Fatih Kurnaz

Pretransplant iron overload may be associated with increased risk of invasive fungal pneumonia (IFP) in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT)

Invasive fungal pneumonia (IFP) has become increasingly common in patients that previously underwent alloHSCT. The aim of this study was to determine the role of hyperferritinemia, via iron overload in invasive fungal pneumonia in patients that underwent alloHSCT. Medical records of 73 patients with pneumonia that underwent alloHSCT were studied retrospectively, whereby a pre-transplantation serum ferritin level measured up to 100 days prior to transplantation of patients with invasive fungal pneumonia (IFP) and non-fungal pneumonia (non-IFP) was compared. Patient records revealed 35 and 38 cases of IFP and non-IFP, respectively. In risk evaluation for IFP, age, gender, HLA status, conditioning regimen, smoking history, and underlying disease were not significantly different among groups (p>0.05). However, performance status (Karnofsky) was significantly lower in patients with IFP (p<0.05). The median ferritin levels were 1,705 ng/ml (41-7198) in the IFP group and 845 ng/ml (18-7099) in non-IFP group and the difference was found statistically significant (p=0.001). Elevated pretransplant serum ferritin level is associated with IFP in patients that underwent alloHSCT, in particular when values exceed 1550 ng/ml.

Contribution of involved-field radiotherapy to survival in patients with relapsed or refractory Hodgkin lymphoma undergoing autologous stem cell transplantation.

Objectives:To assess the outcomes of overall survival and posttransplantation survival in patients with Hodgkin lymphoma (HL) undergoing autologous stem cell transplantation (ASCT) because of the development of relapse or resistance after chemotherapy (CT) or CT plus radiotherapy (combined modality treatment, CMT). Methods:Forty-five patients undergoing ASCT because of the development of relapse or resistance after CT or CMT for HL were enrolled in the study. Radiotherapy was given as involved-field radiotherapy. Patients were treated with CT alone (n=25) or CMT (n=20). These 2 groups were further divided into 2 subgroups: the patients with early-stage (I to II) and advanced-stage (III to IV) HL. Results:Median patients age was 29 years (range, 16 to 60 y) and the median follow-up was 60 months (range, 12 to 172 mo). In the patients with advanced-stage HL, there was no statistically significant difference in overall survival between irradiated and nonirradiated patients (n=18, irradiated n=4 and nonirradiated n=14). However, in the patients with early-stage disease, there was a significant difference in 5- and 10-year overall survival between the irradiated and nonirradiated groups (81% vs. 48% and 66% vs. 24%, respectively, P=0.045; n=26, irradiated n=16 and nonirradiated n=10). In the univariate analysis, irradiated group and involvement of 1 to 2 nodal regions were found to be significant for overall survival, whereas irradiated group, early stage, and involvement of 1 to 2 nodal regions were found to be significant for posttransplantation survival. However, only irradiated group was found to be significant for posttransplantation survival in multivariate analysis (P<0.05). Conclusions:Addition of involved-field radiotherapy to CT in patients undergoing ASCT after relapse or recurrence failed to provide survival benefit in patients with advanced HL, while a survival benefit was observed in patients with early-stage HL. Radiotherapy should be considered as part of CMT in the patients with early-stage HL, which should not be neglected.

The impact of pretransplant hypoalbuminemia on survival in patients with leukemia who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT): a nutritional problem?

OBJECTIVE Serum albumin level is considered to be a marker reflecting the nutritional status in both healthy subjects and patients with malignancies. In this study we sought to investigate the association between pretransplantation serum albumin levels and prognosis among patients with leukemia who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS We retrospectively analyzed the data of 102 patients who underwent alloHSCT from 2004 to 2010. Pretransplant serum albumin, D-dimer, creatinine, and fibrinogen levels drawn within 10 days before transplantation were obtained from patient files. All parameters were divided into 2 groups: normal levels (group 1) versus abnormal levels (group 2). Our normal range of serum albumin is 3.2-5.2 g/dL; patients with pretransplantation albumin level ≥3.2 g/dL were included in group 1 versus group 2 with <3.2 g/dL. RESULTS The patients included 42 (41.1%) female and 60 (58.9%) male patients. The diagnoses were acute myeloblastic leukemia in 65 (63.7%) and acute lymphoblastic leukemia in 37 (36.3%). The median age was 26.0 years (range, 13-57). Univariate and multivariate analysis showed that patients with serum albumin levels <3.2 g/dL experienced significantly lower overall survival (OS) compared with ≥3.2 g/dL (hazard ratio [HR] 2.32 [range, 1.23-4.54] and HR 2.70 [range 1.38-5.26], respectively; P = .009). The median (range) OS in group 2 was 230.0 (184.0-544.0) days versus 570.5 (249.5-1,101.0) days in group 1 (P = .007). For disease free survival (DFS) evaluation, univariate and multivariate analysis showed that patients with serum albumin levels <3.2 g/dL had significantly lower values compared with patients with serum albumin ≥3.2 g/dL. (HR 2.17 [range 0.98-4.76] and HR 2.85 [range, 1.25-6.66], respectively; P = .046). The median (range) DFS in group 2 was 184.0 (61.0-524.0) days versus 445.0 (199.0-917.5) days in group 1 (P = .045). Among the patient characteristics the presence of infection was a significant independent variable for worse OS (HR 2.12 [range, 0.98-4.36], P = .036). The other parameters-age, sex, donor status, time to transplant interval, conditioning regimens, HLA status, and number of total infused CD34(+) cells-showed no significant effect on OS and DFS (P = .05). CONCLUSIONS Pretransplantation decreased serum albumin levels were associated with poor survival in patients with leukemia who underwent alloHSCT.

Is Season a Prognostic Factor in Breast Cancer

BACKGROUND Some studies have indicated an inverse relationship between cancer risk and sunlight exposure. Others have reported that the prognosis of some cancers such as prostate, colon, ovarian and non melanoma skin cancer, were affected by the season in which the cancer was diagnosed. In our study, we evaluated whether season is prognostic in Turkish patients with breast cancer. MATERIALS AND METHODS A total of 517 patients from Kayseri Training and Research Hospital were analysed retrospectively. Patients were divided into 4 groups according to season of cancer diagnosis: winter, spring, summer and autumn. The prognostic factors for disease free survival and overall survival were investigated. RESULTS No significant differences were found among groups regarding prognostic factors overall. Only estrogen receptor status and lymphovascular invasion were independent prognostic factors (p=0.001 and p=0.001 respectively). We found significantly differences for mean disease free survival among groups (p=0.019). Winter group had better mean DFS while summer group had worse DFS. Mean overall survival was similar in the four groups (p=0.637). CONCLUSIONS The season is not an independent predictive factor. However, due to interaction with other factors, we think that the season of cancer diagnosis is important for cancer prognosis.

A case of Crimean-Congo haemorrhagic fever successfully treated with therapeutic plasma exchange and ribavirin.

Crimean-Congo haemorrhagic fever (CCHF) has become an important problem in certain parts of the world. Cytokine storm plays a critical role in the pathogenesis of CCHF. Early diagnosis, supportive therapy and invasive monitoring are the cornerstones of the management of CCHF. Ribavirin is active against CCHF virus in vitro, however, evidence of clinical efficacy is still conflicting. Here, we describe a patient successfully recovered from CCHF with a combination of plasma exchange and ribavirin therapy.

Peripheral blood stem cell mobilization failure.

Autologous hematopoietic stem cell transplantation (HSCT) is an important and often life saving treatment for many hematological malignancies and selected solid tumors. To rescue hematopoiesis after high-dose chemotherapy in autologous HSCT depends on maintaining sufficient stem cells. Hematopoietic stem cells and progenitor cells expressing CD34 in the BM are mobilized into the circulation with granulocyte-colony stimulating factor ± chemotherapy prior to autologous HSCT. One of the most important factors for success of autologous HSCT is hematopoietic stem cell (HSC) count. Minimum threshold for the engraftment of hematopoietic cells is accepted as 2 × 10(6) CD34 + cells/kg especially for platelet engraftment. Below this level it is defined as stem cell mobilization failure. There are several factors affecting stem cell mobilization: prior chemotherapy (such as fludarabine, melphalan, lenalidomide) and radiotherapy, age, type of disease, bone marrow cellularity. We tried to summarize the reasons of peripheral stem cell mobilization failure.

Encephalitozoon intestinalis: A Rare Cause of Diarrhea in an Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipient Complicated by Albendazole-Related Hepatotoxicity.

A 50-year-old male patient previously diagnosed with acute myelomonocytic (M4) leukemia in July 2009 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the pre-transplant period complete blood count (CBC), liver and renal function tests, coagulation tests, and other parameters were normal. On the first day of transplantation teicoplanin (400 mg d–1 for the first 3 d, and then 400 mg d-1) and caspofungin (first dose was 1×70 mg d–1, followed by 1×50 mg d–1) were started intravenously due to white plaques and oropharyngeal candidiasis in the patient’s mouth and perianal erythema. On the 14th d of transplantation watery diarrhea occurred, along with abdominal discomfort, nausea, and fatigue. Stool examination was negative for findings of bleeding. Investigation of Microsporidia confirmed a rare pathogen Encephalitozoon intestinalis in the patient’s stool sample via species-specific immunofluorescence antibody (IFA) assay and albendazole treatment was started at a dose of 2×400 mg d–1. On the 5th d of albendazole treatment (d 18 of treatment) liver function test (LFT) results began to deteriorate. As LFT results continued to deteriorate, albendazole was withdrawn on the 7th d of treatment. Biopsy was performed on the 22nd d of transplantation and histopathological analysis confirmed the diagnosis of toxic hepatitis. LFT results began to decrease after withdrawal of albendazole treatment. On the 13th d of albendazole treatment all LFT values returned to normal. The presented allo-HSCT case had a rare pathogenic agent (E. intestinalis) that caused diarrhea, as well as hepatotoxicity due to albendazole treatment. This is the first reported case of E. intestinalis diagnosed via IFA in Turkey. Conflict of interest:None declared.

Can low-dose preemptive valganciclovir replace standard intravenous ganciclovir treatment in recipients of allogeneic stem cell transplantation?

Abstract The aim of this retrospective study was to compare the efficacy and safety of standard intravenous ganciclovir (GCV) with low-dose oral valganciclovir (VGC) in preemptive treatment of cytomegalovirus (CMV) infection in patients who received allogeneic stem cell transplantation (ASCT). Fifty-nine adult ASCT patients with asymptomatic 68 CMV reactivations were included. For preemptive CMV treatment, VGC (900 mg/day) in 44 reactivations or GCV (5 mg/kg twice daily during the first week and once daily afterwards) in 24 CMV reactivations were administered for 21 days. Two consecutive negative results for PCR and/or CMV antigenemia were considered as treatment success. All patients with CMV reactivations were on immunosuppressive treatment. While no positivity was identified in any of the patients who received GCV on day 21, low-titer CMV positivity was noted in three of the patients in the VGC group (P  =  0·264). In all three patients, VGC was continued at same dose and no positivity result was detected after 2–3 weeks. Low-grade neutropenia and high grade thrombocytopenia were significantly higher in the GCV group than in the VGC group (P  =  0·018 and P  =  0·04 respectively). Preemptive strategy of oral low-dose VGC appears preferable to the prevention of CMV disease in ASCT. These results require confirmation in prospective larger clinical studies.

Comparison of chemotherapy and hematopoietic stem cell transplantation pre and postterm DMFT scores: a preliminary study.

AIMS Chemotherapy is frequently used as a conditioning regimen to destroy malignant marrow cells before transplantation. Xerostomia, dysphagia, altered taste perception, mucositis, soft-tissue ulceration, and infection are common adverse oral effects of chemotherapy. The study was aimed to compare decayed, missing, filled teeth (DMFT) scores before and after hematopoietic stem cell transplantation (HSCT) and chemotherapy. MATERIALS AND METHODS Thirty-six patients undergoing HSCT were included in the study. A pre-HSCT dental treatment protocol was implemented that consisted of restoration of all active carious lesions, treatment of periodontal infections, and extraction of all teeth with advanced periodontal disease. Upon completion of dental treatment, the importance of rigorous and effective oral hygiene was reemphasized, and patients were recalled 6 months later. DMFT scores were calculated prior to the initiation of HSCT treatment and 6 months after transplantation. STATISTICAL ANALYSIS USED Regression analysis was used to evaluate the effects of HSCT and chemotherapy on DMFT scores. RESULTS Wilcoxon T test showed a statistically significant difference in DMFT scores before and after HSCT ( P < 0.001). CONCLUSIONS DMFT scores were found to increase after chemotherapy and HSCT, suggesting that the risk of infection is higher among HSCT patients when compared to other individuals. The results emphasize the need for dental examinations as an integral part of examination and treatment planning for patients undergoing HSCT and chemotherapy.

Diarrhea in peripheral stem cell transplant recipients: a developing country's experience

INTRODUCTION We aimed to determine the frequency and microbiological causes of diarrhea occurring during the first 100 days in allogeneic (allo-) and autologous (auto-) stem cell transplantation (SCT) patients. METHODOLOGY A total of 452 patients who underwent transplantation due to hematological or solid organ malignancy were included. From the administration of the conditioning regimen up to day 100 post-transplant, diarrhea cases lasting at least three days with a minimum of three episodes per day were evaluated. RESULTS Cases of diarrhea were observed in 94 patients out of 227 subjects who received allo-SCT and in 107 patients out of 225 who received auto-SCT. The incidence rate of diarrhea in both patients undergoing autologous and allogeneic transplant was 47.5% and 41.4%, respectively. The cause of the diarrhea could be detected in 20.5% of auto-SCT patients and in 30.8% of allo-SCT patients. Parasitic infections were frequently observed in both autologous and allogeneic transplant patients in the first 20 days. In the late period, significantly more patients developed diarrhea in the allo-SCT recipient group than in the auto-SCT recipients due to graft versus host disease (GVHD) and cytomegalovirus (CMV) colitis. CONCLUSIONS This study revealed the causes of diarrhea and the prevalence and factors of parasitic infections in transplant patients in Turkey. All causative factors of diarrhea should be considered in detail, feces analyses should be evaluated for each patient, and endoscopic biopsy samples should be obtained when required in immunosuppressive patients undergoing stem cell transplantation.