Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.
Adult ; Aged ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemophilia A/*complications ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Liver/pathology ; Male ; Middle Aged ; Neutropenia/etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; RNA, Viral/blood ; Recombinant Proteins/adverse effects/therapeutic use ; Recurrence ; Republic of Korea ; Ribavirin/adverse effects/*therapeutic use ; Treatment Outcome

OBJECTIVETo retrospectively compare the efficacy of postoperative radiotherapy (RT) alone with that of postoperative radiotherapy with concurrent chemotherapy (CRT) for thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes, and to evaluate the clinical value of RT + CRT.

METHODS304 EPC patients underwent esophagectomy with three-field lymph node dissection had pathological lymph node metastases, but no hematogenous distant metastasis. Among them, 140 cases underwent postoperative RT alone, and 164 cases underwent postoperative CRT. The dose of irradiation was 50 Gy, and the chemotherapy regimen was taxol and cis-platinum, and a cycle was 21 days.

RESULTSThe 1-, 3- and 5-year total survival rates of the whole group were 90.1%, 56.6% and 43.3%, respectively, with a median survival time of 49.7 months. The 5-year overall survival rates of the CRT and RT groups were 47.4% and 38.6%, respectively (P = 0.030), with a median survival time of 53.5 and 41.7 months, respectively (P = 0.030). The overall survival rates of the patients who underwent 1, 2, 3, 4 cycles of chemotherapy were 24.4%, 53.0%, 58.1% and 43.3%, respectively (P = 0.007). Among them, the 5-year total survival rate of patients with 2-4 cycles of chemotherapy was significantly better than that of patients who underwent one cycle of chemotherapy (P = 0.001). Univariate analysis showed that number of metastatic lymph nodes, pT stage, therapeutic regimen and number of chemotherapy cycles were significantly correlated with the prognosis of the patients (P < 0.05 for all). Multivariate analysis showed that number of metastatic lymph nodes, pT stage, and number of chemotherapy cycles were independent prognostic factors of the patients (P < 0.05 for all). Early toxic effects including neutropenia, radiation esophagitis, and gastrointestinal effects were significantly more severe in the CRT group than that in the RT group (P < 0.05), however, there were no significant differences of late toxic effects between the two groups (P > 0.05).

CONCLUSIONPostoperative CRT for thoracic EPC with positive lymph nodes can improve the survival rate, with tolerable adverse effects.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy ; adverse effects ; Cisplatin ; administration & dosage ; Esophageal Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Esophagectomy ; Esophagitis ; etiology ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Irradiation ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; etiology ; Paclitaxel ; administration & dosage ; Particle Accelerators ; Postoperative Period ; Retrospective Studies ; Survival Rate

Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age > or =65 yr, comorbidities, bone marrow involvement, and baseline serum albumin < or =3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.
Adolescent ; Adult ; Age Factors ; Aged ; Antibodies, Monoclonal, Murine-Derived/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chemotherapy-Induced Febrile Neutropenia/*etiology ; Cyclophosphamide/administration & dosage/adverse effects/therapeutic use ; Demography ; Doxorubicin/administration & dosage/adverse effects/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/*drug therapy ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia/etiology/pathology ; Prednisone/administration & dosage/adverse effects/therapeutic use ; Retrospective Studies ; Risk Factors ; Sex Factors ; Vincristine/administration & dosage/adverse effects/therapeutic use ; Young Adult

The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9-111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; Child ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; etiology ; Lung Neoplasms ; secondary ; Male ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia ; etiology ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; adverse effects ; methods ; Retrospective Studies ; Stomatitis ; etiology ; Survival Rate ; Xerostomia ; etiology ; Young Adult

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a "MELODIE" multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2% for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1% for Arm A and 90.2%, 85.2%, and 81.7% for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Dose Fractionation ; Drug Chronotherapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; adverse effects ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Neutropenia ; chemically induced ; Radiotherapy, High-Energy ; Stomatitis ; etiology ; Survival Rate ; Young Adult

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/microL with body temperature over 38degrees C; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.
Adult ; Age Factors ; Antineoplastic Agents, Phytogenic/*therapeutic use ; Body Temperature ; CD4 Lymphocyte Count ; Fever/*etiology ; HIV Infections/complications ; Humans ; Lymphoma, AIDS-Related/complications/*drug therapy/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neutropenia/*etiology ; Retrospective Studies ; Risk Factors ; Vincristine/*therapeutic use

Severe congenital neutropenia is a rare hematological disease characterized by a selective decrease in circulating neutrophils, maturation arrest of granulocytic precursors at the promyelocyte stage, and recurrence of infections. A 2-month-old male infant (patient A) and a 14-month-old female child (patient B) were referred to our hospital due to severe neutropenia. Sequencing analysis of ELA2 and HAX1 genes was performed. Two single nucleotide polymorphisms of HAX1 gene were found. They were 5,104T-->G point mutation of exon 1 and 5,474A-->G point mutation of intron 1 in HAX1 gene. The mutation of ELA2 gene was not found. The patient A showed a good response to granulocyte colony-stimulating factor (G-CSF) treatment and the absolute neutrophil count recovered to 1,195/microliter. But the patient B showed a partial response to G-CSF treatment and experienced several episodes of herpetic gingivostomatitis, oral ulcer, acute pharyngotonsillitis and otitis media during follow-up.
Adaptor Proteins, Signal Transducing/genetics ; Bone Marrow/pathology ; Female ; Granulocyte Colony Stimulating Factor, Recombinant/adverse effects/therapeutic use ; Humans ; Infant ; Male ; Neutropenia/congenital/drug therapy/*genetics ; Neutrophils/cytology/pathology ; Oral Ulcer/etiology ; Otitis Media/etiology ; Polymorphism, Single Nucleotide ; Serine Endopeptidases/genetics ; Stomatitis, Herpetic/etiology

BACKGROUND AND OBJECTIVEConcurrent chemoradiation therapy (CCRT) is the standard treatment for patients with locally advanced nasopharyngeal carcinoma (NPC). The effect of neoadjuvant chemotherapy followed by CCRT has not been determined. Therefore, we conducted 2 phase II studies to evaluate the efficacy and safety of neoadjuvant chemotherapy with a regimen of docetaxel, cisplatin, and 5 fluorouracil (5-Fu) (TPF) followed by radiotherapy and concurrent cisplatin in patients with stage III and IV(A - B) NPC. This article is the preliminary report on treatment related toxicities and response.

METHODSGraded according to the 2002 American Joint Committee on Cancer (AJCC) staging criteria, only patients with stage III or IV(A-B) poorly differentiated or undifferentiated NPC (World Health Organization type II/III) were included. We planned to recruit 52 patients with stage III disease and 64 patients with stage IV(A - B) disease. All patients received neoadjuvant chemotherapy with TPF (docetaxel 75 mg/m(2), day 1; cisplatin 75 mg/m(2), day 1; 5 Fu 500 mg/(m2 x day), continuous intravenous infusion for 120 h), every 3 weeks for 3 cycles, followed by weekly cisplatin (40 mg/m(2)) concurrent with radiotherapy. Three dimensional conformal radiotherapy (3D CRT) and intensity modulated radiotherapy (IMRT) were used. Gross disease planning target volume (PTV), high risk and low risk subclinical PTV doses were prescribed at 70-76 Gy, 66-70 Gy, and 60-61.25 Gy at 1.75-2.0 Gy per fraction. The lower neck or supraclavicular fields may be treated with conventional AP/PA fields for a total of 54 Gy at 1.8 Gy per fraction. Patients were evaluated for tumor response after the completion of neoadjuvant chemotherapy, and at 3 months after radiation according to the Response Evaluation Criteria In Solid Tumors (RECIST). The latest version of the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE 3.0) was used for grading all adverse events.

RESULTSFifty nine patients were evaluable for treatment response. Thirty patients had stage III disease and 29 patients had stage IV(A-B). All patients completed RT to the prescribed dose and 2 cycles of neoadjuvant chemotherapy, with 51 patients (86.4%) completing 3 cycles. A total of 50 (84.7%) and 39 patients (66.1%) completed 4 weeks and 5 weeks of cisplatin during CCRT, respectively. The overall response rate in the primary site and the neck region were 94.9% [complete response (CR) in 25.4%] and 100% (CR in 19.6%) after completing neoadjuvant chemotherapy. At 3 months after RT, the CR rates increased to 96.6% and 90.2%, respectively. After a median follow up of 14.3 months, we observed 5 treatment failures and 2 deaths. The 1 year overall survival, distant metastasis free survival, and locoregional relapse free survival rates were 100%, 95.7%, and 97.7%, respectively. The rates of grade 3/4 myelosuppression and anorexia/nausea/vomiting during neoadjuvant chemotherapy were 55.9% and 16.9%, respectively. The corresponding rates were 11.9% and 23.7% during CCRT. Grade 3/4 mucositis, skin desquamation, and xerostomia occurred in 6.8%, 44.1%, and 27.1% of patients, respectively. There were no treatment related deaths.

CONCLUSIONSNeoadjuvant chemotherapy with TPF followed by CCRT was well tolerated with a manageable toxicity profile. Preliminary results are encouraging and warrant further investigation.

Adult ; Aged ; Anemia ; chemically induced ; etiology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Chemoradiotherapy ; adverse effects ; Chemotherapy, Adjuvant ; adverse effects ; Cisplatin ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; etiology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; therapy ; Nausea ; chemically induced ; etiology ; Neoadjuvant Therapy ; adverse effects ; Neoplasm Staging ; Neutropenia ; chemically induced ; etiology ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Remission Induction ; Survival Rate ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

Upper airway disease, especially nasal and paranasal sinus involvement, is the most common manifestation of Wegener's granulomatosis. Chronic otitis media and facial palsy are rare but well known presenting features of Wegener's granulomatosis. We report a 40-year-old woman who presented with complaints of ear discharge, deep-seated ear pain and loss of hearing in her right ear. Early diagnosis demands heightened suspicion in a patient with otological symptoms and facial paralysis.
Administration, Oral ; Adult ; Biopsy ; Chronic Disease ; Cyclophosphamide ; therapeutic use ; toxicity ; Diagnosis, Differential ; Drug Therapy, Combination ; Facial Paralysis ; etiology ; pathology ; Fatal Outcome ; Female ; Granulomatosis with Polyangiitis ; diagnosis ; pathology ; Humans ; Immunosuppressive Agents ; therapeutic use ; toxicity ; Nasal Mucosa ; pathology ; Neutropenia ; chemically induced ; Otitis Media with Effusion ; etiology ; pathology ; Plasma Exchange ; Prednisolone ; therapeutic use ; toxicity ; Renal Dialysis