Anatomical change of SMV branches after the Cattell Braasch maneuver facilitates safe resection around the uncinated process in pancreatoduodenectomy.

BACKGROUND: The aims of the present study were to demonstrate the anatomical change of superior mesenteric vein (SMV) branches and to show how the Cattell Braasch maneuver facilitates a safer ligation of these venous branches during a pancreatoduodenectomy (PD). METHODS: Between January 2010 and December 2019, 97 patients with peripancreatic tumors underwent pancreatectomy. We retrospectively reviewed preoperative triple-phase enhanced computed tomography (CT) images and analyzed variations in SMV branches. Anatomical changes in SMV branches after the Cattell Braasch technique were observed using our operation video and illustrations. RESULTS: The first jejunal vein (J1v) in 75% of patients ran posterior to the superior mesenteric artery (SMA), while the remainder (25%) ran anterior to it. The inferior pancreatoduodenal vein (IPDV) was preoperatively detected in 91% of patients. The IPDV drained into the J1v in 74% of patients and into the SMV in 37%. After the Cattell Braasch maneuver, the J1v which ran posterior to the SMA now was found to lie to the right anterolateral side the SMA and the visualization of both the J1v and the IPDV were much more clearly visualized. CONCLUSIONS: The most frequent venous variation was the IPDV draining into the J1v posterior to the SMA. After the Cattell Braasch maneuver, the IPDV was now located to the right anterolateral anterior aspect of the SMA which facilitates its visualization and should allow a safer ligation.

Evaluation of staging and early response to chemotherapy with whole-body diffusion-weighted MRI in malignant lymphoma patients: A comparison with FDG-PET/CT.

BACKGROUND: To examine the utility of diffusion-weighted MRI (DW-MRI) for staging and early response to chemotherapy assessment in lymphoma patients as compared with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). METHODS: Twenty-eight patients with histologically confirmed malignant lymphoma underwent both MRI and FDG-PET/CT before (pretreatment) and after two courses of chemotherapy (mid-treatment). Staging with MRI (DW-MRI alone and with T2-weighted images) and FDG-PET was compared visually, and the concordance rate (kappa value, κ) was calculated. To evaluate early response to chemotherapy, patients were divided into two groups, lesion-positive (LP) and lesion-negative (LN), based on a proposed original criterion. Progression-free survival (PFS) was compared between the groups using the Kaplan-Meier method. RESULTS: The stage diagnosed with DW-MRI alone and with FDG-PET/CT was concordant in 22 patients (κ = 0.71; P < 0.05), and by adding T2-weighted images, the number of concordant patients increased to 26 (κ = 0.90; P < 0.05). On mid-treatment imaging, 19 patients were diagnosed as LN from both modalities. PFS differed significantly between LP and LN on both DW-MRI (P = 0.0013) and FDG-PET/CT (P = 0.037). CONCLUSION: DW-MRI is a promising tool for staging and evaluation of early response to chemotherapy in patients with lymphoma.

[Sudden blast crisis of chronic myeloid leukemia after a 13-year durable remission following allogeneic bone marrow transplantation and donor lymphocyte infusion].

We describe a rare case of sudden blast crisis of chronic myeloid leukemia that occurred after a 13-year durable remission, following allogeneic bone marrow transplantation and donor lymphocyte infusion. A 55-year-old Japanese man was diagnosed with chronic-phase chronic myeloid leukemia 24 years previously. He underwent allogeneic bone marrow transplantation 2 years after diagnosis. Although the disease recurred 6 years after transplantation, the patient achieved remission again by a donor lymphocyte infusion. Despite a 13-year durable remission, the disease later relapsed into a sudden blast crisis. Prednisolone and vincristine combined with imatinib mesylate effectively achieved a major molecular response. However, the disease relapsed repeatedly with central nervous system infiltration. Dasatinib and intrathecal methotrexate, cytarabine, and dexamethasone administration via the Ommaya reservoir controlled disease progression. Nevertheless, the disease became refractory to treatment with the emergence of a T315I Bcr-Abl gene mutation. The patient eventually died 43 months post crisis.

[Chemotherapy].

The progress of cancer chemotherapy has made a large contribution to the significant improvement of cure rate in patients with hematological malignancy including malignant lymphoma. Interpatient variability characterizes the disposition of many drugs. In the case of drugs with a wide therapeutic index, such variability is unlikely to affect either clinical efficacy or toxicity. With anticancer drugs, however, there is much less margin for error, due to their very narrow therapeutic index. Therefore, it is crucially important to understanding the mechanism of action, pharmacokinetics and pharmacodynamics of each anticancer drug in order to give chemotherapy in safety. Overview of the pharmacological functions of anticancer agent using in malignant lymphoma is the subject of this chapter.

Marked upregulation of Survivin and Aurora-B kinase is associated with disease progression in the myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Survivin is a member of the inhibitor of apoptosis family and suppresses apoptosis. Survivin also functions as a subunit of the chromosomal passenger complex for regulating mitosis with Aurora-B. Survivin and Aurora-B play an important role in maintaining genome stability. The aim of this study was to determine the role of Survivin and Aurora-B kinase in disease progression and prognosis of myelodysplastic syndromes. DESIGN AND METHODS: We evaluated the expression levels of these two genes in CD34(+) cells prepared from 64 patients with myelodysplastic syndrome or leukemic blasts from 50 patients with de novo acute myeloid leukemia using quantitative real-time PCR. RESULTS: Survivin and Aurora-B expression levels were highly correlated with the type of myelodysplastic syndrome, were much higher in refractory anemia with excess blasts-1, refractory anemia with excess blasts-2, and secondary acute myeloid leukemia following myelodysplastic syndrome than in normal control, and increased during disease progression. There was a significant correlation between these expression levels and the International Prognostic Scoring System. Interestingly, these levels were remarkably higher in patients with secondary acute myeloid leukemia following myelodysplastic syndromes than in those with de novo acute myeloid leukemia. CONCLUSIONS: This is the first report showing that high levels of Survivin and Aurora-B kinase expression in CD34(+) cells are distinctive molecular features of high-risk myelodysplastic syndromes and secondary acute myeloid leukemia following myelodysplastic syndrome. Marked upregulation of Survivin and Aurora-B kinase may contribute to genetic instability and disease progression of myelodysplastic syndromes. Our data may explain why patients with high-risk myelodysplastic syndromes frequently show complex chromosomal abnormality.

Population pharmacokinetic model development and exposure-response analysis of vincristine in patients with malignant lymphoma.

PURPOSE: Vincristine (VCR) is a key drug for treating various malignancies. However, few data are available on the pharmacokinetics of VCR, especially in adult patients. The objective of this study was to clarify the population pharmacokinetics and exposure-response relationships of VCR in adult malignant lymphoma patients. METHODS: Blood samples were collected from patients who were administered R-CHOP-like regimens, and the VCR plasma concentration was determined using liquid chromatography-mass spectrometry. Using NONMEM software, population pharmacokinetic parameters were estimated, and covariates were evaluated. The relationships between the individual parameters and adverse events or therapeutic effects were also investigated. RESULTS: Plasma concentrations were measured in 30 patients. In the final population pharmacokinetics model, body surface area and age were incorporated into clearance as significant covariates. The inter-individual variations in clearance and volume of distribution in the central and third compartments were 17.0, 26.6, and 66.3%, respectively, and the residual variability in the plasma concentration was 23.8%. Although the variability observed in the volume of distribution was large, good predictability was obtained in the individual estimation. The severity of anemia and peripheral neuropathy was correlated with clearance and peak concentration, respectively (adjusted P = 0.040 and 0.024, respectively). In diffuse large B cell lymphoma patients, those with higher area under the curve and dose experienced longer progression-free survival (P = 0.023 and 0.013, respectively). CONCLUSION: The population pharmacokinetics of VCR were evaluated in adult malignant lymphoma patients. VCR pharmacokinetic data could explain in part the adverse events and prognosis of these patients.

A case report of a gastrobronchial fistula and lung abscess caused by leakage from the staple line of a gastric tube after esophagectomy for esophageal cancer.

BACKGROUND: Gastrobronchial fistulas are rare, but life-threatening, complications of esophagectomy. They are caused by anastomotic leakage and mainly occur around anastomotic sites. In the present paper, we report a rare case of leakage from the staple line of a gastric tube after esophagectomy for esophageal cancer, which was successfully treated using an intercostal muscle flap and lung resection. CASE PRESENTATION: A 61-year-old male underwent subtotal esophagectomy with regional lymphadenectomy for esophageal cancer. The sutures along the staple line of the gastric tube failed 11 days after surgery, and a pulmonary abscess was also found on imaging. The abscess did not heal after conservative treatment; therefore, right lower lobectomy, gastrobronchial fistula resection, primary closure, and patching of the leaking portion of the gastric tube with an intercostal muscle flap were performed 9 months after the first operation. The patient's postoperative course was uneventful, and he was discharged on the 354th day. CONCLUSIONS: We experienced a case involving a gastrobronchial fistula caused by leakage from the staple line of a gastric tube and successfully treated it by performing right lower lobectomy and patching the leak with an intercostal muscle flap.

Glutathione S-transferase M1 inhibits dexamethasone-induced apoptosis in association with the suppression of Bim through dual mechanisms in a lymphoblastic leukemia cell line.

Glutathione S-transferase mu (GSTM1) is mainly known as a detoxification enzyme but it has also been shown to be a negative regulator of apoptosis-related signaling cascades. Recently GSTM1 has been reported to be a significant risk factor for hematological relapse in childhood acute lymphoblastic leukemia, although the underlying mechanism remains largely unknown. Glucocorticoids play a crucial role in the treatment of childhood acute lymphoblastic leukemia, therefore we hypothesized that GSTM1 plays important roles in glucocorticoid-induced apoptotic pathways. To clarify the relationship between GSTM1 and drug resistance, GSTM1 was transfected into a T-acute lymphoblastic leukemia cell line, CCRF-CEM (CEM), and we established the GSTM1-expressing cell lines CEM/M1-4 and CEM/M1-9. Transduction of GSTM1 into CEM selectively decreased cellular sensitivity to dexamethasone in a manner that was independent of glutathione conjugation, but was due to apoptosis inhibition. Dexamethasone-induced p38-MAPK and Bim activation were concomitantly suppressed. Interestingly, nuclear factor kappa b (NF-kappaB) p50 activity was upregulated in GSTM1-expressing CEM. Inhibition of NF-kappaB by the pharmacological agent BAY11-7082 greatly enhanced the sensitivity of the GSTM1-expressing CEM to dexamethasone and was accompanied by an increase in Bim expression. Thus, we propose that GSTM1, a novel regulator of dexamethasone-induced apoptosis, causes dexamethasone resistance by suppression of Bim through dual mechanisms of both downregulation of p38-MAPK and upregulation of NF-kappaB p50.

First Case Report of a Huge Giant Cell Tumor of Soft Tissue Originating from the Retroperitoneum.

BACKGROUND Giant cell tumor of soft tissue (GCT-ST) is a rare disease generally generated from superficial tissue. We report an extremely rare case of giant cell tumor of soft tissue arising from retroperitoneal tissue. CASE REPORT A 78-year-old man visited our medical center with the chief complaint of fatigue and weight loss for 1 month. He had a hard and immobilized mass without pain in the left upper quadrant. Contrast-enhanced CT showed a huge tumor (22×20×16 cm) in the retroperitoneal space, and it invaded into the stomach, colon, pancreas, spleen, and left kidney. MRI demonstrated the tumor had a serous cystic component as T1 was low, T2 was high, and DWI was slightly high. We diagnosed the retroperitoneal malignant tumor, and tumor resection was performed with total gastrectomy, partial colectomy, distal pancreatectomy, left nephrectomy, and left adrenalectomy for complete resection, without any postoperative complications. The tumor predominantly consisted of a solid mass, and had necrotic lesions, cystic lesions, and calcification. The histological exam showed it was composed of spindle and multinucleated giant cells; however, there was no cellular atypia or pleomorphism. Immunohistochemical staining characterized the tumor with CD68+, SMA+, CD34-, Desmin-, and S-100-. We finally diagnosed it as GCT-ST with the intermediate group of malignancy, according to WHO criteria. Thereafter, the patient had no recurrence at 1 year after resection. CONCLUSIONS The huge GCT-ST arising from the retroperitoneal space, which has never before been reported, was successfully resected. We report it with pathological findings to add to the relevant literature.

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia.

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

Fludarabine-mediated circumvention of cytarabine resistance is associated with fludarabine triphosphate accumulation in cytarabine-resistant leukemic cells.

The combination of cytarabine (ara-C) with fludarabine is a common approach to treating resistant acute myeloid leukemia. Success depends on a fludarabine triphosphate (F-ara-ATP)-mediated increase in the active intracellular metabolite of ara-C, ara-C 5'-triphosphate (ara-CTP). Therapy-resistant leukemia may exhibit ara-C resistance, the mechanisms of which might induce cross-resistance to fludarabine with reduced F-ara-ATP formation. The present study evaluated the effect of combining ara-C and fludarabine on ara-C-resistant leukemic cells in vitro. Two variant cell lines (R1 and R2) were 8-fold and 10-fold more ara-C resistant, respectively, than the parental HL-60 cells. Reduced deoxycytidine kinase activity was demonstrated in R1 and R2 cells, and R2 cells also showed an increase in cytosolic 5'-nucleotidase II activity. Compared with HL-60 cells, R1 and R2 cells produced smaller amounts of ara-CTP. Both variants accumulated less F-ara-ATP than HL-60 cells and showed cross-resistance to fludarabine nucleoside (F-ara-A). R2 cells, however, accumulated much smaller amounts of F-ara-ATP and were more F-ara-A resistant than R1 cells. In HL-60 and R1 cells, F-ara-A pretreatment followed by ara-C incubation produced F-ara-ATP concentrations sufficient for augmenting ara-CTP production, thereby enhancing ara-C cytotoxicity. No potentiation was observed in R2 cells. Nucleotidase might preferentially degrade F-ara-A monophosphate over ara-C monophosphate, leading to reduced F-ara-ATP production and thereby compromising the F-ara-A-mediated potentiation of ara-C cytotoxicity in R2 cells. Thus, F-ara-A-mediated enhancement of ara-C cytotoxicity depended on F-ara-ATP accumulation in ara-C-resistant leukemic cells but ultimately was associated with the mechanism of ara-C resistance.

Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia.

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.

3A Comparison between R-THP-COP and R-CHOP Regimens for the Treatment of Diffuse Large B-cell Lymphoma in Old Patients: A Single-institution Analysis.

Objective We retrospectively compared the clinical efficacy and toxicity of rituximab (R)-THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone) with that of R-CHOP (rituximab, adriamicin, cyclophosphamide, vincristine, and prednisolone) in previously untreated old patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients admitted to our institution between 2004 and 2013 were examined. The patients received either R (375 mg/m2, day 1)-THP-COP (pirarubicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5) or R-CHOP (adriamicin 50 mg/m2 day 1, cyclophosphamide 750 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, and prednisolone 100 mg day 1-5). The doses of chemotherapeutic agents were adjusted depending on the patient's age and associated complications. The treatment was performed for 6 to 8 cycles. Results Among 74 patients with DLBCL (median 76, range 65-90 years; male 39, female 35), 29 received R-THP-COP, while 45 received R-CHOP. The overall response rates were 94.6% (complete response 86.4%, partial response 8.1%). The 2-year overall and progression-free survival rates were 77.6% and 68.5% for the R-THP-COP regimen and 79.2% and 78.9% for R-CHOP, respectively. No significant differences were found between these two regimens regarding the clinical efficacies. The most frequent adverse event was neutropenia (72.4% for the R-THP-COP regimen, 88.9% for the R-CHOP regimen). The cardiac function as evaluated by ejection fraction values was not impaired in either regimen. Conclusion R-THP-COP was effective and safe as an alternative to R-CHOP.

YM155 exerts potent cytotoxic activity against quiescent (G0/G1) multiple myeloma and bortezomib resistant cells via inhibition of survivin and Mcl-1.

YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma activity in mouse xenograft model. YM155 suppressed the expression of survivin and rapidly directed Mcl-1 protein for proteasome degradation. YM155 abrogated the interleukin-6-induced STAT3 phosphorylation, subsequently blocked Mcl-1 expression and induced apoptosis in MM cells. Triple-color flow cytometric analysis revealed that YM155 potently induced cell death of MM cells in G0 phase. Quiescent primary MM cells were also sensitive to YM155. We established bortezomib-resistant MM cell line, U266/BTZR1, which possess a point mutation G322A. YM155 exhibited similar cytotoxic potency against U266/BTZR1 compared with parental cells. Interestingly, survivin expression was markedly elevated in U266/BTZR1 cells. Treatment with YM155 significantly down-regulated this increased survivin and Mcl-1 expression in U266/BTZR1 cells. In conclusion, our data indicate that YM155 exhibits potent cytotoxicity against quiescent (G0/G1) MM cells and bortezomib-resistant cells. These unique features of YM155 may be beneficial for the development of new therapeutic strategies to eliminate quiescent MM cells and overcome bortezomib resistance.

A precise pharmacodynamic study showing the advantage of a marked reduction in cardiotoxicity in continuous infusion of doxorubicin.

We have already shown that the antileukemic activity of daunorubicin that had been reported to be dependent on the area under the concentration - time curve (AUC) was actually peak concentration (Cmax) dependent. The antitumor activity of doxorubicin (DXR) has also been reported to be dependent on AUC, whereas its cumulative cardiotoxicity has been reported to be Cmax dependent. In this study, we evaluated whether the antileukemic and cardiotoxic effects of DXR were AUC or Cmax dependent, and compared their cytotoxic effects, utilizing the computer-controlled in vitro pharmacokinetic simulation system or a conventional culture system for a leukemic cell line and measuring the intracellular ATP amount or the proportion of beating cells for the cardiotoxicity. In leukemic cells, the cytotoxic rate decreased as the simulated infusion time or exposure time increased with the same AUC value in the simulation and conventional culture system (P < 0.05 and <0.01, respectively). The intracellular ATP and proportion of beating cells also increased with prolonged DXR exposure time with the same constant concentration - time product value (P < 0.05 and <0.0001, respectively) in heart cells. These results indicated that both the antileukemic effects and the cardiotoxicity were Cmax dependent. However, a comparison of the two showed that cardiotoxicity was more Cmax dependent than the antileukemic effect. These results suggested that the continuous infusion treatment schedule of DXR may have the clinical advantage of reducing cardiotoxicity more markedly than the antileukemic effect.

High Risk of Tumor Lysis Syndrome in Symptomatic Patients with Multiple Myeloma with Renal Dysfunction Treated with Bortezomib.

BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases). CONCLUSION: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.

Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia.

PURPOSE: Despite its clinical success, methotrexate (MTX) therapy is associated with toxicities such as seizures, the pathogenesis of which remains unclear. It has been suggested that hyperhomocysteinemia is caused by MTX and is responsible for its neurotoxic effects. The purposes of this study were to explore whether hyperhomocysteinemia was related to MTX administration and toxicity and whether homocysteine or MTX toxicity differed by methylenetetrahydrofolate reductase (MTHFR) or reduced folate carrier (RFC) genetic polymorphisms. PATIENTS AND METHODS: We studied 53 children with newly diagnosed acute lymphoblastic leukemia who were consecutively treated on a single clinical protocol that included two courses of high-dose MTX (high-dose methotrexate [HDMTX]; 2.5 or 5.0 g/m2 per day) as consolidation therapy. RESULTS: The study participants' median plasma homocysteine concentrations at 23 and 44 hours after HDMTX (9.00 micromol/L and 10.12 micromol/L, respectively) were greater than the concentrations immediately before HDMTX (5.77 micromol/L, P <.0001 for both comparisons). Seven days after HDMTX treatment, their plasma concentration returned to baseline. Nine patients experienced seizures, and five patients experienced thrombosis during the first 15 months of therapy, with a tendency for there to be higher plasma homocysteine in patients with seizures across all time points (P =.063) but not in patients with thrombosis (P =.59). We observed no significant differences in plasma or cerebrospinal fluid homocysteine levels or in toxicity based on the MTHFR 677C/T or RFC 80G/A genotypes. CONCLUSION: We conclude that homocysteine was transiently elevated after HDMTX and may be related to seizure risk in children with leukemia.

Prognostic effect of peripheral blood cell counts in advanced diffuse large B-cell lymphoma treated with R-CHOP-like chemotherapy: A single institution analysis.

The primary objective of the present study was to correlate blood cell counts (lymphocyte, monocyte and platelet counts) with early disease relapse following the attainment of complete remission (CR) by the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)-like regimen in patients with advanced diffuse large B-cell lymphoma (DLBCL). In total, 30 patients were evaluated, with a median follow-up period of 43 months. All the participating patients attained CR. In total, eight patients experienced relapse within two years of the diagnosis, and the three-year overall survival rate was recorded as 77%. The peripheral counts for lymphocytes, monocytes and platelets, and the lymphocyte-monocyte ratio, all of which have been reported to be prognostic in DLBCL, were assessed. None of these parameters were correlated with the incidence of early relapse or with the prognosis. The lymphocyte count was higher in the patients with durable remission than in those who relapsed, however, no significant differences were identified. Thus, the present study concluded that early disease relapse was not predicted by peripheral blood cell counts in advanced DLBCL that reached CR using the R-CHOP-like regimen.

Reduced administration of rasburicase for tumor lysis syndrome: A single-institution experience.

In the present study, the dosage and duration of rasburicase administration were retrospectively evaluated for the ability to control the serum uric acid (S-UA) level in 13 patients diagnosed with hematological malignancies and tumor lysis syndrome (TLS), or those at risk of developing TLS, at the University of Fukui Hospital. At the time of diagnosis, seven patients already exhibited laboratory TLS, and three demonstrated clinical TLS. All patients received rasburicase in addition to chemotherapy agents. The median dose was 0.19 mg/kg (range, 0.13-0.25 mg/kg), and the median duration was four days (range, 1-7 days). Six patients sequentially received a xanthine oxidase inhibitor, allopurinol or febuxostat. The primary estimate was the normalization of the S-UA level at the end of rasburicase treatment and on treatment day seven. The average S-UA level prior to treatment was 10.4±4.5 mg/dl (mean ±standard deviation), and 11 out of 13 patients demonstrated a S-UA level >7 mg/dl. The S-UA level at the end of rasburicase administration was 0.5±1.5 mg/dl and the S-UA level at day seven was 1.4±1.5 mg/dl. All the patients achieved normalization of the S-UA level. On day seven subsequent to the initiation of treatment, the patients receiving rasburicase for a maximum of three days exhibited an S-UA level of 1.9±1.8 mg/dl, while the patients receiving rasburicase for longer than three days demonstrated an S-UA level of 1.0±1.3 mg/dl (P=0.20; Mann-Whitney test). The administration of 0.13 mg/kg and 0.22 mg/kg resulted in comparable UA level reductions. The administration of allopurinol or febuxostat following rasburicase administration suppressed the re-increase in S-UA level. Therefore, it was concluded that reduced administration of rasburicase successfully controlled the S-UA level in TLS.