FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia

FIP1-like 1 (FIP1L1) is associated with two leukemogenic fusion genes: FIP1L1-retinoic acid receptor alpha (RARA) and FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA). Analyses of a series of deletion mutants revealed that the FIP1 motif in FIP1L1-RARA plays a pivotal role in its homodimerization and transcriptional repressor activity. However, in FIP1L1-PDGFRA, the C-terminal PDGFRA portion possesses the ability of forming a homodimer by itself, making FIP1L1 dispensable for constitutive activation of this kinase. Both the full-length and the C-terminal PDGFRA portion of FIP1L1-PDGFRA could transform the IL-3-dependent hematopoietic cell line, BAF-B03. Moreover, when either the full-length or the C-terminal PDGFRA portion of FIP1L1-PDGFRA was introduced in these cells, they grew in the absence of IL-3. The cells having the C-terminal PDGFRA portion of FIP1L1-PDGFRA, however, were partially IL-3 dependent, whereas the cells having the full-length FIP1L1-PDGFRA became completely IL-3 independent for their growth. Taken together, these results show that FIP1L1 differentially contributes to the pathogenesis of distinct types of leukemia

Efficacy and safety of Micafungin in Febrile NeutropenicPatients Treated for Hematological Malignancies

Objective: The purpose of this study was to prospectively evaluate the efficacy and safety of micafungin (MCFG) in empirical therapy for febrile neutropenic patients for whom antibiotic therapy was not effective for hematological malignancies. Patients and Methods: Twenty-three hematological patients aged 27-82 years with febrile neutropenia for whom antibiotic therapy was not effective were enrolled in this study and responses to treatment were evaluated. Results: Treatment success rate was 73.9%. Treatment success rates by primary diagnosis were 77.8% in patients with AML, 50.0% in patients with NHL and 87.5% in patients with other diseases. Moreover, MCFG at a dose of 100 mg or more have a tendency to be effective. One or more adverse events occurred in five (27.7%) of the patients during the study. All of these adverse events were below grade 2 toxicity. Conclusions: Although the number of patients studied was limited, MCFG as a monotherapy seems to be effective and safe as an empirical therapy in patients with febrile neutropenia. However, further investigation using large-scale studies is needed. This study demonstrated the clinical efficacy and safety of MCFG in patients with febrile neutropenia and with hematological malignancies

Cytogenetic analysis in a multiple myeloma patient who developed myelomatous pleural effusion and plasma cell leukemia

We report on a patient with multiple myeloma who developed myelomatous pleural effusion and plasma cell leukemia. After the fourth course of chemotherapy, pleural effusion developed, and plasma cells were observed in peripheral blood after the sixth course of chemotherapy. Homozygous loss of chromosome 16 and monosomy X developed before the fourth course of chemotherapy. In this case, such cytogenetic abnormalities may be related to the myelomatous effusion and leukemic changes in multiple myelomas

Cytogenetic analysis in a multiple myeloma patient who developed myelomatous pleural effusion and plasma cell leukemia

We report on a patient with multiple myeloma who developed myelomatous pleural effusion and plasma cell leukemia. After the fourth course of chemotherapy, pleural effusion developed, and plasma cells were observed in peripheral blood after the sixth course of chemotherapy. Homozygous loss of chromosome 16 and monosomy X developed before the fourth course of chemotherapy. In this case, such cytogenetic abnormalities may be related to the myelomatous effusion and leukemic changes in multiple myelomas

Sequential chemotherapy and myeloablative allogeneic hematopoietic stem cell transplantation for refractory acute lymphoblastic leukemia

The prognosis of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for refractory acute lymphoblastic leukemia (ALL) is very poor. To improve survival rates, we attempted to intensify the conditioning regimen with daunorubicin, vincristine, prednisolone, medium-dose etoposide, cyclophosphamide, and total body irradiation (DNR/VCR/PSL plus medium-dose VP/CY/TBI). Four patients in relapse or induction failure of B-precursor ALL without other complications underwent allogeneic HSCT. Initially, chemotherapy comprising DNR 60 mg/m2 for 3 days, VCR 1.4 mg/m2 for 1 day, and PSL 60 mg/m2 for 3 days was administered, which was followed by medium-dose VP/CY/TBI; some modifications were made for individual patients. All patients achieved engraftment and complete remission after HSCT. Regimen-related toxicities were tolerable and no patient died within 100 days. Two patients were alive without disease on days 563 and 1055. The third patient relapsed on day 951, while the fourth died on day 179 without disease. Our results indicate that intensified myeloablative HSCT should be considered for patients with refractory ALL

Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD

Since the safety of folinic acid administration and its efficacy for reducing the toxicity of methotrexate (MTX) remain controversial, we assessed the effect of folinic acid administration after MTX treatment for GVHD prophylaxis on the incidence of oral mucositis and acute GVHD. We retrospectively analyzed data for 118 patients who had undergone allogeneic hematopoietic stem cell transplantation and had received MTX for GVHD prophylaxis. Multivariate analysis showed that systemic folinic acid administration significantly reduced the incidence of severe oral mucositis (OR = 0.13, 95%CI 0.04-0.73, P = 0.014). There was also a tendency for lower incidence of severe oral mucositis in patients who received folinic acid mouthwash (OR = 0.39, 95%CI 0.15-1.00, P = 0.051). No significant difference was observed in the incidence of acute GVHD between patients who received systemic folinic acid administration and those who did not (P = 0.88). Systemic folinic acid administration and mouthwash appear to be useful for reducing the incidence of severe oral mucositis in patients who have received allogeneic hematopoietic mucositis in patients who have received allogeneic hematopoietic stem cell transplantation using MTX as GVHD prophylaxis