First report of drug-induced esophagitis by deferasirox.

Deferasirox is a new oral iron chelator used to treat transfusional iron overload. We describe a case of a 79-year-old man with myelodysplastic syndrome (MDS) who developed esophagitis induced by deferasirox. He repeatedly received multiple red blood cell transfusions after a diagnosis of MDS. Two years after starting red blood cell transfusions, he was diagnosed with iron overload, and was then started on deferasirox at 1 g/day with about 400 ml of water. He was admitted to our institution because he was unable to swallow his own saliva 1 month after starting deferasirox. Esophagogastroendoscopy revealed white-coated mucosa covering the entire esophagus. A component analysis of biopsy specimens using high-performance liquid chromatography identified deferasirox. Symptoms resolved within about 2 weeks after discontinuing deferasirox, and repeated endoscopy showed marked improvement of esophagitis after 1 month. Re-administration of deferasirox was not attempted. Unfortunately, the patient died due to pneumonia 6 months after administration of deferasirox was started. This is the first report of drug-induced esophagitis associated with deferasirox.

Long-term survival of a patient with splenic angiosarcoma after resection, high-dose chemotherapy, and autologous peripheral blood stem cell transplantation.

A 48-year-old woman was admitted to our hospital in 2003, complaining of weight loss. Complete blood cell count revealed thrombocytopenia. Abdominal CT demonstrated marked splenomegaly. FDG-PET revealed a hot spot in the whole spleen. A splenectomy was performed. Histological examination was typical for angiosarcoma. Adjuvant chemotherapy was given, and high-dose chemotherapy with autologous peripheral blood stem cell transplantation was performed. Thrombocytopenia developed again in 2008. CT scan showed a hepatic tumor. A fine-needle biopsy of the liver revealed the first relapse. Despite hepatic lobectomy, radiofrequency ablations and administration of recombinant interleukin-2, she died from respiratory failure in 2009.

Pure erythroid leukemia with hemophagocytosis.

A 53-year-old man was admitted with pancytopenia, fever and splenomegaly. Biochemistry showed increased ferritin levels. Bone marrow examination revealed increased erythrocytic precursors (94.9%) and active hemophagocytosis. Pure erythroid leukemia with hemophagocytic syndrome (HPS) was diagnosed. Induction chemotherapy comprising idarubicin and cytarabine was administered and steroid pulse therapy was added. Complete remission was attained, and HPS also improved. However, leukemia relapsed during chemotherapy and the patient died. This is the first report of pure erythroid leukemia complicated with HPS.

Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony-stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy.

BACKGROUNDS AND OBJECTIVES: The optimal strategy for the management of elderly patients with acute myeloid leukaemia (AML) is still controversial. We previously reported the effectiveness of low dose cytarabine (Ara-C) and etoposide (VP-16) (AV therapy) for those elderly AML patients ineligible for intensive chemotherapy. We initiated the present feasibility study to improve the efficacy by using glanulocyte-colony stimulating factor (G-CSF) with AV therapy (AVG therapy). PATIENTS AND METHODS: The eligibility for enrolment was AML patients according to the World Health Organization (WHO) criteria who were over 60 years of age and who had difficulty in tolerating intensive chemotherapy due to their poor performance status (PS) or some comorbidities. They were given continuous drip infusion of Ara-C (20 mg/body) and VP-16 (50 mg/body) for 7-14 days, and were also simultaneously administered G-CSF (150 microg/m2) once daily. RESULTS: The median age of consecutively enrolled 25 patients was 73 years. Eighteen (72%) patients achieved complete remission (CR). The 1-year overall survival (OS) and the 3-year OS rates were 69% and 22%, respectively. The 1-year disease free survival (DFS) rate in CR patients was 44%. The major regimen related toxicities of grade 3 or 4 were only febrile neutropenia in 15 patients (60%). No regimen-related mortality was observed. CONCLUSION: AVG therapy was therefore found to be an effective and well-tolerated regimen for remission induction in elderly AML patients with poor PS or comorbidity.

Therapeutic strategy of untreated de novo acute myeloid leukemia in the elderly: the efficacy of continuous drip infusion with low dose cytarabine and etoposide.

PURPOSE: To evaluate the efficacy and safety of a novel low dose chemotherapy as a remission induction regimen for elderly de novo AML patients ineligible for intensive chemotherapy. METHOD: Fifty consecutive patients, aged 60 to 85, with untreated de novo AML were enrolled. Patients with poor PS or defined non-hematological complications were given continuous drip infusion of low dose cytarabine (Ara-C), 20 mg/body and etoposide (VP-16), 50 mg/body for 10 days (AV group). Patients without those comorbidities were given intensive induction therapy (S group). After achieving complete remission (CR), S group patients and those with improved PS in AV group received consolidation chemotherapy with intensive regimen (S-S or AV-S group), and other patients received AV regimen repeatedly (AV-AV group). RESULTS: Eighteen (64%; 95% confidence interval (CI), 0.47-0.82) of 28 patients in AV group and 16 (73%; 95% CI, 0.54-0.91) of 22 patients in S group achieved CR, respectively. The 1-year OS rates of the patients in the AV-AV group (n = 9), AV-S group (n = 9), and S-S group (n = 16) were 22, 81, and 78%, respectively. Although the sample size was small, no significant difference was observed for the 1-year OS rate between the AV-S and S-S groups. Regimen related death were 4 patients in S group, while no patient in AV group. CONCLUSION: Therapeutic strategy consisting of remission induction using AV regimen and consolidation using intensive regimen after improving PS is beneficial in the management of elderly AML patients who have difficulty in tolerating for intensive induction chemotherapy.

Prevalence of hepatitis B and C virus infection in haematological malignancies and liver injury following chemotherapy.

The aim of this study was to determine the carrier rate of hepatitis virus in patients with haematological malignancies and the incidence of liver injury in these patients following chemotherapy. From January 1996 to September 2002, we studied 601 consecutive, unselected series of patients with haematological malignancies admitted in our hospital unit (Japan). They consisted of 246 cases of acute leukaemia, 218 non-Hodgkin's lymphoma (NHL), 13 adult T-cell leukaemia, and 124 multiple myeloma. Of these 601 patients, 373 were men and 228 were women; their mean age was 61 yr, with a range from 18 to 89 yr. The prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) were 7.3% and 10.1%, respectively, in NHL, both higher than those in acute leukaemia (1.7% and 2.9%, P < 0.005) and in general Japanese population (1.2% and 2.6%). The incidence of post-chemotherapy liver injury in 25 HBV carriers (36.0%) was significantly higher than that in 539 non-hepatitis virus carriers (12.6%, P = 0.003) and 37 HCV carriers (10.8%, P = 0.026). Liver injury in HBV carriers was more often present in patients who had been treated with steroids than in those without steroids (72.7% and 0%, P = 0.013). After lamivudine became available in our institution, the incidence of liver injury in HBV carriers was reduced from 53.3% to 10.0% (P = 0.041). The therapeutic strategy for haematological malignancies in hepatitis virus carriers should be further investigated.

Low-dose granulocyte colony-stimulating factor overcomes neutropenia in the treatment of non-Hodgkin's lymphoma with higher cost-effectiveness.

To facilitate more economical medical care, we carried out a prospective study of whether a THP-COP regimen (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with low-dose granulocyte colony-stimulating factor (G-CSF) would effectively treat non-Hodgkin's lymphoma (NHL). From April 2003 through March 2004, we enrolled 19 consecutive patients with newly diagnosed NHL treated at our hospital. The patients were divided into young and elderly groups. Each patient underwent chemotherapy with 8 courses of a THP-COP regimen with a 50-microg dose of lenograstim. Age- and sex-matched historical control patients (n = 141) received NHL diagnoses between 1998 and 2003. Each patient in the control group underwent the same chemotherapy and received a 100-microg dose of lenograstim. The mean (+/-SD) total amounts of G-CSF per cycle of chemotherapy were 332 +/- 103 microg (young patients) and 345 +/- 128 microg (elderly patients) in the low-dose group and 594 +/- 439 microg (young) and 730 +/- 551 microg (elderly) in the control group. The duration of fever in 1 cycle of chemotherapy was 0.3 +/- 1.0 days (young) and 0.1 +/- 0.8 days (elderly) in the low-dose group and 0.5 +/- 1.3 days (young) and 0.8 +/- 2.0 days (elderly) in the control group. A THP-COP regimen with low-dose G-CSF could be administered to NHL patients with safety. Administration of a 50-microg dose of lenograstim is sufficient and recommended for the treatment of NHL.

Biweekly CHOP or THP-COP regimens in the treatment of newly diagnosed aggressive non-Hodgkin's lymphoma. A comparison of doxorubicin and pirarubicin: a randomized phase II study.

PURPOSE: To compare the efficacy and safety of a biweekly CHOP regimen consisting of cyclophosphamide (CPA), doxorubicin (DOX), vincristine (VCR), and prednisolone (PSL) and those of a biweekly THP-COP regimen containing pirarubicin (THP), an anthracyclin with less cardiotoxicity than DOX. METHODS: A prospective, randomized phase II study with 80 patients (40 receiving CHOP or THP-COP) less than 70 years of age with previously untreated aggressive non-Hodgkin's lymphoma (NHL). The regimens consisted of DOX or THP 50 mg/m2, CPA 750 mg/m2, VCR 1.4 mg/m2, and PSL 100 mg/body administered for 5 days every 2 weeks for eight cycles. RESULTS: No significant differences in known prognostic factors were found between the two groups. Complete remission rate was 72.5% (72.5% for CHOP, 72.5% for THP-COP). The 5-year overall survival rate was 49.2% (43.7% for CHOP, 54.0% for THP-COP). When the patients were divided into groups with favorable or poor prognostic factors according to the International Prognostic Index, survival of the former group (L/LI) was superior to that of the later group (HI/H), regardless of chemotherapy regimen ( P < 0.001). Although grade 3 cardiotoxicity occurred in one patient in the CHOP group, no fatal toxic reactions occurred in either group. The THP-COP produced results equivalent to those of CHOP regarding efficacy and safety in aggressive NHL patients less than 70 years of age. CONCLUSIONS: Although both regimens effectively treated those patients with favorable prognostic factors, neither was satisfactory for treating those with poor prognostic factors.

Genital ulcers during treatment with ALL-trans retinoic acid for acute promyelocytic leukemia.

Scrotal ulcer is a unique adverse effect of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The pathogenesis of scrotal ulceration remains unknown. We describe genital ulcers that developed in four patients with APL who were undergoing ATRA therapy (45 mg/m2 per day p.o.). Two of the patients were female, in whom this condition is quite rare. Genital ulcers with concomitant fever appeared between 17 and 32 days of therapy in all four patients. Genital ulcers healed in three of the patients while another patient developed Fournier's gangrene and underwent left testectomy. Ulcer healing was brought by either local or intravenous corticosteroids. Intravenous dexamethasone actually enabled continued ATRA administration in one patient, while ATRA was discontinued in other two patients. If corticosteroids cannot control progression of genital ulcers nor concomitant fever, ATRA administration should be discontinued so as not to induce Fournier's gangrene nor retionic acid syndrome. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin's lymphoma who had previously received CHOP therapy as first-line chemotherapy.

The purpose of this study was to determine the efficacy of salvage chemotherapy with, P-IMVP-16/CBDCA, consisting of carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX), for patients with aggressive non-Hodgkin's lymphoma (NHL) who had previously received CHOP [a regimen of cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisolone], as first-line chemotherapy. The 45 consecutively enrolled patients received methylprednisolone (mPSL) 1000 mg per body for 3 d (from day 1 to day 3), IFM 1000 mg/m(2) for 5 d (from day 1 to day 5), MTX 30 mg/m(2) on day 3 and day 10, VP-16 80 mg/m(2) for 3 d (from day 1 to day 3), and CBDCA 300 mg/m(2) on day 1, with granulocyte colony-stimulating factor every 21 d. Patients 70 yr of age or older were given 75% of the standard dose. The response rate [complete response (CR) plus partial response (PR)] was 55.6% (25/45), including 12 (26.7%) CR and 13 (28.9%) PR. The overall survival rate for the 45 patients was 31.1% at 1 yr and 17.3% at 2 yr. The failure-free survival rate for the 45 patients was 6.7% at 1 yr and 4.4% at 2 yr. The survival rate for the 25 responders was 48.0% at 1 yr and 24.0% at 2 yr, and the survival rate for the 20 non-responders was 10.0% at 1 yr (P<0.001). Multivariate analysis demonstrated that prior chemotherapy (reduced-dose CHOP for age 70 yr or older) and the number of cases of extranodal involvement (>1) were significant unfavorable factors for overall survival. Although the major toxicity was neutropenia, no patient died of infection related to neutropenia. Non-hematological adverse effects were predominantly mild and tolerable. Unfortunately, the clinical outcome with P-IMVP-16/CBDCA was unfavorable, possibly because the study comprised consecutive patients who had received identified intensive chemotherapy, such as biweekly CHOP. Salvage chemotherapy with P-IMVP-16/CBDCA is not sufficient to cure relapsed or refractory aggressive NHL. Aggressive NHL should be cured by first-line chemotherapy with or without hematopoietic stem cell transplantation.