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The combination of NK1 receptor antagonist (NK1 RA), setron and dexamethasone is necessary for the optimal prevention of chemotherapy induced nausea and vomiting (CINV) after highly emetogenic chemotherapy (HEC: AC and non-AC) and carboplatin. Palonosetron is the preferable setron when NK1 RA is not available. To evaluate availability and accessibility of antiemetics (AE) recommended by the MASCC/ESMO 2016 antiemetic guidelines in hospitals of the Eastern European and Balkan region. Data were collected by countries participating at the First Regional Education Meeting on Supportive Care for Eastern European and Balkan region. Availability was evaluated by the formulary availability and marketing authorization (registered or not). Accessibility was assessed by the coverage of the National Health Insurance Fund: fully reimbursed, partially reimbursed and not accessible (out--of--pocket). Results There is unequality in the access to AE across Eastern European and Balkan region. Clinically most important is the lack of access to NKIRAs which coupled with the lack of access to palonosetron, creates an important barrier for the prevention of CINV after HEC and carboplatin. Off-label use of olanzapine, as an effective alternative, is another barrier in successful prevention and control of CINV.

Cancer pain is the most common symptom of cancer. The implementation of the cancer pain guidelines depends on availability of and accessibility to guideline-recommended medications. The purpose of this research was to investigate the availability and accessibility of strong opioids in Eastern Europe and Balkans. The survey was conducted among 15 countries of the region with data collected for morphine, hydromorphone, oxycodone, methadone, transdermal fentanyl (fentanyl TD) and fentanyl for the breakthrough pain (fentanyl BTP). Methadone for substitution therapy was not included in this survey. Availability was evaluated by the formulary availability and marketing authorization. Accessibility was evaluated by the National Health Insurance Fund coverage as fully reimbursed, partially reimbursed or not accessible (out-of-pocket). Slovenia is the only country with all investigated strong opioids available and fully reimbursed (Table 1). Morphine is available and fully reimbursed in all countries. Fentanyl TD is available and fully reimbursed in 14/15 countries except in Albania in which it is out-of-pocket medication. Morphine in the only available and fully reimbursed strong opioid in Albania. Hydromorphone, oxycodone, methadone and fentanyl BTP are not available in 8/15, 4/15, 6/15 and 4/15 countries, respectively. All countries have at least one first-line strong opioid available and accessible with major differences among countries in the region.

Background: Corticosteroid-resistant acute GVHD is difficult to manage, and is associated with high morbidity and mortality. No standard treatment exists. We had previously seen encouraging results with pulse cyclophosphamide (Cy) in the treatment of liver GVHD in contrast to gastrointestinal GVHD, and we report here the long-term results of pulse Cy for the treatment of steroid-refractory liver GVHD, with no association to the gut. Methods: This is a retrospective study of 21 patients (pts) with hematological malignancies after allogeneic stem cell transplantation. Twelve pts had acute GVHD (2 pts grade I, 3 pts grade II, 7 pts grade III), 4 pts had chronic extensive GVHD and 5 pts developed liver GVHD upon DLI. Two pts had only liver GvHD, 19 pts had GVHD with involvement of liver and/or oral mucosa, and/or skin. All pts had hepatitic variant of liver GVHD (serum aminotransferase ALT or AST elevation > 10 times the upper normal limit), classical GVHD with elevation of bilirubine was observed at 9/21 pts. All pts were treated by cyclosporine A and steroids in dose 2 mg/kg before pulse Cy, five pts had another previous therapy (mycophenolate mofetil, alemtuzumab). Steroid-refractory GVHD was defined as the lack of response to steroids administered for at least 5 consecutive days. Cy was infused at a dose of 1000 mg/[m.sup.2]. Twenty-nine Cy administrations were given in 21 pts. The median time of GVHD onset and Cy administration after transplantation, or DLI, were 58 and 69 days, respectively. Results: Eleven pts (52%) achieved CR and 6 pts (29%) achieved PR. Four pts (19%) did not respond, however their condition stabilized and upon additional therapy, 3 achieved PR and one CR. Leukopenia and/or thrombocytopenia WHO grade 4 developed after 5 Cy pulses, it was usually short-lived with a median of 7 days. Twelve infectious complications occurred in 8 of 21 pts, all of them resolved after antimicrobial therapy. Neither other significant toxicity after Cy pulse nor influence of pulse Cy therapy to chimerism or disease status were observed. Three pts died, all deaths were without direct relationship to pulse Cy. Overall survival of all 21 pts is 86% with median and maximal follow-up of 33 and 81 months, respectively. Conclusion: Pulse Cy is an effective treatment for steroid-refractory liver GVHD with overall response rate 81% and remarkably good toxicity profile, which may favor its use instead of drugs with more pronounced immunosuppressive effects.

Background: Sequential use of intensive chemotherapy and reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT) in high-risk patients (pts) represents a promising approach (Schmid et al., JCO 23, 2005: 5675-87). Here, we wanted to explore if these results are reproducible at another group of pts. Methods: We retrospectively analyzed 36 pts with advanced hematological malignancies (AML, n=22; ALL, n=4; MDS, n=3; others, n=7) undergoing chemotherapy and RIC SCT in our centre from March 2006 to May 2008. Fludarabine (30 mg/[m.sup.2]), cytarabine (2 g/[m.sup.2]), and amsacrine (100 mg/[m.sup.2]) for 4 days (FLAMSA) were used for cytoreduction. Amsacrine was not administered to pts with lymphoid malignancies (8/36). After 3 days of rest, RIC consisting of 4 Gy TBI, ATG (Fresenius) 10-20 mg/kg/day for 3 days, and cyclophosphamide 40-60 mg/kg/day for 2 days followed. Disease status before SCT was: CR1, n=5; CR2, n=9; CR3, n=1; refractory disease or relapse, n=21, type of donors: HLA identical sibling, n=12; unrelated donor, n=24, and grafts used were: PBSCs, n=35; BM, n=1. Median age of pts was 49 years (range 19-61). Results: The neutrophil engraftment (above 0.5x10E9/L) was achieved at a median time of 18.0 days. No graft rejection was observed. Transplant-related mortality (TRM) to the day +100 was 25% (9/36). Causes of death were GVHD (n=2), septic shock (n=3), multiorgan failure (n=2), and brain hemorrhage (n=2). All early deaths were seen in very high risk pts only: relapse or refractory disease, n=8; CR3, n=1. Incidence of acute GVHD was evaluated in 29 pts: 55% (16/29) of pts had GVHD (grade I+II in 14 pts, grade III in 2 cases). Incidence of chronic GVHD was evaluated in 24 pts, 58% (14/24) of pts had GVHD (limited in 11 cases, extensive in 3 cases). Treatment response was evaluated in 29 pts: remission was achieved in 27 pts (93%), only 2 pts had progression of leukemia. With median follow-up 225 days (range 1-900), 56% of all pts (20/36) were alive (19 pts in remission, 1 pt with relapse), 16 pts died (9 deaths from TRM, 7 deaths from relapse or progression of leukemia), nine relapses (31%; 9/29) occurred. Conclusion: FLAMSA-RIC protocol seems to be effective salvage treatment in pts with advanced both myeloid and lymphoid malignancies. Response rate is high (93%) and the toxicity moderate with low frequence of serious GVHD. Early deaths in very high risk pts call for careful indication of this treatment. However, longer follow-up is needed.

Corticosteroid-resistant GVHD is difficult to manage and is associated with high morbidity and mortality. Cyclophosphamide (Cy) is an established immunosuppressive and cytotoxic drug widely used as part of pretransplant conditioning regimens. In a retrospective study of 15 patients who had not responded to corticosteroids (nine with acute GVHD, three with GVHD after donor leukocyte infusion, and three progressive chronic GVHD), pulse Cy at a median dose of 1 g/m(2) was very effective in the treatment of skin (100% response), liver (70% response), and the oral cavity (100% response). Severe intestinal GVHD responded poorly. The toxicity profile was acceptable, with manageable, short-term myelosuppression in some patients. The risk of opportunistic infections, mixed chimerism, relapses, or post-transplant lymphoproliferative disease was not increased. Overall survival was 57%, with median and maximum follow-up of 9 and 37 months, respectively. The cost of the drug was negligible, especially when compared to monoclonal antibodies. Pulse Cy requires further investigation in corticosteroid-resistant GVHD.

Corticosteroid-resistant GVHD is difficult to manage and is associated with high morbidity and mortality. Cyclophosphamide (Cy) is an established immunosuppressive and cytotoxic drug widely used as part of pretransplant conditioning regimens. In a retrospective study of 15 patients who had not responded to corticosteroids (nine with acute GVHD, three with GVHD after donor leukocyte infusion, and three progressive chronic GVHD), pulse Cy at a median dose of 1 g/m 2 was very effective in the treatment of skin (100% response), liver (70% response), and the oral cavity (100% response). Severe intestinal GVHD responded poorly. The toxicity profile was acceptable, with manageable, short-term myelosuppression in some patients. The risk of opportunistic infections, mixed chimerism, relapses, or post-transplant lymphoproliferative disease was not increased. Overall survival was 57%, with median and maximum follow-up of 9 and 37 months, respectively. The cost of the drug was negligible, especially when compared to monoclonal antibodies. Pulse Cy requires further investigation in corticosteroid-resistant GVHD.