A prospective study of incidence, clinical and quality of life consequences of oral mucositis post palifermin prophylaxis in patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation.

Autologous hematopoietic cell transplantation (AHCT) has presented a revolutionary advance in the management of hematologic malignancies with low toxicity. However, oral mucositis (OM) remains a distressing toxic effect of AHCT and one of the major side effects of the conditioning. This prospective, observational study aimed to evaluate the severity of oral cavity pain and quality of life (QOL) and explore incidence, duration, and potential risk factors of moderate/severe OM. Thirty-nine patients receiving prophylactic palifermin post-AHCT were enrolled. QOL and severity of pain were assessed using validated questionnaires (Functional Assessment of Cancer Therapy-General (FACT-G) and mouth and throat soreness (MTS), respectively). The incidence of moderate/severe OM was 28.2 % with a median duration of 5 days and was associated with younger age and female gender. Severity of pain related to OM was generally low or moderate with only 25 % of patients reporting a score >6 on the MTS scale of 0-10 on day +7. Health-related QOL was worse on day +7 in the transplant unit compared to day 1, while on discharge day, all scores recovered and the total FACT-G score was not different from that on day 1. In our population, the incidence and duration of OM and the severity of pain related to OM appeared to be lower compared to that reported in previous studies. The impact of OM on QOL assessments seemed to be reversible with optimal supportive care despite the major transient disabilities mainly attributable to OM.

Dasatinib inhibits proliferation and induces apoptosis in the KASUMI-1 cell line bearing the t(8;21)(q22;q22) and the N822K c-kit mutation.

Activating mutations of the c-kit gene are frequently found in CBF (core binding factor) leukemias. We evaluated the effect of tyrosine kinase inhibitor dasatinib in leukemic cell lines bearing or not c-kit mutations. Our data demonstrate that in the AML Kasumi-1 cell line, bearing the N822K c-kit mutation, dasatinib is a potent suppressor of c-kit and Src kinase activity and inhibits the phosphorylation of their downstream target AKT, possibly through the Src-mediated VEGF/VEGFR receptor type 2 pathway. Dasatinib also effectively blocks proliferation and induces apoptosis through caspase-3 activation in Kasumi-1 cells. These data further encourage the integration of dasatinib in the treatment of CBF AML with c-kit mutations in the context of clinical trials, which are eagerly anticipated.

Lobomycosis: A case from Southeastern Europe and review of the literature.

BACKGROUND: Lobomycosis, also known as Jorge Lobo's disease, represents a rare chronic subcutaneous mycosis caused by the fungus Lacazia loboi, an organism that is found within lesions but has not been cultured to date. The natural reservoir of L. loboi is unknown but it is believed to be aquatic, or associated with soil and vegetation. More than 550 human cases have been reported, especially in patients with a history of travel or residence in endemic areas (Central and South America, particularly Brazil) or in communities along rivers. MAIN OBSERVATIONS: We describe a 64-year-old Greek female farmer living in a coastal region, who presented with an erythematous plaque on her left inner thigh resembling a keloid. The diagnosis was based on the triad: 1) absence of fungal growth in cultures, 2) positive direct microscopic examination of the lesion and 3) histopathology, all consistent with lobomycosis. Particularly, skin biopsy showed deep cutaneous fungal infection with granulomatous reaction. Fungal cells were found inside giant cells. The fungi were thick-walled with some budding, isolated or in short chains. Dermal fibrosis was present. Our patient had a medical history of common variable immunodeficiency but no history of travel to South or Central America. She probably acquired this rare infection by injury during her agricultural works. CONCLUSION: Our case represents probably the first documented case of human lobomycosis in Southeastern Europe. This case is unusual due to the rarity of lobomycosis in Mediterranean countries, particularly in Southeastern Europe.

Outcomes of Hodgkin's lymphoma patients with relapse or progression following autologous hematopoietic cell transplantation.

Patients with relapsed/progressed Hodgkin's lymphoma (HL) following autologous hematopoietic cell transplantation (AHCT) may not have an invariably dismal outcome as previously considered. In a multicenter retrospective study, we evaluated 126 patients who relapsed/progressed after a median of 5 (1-132) months post first AHCT. Management consisted of irradiation, chemotherapy ± irradiation, second HCT, or palliation. Currently, 53 of 126 (42%) patients are alive for a median of 32 months since relapse/progression and 44 (35%) of them remain progression-free. Interval of <12 months to relapse/progression, presence of B-symptoms, and disease refractoriness at first AHCT failure adversely influenced overall survival (P < .05). The type of treatment had no impact on survival. Furthermore, to predict the outcome at the time of relapse/progression, we constructed a prognostic model based on 3 factors: interval of <12 months from first AHCT to relapse/progression, presence of B-symptoms, and pre-AHCT disease refractoriness. Patients with 0 to 1 factors achieved a median survival of 70 months compared to 17 months only in those with 2 to 3 factors (P < .001). This study, the largest reported to date, suggests that selected patients with relapse/progression after first AHCT can be rescued with current treatment modalities. However, relapsed/progressed HL following AHCT still poses a therapeutic challenge, and prospective trials are needed to determine the most appropriate approach in this setting.

Extracorporeal photopheresis in the treatment of chronic graft-versus-host disease. The Hellenic experience: a study by the Hellenic association of hematology.

The Hellenic experience regarding the efficacy of extracorporeal photopheresis (ECP) in the treatment of 58 patients with chronic graft-versus-host disease (cGVHD) is presented in this article. All 58, except one patient, had failed at least one line of immunosuppressive treatment including steroids. Thirty-three out of 58 patients showed an objective overall response to ECP in a median time of 10 weeks after the onset of treatment. The cumulative incidence of overall response was 65.1%. In multivariate analysis, the presence of severe chronic GVHD was the only parameter associated with a significantly lower probability of response to treatment (RR=0.4, CI 95% 0.2-0.9, p=0.03). Responders to treatment with ECP were more likely to discontinue immunosuppression, had a lower probability of non-relapse mortality (RR=0.2, CI 95% 0.1-0.5, p=0.002), and a higher probability of overall survival (RR=7.8, CI 95% 3-20, p<0.001) in comparison with non-responders. Eight out of 58 patients experienced relapse of the original disease. The cumulative incidence of relapse in the group of responders to ECP was 6%, while it was 25% in the group of non-responders to ECP. In multivariate analysis, response to treatment with ECP was the only parameter statistically associated with a significantly decreased hazard of relapse (RR=0.1, CI 95% 0.1-0.7, p=0.02). ECP should be tested as first-line treatment in patients with cGVHD with the aim to minimize the duration of immunosuppression and the rate of relapse of the malignant disease.