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1.  Use of Healthy-Donor Granulocyte Transfusions to Treat Infections in Neutropenic Patients with Myeloid or Lymphoid Neoplasms: Experience in 74 Patients Treated with 373 Granulocyte Transfusions 
Acta haematologica  2013;131(1):50-58.
Despite limited evidence for efficacy, granulocyte transfusions (GTX) are used to prevent and treat opportunistic infections in patients with neutropenia.
Three hundred and seventy three GTX given to 74 patients were assessed retrospectively.
GTX were discontinued because of clinical improvement more often in patients with severe infections than in patients without severe infections (27% vs. 12%; P≤ 0.002), whereas deaths resulted in discontinuation of GTX therapy less often in patients with severe infections than without (8% vs. 39%; P≤0.002). Patients who died by 12 weeks after beginning GTX were more likely to have leukemia (P=0.03), not to have recovery of neutrophil counts (P<0.0001), and to have started GTX during a critical care unit stay (P<0.001). Uses of granulocyte colony-stimulating factor (P≤0.02) and interferon-γ (P≤0.04) were more common in patients who survived. Patients with comorbidities (31%) (Odds ratio [OR] 12.6; 95% confidence interval [CI] 2.4, 65.7; P≤0.003), GTX started in critical care unit (OR 8.8; 95% CI 2.5, 30.9; P <0.001) and high total bilirubin level at the end of GTX (OR 2.1; 95% CI 1.1, 4.2; P = 0.03) had a higher probability of death 12 weeks after GTX were commenced.
The possibility that a niche population may benefit from GTX requires further assessment.
PMCID: PMC4221098  PMID: 24051981
Granulocyte transfusions; life-threatening infections; leukemia; immunosuppression; toxicity; infection-attributed deaths
2.  Aplastic Anemia in Adolescents and Young Adults 
Acta haematologica  2014;132(0):331-339.
Adolescent and young adult patient presentations of aplastic anemia require a particular perspective on both diagnosis and treatment. This unique age group necessitates a thorough diagnostic evaluation to ensure the etiology, acquired or inherited, is sufficiently determined. The treatment options include human leukocyte antigen-identical sibling hematopoietic cell transplantation or immunosuppressive therapy, and both require attention to the specific medical and social needs of these adolescents and young adults. Longitudinal surveillance throughout life for the development of late complications of the disease and treatment is mandatory.
PMCID: PMC4183226  PMID: 25228559
Aplastic anemia; Bone marrow failure; Adolescent; Hematopoietic cell transplant; Immunosuppressive therapy
3.  Granulocyte Macrophage Colony-Stimulating Factor in 66 Patients with Myeloid or Lymphoid Neoplasms and Recipients of Hematopoietic Stem Cell Transplantation with Invasive Fungal Disease 
Acta haematologica  2012;129(1):26-34.
Adding granulocyte macrophage colony-stimulating factor (GM-CSF) may improve the response to antifungal therapy in immunosuppressed patients with invasive fungal disease (IFD).
We retrospectively assessed 66 patients in whom GM-CSF was given during antifungal therapy.
Severe neutropenia (77%) and refractory/relapsed cancer (65%) were common in the group. Prior to GM-CSF therapy, 15% of patients received high-dose corticosteroids for a median of 30 ± 16 days (median cumulative dose [c.d.], 1184 ± 1019 mg), and 9 received steroids during GM-CSF therapy for a median of 16 ± 12 days (median c.d., 230 ± 1314 mg). Mild toxic effects were noted in 9% of patients; there were no cases of cardiopulmonary toxicity. All cause deaths were observed in 68% and 48% of patients died of progressive IFD. High-dose corticosteroids prior to GM-CSF (OR, 24; 95% CI, 2.21–264.9; P ≤ 0.009), GM-CSF started in the intensive care unit (OR, 10; 95% CI, 1.66–63.8; P ≤ 0.01), concurrent granulocyte transfusions (OR, 5; 95% CI, 1.27–16.8; P ≤ 0.02), and proven/probable IFD (OR, 4; 95% CI, 1–16.2; P ≤ 0.05) predicted antifungal treatment failure.
GM-CSF adjuvant therapy was tolerated without serous toxicity and antifungal treatment failure remained a challenge in patients treated with high-dose systemic corticosteroids.
PMCID: PMC3622475  PMID: 23038157
invasive fungal disease; granulocyte macrophage colony-stimulating factor; stem cell transplant; leukemia; combination antifungal agents; immune suppression
4.  Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral? 
Acta haematologica  2012;128(2):10.1159/000337344.
There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism.
PMCID: PMC3864664  PMID: 22678347
Ferritin; Hemoglobinopathy; Hypogonadism; Testosterone
5.  Familial Aggregation of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia with Solid Tumors and Myeloid Malignancies 
Acta Haematologica  2012;127(3):173-177.
Lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3–4 cases per million people per year. Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients.
PMCID: PMC3326274  PMID: 22310551
Autoimmunity; Familial aggregation; Hematological malignancies; Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia; Monoclonal gammopathy of undetermined significance; Solid tumors; Susceptibility
6.  Disseminated Strongyloides stercoralis Infection in HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma 
Acta Haematologica  2011;126(2):63-67.
A 55-year-old woman with human T-cell lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL) and a history of previously treated Strongyloides stercoralis infection received anti-CD52 monoclonal antibody therapy with alemtuzumab on a clinical trial. After an initial response, she developed ocular involvement by ATL. Alemtuzumab was stopped and high-dose corticosteroid therapy was started to palliate her ocular symptoms. Ten days later, the patient developed diarrhea, vomiting, fever, cough, skin rash, and a deteriorating mental status. She was diagnosed with disseminated S. stercoralis. Corticosteroids were discontinued and the patient received anthelmintic therapy with ivermectin and albendazole with complete clinical recovery.
PMCID: PMC3080579  PMID: 21474923
Adult T-cell leukemia; Alemtuzumab; Corticosteroid; Disseminated Strongyloides; HTLV-1; Human T-cell lymphotropic virus type-1
7.  Plasma Glial Fibrillary Acidic Protein Levels in a Child with Sickle Cell Disease and Stroke 
Acta Haematologica  2010;125(3):103-106.
A 12-year-old boy with HbSS sickle cell disease (SCD) was admitted with an acute febrile illness and developed overt stroke 3 days later. Plasma glial fibrillary acidic protein levels were elevated, as compared to pediatric controls, 32 h prior to the clinical diagnosis of stroke, peaked immediately prior to the exchange transfusion, and remained elevated 1 year later despite chronic transfusion therapy. Stroke in SCD can occur in the setting of acute illness, and a biomarker that could predict the onset and triage ill children to therapeutic intervention more quickly would be useful.
PMCID: PMC3202928  PMID: 21099215
Chronic transfusion; Glial fibrillary acidic protein; Sickle cell; Stroke
8.  MicroRNA Profiles of Drug-Resistant Myeloma Cell Lines 
Acta Haematologica  2010;123(4):201-204.
PMCID: PMC2881892  PMID: 20357429
9.  The Role of Hepcidin in Iron Metabolism 
Acta Haematologica  2009;122(2-3):78-86.
Hepcidin is the central regulator of systemic iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemias, and hepatitis C. Hepcidin excess is associated with anemia of inflammation, chronic kidney disease and iron-refractory iron deficiency anemia. Diagnostic and therapeutic applications of this new knowledge are beginning to emerge. Dr. Ernest Beutler played a significant role in advancing our understanding of the function of hepcidin. This review is dedicated to his memory.
PMCID: PMC2855274  PMID: 19907144
Anemia of inflammation; Bone morphogenetic protein; Hemochromatosis; Hepcidin; Iron-loading anemia
10.  Role of Matriptase-2 (TMPRSS6) in Iron Metabolism 
Acta Haematologica  2009;122(2-3):87-96.
Iron, an essential element for life, is regulated primarily at the level of uptake, storage, and transport in order to maintain sufficient availability for normal physiology. The key protein in iron homeostasis is a 25-amino-acid peptide, hepcidin, which modulates the amount of iron in the circulation by binding and promoting the degradation of the iron exporter ferroportin. Given the central importance of hepcidin, recent studies have focused on how iron is sensed and how the iron signal is transmitted to hepcidin. Mutations in a type II serine protease, matriptase-2/TMPRSS6, were recently identified to be associated with severe iron deficiency caused by inappropriately high levels of hepcidin expression. A key biologically relevant substrate for the proteolytic activity of matriptase-2/TMPRSS6 was found to be hemojuvelin, a cell surface protein that regulates hepcidin expression through a BMP/SMAD pathway. In this review, we discuss the putative role of matriptase-2/TMPRSS6 in iron homeostasis.
PMCID: PMC2855275  PMID: 19907145
CUB; Hemojuvelin; Hepcidin; Iron; LDLa; Matriptase; TMPRSS; Type II serine protease
11.  Antioxidant-Mediated Effects in a Gerbil Model of Iron Overload 
Acta haematologica  2007;118(4):193-199.
Iron cardiomyopathy is a lethal complication of transfusion therapy in thalassemia major. Nutritional supplements decreasing cardiac iron uptake or toxicity would have clinical significance. Murine studies suggest taurine may prevent oxidative damage and inhibit Ca2+-channel-mediated iron transport. We hypothesized that taurine supplementation would decrease cardiac iron-overloaded toxicity by decreasing cardiac iron. Vitamin E and selenium served as antioxidant control.
Animals were divided into control, iron, taurine, and vitamin E/selenium groups. Following sacrifice, iron and selenium measurements, histology, and biochemical analyses were performed.
No significant differences were found in heart and liver iron content between treatment groups, except for higher hepatic dry-weight iron concentrations in taurine-treated animals (p < 0.03). Serum iron increased with iron loading (751 ± 66 vs. 251 ± 54 μg/dl, p < 0.001) and with taurine (903 ± 136 μg/dl, p = 0.03).
Consistent with oxidative stress, iron overload increased cardiac malondialdehyde levels, decreased heart glutathione peroxidase (GPx) activity, and increased serum aspartate aminotransferase. Taurine ameliorated these changes, but only significantly for liver GPx activity. Selenium and vitamin E supplementation did not improve oxidative markers and worsened cardiac GPx activity. These results suggest that taurine acts primarily as an antioxidant rather than inhibiting iron uptake. Future studies should illuminate the complexity of these results.
PMCID: PMC2892915  PMID: 17940334
Iron overload; Taurine; Heart; Liver; Antioxidants
12.  Safety and Efficacy of Combined Chelation Therapy with Deferasirox and Deferoxamine in a Gerbil Model of Iron Overload 
Acta haematologica  2008;120(2):123-128.
Combined therapy with deferoxamine (DFO) and deferasirox (DFX) may be performed empirically when DFX monotherapy fails. Given the lack of published data on this therapy, the study goal was to assess the safety and efficacy of combined DFO/DFX therapy in a gerbil model.
Thirty-two female Mongolian gerbils 8–10 weeks old were divided into 4 groups (sham chelated, DFO, DFX, DFO/DFX). Each received 10 weekly injections of 200 mg/kg iron dextran prior to initiation of 12 weeks of chelation. Experimental endpoints were heart and liver weights, iron concentration and histology.
In the heart, there was no significant difference among the treatment groups for wet-to-dry ratio, iron concentration and iron content. DFX-treated animals exhibited lower organ weights relative to sham-chelated animals (less iron-mediated hypertrophy). DFO-treated organs did not differ from sham-chelated organs in any aspects. DFX significantly cleared hepatic iron. No additive effects were observed in the organs of DFO/DFX-treated animals.
Combined DFO/DFX therapy produced no detectable additive effect above DFX monotherapy in either the liver or heart, suggesting competition with spontaneous iron elimination mechanisms for chelatable iron. Combined therapy was well tolerated, but its efficacy could not be proven due to limitations in the animal model.
PMCID: PMC2884393  PMID: 19018129
Deferasirox; Deferoxamine; Iron overload

Results 1-13 (13)