Secondary hypophysitis associated with Rathke's cleft cyst resembling a pituitary abscess.

Background: Although rare, cases of hypophysitis resembling a pituitary abscess (PA) have been reported. Differential diagnosis between hypophysitis and PA is crucial as the two diseases require different treatments. Case Description: A 38-year-old woman with headaches underwent head magnetic resonance imaging (MRI), which revealed an 11-mm mass lesion in the sella turcica. Due to breastfeeding, contrast-enhanced MRI was avoided. Pituitary adenomas and Rathke's cleft cyst (RCC) were suspected, and she was initially treated conservatively. Five months later, she acquired syndrome coronavirus two infections, and while the fever subsided with acetaminophen, the headache persisted. One month later, the headache worsened, followed by fever and diabetes insipidus. MRI revealed a pituitary cystic mass with ring-shaped contrast enhancement on T1-weighted MRI and increased signal intensity on diffusion-weighted imaging (DWI). PA was suspected, and emergency endoscopic transsphenoidal surgery was performed. The microbiological examination of the yellowish-brown content drained from the cystic mass was negative. Microscopically, the cystic lesion was covered with ciliated columnar epithelium and stratified squamous epithelium, with a dense inflammatory cell infiltrate consisting mainly of lymphocytes and plasma cells observed around the cyst. This supported the diagnosis of secondary hypophysitis associated with RCC without PA. Conclusion: We report a case of hypophysitis secondary to RCC resembling PA with ring-shaped contrast enhancement on MRI and increased signal intensity on DWI. This case emphasizes the need for cautious diagnosis of secondary hypophysitis due to RCC in individuals with MRIs and clinical manifestations resembling an abscess.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Risk factors for radiation pneumonitis after rotating gantry intensity-modulated radiation therapy for lung cancer.

The risk factors for severe radiation pneumonitis (RP) in patients with lung cancer who undergo rotating gantry intensity-modulated radiation therapy (IMRT) using volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT) are poorly understood. Fifty-two patients who received rotating gantry IMRT for locally advanced lung cancer were included in this retrospective study. In total, 31 and 21 patients received VMAT and HT, respectively. The median follow-up duration was 14 months (range, 5.2-33.6). Twenty (38%) and eight (15%) patients developed grade ≥ 2 and ≥ 3 RP, respectively. In multivariate analysis, lung V5 ≥ 40% was associated with grade ≥ 2 RP (P = 0.02), and past medical history of pneumonectomy and total lung volume ≤ 3260 cc were independently associated with grade ≥ 3 RP (P = 0.02 and P = 0.03, respectively). Rotating gantry IMRT was feasible and safe in patients with lung cancer undergoing definitive radiotherapy. Reducing lung V5 may decrease the risk of symptomatic RP, and care should be taken to avoid severe RP after radiotherapy in patients with a past medical history of pneumonectomy and small total lung volume.

Factors predictive of the development of hypothyroidism after intensity-modulated radiation therapy for pharyngeal cancer.

BACKGROUND: Hypothyroidism is a common adverse event after radiotherapy for head and neck tumors and the incidence need to be re-evaluated because of using intensity-modulated radiotherapy (IMRT). AIMS/OBJECTIVES: Confirm the dose-volume effect of IMRT for pharyngeal cancer on hypothyroidism. MATERIALS AND METHODS: This was a retrospective analysis of patients underwent IMRT for pharyngeal cancer from June 2011 to May 2018. Patients were classified into group A (thyroid stimulating hormone (TSH) <5µU/ml), group B (5< =TSH < 10), and group C (10< =TSH) based on TSH over 36 months post-radiation. Radiation dose, thyroid volume, and the proportion of the thyroid that received X Gy or greater (Vx) were measured. RESULTS: Fifty-two patients were included in this work. Hypothyroidism developed in 33/52 (63%) patients, 13 in group B and 20 in group C. The mean radiation dose to the thyroid was 49.4 Gy and the median time until hypothyroidism was 39 months after irradiation. Hypothyroidism was significantly related to neck dissection (ND) and radiation dose to the thyroid. Patients whose thyroid received 45 Gy or more (V45) >67% had a significantly higher incidence of hypothyroidism. CONCLUSIONS AND SIGNIFICANCE: Patients with pharyngeal cancer who had ND and V45 to the thyroid >67% are at risk of hypothyroidism.

Dose-volume Histogram Analysis of Knowledge-based Volumetric-modulated Arc Therapy Planning in Postoperative Breast Cancer Irradiation.

BACKGROUND/AIM: We evaluated the dosimetric profiles of manually generated volumetric-modulated arc therapy (VMAT) plans and performance of a commercial knowledge-based planning system (KBP) in treating breast cancer. MATERIALS AND METHODS: We defined the manually generated VMAT plan as the manual plan (MP). Twenty MPs were generated for left-sided breast cancer patients who underwent breast-conserving surgery and used to develop a KBP training set. The other five patients were used for validation. The dosimetric parameters among MPs, tangential irradiation plans (TPs), and KBP-VMAT plans (KBP-Ps) were compared. RESULTS: D95 and homogeneity of the planning target volume (PTV) were significantly higher and greater in MPs and KBP-Ps than in TPs. Lung V20, V40 The Dmean for the left anterior descending artery was lower in MPs and KBP-Ps than in TPs. KBP could save time in generating VMAT plans. CONCLUSION: MPs and KBP-Ps could ensure higher dose uniformity of PTV than TPs. KBP could faster generate comparable MPs for breast cancer.

Mediastinal metastasis from ovarian serous carcinoma 29 years after initial treatment.

Ovarian cancer is a critically lethal gynecologic malignancy. More than 80% of patients with ovarian cancer have relapses within 5 years after initial treatment. However, recurrence from ovarian cancer more than 20 years later is extremely rare. We report a case of a 67-year-old female with mediastinal metastasis from ovarian cancer 29 years after initial gynecologic surgery and chemotherapy.

Fatal case of TAFRO syndrome associated with over-immunosuppression: a case report and review of the literature.

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant Staphylococcus aureus sepsis, gastrointestinal bleeding, peritonitis caused by Stenotrophomonas maltophilia, gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients' clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.

Recent Progress in Therapeutics for Inflammation-Associated Preterm Birth: A Review.

Preterm birth is one of the most common obstetrical complications, with an incidence of about 5% to 18% of all pregnancies worldwide. Acute chorioamniotic infection is likely antecedent to preterm birth through the local production of inflammatory mediators, followed by uterine contraction and cervical ripening. Microbial chorioamnionitis and local inflammation synergistically form a vicious circle toward preterm birth. Principal therapeutic interventions focus on anti-infection and anti-inflammation strategies to block this vicious circle. Anti-inflammatory therapeutics include agents that directly inhibit inflammatory cytokine production/reaction and that resolve supraphysiological inflammation toward a normal condition. In particular, naturally produced compounds, including polyphenols, omega-3 polyunsaturated fatty acid metabolites, and statins, are attractive agents in terms of safety for pregnant women and their infants. This review summarizes the mechanisms of perinatal inflammation induced by acute chorioamnionitis and therapeutic resolution of inflammation of the uterus to avoid the harmful exposure of preterm infants to inflammation in utero.

Resveratrol Protects Against Pathological Preterm Birth by Suppression of Macrophage-Mediated Inflammation.

Inflammatory cytokines play a major role in spontaneous preterm birth. Resveratrol has strong anti-inflammatory effects, but its effect on preterm birth in vivo is unknown. We investigated whether resveratrol protects against preterm birth in the lipopolysaccharide (LPS)-induced preterm mouse model. Twelve-day-old pregnant mice were fed 20 to 40 mg/kg resveratrol daily. On day 15, 10 µg of LPS was injected into uterine cervices. Resveratrol administration significantly decreased the rate of preterm birth. Resveratrol administration abolished LPS-induced elevation of tumor necrosis factor α (TNF-α) and interleukin (IL) 1ß but not IL-6 levels. The TNF-α messenger RNA levels were decreased in the cervices of resveratrol-administered mice compared with controls. Resveratrol treatment suppressed the elevation in TNF-α and IL-1ß levels in LPS-exposed peritoneal macrophages. Further resveratrol treatment eradicated the proinflammatory cytokine-mediated elevation in cyclooxygenase 2 (COX-2) in peritoneal macrophages. Resveratrol may protect against pathological preterm birth by suppression of elevated proinflammatory cytokines and consequent elevation of COX-2 in macrophages.

A patient with relapsing polychondritis who had been diagnosed as intractable bronchial asthma.

A 62-year-old woman, diagnosed as bronchial asthma 3 years previously, was admitted due to acute severe dyspnea. Physical examination revealed saddle nose, flare/swelling of the ear auricles, and stridor. Computed tomography demonstrated thickening of tracheal/bronchial walls and stenosis of the lumen that deteriorated on expiration, suggesting tracheobronchomalacia. Auricle biopsy indicated cartilage destruction. Based on these findings, the patient was diagnosed as relapsing polychondritis. As demonstrated in this case, relapsing polychondritis involving airways might be misdiagnosed as bronchial asthma due to stridor and transient corticosteroid-related improvement. Early diagnosis is necessary to prevent irreversible airway stenosis and progression to tracheobronchomalacia.

[Membranous nephropathy with nephrotic syndrome developed after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia].

A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.

Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation.

BACKGROUND: There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation. METHOD: We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%). RESULTS: Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively. CONCLUSION: Graft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.

Reduced-intensity conditioning by fludarabine/busulfan without additional irradiation or T-cell depletion leads to low non-relapse mortality in unrelated bone marrow transplantation.

In reduced intensity, allogeneic stem cell transplantation from unrelated donors (u-RIST), graft-versus-host disease (GVHD), graft failure, and non-relapse mortality (NRM) are persistent problems. Although anti-thymocyte globulin, alemtuzumab, and total body irradiation (TBI) have been explored as conditioning modalities for u-RIST, the necessity for T-cell depletion or TBI to prevent GVHD or facilitate engraftment in u-RIST has not been determined. We here report the use of u-RIST with bone marrow grafting, following a simple conditioning regimen of 180 mg/m(2) fludarabine and 8 mg/kg of oral or intravenous busulfan without TBI or T-cell depletion. The study population was exclusively Japanese patients with a history of prior chemotherapy. We retrospectively analyzed 31 consecutive patients (median age 53 years). Twenty-five patients (81%) were transplanted from HLA-A, -B, and -DRB1 allele-matched donors. In all patients, neutrophil engraftment was achieved. The cumulative incidence of grade II-IV acute GVHD was 42%. However, 77% of patients with acute GVHD improved with, and could be managed by, initial, systemic, high-dose steroid treatment alone. Two-year overall and event-free survival was 62 and 53%, respectively. The NRM of 10% at 2 years was relatively low. Our results suggest that u-RIST without TBI or T-cell depletion may improve the prognosis after u-RIST in certain patient populations.

12-oxo-phytodienoic acid-glutathione conjugate is transported into the vacuole in Arabidopsis.

While exogenous toxic compounds such as herbicides are thought to be sequestered into vacuoles in the form of glutathione (GSH) conjugates, little is understood about natural plant products conjugated with GSH. To identify natural products conjugated with GSH in plants, metabolites in the Arabidopsis γ-glutamyl transpeptidase (ggt) 4 knockout mutants that are blocked in the degradation of GSH conjugates in the vacuole were compared with those in wild-type plants. Among the metabolites identified, one was confirmed to be the 12-oxo-phytodienoic acid (OPDA)-GSH conjugate, indicating that OPDA, a precursor of jasmonic acid (JA), is transported into the vacuole as a GSH conjugate.

Serum cytokine profiles at the onset of severe, diffuse alveolar hemorrhage complicating allogeneic hematopoietic stem cell transplantation, treated successfully with pulse intravenous cyclophosphamide.

A 59-year-old man with lymphoma-type adult T-cell leukemia/lymphoma was admitted to hospital for treatment of a skin relapse on day 398 after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To induce a graft-versus-adult T-cell leukemia/lymphoma effect, we discontinued methylprednisolone and tacrolimus. About a month after the discontinuation, he developed grade II acute graft-versus-host disease (GVHD) with a high fever. Soon after the development of GVHD, all the skin lesions regressed in size and finally vanished. However, he developed diffuse alveolar hemorrhage (DAH), which was resistant to high-dose corticosteroid therapy. He was intubated for respiratory insufficiency on day 451. Cyclophosphamide pulse therapy was administered at a dose of 1 g per day for 2 days and his oxygen saturation then improved, and ventilatory support was released on day 465. On analysis of cytokine profiles at the onset of DAH, we found elevated serum levels of T-helper 2 cytokines as well as T-helper 1 cytokines, suggesting that both T-helper 1 and T-helper 2 cytokines might play a role in the occurrence of DAH following allo-HSCT. Pulse cyclophosphamide treatment might be very effective in suppressing the exaggerated allogeneic immune response in DAH.

[A modified myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation, consisting of intravenous busulfan, cyclophosphamide and total lymphoid irradiation, in advanced leukemia].

In nine patients with advanced acute or chronic leukemia, we performed allogeneic hematopoietic stem cell transplantation (HSCT) following a modified myeloablative conditioning regimen intended to optimize the intensity of conditioning. This regimen consisted of intravenous busulfan 8mg/kg, cyclophosphamide 120mg/kg and total lymphoid irradiation 7.5 Gy. The median age of the patients was 30 years (range 18-59). Stem cell sources were related bone marrow in two, related peripheral blood in one, and unrelated bone marrow in six patients. Prophylaxis against acute graft-versus-host disease (GVHD) was cyclosporine and short-term methotrexate. Acute GVHD appeared in six patients (67%), grade II in all. Extensive chronic GVHD occurred in three of seven evaluable patients. The median follow-up period after HSCT was 813 days (248- 1,702). Of nine patients, five relapsed or progressed after HSCT. However, no patient relapsed or progressed within 100 days after HSCT. During the full follow-up period, transplant-related mortality (TRM) was not observed. The two-year overall survival and event-free survival were 88.9% and 50.0%, respectively. Our results suggested that we might reduce the incidence of TRM and simultaneously control disease by using an optimized conditioning regimen for HSCT.

[A case of multiple and metachronous pleural tuberculomas during the course of anti-tuberculous chemotherapy and follow-up of a caseous pneumonia].

A 21-year-old woman was admitted to our hospital because of high fever, a productive cough and general fatigue. Her chest radiography scan revealed dense consolidation with air-bronchograms in the left lower lobe. Bacterial pneumonia was diagnosed and she was treated with antibiotics, although the specific cause could not be identified. After one month, a bronchoscopy was performed due to lack of improvement of consolidation in chest radiography. A smear examination of the bronchial washing specimen was positive for acid-fast bacilli (AFB) and Mycobacterium tuberculosis (MTB) was confirmed by PCR. After anti-tuberculous drugs (INH, RFP, EB, and PZA) were prescribed for 6 months, chest X-ray findings improved markedly. Two pleural tuberculomas were found in the left upper and lower lung fields 3 months after beginning therapy, and a new pleural tuberculoma appeared in the left upper lung fields 6 months after finishing therapy. Histopathological findings (HE stain) of a CT-guided needle lung biopsy showed epithelioid cell granulomas without caseous necrosis with multinuclear giant cells which were negative for acid-fast bacterium. All of the pleural tuberculomas improved without any additional therapy 18 months after finishing therapy. It was thought that such cases of multiple and metachronous pleural tuberculomas during the course of anti-tuberculous chemotherapy and follow-up of caseous pneumonia are rare. We suggest the possibility that the pleural tuberculomas were due to a paradoxical or hypersensitive reaction to the anti-tuberculous chemotherapy in this case.

[Epstein-Barr virus-associated post-transplant lymphoproliferative disorder diagnosed by the episode of intestinal perforation following allogeneic hematopoietic stem cell transplantation].

A 64-year-old man was diagnosed as having acute myeloid leukemia. We performed sequential treatment with chemotherapy and reduced-intensity stem cell transplantation from an unrelated donor while the patient was in partial remission. After engraftment, he developed acute graft-versus-host disease of the gut on day 42 and steroid therapy was started. Despite transient aggravation of diarrhea, his symptoms slowly improved and the dose of steroid was tapered. On day 159, he complained of acute left lower abdominal pain. A CT scan showed perforation of the digestive tract and ileectomy was performed. At surgery, multiple ulcers of the intestine were found and one of the ulcers was perforated. Pathologically, transmural and diffuse proliferation of atypical cells in the ulcer were confirmed. Since these cells were positive for CD20 and Epstein-Barr-virus (EBV) encoded RNA, we made a diagnosis of EBV-associated post-transplant lymphoproliferative disorder (PTLD). Reduction in the dose of immunosuppressive agents and rituximab led to complete remission of PTLD. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare, and the development of gastrointestinal perforation after allo-HSCT is very rare.

[The sequential changes of the serum levels of KL-6, SP-D, and DLCO were followed for a long term in a case of acute bird fancier's lung].

The sequential changes of the serum levels of KL-6, SP-D, and DLco were followed for a long term in a case of acute bird fancier's lung, A 52 years-old-male was admitted to our hospital because of cough, dyspnea on exertion and fever. He has been breeding 12 pigeons in home for the last five years. HRCT of the chest demonstrated diffuse centrilobular nodules and ground-glass opacities with mosaic pattern in bilateral lung fields. Bronchoalveolar lavage (BAL) showed an increased number of lymphocytes with a increased CD4/CD8 ratio, and transbronchial lung biopsy (TBLB) specimen revealed alveolitis with infiltration of lymphoid cells and Masson body in the air spaces. He was diagnosed as having bird fancier's lung because of the elevated antibodies against pigeon dropping extracts (PDE) in the serum and BALF. Respiratory failure continued after complete avoidance of contact with pigeons for a week. Clinical symptoms and chest X-ray findings improved markedly after administration of steroid, and he left the hospital to move into a new house. The serum levels of KL-6 and SP-D were unchanged by antigen avoidance, although those were returning to normal gradually after treatment of steroid. SP-D and KL-6 returned to normal in 8 months and 18 months respectively and DLco was also improved slowly in parallel with a decrease of these markers. These results suggest that the serum KL-6 level and DLco reflect the disease activity showing gradual recovery of alveolitis in such a long period.

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma.

BACKGROUND: Recently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma. METHODS: We retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients. RESULTS: A multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6-1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI. CONCLUSION: Our data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.