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Background: The treatment of acute lymphoblastic leukemia in adults with UKALL XII regimen including vincristin is aggressive. Invasive aspergillosis is a common life-treatening infection in patients with acute leukemia. The presence of construction works near hospital wards is an important risk factor for the development of invasive aspergillosis. Case presentation: A 59-year old woman with common ALL relapsed after 22 years (normal cytogenetics). She was treated according to the UKALL XII regimen and achieved complete second remission. She received four cycles of vincristine 2 mg i.v. In a retrospective cohort study, prolonged neutropenia, use of steroids, nursing unit without laminar air flow during a period of construction works were associated with an increased incidence of invasive aspergillosis in patients who did not receive primary antifungal prophylaxis. Intravenous caspofungin was administered to the patient as primary aspergillosis prophylaxis on the first day of chemotherapy. Galactomannan antigen tests were negative during the period of neutropenia. There was no infection in the period of prolonged neutropenia. Conclusions: The author discusses primary prophylaxis of invasive aspergillosis with caspofungin during construction works in patients with acute lymphoblastic leukemia treated with vincristine. Because of non-conventional unit without laminar air flow during induction chemotherapy treatment, which leads to an increased risk of invasive fungal infection with Aspergillus, caspofungin prophylaxis is recommended at least until upgrade to laminar flow or cessation of construction works.

BACKGROUND The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosomepositive CML (chronic myeloid leukemia), but relaps occurs, mainly as a reults of the outgrowth of leukemic subclones with imatinib resistant BCR-ABL mutation.Some patientswith various phases of CML note tolerate imatinib. Dasatinib is an orally available ABLkinase inhibitor that differs from imatinib in that it can bind to both the active andinactive conformation of the ABL kinase domain.The oral inhibitor tirozin kinazedasatinib was approved in 2006 for use in patients with CML who are unable to tolerate orhave not responder to other treatments.Patients We treated 2 patients in chronic phase CML who dident tolerate imatinib (400 mg per day)and one patient in accelerated phase CML (imatinib 800 mg per day) withdasatinib.Dasatinib was administered orally (50 to 140 mg per day) once or twice daily. Hematologic and cytogenetic responses were seen in 2 patients. Myelosuppression was commonbut not dose – limiting. One patients in chronic phase CML didnt tolerate also dasatinib.He had rush, nausea and vomiting. CONCLUSIONS Dasatinib induces hematologic and cytogenetic responses in patients with CML whocannot tolerate or are resistant to imatinib. Dasatinib has shown clinical benefit andtolerability in patients in all phases of CML

Background: The prognosis of acute lymphoblastic leukemia (ALL) in adults is far worse than in children. The results of several collaborative trials for the treatment of ALL indicate that complete remission can now be achieved in 90 % of patient under the age of 60, but most patients relapse.Patients and methods: Between January 2007 and December 2011, 27 adults patients with newly diagnosed ALL were treated at the Department of Haematology in Ljubljana (22 patients had B-ALL, 5 patients T-ALL). The median age spreof the patients was 48 years, range 21–77 years. Cytogenetic investigations of the bone marrow were performed in 26 patients, 8 patients had t(9;22). 19 patients were eligible for induction chemotherapy according to UKALL XII regimen (the median age 44 years), 3 patients for induction chemotherapy with children ALL regimen and 5 older patients received VAD regimen. We conducted 9 allogenic stem-cell transplantations (SCT), including 2 related donor SCT and 7 unrelated donor SCT, no autologous SCT was done.Results: 17 patients (88 %) achieved complete remission with UKALL XII regimen; 6 of these patients died within 6 weeks after start of chemotherapy. Predominant causes of death were infections and respiratory failure. Three younger patients achived complete remission with children ALL regimen, 1 relapsed. Three patients died after allogenic SCT in remission because of chronic GVHD and infection-related complications of immunosupresion treatment, 1 patient died because of respiratory failure in remission.Conclusions: The UKALL XII regimen and children ALL regimen represent an aggressive approach, including high-dose corticosteroids. We conclude that cytogenetics is a strong independent prognostic factor. In most patients we can achieve a complete remission, but most patient relapse .We had more deaths in remission induction treatment with UKALL XII regimen. Allogenic SCT or prolonged consolidation and maintenance treatment is warranted. In patients over 70 years of age we do not use intensive chemotherapy.

BACKGROUND The prognosis of acute lymphoblastic leukemia (ALL) in adults is far worse than that inchildren in terms of induction of complete remision (61–85 %) and leukemia-free survival3–5 years (35 %). The UKALL XII regiment was studied at the Department of Haematology, Universitiy Medical Centre Ljubljana.Patients and Between January 2000 and December 2007 41 adults patients with newly diagnosed ALLmethods were eligible for induction chemotherapy (UKALL XII regiment). The median age of thepatients was 33 years, range 17–68 years. We conducted 18 hematopoietic cell transplantation (HCT), including 9 avtologous, 5 related donor HCT and 4 unrelated donor HCT. RESULTS 33 patients (81 %) achieved complete remission. Overall 5-year survival in all patients was48 %. In those younger than 30 years in was 66 % and in those older than 30 years it was38 %. 4 patients (10 %) died within 6 weeks of diagnosis. The cause of mortality proved tobe infection. CONCLUSIONS The UKALL XII regiment is an aggressive approach. We conclude that cytogenetics is astrong independent prognostic factor. In most patients we can achieve a complete remission, but most patients relapse. Therefore allogeneic HCT or prolonged consolidation andmaintainance tretment is warranted. There is probable no benefit of avtologous HCT inpatients with ALL

BACKGROUND The BCR-ABL tyrosine kinase inhibitor imatinib is effective in Philadelphia chromosomepositive CML (chronic myeloid leukemia), but relaps occurs, mainly as a reults of the outgrowth of leukemic subclones with imatinib resistant BCR-ABL mutation.Some patientswith various phases of CML note tolerate imatinib. Dasatinib is an orally available ABLkinase inhibitor that differs from imatinib in that it can bind to both the active andinactive conformation of the ABL kinase domain.The oral inhibitor tirozin kinazedasatinib was approved in 2006 for use in patients with CML who are unable to tolerate orhave not responder to other treatments.Patients We treated 2 patients in chronic phase CML who dident tolerate imatinib (400 mg per day)and one patient in accelerated phase CML (imatinib 800 mg per day) withdasatinib.Dasatinib was administered orally (50 to 140 mg per day) once or twice daily. Hematologic and cytogenetic responses were seen in 2 patients. Myelosuppression was commonbut not dose - limiting. One patients in chronic phase CML didnt tolerate also dasatinib.He had rush, nausea and vomiting. CONCLUSIONS Dasatinib induces hematologic and cytogenetic responses in patients with CML whocannot tolerate or are resistant to imatinib. Dasatinib has shown clinical benefit andtolerability in patients in all phases of CML

Background. Imatinib mesylate is an Abl kinase inhibitor capable of producing a sustained complete molecular response in chronic myelogenous leukemia (CML). It is effective in all three phases of CML with the longest response in the chronic phase. Imatinib has been in use only since 1998 and many questions about its efficacy and use are still unanswered.Methods and results. From October 2001 until January 2004 thirty-one patients with CML have been treated with imatinib (300–600 mg/day) at our institution. Twelve patients were in chronic phase of CML, 13 in accelerated phase and 3 in blast crisis. Two were treated after unrelated peripheral blood stem cell transplantation (PBSCT) due to CML reactivation. All had been treated prior to instituting imatinib (hydroxiurea, interferon – alpha, cytarabine). Complete cytogenetic response (CCR) in patients in chronic phase occured in 33.3% and complete molecular response (CMR) occured in 41.7%. CCR in patients in accelerated phase occured in 30.8% and CMR occured in 46.2%. None of the patients in blast crisis had CCR or CMR. Several side effects were reported during the treatment. However, among them there was not the most common side effect reported in other studies. Limb muscle and bone pains (20%) were the most frequently reported side effects in our group of patients.Conclusions. Imatinib has be found to be most effective in chronic and accelerated phase of CML. However, there is still not enough data about its long-term use and prognosis. For the time being, PBSCT remains the only proven curative treatment of CML.

BACKGROUND The prognosis of acute lymphoblastic leukemia (ALL) in adults is far worse than that inchildren in terms of induction of complete remision (61-85 %) and leukemia-free survival3-5 years (35 %). The UKALL XII regiment was studied at the Department of Haematology, Universitiy Medical Centre Ljubljana.Patients and Between January 2000 and December 2007 41 adults patients with newly diagnosed ALLmethods were eligible for induction chemotherapy (UKALL XII regiment). The median age of thepatients was 33 years, range 17-68 years. We conducted 18 hematopoietic cell transplantation (HCT), including 9 avtologous, 5 related donor HCT and 4 unrelated donor HCT. RESULTS 33 patients (81 %) achieved complete remission. Overall 5-year survival in all patients was48 %. In those younger than 30 years in was 66 % and in those older than 30 years it was38 %. 4 patients (10 %) died within 6 weeks of diagnosis. The cause of mortality proved tobe infection. CONCLUSIONS The UKALL XII regiment is an aggressive approach. We conclude that cytogenetics is astrong independent prognostic factor. In most patients we can achieve a complete remission, but most patients relapse. Therefore allogeneic HCT or prolonged consolidation andmaintainance tretment is warranted. There is probable no benefit of avtologous HCT inpatients with ALL

Background. Angiogenesis is a crucial process in progression of multiple myeloma. Vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) are multifunctional cytokines that stimulate angiogenesis and myeloma growth. Matrix metalloproteinase 9 (MMP-9) plays a critical role in osteolytic bone destruction, angiogenesis and invasive growth of myeloma cells. We evaluated serum concentrations of these factors in patients with multiple myeloma.Methods. Levels of active and pro-matrix metalloproteinase 9 (total MMP-9), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were determined with a commercial quantitative enzyme immunoassay Quantikine  (R&D Systems, USA). All of these factors were measured in the serum obtained from pheripheral blood of 36 patients affected by multiple myeloma.This series included 12 patients with disease in plateau phase and without treatment, 14 patients on Thalidomide therapy and 10 patients at the beginning of chemotherapy because of active disease.Results. VEGF showed a strong correlation with MMP-9 while VEGF and bFGF did not correlate with each other. Blood platelets correlated with VEGF and MMP-9.The concentration of MMP-9 and VEGF were the highest in group of patients with active disease where the chemotherapy started. The level of bFGF was the lowest in the group devoid of treatment (plateau phase of disease).Conclusions. Production of the angiogenic factors such as VEGF, bFGF and MMP-9 are increased in multiple myeloma patients. The levels of these factors correlate with the activity of disease.

To improve our understanding of the regulation of circulating platelet counts (PC) by thrombopoietin (TPO), we studied serum TPO levels and PC before and after myelosuppressive chemotherapy in 12 patients with acute myeloid leukaemia (AML). Serum TPO levels were measured by the quantitative sandwich enzyme-linked immunosorbent assay (Quantikine, RD Systems). At the start of the induction chemotherapy, the patients had a median serum TPO level of 199 pg/ml (range 120-2,150 pg/ml), while 10 to 12 days after the end of chemotherapy, their TPO levels were substantially increased, the median value being 1,907 pg/ml (range 1,049-4,194 pg/ml). The correlation between PC and TPO was statistically significant prior to chemotherapy (p < 0.03) and insignificant after chemotherapy. As a result of chemotherapy, the patients developed aplasia; after the administration of platelet transfusions, their median PC increased to 21 x 10(9)/l (range 5-55 x 10(9)/l), while the median TPO value decreased by 300 pg/ml (range 11-1,125 pg/ml). Our results suggest that platelet mass directly regulates serum TPO levels in acute leukaemia patients prior to chemotherapy and after the administration of platelet transfusions. Serum TPO levels may also be influenced by the cytokine response during complicating infections in patients with chemotherapy-induced cytopenia.

Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 x 10(9)/L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 microg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 microg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.