeloid leukemia. Treatment with cefepime rapidly improved his condition. The number of reported cases of sepsis due to Citrobacter braakii is limited. Further accumulation of cases is necessary to obtain accurate data such as the risk factors for Citrobacter braakii infections.

Optimal salvage chemotherapy has not been established for patients with acute myeloid leukemia (AML) who fail to attain complete remission (CR) after one course of induction chemotherapy. This retrospective study aimed to assess the efficacy and safety of an MEC (mitoxantrone, 6 mg/m 2 , 1-3 days; etoposide, 80 mg/m 2 , 1-6 days; cytarabine, 1 g/m 2 , 1-6 days) regimen in patients with AML who failed to attain CR after one course of induction chemotherapy. Twenty-four patients were included in this study (median age, 58 years; range, 28-79 years). After one course of MEC, 11 patients (45.8%) attained CR. Febrile neutropenia was observed in all patients, and acute infection was observed in 7 patients (29.2%). However, no therapy-related death occurred. All patients eligible for transplantation and who attained CR after MEC salvage chemotherapy underwent allogeneic hematopoietic stem cell transplantation. The MEC regimen exhibited a good response rate with tolerable adverse events. Therefore, the MEC regimen can be safely used as a salvage treatment for patients with AML who failed to attain CR after one course of induction chemotherapy.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by CD5+, CCND1+, and the CCND1-IGH translocation. Although patients with MCL respond, at least temporarily, to conventional chemotherapy, they eventually have a relapse and the prognosis is generally poor. As a primary treatment option for patients with untreated MCL, a rituximab-containing chemotherapy regimen is administered according to the patient's eligibility for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). For ASCT-eligible patients, an induction chemotherapy that includes high-dose cytarabine followed by ASCT is recommended. For ASCT-ineligible patients, a less intensive therapy, such as R-CHOP, bortezomib-containing therapy (VR-CAP), or bendamustine plus rituximab, is recommended. These induction therapies can be followed by rituximab maintenance. For those with relapsed/refractory MCL, fludarabine, bendamustine, 90Y-ibritumomab tiuxetan, and conventional cytotoxic agents can be used. Recently, ibrutinib, an inhibitor of Bruton tyrosine kinase, has been approved for relapsed/refractory MCL. Recent advances in the management of MCL will improve the prognosis of patients with MCL.

From June 1975 through December 1983, 48,604 individuals consisting of 34,535 males and 14,069 females underwent health examinations at the Automated Multiphasic Health Testing and Services (AMHTS) Center in Tokai University Hospital. There were five patients with renal cell carcinoma and three with bladder cancer. We reviewed the clinical courses of these patients and discussed the early detection of urological cancers in AMHTS. Patients with renal cell carcinoma were brought to the urology department with various findings in AMHTS. A 44-year-old male was referred to us for the investigation of multiple metastatic shadows in the chest X-P and left renal tumor was diagnosed by intravenous pyelography (IVP) and computed tomography (CT). Renal tumor of a 57-year-old male was diagnosed by the investigations of abnormal renal calcifications found in AMHTS. A 39-year-old female had undergone health check-ups several times but was not found to have a renal tumor. The diagnosis of left renal tumor was made by the abdominal CT carried out after the operation on cerebellar hemangioblastoma. The fourth patient was a 60-year-old female with microscopic hematuria found in AMHTS and the diagnosis was confirmed by calyceal deformity shown in IVP. The last patient was a 64-year-old male and was accidentally demonstrated to have a right renal mass by ultrasonography when he was reexamined for the hepatic abnormality found in AMHTS. He showed microscopic hematuria in the AMHTS urinalysis. The diagnosis was confirmed by IVP, CT and renal angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of thyrotropin releasing hormone tartrate (TRH-T) on the behavior of cytosine arabinoside (Ara-C) induced ataxic mice were studied. The ataxic mice were prepared by injecting 50 mg/kg/day subcutaneously on the 2nd, 3rd and 4th postnatal days. Spontaneous motor activities were measured with a movement spectrum analyzer (ANIMEX-2) and the degree of ataxic gait determined by an open-field study. Cerebella from these animals were subjected to histopathologic examination at 4, 8 and 12 weeks of age. Ataxic gait became improved moderately and spontaneous motor activities increased slightly following administration of TRH-T. The effects of TRH-T on ataxia and spontaneous motility in the Ara-C injected mice varied with the age, and resembled those seen in weaver mice but not those in the Rolling mouse Nagoya. The results also suggest that the effects of TRH-T on the behavior of ataxic mice correlate with the extent of pathologic changes evoked in their cerebella.

Pregnant mice were injected intraperitoneally on different gestational day with either one or three successive doses of 30 mg/kg of cytosine arabinoside (ara-C), which has been known to interfere with DNA synthesis. Some of them were injected intraperitoneally with tritiated thymidine (3H-TdR) consecutively. The fetuses and the youngs were sacrificed at various hours and days after treatment. Pyknotic nuclei or nuclear debris were observed at the matrix layer three hours after the injection of single dose of ara-C. Nuclear debris were increased as time elapse and they were most prominent 12 hours after treatment. However, 24 hours later, new matrix layer was regenerating. Twenty-four hours after treatment with two successive doses of ara-C, labeling index in the matrix layer was about one third of that of control. Cerebral hemispheres of the treated youngs were reduced in size. The youngs, treated with three successive doses of ara-C on day 13, 14 and 15 of gestation, showed most severe microcephalus. Cytoarchitecture in the cortices of these microcephalic mice was characterized by irregular arrangement of the pyramidal neurons and their dendritic branches. Autoradiographic study revealed that cortical neurons which were produced at the regenerated matrix layer after ara-C treatment migrated to the surface of the cortex.