Sahika Zeynep Aki

The role of liver biopsy in the workup of liver dysfunction late after SCT: is the role of iron overload underestimated?

Abnormalities in liver function tests are common in hematopoietic SCT (HSCT) recipients. We retrospectively investigated the role of liver biopsy in determining the cause of elevated liver enzymes and its impact on the management of patients in the post-HSCT setting. A total of 24 consecutive liver biopsies were obtained from 20 patients from September 2003 to December 2007. A definite histopathologic diagnosis was obtained in 91.7% of the biopsies. Iron overload (IO) was found in 75% and GVHD in 54.2% of the patients. The initial clinical diagnosis of GVHD was confirmed in 56.5% and refuted in 43.5% of the allogeneic HSCT recipients. The median number of post transplant transfusions, percent transferrin saturation and ferritin levels were found to be higher in patients who had histologically proven hepatic IO (p1=0.007, p2=0.003 and p3=0.009, respectively). Regression analysis showed a significant correlation between serum ferritin levels and histological grade of iron in the hepatocytes. Our data suggest that hepatic IO is a frequent finding in the post-HSCT setting, which contributes to hepatic dysfunction and it should be considered in the differential diagnosis, particularly in patients with high serum ferritin levels.

Risk factors for fungal pulmonary infections in hematopoietic stem cell transplantation recipients: the role of iron overload

Fungal pulmonary infections (FPIs) are frequent causes of mortality in hematopoietic stem cell transplantation (HSCT) recipients. Determination of the specific risk factors may improve the prognosis. The aim of this study was to evaluate the risk factors of FPIs due to HSCT. Patient history, physical examination, chest X-rays and the consultation records of the pulmonary disease department which were a part of the routine evaluation before and at first, third, sixth, ninth and twelfth months of HSCT were retrieved in 148 adult HSCT recipients. Results of the high-resolution computed tomography, fiber-optic bronchoscopy and the microbiological data were also included. FPI was diagnosed in 22 patients (14.9%). Multivariate analysis showed that increased ferritin levels (>1000 ng/ml; OR: 3.42, 95% CI 1.03–11.42, P=0.045) and the development of sinusoidal obstruction syndrome (SOS; OR: 5.09, 95% CI 1.53–16.90, P=0.008) were significant risk factors for FPIs. The sensitivity and specificity of ferritin >1000 ng/ml for the prediction of FPIs were 67 and 70%, respectively. There was a positive correlation between the increased risk of FPIs and pretransplantation ferritin levels (r=0.413, P<0.001) and increased ferritin levels and SOS (r=0.331, P<0.001). Increased pretransplantation ferritin levels and development of SOS are predictive factors of FPIs during HSCT.

Impact of ABO-Incompatible Donor on Early and Late Outcome of Hematopoietic Stem Cell Transplantation

ABO incompatibility is not a barrier to allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of an ABO mismatch on the outcome of the HSCT remains controversial. We analyzed whether ABO incompatibility leads to an increased risk of early/late complications, mortality, or increased transfusion requirements. The 147 consecutive allogeneic HSCTs includes 80 ABO-identical and 25 major, 30 minor, and 12 bidirectional ABO-mismatched grafts. The four groups were balanced with respect to disease status at transplantation. Transplantation-related mortality was significantly greater (P < .01) and overall survival significantly shorter (P = 0.2) among HSCT recipients with minor ABO-mismatched grafts. The relapse rate, progression-free survival, and transfusion requirements until discharge were not different between ABO-identical and ABO-mismatched groups. Pure red cell aplasia (PRCA); (P < .0001) and delayed red blood cell (RBC) engraftment (P < .001) were more frequent in HSCT recipients with major mismatched donors. Delayed RBC engraftment was associated with posttransplantation hyperferritininemia and increased mortality risk (P = .05). The greater frequency of sinusoidal obstruction syndrome and graft-versus-host disease (GVHD) in patients with minor mismatched transplants, did not show statistical significance. In contrast severe GVHD was significantly more frequent among minor mismatched patients (P = .04). ABO-mismatched HSCT might have an unfavorable impact on transplant outcomes. Selection of ABO-compatible donors when possible, strategies to prevent and treat PRCA, modifications in transfusion practice, and effective iron chelation are among the measures that can improve transplant outcomes.

The positive impact of regular exercise program on stem cell mobilization prior to autologous stem cell transplantation

AIM The present study was planned to determine the effects of regular exercise program on hematopoietic stem cell (HSC) mobilization prior to autologous stem cell transplantation. METHOD Twenty-two consecutive patients were enrolled in the study. A regular 20 min exercise program was administered to the patients. The hematopoietic stem cell mobilization outcome, number of Granulocyte Colony-Stimulating Factor (G-CSF) and aphaeresis application days were compared with 20 case-matched controls who did not receive exercise program during HSC mobilization. RESULTS The median number of CD34(+) stem cells collected in the exercise and control groups were 8.15 × 10(6)/kg (range: 2.85-33.06 × 10(6)/kg) and 7.3 × 10(6)/kg (range: 1.78-25.9 × 10(6)/kg), respectively (p=0.696). G-CSF was administered for a median of 8 days (range, 5-10) in the exercise group and 8 days (range, 5-12) in the control group (p=0.848). The median apheresis duration was 1 day (range, 1-3) in both exercise and control groups (p=0.226). CONCLUSION Exercise seems to have a positive impact on stem cell mobilization though without statistical significance.

Cytarabine induced noncardiogenic pulmonary edema in a case of acute lymphoblastic leukemia

Sir, noncardiogenic pulmonary edema (NCPE) is a serious complication of high-dose cytarabine (HDC) treatment, which has become a popular treatment option for acute leukemia (Andersson et al., 1990). Here, we present a case of acute lymphoblastic leukemia (ALL), who developed acute respiratory failure because of HDC and responded to steroid therapy. A 17-year-old female patient was diagnosed as precursor B ALL. HYPER CVAD regimen, consisting of cyclophosphamide and mesna 600 mg/m/daily on day 1, 2, and 3; vincristine 2 mg/daily on day 4 and 11; doxorubicine 50 mg/m/daily on day 4; dexamethasone 40 mg/ daily on day 1–4 and 11–14, was commenced and the patient achieved complete hematologic remission. Consolidation chemotherapy was instituted with methotrexate 1000 mg/m/daily on day 1, cytarabine 3000 mg/m/ twice a day on day 2 and 3, methyl prednisolone 100 mg/daily on day 1–3 and granulocyte colony stimulating factor (G-CSF) 5 lg/kg/daily starting on day 5. Cytarabine was infused over 2 h. On the fourth day of the HDC infusion, the patient developed fever, dyspnea, and diarrhea. Chest radiogram yielded bilateral alveolar infiltrates (Figure 1). A high resolution computed tomography showed bilateral pleural effusion with diffuse ground-glass opacities (Figure 2). Echocardiogram was normal and there was no pericardial effusion. Empirical i.v. antibiotic therapy was administered as it was difficult to rule out infection in the setting of severe neutropenia. In 12-h time, the patient required mechanic ventilation support because of worsening hypoxemia. As there were co exisiting peripheral edema, weight gain, and hypoalbuminemia, diuretics with albumin replacement therapy and prednisolone 1 mg/kg/day were given with the consideration of chemotherapy-induced NCPE. Hypoxemia LETTER TO THE EDITOR INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY

Evaluation of 143 cases of immune thrombocytopenic purpura with regards to clinical course and response to treatment.

OBJECTIVE Immune thrombocytopenic purpura (ITP) is also known as idiopathic thrombocytopenic purpura. Increased platelet destruction and insufficient platelet production are both responsible for its etiopathogenesis. ITP can be diagnosed after excluding other possible causes of thrombocytopenia. MATERIALS AND METHODS One hundred forty-three cases of chronic ITP that were monitored in a hematology clinic were retrospectively evaluated. All cases received first line treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases and corticosteroid-dependent (CD) cases underwent splenectomies. RESULTS The rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41, including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter pylori (Hp) eradication, immunosuppressive agents and danazol treatments were administered to patients (n=10, n=14 and n=4, respectively). Currently, 13 patients are being monitored without treatment. Fifteen patients who were non-responsive to Hp eradication treatment, immunosuppressive treatment or danazol treatment are still being monitored without any treatment. CONCLUSION Optimal treatment is not available for splenectomy-resistant cases of ITP. The response rates for Hp eradication treatment, immunosuppressive treatments and anabolic agents are low. Therefore, larger studies with more patients are required using new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20 monoclonal antibodies.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients

OBJECTIVES Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

Maximal exercise capacity and quality of life in allogeneic hematopoietic stem cell transplantation recipients

Introduction: Deterioration in muscle strength, exercise capacity and quality of life (QOL) may result from chemotherapy, radiotherapy, corticosteroids use before hematopoietic stem cell transplantation (HSCT) and transplantation itself. Limited number of study investigated dyspnea, pulmonary functions, maximal exercise capacity and QOL in allogeneic HSCT recipients. Aim: To compare dyspnea, pulmonary functions, maximal exercise capacity and QOL in allo-HSCT recipients with healthy controls. Methods: Fifty-one recipients (post-transplantation˃100 days) (38.26±13.78y, 18F) and 52 controls (34.73±11.07y, 22F) were compared. Dyspnea [Modified Medical Research Council Dyspnea Scale (MMRC)], pulmonary functions (spirometry), maximal exercise capacity [Modified Incremental Shuttle Walk Test (ISWT)] and QOL [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTCQLQ-C30version 3.0)] were evaluated. Results: Symptom and fatigue subscales of EORTCQLQ (p 0.05). Discussion: Dyspnea in daily activities, decreased maximal exercise capacity, poorer QOL and prominent fatigue are prevalent in survived allo-HSCT recipients, even though the recipients have normal lung functions. Routine evaluations of these outcomes and pulmonary rehabilitation especially exercise training are crucial for allo-HSCT recipients.

Acute physiological responses to physiotherapy applications pre and post autologous stem cell transplantation: an experimental study

Abstract Objective We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR. Methods Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT. Results Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT. Conclusion There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning.

Lamivudine therapy in acute leukemia patients who are hepatitis B surface antigen carriers.

Abstract Background: Reactivation of hepatitis B in patients receiving chemotherapy for acute leukemia may give rise to a variety of clinical patterns including hepatitis, asymtomatic hepatic dysfunction, massive hepatic necrosis and fatal hepatic failure. Lamivudine is a nucleoside analogue which can directly suppress Hepatitis B virus (HBV) replication. We reviewed our combined experience to evaluate the role of lamivudine as prophylaxis in acute leukemia patients who were HBsAg carriers treated with chemotherapy between July 2000 and October 2002 at the Numune Education and Research Hospitals (Ankara, Turkey) retrospectively. Methods: We investigated 75 acute leukemia patients who received chemotherapy. Thirteen (17.3%) of 75 acute leukemia patients were HbsAg positive and of 7 (53.3%) were HBV DNA positive. Two patients (patients 5 and 6) had a chemotherapy regimen that included corticosteroids and were HBsAg and HBV DNA negative but anti HBc total positive. HBsAg positive patients with or without HBV DNA positivity were treated with a dose of 100 mg/day lamivudine commencing when chemotherapy was initiated. Lamivudine started at the beginning of chemotherapy and was maintained for 6 months following the cessation of chemotherapy. During lamivudine treatment, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gama glutamile transpeptidase (GGT), Alkaline phosphatase (ALP) were followed. Results: Of the 8 patients who presented with hepatic dysfunction during the first chemotherapy cycle, 4 improved during the second course. After completing chemotherapy, the levels of hepatic enzymes were in the normal range in all but one patient. With lamivudune prophylaxis, HBV DNA positivity did not develop in any of the HBV DNA negative patients. The two patients who received corticosteroids with their first chemotherapy cycle became positive for HBsAg and HBV DNA and were given Lamivudine when the seroconversion was established. Median follow up from the diagnosis of leukemia was 14.5 months. Survival rate at the end of follow up was 5 (38%) for the 13 patients. Conclusions: As this infection is endemic in our country and the exposure to blood products is high in these patients, HBV infection is more common. Prophylaxis with daily administration of lamivudine to HBsAg carriers who are candidates for chemotherapy seems to be effective and may prevent chemotherapy induced HBV reactivation and hepatic failure.