Türker Çetin

Total parenteral nutrition delays platelet engraftment in patients who undergo autologous hematopoietic stem cell transplantation

OBJECTIVES One of the major challenges in the post-transplant period is nutrition. In this prospective, non-randomized study, total parenteral nutrition (TPN) was given to 31 patients and partial parenteral nutrition (PPN) was given to 30 patients undergoing autologous hematopoietic stem cell transplantation for solid tumors or hematologic malignancies to compare the effects of these parenteral nutrition modalities on post-transplant hematological engraftment, blood chemistry, and supportive therapy requirements. METHODS All patients in the TPN group and 17 patients in the PPN group received growth factor in the post-transplant period. Both groups did not differ with respect to sex, age, and reinfused CD34(+) cell numbers. RESULTS After transplantation body mass index and body weight decreased significantly in both groups (P < 0.001). Whereas serum albumin concentrations did not decrease significantly in the TPN group, it fell markedly in the PPN group at the end of parenteral nutrition (P = 0.019). After parenteral nutrition, blood chemistry was also remarkable for serum urea and glucose levels, which were elevated significantly in the TPN group (P < 0.001 and P = 0.03, respectively). Patients receiving TPN had a higher incidence of positive microbial cultures and clinical infection than did patients receiving PPN (64.5% versus 40%, P = 0.05). The most striking result was a delay in platelet engraftment for the TPN group compared with the PPN group (15.54 and 12.93 d, respectively; P = 0.014). This difference was also noted in patients using growth factor in the PPN group (P = 0.017). Parallel to these results, platelet transfusion requirement increased in the TPN group compared with the PPN group (1.93 versus 1.16 U, P = 0.004). Both groups were unremarkable for leukocyte recovery and red blood cell transfusion requirement. CONCLUSIONS Consequently, TPN has some pitfalls of hyperglycemia, infection tendency, delayed platelet engraftment, and increased platelet transfusion requirement. Therefore, it should not be used as a standard nutrition support for patients undergoing autotransplantation.

Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantation

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 μg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 μg/kg/day is equavalent to 10 μg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G‐CSF was given at 5 μg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G‐CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 μg/kg/day is as efficious as filgrastim 10 μg/kg/day for autologous PBSC mobilization and transplantation. Am. J. Hematol., 2008.

Effect of plateletpheresis on complete blood count values using three different cell separator systems in healthy donors

The aim of this study is to investigate changes of CBC values after plateletpheresis in healthy and volunteer donors by using three different cell separator systems. The platelets were collected from 95 donors using the COBE Spectra, from 87 donors using the Fenwal CS-3000 Plus, and from 83 donors using the Fresenius AS-204. After plateletpheresis, white blood cells (WBC), hemoglobin (HGB), hematocrit (HCT), and platelets (PLT) were decreased significantly. When we used the COBE Spectra, the drop in the values of HGB and HCT was significantly less than for the other devices. It is recommended that hematological parameters should be monitored carefully in donors who are supposed to undergo long-term regular apheresis, and to prevent the occurrence of an artificial anemia, which is likely to happen. Selection of cell separator systems should be based on this possibility.

Mononeuropathy multiplex in the course of idiopathic thrombocytopenic purpura a case report

We report the simultaneous occurrence of idiopathic thrombocytopenic purpura and mononeuropathy multiplex in a 21-year-old man. Electromyographic study revealed various axonal degenerative alterations in the right and left peroneal and right tibial nerves.

The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients.

Objective: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients. Materials and Methods: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. Results: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML. Conclusions: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings.

The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high-dose chemotherapy in patients with Stage III breast cancer

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34+ selection and high‐dose chemotherapy in patients with Stage III breast cancer. Fifty‐five patients were enrolled in this prospective cohort study. Whereas CD34+ positive selection was not carried out in the first group (unselected group, n:31), CD34+ positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high‐dose chemotherapy. CD34+ selection does not change survivals, but it may decrease the distant metastases. J. Clin. Apheresis 2009.

587 Plasmapheresis in a Patient with “Refractory” Urticarial Vasculitis

Background Immune complexes have been found in the circulation approximately 30 to 75% of patients with urticarial vasculitis and much evidence supports the role of these immune complexes in the pathogenesis of urticarial vasculitis. Plasmapheresis is effective in removal of these immune complexes. However, few cases have been reported regarding the use of plasmapheresis in the treatment of urticarial vasculitis. Methods A 35-year-old woman presented with history of recurrent episodes of generalized painful urticarial plaques often lasting 9 years associated with swelling of her parts of body. Examination revealed multiple urticarial plaques distributed all over the body (particularly in the extremities, palms and soles). The initial laboratory studies, including a complete blood count, thyroid function tests - thyroid autoantibodies, erythrocyte sedimentation rate, hepatitis markers, liver and renal function tests, urinary analysis, stool analysis for parasite ova, total IgE, C3, C4, C1q, CH50, C1 inhibitor levels and antinuclear antibodies were found to be within normal range. Skin prick tests were performed with commonly consumed foods in Turkey found to be negative. A biopsy from an affected area of skin revealed an urticarial vasculitis. Based on the biopsy results, the patient was diagnosed with UV. Treatment with H1/ H2-antihistamines and oral corticosteroids (1 mg/kg/day) had been unsuccessful; therefore hydroxychloroquine 400 mg/day was added. Unfortunately hydroxychloroquine was stopped in the second month due to the emergence of an adverse event (keratopathy). The patient underwent plasma exchange 2 times with an interval of 6 months. Five percent albumin solution as replacement fluid was used. One plasma volume was processed in each session. Apheresis procedure was performed with the “Cell Separator” device. The plasmapheresis procedures were completed without any adverse events. At 13 months after the plasmapheresis, the urticarial plaques were reappeared, but the severity and duration of symptoms were lower than before the plasmapheresis. The newly lesions were re-treated with short-term oral antihistamine regimen. Conclusions In conclusion, the presented report supports the usability of plasmapheresis in patients with “refractory” UV. Further clinical studies are needed to confirm our experience.

Increasing the target number of nucleated cells and administration of r-metHuG-CSF expedite neutrophil engraftment in allogeneic bone marrow transplantation.

SINCE 1960, allogeneic bone marrow transplantation (AlloBMT) has been instituted to treat various malignant or nonmalignant disorders. However, AlloBMT has being increasingly replaced by allogeneic peripheral blood stem cell transplantation (AlloPBSCT) over the past 10 years. As Gratwohl and colleagues reported, AlloPBSCT accounted for 30% of whole allogeneic hematopoietic stem cell transplantations (AlloHSCT) performed in European countries in 1997, whereas all AlloHSCT were bone marrow derived in 1991. Faster neutrophil and platelet engraftment and no risk of general anesthesia for donors seems to be the major reasons for this trend. To obtain faster neutrophil engraftment, and reduce morbidity from infections in the allogeneic bone marrow setting, and because of the relatively prolonged neutropenia compared to AlloPBSCT, G-CSF or GM-CSF have been successfully employed. However, the hematologic recovery provided by AlloBMT has always remained slower than that provided by AlloPBSCT. Lower infectious complications, rapid immunologic recovery, shorter hospitalization stay, and lower cost appear as other advantages of AlloPBSCT. Despite these advantages, AlloPBSCT has certain drawbacks. One of the most serious complication is the concern that AlloPBSCT is associated with an increased incidence and severity of chronic graft-versus-host disease (GVHD) as compared to AlloBMT. Furthermore, whether chronic GVHD decreases relapse rate due to graft-versus-leukemia (GVL) effect in patients undergoing AlloPBSCT remains to be determined. Standards for AlloBMT or AlloPBSCT have not yet been optimized. Therefore, some centers have sought to combine both modalities by giving bone marrow and peripheral blood stem cells. In this report, the results of patients undergoing AlloBMT in which the targeted nucleated cell count was 3 10/kg and in which r-metHuG-CSF was administered after the transplantation are presented. Of interest, our patients had fast neutrophil engraftment, low infectious complications, and an acceptable relapse rate, which are comparable to those in AlloPBSCT as reported in the literature. Chronic GVHD rate seems to be less than that in AlloPBSCT.

Facial paresis after fludarabine treatment for advanced chronic lymphocytic leukaemia.

This case report discusses a case with advanced-stage chronic lymphocytic leukaemia (CLL) that presented with facial paresis after fludarabine treatment. A 68-year old patient with CLL (Rai classification, stage IV) was admitted to Gülhane Military Medical Academy for treatment. Fludarabine, 30 mg/m2 daily for 5 days, was given. Right facial paresis was observed at day 8 after administration of fludarabine. The general and psychiatric condition of the patient in myelosuppression did not permit aetiological investigation for paresis. Thereafter, the patient died due to septic shock. Possible aetiological reasons why the patient being treated for advanced-stage CLL had facial paresis after the administration of fludarabine ended are discussed.

Does amphotericin B lipid complex (Abelcet ® ) affect haematological parameters erroneously?

Abelcet is composed of large particles which could be misinterpreted as blood cells on measurements with blood cell counters. The direct measurement of drug suspensions on blood cell counters has been performed in an in vitro study. In an ex vivo study, the haematological parameters were compared before and during Abelcet infusions. A significant interference effect was observed in platelet counts, together with minimal differences in the WBC, RBC, and Hb parameters in the in vitro study. In the ex vivo study, there were statistically significant deviations only in RBC counts and in haemoglobin (Hb) level, while there was no difference in the other parameters. It is been reported that the drug accumulates very rapidly in the reticuloendothelial system and circulates minimally in the plasma. That is why there is a significant deviation in the direct counting of platelets, while the platelet counts taken from the patients do not differ statistically.