Zafer Gulbas

Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group.

The combination of melphalan–prednisone–thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan–prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n = 122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m2/d) and P (60 mg/m2/d) for 4 d every 6 wk (n = 62) or MP and thalidomide (100 mg/d) continuously (n = 60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease‐free (DFS) and overall survival (OS). Overall, MPT‐treated patients were younger (median 69 yr vs. 72 yr; P = 0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P = 0.057). After 4 cycles of treatment (n = 115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P = 0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow‐up (median OS 26.0 vs. 28.0 months, P = 0.655; DFS 21.0 vs. 14.0 months, P = 0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3–4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P = 0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n = 8, 14.0%) than in the MPT arm (n = 2, 3.4%; P = 0.053). Long‐term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P = 0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation. This study is registered at http://www.clinicaltrials.gov as #NCT00934154.

Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome.

Glutamine is an important substrate for enterocyte and other rapidly proliferating cells. Low plasma and tissue levels present in glutamine in critically ill patients suggest that demand may exceed endogenous supply. Because commercially available amino acid solutions do not contain glutamine because of its instability in aqueous solution, conventional total parenteral nutrition (TPN) does not prevent stress-induced glutamine depletion. In this study, we administered intravenous glutamine-supplemented TPN to patients with systemic inflammatory response syndrome (SIRS) to investigate the effect of glutamine supplementation on immune states. This study is a prospective, randomized clinical trial. All patients received TPN given continuously for 6 days. Thirty patients with SIRS were allocated to either a glutamine group (l-glutamine 0.4g/[kg d]) (n = 15) or a control group (n = 15). Blood samples were collected on day 1 and day 6 after admission for C-reactive protein, immunoglobulin (Ig) M, IgG, IgA, C(3), C4, and lymphocyte analysis. The Acute Physiologic and Chronic Health Evaluation II score and the Simplified Acute Physiologic II (SAPS II) score were used to evaluate the patients after admission. Although there was a tendency for decreased T cytotoxic cells and natural killer cells in the control group, no significant difference was observed between the 2 groups. However, an increase in lymphocyte and lymphocyte subgroups in the glutamine group was observed; but there was no difference between the groups. A low SAPS II score was observed on the sixth day in the glutamine group, whereas no difference in SAPS II and Acute Physiologic and Chronic Health Evaluation II scores was observed between the 2 groups. There was no difference in IgM, IgG, IgA, C(3), and C4 levels and numbers of B-lymphocytes between the groups. Glutamine-added TPN significantly decreases leukocyte and natural killer cell count and therefore suppresses inflammation. Furthermore, total lymphocyte count, B- and T-lymphocytes, and their subgroups (helper T-lymphocytes, cytotoxic T-lymphocytes) are increased; although not statistically significant, these increases might be playing a role in improving the immune system.

A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia

BackgroundIn the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT) from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo) versus matched (MUD 10/10) or mismatched unrelated donor at a single HLA-locus (MMUD 9/10) for patients with acute leukemia in remission.MethodsTwo hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups.ResultsThe weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS) and overall survival (OS) were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease.ConclusionsPatients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD.Key point 1Better outcomes using fully (10/10) matched unrelated donor for allo-SCT in acute leukemia in remission.Key point 2Similar outcomes after allo-SCT from unmanipulated haploidentical graft or mismatched (9/10) unrelated donor in acute leukemia in remission.

Lymphadenitis Caused by Scedosporium apiospermum in an Immunocompetent Patient

A case of lymphadenitis caused by Scedosporium apiospermum in a 25-year-old immunocompetent woman had been misdiagnosed as tuberculous lymphadenitis. Clinical response to itraconazole therapy was obtained in 6 months; to our knowledge, this is the first report of lymphadenitis caused by S. apiospermum in humans.

Case Report. Rhodotorula rubra fungaemia due to use of indwelling venous catheters

Rhodotorula has been an infrequent cause of infection in humans but there have been some case reports about this systemic yeast infection. In this article, a Rhodotorula rubra fungaemia due to an indwelling catheter in a 23‐year‐old woman who had been diagnosed with non‐Hodgkins lymphoma grade IV B is described.

Acute Liver Failure due to Hodgkin’s Lymphoma

Objective: To describe an unusual case of acute liver failure due to Hodgkin’s lymphoma. Case Presentation and Intervention: A 37-year-old man was admitted with jaundice and abdominal distension. Physical examination showed tender hepatosplenomegaly, ascites, grade I encephalopathy, left cervical (2 × 1 cm) and axillary (1 × 1 cm) lymph nodes. The laboratory data revealed elevated serum bilirubin, transaminases, lactate dehydrogenase, and coagulation defects. Initially, primary liver disease was considered, but a liver biopsy revealed infiltration of the liver by Hodgkin’s lymphoma that was confirmed by lymph node biopsy. Hodgkin’s lymphoma was of lymphocyte depletion type. Conclusion: This case demonstrates that in the presence of lymphadenopathy involving acute liver failure, hematological malignancies should be taken into consideration. Liver and lymph node biopsies should be performed as early as possible.

Catheter-related bacteremia due to Chryseobacterium indologenes in a bone marrow transplant recipient.

Catheter-related bacteremia due to Chryseobacterium indologenes in a bone marrow transplant recipient

Abnormality of regulatory T-cells in remission and non-remission idiopathic thrombocytopaenic purpura patients

Primer immunologic defect in patients with idiopathic thrombocytopaenic purpura (ITP) result from autoreactive B-lymphocytes secreting antiplatelet antibodies. Dysfunctional cellular immunity has also great importance in ITP pathogenesis. CD4+CD25+ regulatory T-cells have immunoregulatory features and it is able to inhibit CD4+CD25− and CD8+ responses. ITP is also an autoimmune disease; the CD4+CD25+ T-cell levels of the patients decrease during the active state. According to our findings, immunosuppressive treatments increase the CD4+CD25+ Treg cell levels in the non-remission ITP patients. However, this level is not enough to overcome the resistance. CD4+CD25−Foxp3+ and CD4+Foxp3+ Treg cells are responsible for the pathogenesis of the non-remission ITP patients and other factors exist, which are responsible for the resistance of ITP treatment.

Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura

Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in idiopathic thrombocytopenic purpura (ITP) patients. Thirty nine patients with ITP (platelet count < 100 × 103  µl−1) were included in the study. Age-matched 17 patients with thrombocytopenia due to chemotherapy were selected as a control group. Platelet count was positively correlated with maximum clot formation (MCF) in INTEM (r = 0.716, p < 0.001) and MCF in EXTEM (r = 0.679, p < 0.001); negatively correlated with clot formation time (CFT) in INTEM (r = −0.755, p < 0.001) and CFT in EXTEM (r = −0.585, p < 0.001) in ITP patients. Platelet count was positively correlated with MCF in INTEM (r = 0.776, p < 0.001) and MCF in EXTEM (r = 0.878, p < 0.001); negatively correlated with CFT in INTEM (r = −0.627, p < 0.001) in control group. Receiver operating characteristic curves to describe the critical platelet count and fibrinogen level that affect MCF revealed 31 × 103 µl−1 and 375 mg dl−1 as cut-off values, respectively. In conclusion, ROTEM determines the contribution of fibrinogen and platelets to clot strength in patients with ITP. MCF appears to be the most important TEG parameter in predicting bleeding in ITP patients that makes TEG superior to other hemostatic tests.

Effect of spironolactone on impaired fibrinolysis of hypertensive patients.

Background/Aims: Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have beneficial effects on impaired fibrinolytic activity of hypertensive patients. The aim of the study was to evaluate the effect of antialdosterone treatment on impaired fibrinolysis of hypertensive patients. Methods: Fourteen hypertensive outpatients and 14 normotensive healthy volunteers participated in this study. Blood samples for plasminogen activator inhibitor-1 (PAI-1) antigen and tissue plasminogen activator (t-PA) antigen were obtained at baseline in all patients and control subjects. Then all hypertensive patients used spironolactone 50 mg/day for a week. Blood samples were again obtained after a week of spironolactone treatment. Results: The mean basal plasma level of PAI-1 of hypertensive patients was higher than those of the normotensive control group (60.98 ± 4.2 vs. 24.09 ± 1.61 ng/ml, p < 0.01) The mean basal t-PA level was similar in the hypertensive and control subjects (7.49 ± 0.65 vs. 8.78 ± 0.92 ng/ml, p > 0.05). The mean PAI-1 level decreased after a week of spironolactone treatment (60.98 ± 4.2 vs. 42.99 ± 7.98 ng/ml, p < 0.05). The mean plasma t-PA level of hypertensive patients increased after spironolactone treatment (7.49 ± 0.65 vs. 11.09 ± 1.33 ng/ml, p < 0.05). Conclusion: This study shows that spironolactone improves impaired fibrinolysis in systemic hypertension. It provides evidence for a direct link between aldosterone and the fibrinolytic system in humans.