Münci Yağcı

Acinetobacter baumannii infection in patients with hematologic malignancies in intensive care unit: Risk factors and impact on mortality ☆

PURPOSE We investigated the characteristics of Acinetobacter baumannii infection in critically ill patients with hematologic malignancies. MATERIALS AND METHODS The prospectively collected data of patients with hematologic malignancies admitted to a medical intensive care unit of a university hospital from 2007 through 2010 were reviewed retrospectively. RESULTS One hundred twenty-eight patients were included in the study, among whom 35 (27%) developed 39 A baumannii infections. Pneumonia was the most common infection site of A baumannii. Presence of neutropenia, underlying hematologic malignancy, and the disease status did not affect the acquisition of the infection. Advancing age, prior exposure to aminoglycosides, central venous catheterization, and presence of nasogastric tube were the independent risk factors for the development of A baumannii infections. The mortality rate was higher in patients with A baumannii infections compared with the ones without (P = .009). However, in multivariate analysis, low Glasgow coma scale, prior immunosuppressive treatment, neutropenia, invasive mechanical ventilation, and severe sepsis were independently associated with mortality, whereas presence of A baumannii infection was not. CONCLUSIONS Despite the high mortality rate in critically ill patients with hematologic malignancies, presence of A baumannii infection was not an independent risk factor for mortality.

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.

Iron Overload: Predictor of Adverse Outcome in Hematopoietic Stem Cell Transplantation

INTRODUCTION Iron overload is an important problem in candidates for and survivors of hematopoietic stem cell transplantation (HSCT), and affects long-term outcome and survival. The objective of the present study was to determine the effect of iron overload on early toxic or infectious complications and survival. PATIENTS AND METHODS We retrospectively reviewed the medical records for 250 adult patients (162 men and 88 women; median [range] age, 34 [16-71] years who underwent HSCT between September 2003 and August 2008. The HSCT grafts were autologous in 102 patients, and allogeneic in 148. RESULTS Follow-up was 315 (1-1809) days. Mean (SD) pre-HSCT serum ferritin concentration was 1402.6 (5016.2) ng/mL in the entire group, 647.6 (1204.3 ng/mL in autologous recipients, and 1410.6 (2410.4) ng/mL in allogeneic recipients. Twenty-eight autologous graft recipients (27.4%) and 102 allogeneic recipients (68.9%) demonstrated serum ferritin concentrations of 500 ng/mL or greater, and were classified as the high-ferritin group. High ferritin concentrations were significantly associated with toxic or infectious complications including mucositis, fungal infections, pneumonia, and sinusoidal obstruction syndrome in the early post-HSCT setting. A significant effect of pre-HSCT ferritin concentration on overall survival and transplant-related mortality was observed. The effect of pre-HSCT ferritin on survival was independent of the comorbidity index at Cox regression analysis. In the entire study population, the probability of survival was significantly lower when ferritin concentration was greater than 500 ng/mL. CONCLUSION Transplant-related mortality has decreased substantially with the development of supportive treatments. Pretransplantation risk assessment and risk-adapted strategies such as decreasing iron overload might further improve transplant-related complications.

Hepatitus B virus reactivation in HBV-DNA negative and positive patients with hematological malignancies

Abstract Reactivation of hepatitis B virus (HBV) is a frequent complication of chemotherapy (CT) in patients with HBsAg carriers. In this prospective study, we documented CT induced HBV reactivation risk in patients with hematological malignancies. HBV reactivation risk is influenced by baseline viral load. Therefore, we divided our study population into two groups according to HBV-DNA status. HBV-DNA negative patients (n=18) were treated with nucleoside analogues once HBV reactivation was observed. HBV-DNA positive patients (n=12) commenced lamivudine before the initiation of the CT. In HBV-DNA negative patients HBV reactivation was found in 10 patients (55·5%). HBV reactivation was significantly more frequent in chronic lymphocytic leukemia (CLL) patients (P=0·008) and in patients receiving rituximab containing chemotherapy regimens (P=0·06). Eight patients (80·0%) responded to antiviral treatment after HBV reactivation. Two CLL patients experienced a flare-up after the withdrawal of antiviral therapy. In HBV-DNA positive patients, HBV reactivation was observed in four patients (33·3%) during lamivudine treatment and in two patients after lamivudine withdrawal. This study demonstrated the increased risk of CT-induced HBV reactivation in CLL patients, for the first time.

Extranodal multifocal Rosai-Dorfman disease: response to 2-chlorodeoxyadenosine treatment

Rosai–Dorfman disease (RDD) or “sinus histiocytosis with massive lymphadenopathy” is a rare lymphoproliferative disorder of unknown etiology. The disease usually presents with painless lymphadenopathy with occasional extranodal involvement in various organs. We report a case of a 36-year-old man with a history of non-Hodgkin lymphoma (NHL), who recently presented with inguinal lymphadenopathy. Following the diagnosis of RDD on lymph node biopsy, he developed symptoms of spinal cord compression due to a mass lesion discovered at T6-7 vertebral level. 18F-Fluorodeoxyglucose (18FDG) positron emission tomography (PET-CT) revealed extensive disease with lung, renal and bone involvement. The patient received a short course of steroid therapy for cord compression findings and 2-chlorodeoxyadenosine (2-CdA) treatment was initiated for long-term disease control. He had a dramatic sustained response to treatment with six courses of 2-CdA. These results suggest that 2-CdA can be an effective treatment of choice and positron emission tomography with 18FDG can be used for determining the extent of disease and for follow-up in RDD.

Free light chain: a novel predictor of adverse outcome in chronic lymphocytic leukemia

Objectives: Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. This retrospective study is planned to assess the prognostic value of serum free light chain (sFLC) levels and FLC ratio (FLCR) in CLL. Methods: Quantitative levels of sFLC were measured nephelometrically in sera collected at diagnosis. The expressions of ZAP70 and CD38 were quantified by flow cytometry. Chromosomal abnormalities were determined by interphase fluorescence in situ hybridization (FISH). Results: In a cohort of 101 patients with a median follow‐up of 29 (1–234) months, sFLC levels were found to be high in 55 patients (54.5%). An abnormal FLCR was found in 30 patients (29.7%). FISH‐based genetic risk groups did not differ significantly with respect to sFLC and FLCR (P > 0.05). Median time to first treatment was shorter in patients with high sFLC levels (P = 0.02). Median overall survival (OS) was shorter in patients with high sFLC levels (P = 0.01) and abnormal FLCR (P = 0.05). In patients with early stage disease, median OS was shorter in high sFLC (P = 0.03) and abnormal FLCR groups (P = 0.048). A relationship was observed between abnormal sFLC levels and CD38 positivity on logistic regression analysis (P = 0.003; OR: 4.44; 95% CI: 1.66–11.8). Conclusions: This study highlighted the adverse prognostic impact of high sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage patients. Prospective studies are warranted to validate the adverse impact of sFLC and FLCR on clinical outcome.

Miller-Fisher syndrome associated with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy, with meningeal or peripheral nerve infiltrations being the most commonly encountered neurological complications. In this report, we describe a CLL patient with Miller-Fisher syndrome (MFS) who responded to immune modulation with plasmapheresis. A 47-year-old man diagnosed as B-cell CLL admitted with neutropenic fever. He complained of diplopia and numbness of both arms. Neurological examination revealed a bilateral external ophthalmoplegia, dysphagia, dysarthria, mild shoulder girdle muscle weakness and gait ataxia, accompanied by absent tendon reflexes. Nerve conduction studies were indicative of a predominantly axonal sensori-motor peripheral neuropathy. This association of CLL with MFS had not been previously reported in the literature.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

Abnormal protein bands in patients with multiple myeloma after haematopoietic stem cell transplantation: does it have a prognostic significance?

Abnormal protein bands (APB) unrelated to the original monoclonal protein occasionally appear in serum immunofixation samples from patients with multiple myeloma (MM) following haematopoietic stem cell transplantation (HCT). To investigate the significance of APB, medical records and serum immunofixation patterns of 53 MM patients, who had undergone HCT (49 autologous and 4 allogeneic) at the stem cell transplantation unit of Gazi University Faculty of Medicine, were reviewed. Patients were staged according to Durie–Salmon and International staging systems (ISS) and disease response was determined according to European Bone Marrow Transplantation (EBMT) criteria. Fourteen (26.4%) of the 53 patients developed APBs after HCT. The median time for the appearance and duration of APB was 3 (range 1–24) and 5.5 (range 1.5–14) months, respectively. Probability of overall survival (OS) at the end of the follow‐up was 77 and 61.4% in patients with and without APB, respectively (p = 0.334). The median duration of follow‐up (767 days (range, 220–2905) vs. 726 days (range, 120–1780) p = 0.545) was not different in patients with and without APB. Probability of progression free survival (PFS) at the end of follow‐up was 28.8% in patients with and 27.7% in patients without APB (p = 0.835). PFS (910 days (range 180–2905) vs. 730 days (range 90–1765) p = 0.835) was longer in patients with APB, though without statistical significance. Thus, the occurrence of APB post‐transplantation is not associated with any adverse long‐term consequences and does not require treatment modification. Copyright

High ferritin levels are associated with hepatosplenic candidiasis in hematopoietic stem cell transplant candidates

OBJECTIVES Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders. METHODS The charts of 255 patients (male/female 168/87; median age 35 (range 16-71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed. RESULTS HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two (p>0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization (p=0.001) and Karnofsky scale (p=0.007). Pre-transplantation ferritin (p=0.008) and acute phase reactant levels, including erythrocyte sedimentation rate (p=0.025) and C-reactive protein (p=0.007), were significantly higher in patients with HSC than in patients without HSC. CONCLUSIONS This study shows the predictive role of pre-transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients.