Forty-eight patients with early myelodysplastic syndrome (MDS) without excess of blasts, with average initial serum ferritin levels of 2739.5 μg/L (range 825–11287 μg/L), were treated with deferiprone (L1) in a daily dose of 40–90 mg/kg. Median duration of chelation treatment was 10.9 months (range 4–24 months). Chelation was effective (maintained or decreased iron stores) in 16 out of 22 patients (73%) with serum ferritin levels <2000 μg/L in contrast to only 12 out of 26 patients with serum ferritin levels >2000 μg/L. Combination of L1 with recombinant human erythropoietin (rHuEPO) (30–40 kU/week) resulted in effective chelation in five additional patients with serum ferritin levels >3000 μg/L. Incidence of adverse effects was comparable to that in thalassemic patients. Gastrointestinal symptoms represented the most frequent adverse effect of L1 therapy (37.5% of patients) that limited an effective escalation of the daily dose of the drug and led to discontinuation of the treatment for six patients. A decreased number of granulocytes was observed in five (13%) patients and agranulocytosis occurred in two patients (4%). Granulocyte counts were restored after cessation of L1 treatment and administration of granulocyte colony stimulating factor (G-CSF) in all but one patient. Administration of L1 in a daily dose of at least 75 mg/kg may represent an alternative approach in treatment of mild and moderate iron overload in MDS patients who cannot be treated with deferasirox (DFRA) or deferoxamine (DFO).
The bone marrow transplantation is a curative method in leukemia, lymphomas, immunodeficient states and solid tumors. Graft versus host disease (GVHD) is a significant complication in patients after bone marrow transplantion, most frequently affected of intestine, liver, skin and oral mucosa. Oral mucosa damage is presented by chronic and acute form of GVHD. The acute form is presented by painful ulcers, lichenoid lesions affecting practically whole oral cavity, while the chronic GVHD is compared to autoimmune diseases such as Sjögren syndrome. GVHD is a major complication of bone marrow transplantation with risk to health a therapeutic result. The treatment is long-term and involve interdisciplinary cooperation.
Myelodysplastic syndromes (MDS) are the heterogenous group of diseases with a different risk of development to acute leukemia (AL). The allogeneic stem cell transplantation (alloSCT) is one of the treatment possibilities that is more accessible thanks to availability of recent conditioning regimes. Many questions are still open. The goal of the retrospective analysis was the evaluation of alloSCTs performed in two transplantation centres to estimate the importance of alloSCT for MDS patients (pts), to evaluate prognostic parametres and the course of alloSCTs and overall survival (OS). Patients characteristics: The cohort consisted of 30 pts, male:female ratio was 1:1, transplanted in 1997 – 2010, the age were 23 – 63 year (median 56). According the WHO 2001 classification the pts were initially classified as: 2 (7%) 5q- sy, 2 (7%) RARS, 9 (30%) RCMD, 6 (20%) RAEB I, 11 (36%) RAEB II, according to IPSS as: 2 (6%) low risk, 11 (37%) intermediate-1, 11 (37%) intermediate-2, 6 (20%) high risk. In 13 cases (43%) alloSCT was performed in leukemic phase, in majority of cases after induction/consolidation chemotherapy. 6 (20%) pts underwent alloSCT during the progression into more advanced MDS and 11 (37%) in phase of stabile disease. 11 pts (37%) underwent myeloablative conditioning regime and 19 (63%) pts reduced intensity regime. 14 transplantations were from sibling donors, 16x from unrelated donors, only in 1 case was used bone marrow. Median of follow-up from MDS diagnosis was 33 months, from alloSCT 15 months. Transplantation was performed in median of 11 months from diagnosis of MDS. 11 pts died in the whole cohort – the reason was the progression of disease (4x), infection complications (4x), GVHD and current infection (3x). It dealt initially about the most risky MDS, 8 (27%) transformed into AL, according IPSS 4 (13%) were initially high risk, 7 (23%) intermediate (int-1 and int-2). Median from diagnosis was 12 and from alloSCT 3 months. Other pts have received long time remission and in the low risk MDS transfusion dependence was removed and the quality of life was outstandingly improved. At the moment 19 (63%) pts live with median of follow-up 49 month from MDS diagnosis and 27 months from alloSCT. It is possible curatively influence MDS or secondary AL in favour of patient exploiting aloSCT. Consideration of this curative possibility should have become routine part of diagnostic-prognostic algorithm in MDS patients.
Standard myeloablative conditioning combined busulphan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BU-CY) is associated with high non-hematologic toxicity, significant morbidity and mortality. Regimen combined fludarabin (125 mg/m2), busulphan (12 mg/kg) and thymoglobuline (6 mg/kg) (FLU-BU12-TG) might be less toxic and safer despite the myeloablative dose of busulphan. Retrospective study compared the results of allogeneic SCT after those two regimens in the patients with AML.
Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.
The group of 20 patients treated for non-Hodgkin lymphomas and multiple myeloma was examined by stomatologists before planned autologous transplantation of stem cells. After tooth sanation and removal of the sources of local irritation and potential foci of odontogenic focal infection the patients were observed in the course of 4 to 5 weeks after transplantation for the occurrence of oral mucositis. Oral mucositis of 1st to 2nd degree (according to NCI-CTC classification) became manifest in the course of hemato-oncological treatment in all patients in relation to the type of chemotherapy. After successful termination of hemato-oncological treatment a spontaneous disappearance of oral mucositis developed. Low seriousness of oral complications of hemato-oncological therapy confirms the importance of careful stomatological preparation of the patient before planned autologous transplantation.
In some rats, the hormone corticosterone is reinforcing. High novelty-seeking rats (high responders, HR) self-administered corticosterone at a much higher rate than low novelty-seeking rats (low responders, LR) do [Piazza PV, Deroche V, Deminiere JM, Maccari S, Le Moal M, Simon H, Corticosterone in the range of stress-induced levels possesses reinforcing properties: implications for sensation-seeking behaviors, Proc Natl Acad Sci USA 1993;90:11738–42]. While previous studies demonstrated that corticosterone reinforces nose poking in a self-administration paradigm, no studies to date have examined whether corticosterone is rewarding.Using the conditioned place preference (CPP) paradigm, we examined the rewarding effects of corticosterone in HR and LR rats.Male Sprague–Dawley rats were classified into HR and LR groups based on their locomotor activity in a novel environment. Subsequently, independent groups of HR and LR rats underwent CPP for corticosterone (0, 2.5 or 10 mg/kg; i.p.) or cocaine (12 mg/kg; i.p). CPP for cocaine was used as a positive control.While cocaine produced a strong CPP in both HR and LR rats, corticosterone failed to produce either preference or aversion in both phenotypes.Corticosterone is neither rewarding nor aversive in either behavioral phenotype.