How We Manage Invasive Fungal Disease in Acute Myeloid Leukemia Patients with Glucose 6 Dehydrogenase Deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) represents a common human enzyme defect, particularly prevalent in the Mediterranean, African e Asian area, where malaria was or is still endemic. Recently, we identified G6PD deficiency as a risk factor for developing invasive fungal disease (IFD) and particularly Candida Sepsis in patients undergoing intensive chemotherapy for acute myeloid leukemia (AML), suggesting that there is an urgent need for strategies to properly manage this kind of patients at high risk of invasive mycoses. Here we propose our algorithm for correct identification, prophylaxis, and treatment of IFD in patients with G6PD deficiency undergoing intensive chemotherapy for AML.

Long-term survival of beta thalassemia major patients treated with hematopoietic stem cell transplantation compared with survival with conventional treatment.

Allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia remains a challenge. We reported a single-centre case-control study of a large cohort of 516 children and adult patients treated with HSCT or blood transfusion support and iron chelation therapy; 258 patients (median age 12, range 1-45) underwent sibling (67%) or unrelated (33%) HSCT; 97 patients were adults (age ≥ 16 years). The median follow-up after HSCT was 11 years (range 1-30).

Post-remissional and pre-transplant role of minimal residual disease detected by WT1 in acute myeloid leukemia: A retrospective cohort study.

In acute myeloid leukemia (AML), the detection of minimal residual disease (MRD) is still under investigation. The aim of the present retrospective study was to assess the role of Wilms tumor gene 1 (WT1) overexpression in a large monocentric cohort of AML patients. Among 255 enrolled patients, MRD was investigated in those in complete remission (CR) with an available WT1 at baseline (>250 copies) and at two further time-points: after induction (n=117) and prior allogeneic hematopoietic cell transplantation (allo-HCT), n=65.

HLA-G molecules and clinical outcome in Chronic Myeloid Leukemia.

The human leukocyte antigen-G (HLA-G) gene encodes a tolerogenic protein known to promote tumor immune-escape. We investigated HLA-G polymorphisms and soluble molecules (sHLA-G) in 68 chronic myeloid leukemia (CML) patients. Patients with G*01:01:01 or G*01:01:02 allele had higher value of sHLA-G compared to G*01:01:03 (109.

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation.

Background: Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function.

Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations.

Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder.

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

What Is Known And Objective: Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia.

Methods: We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses.

Bone Marrow Homing and Engraftment Defects of Human Hematopoietic Stem and Progenitor Cells.

Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process.

Glucose-6-phosphate dehydrogenase deficiency and risk of invasive fungal disease in patients with acute myeloid leukemia.

Invasive fungal diseases (IFD) are still a leading cause of morbidity and mortality in patients with acute myeloid leukemia (AML). Glucose-6-phosphate dehydrogenase is an enzyme that leads to the production of NADPH, required to destroy microorganisms in the respiratory burst reaction of white blood cells. We evaluated the role of G6PD deficiency in susceptibility of IFD in 108 AML patients undergoing intensive chemotherapy.

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft.

What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us about Transplant Immunogenetics.

Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT) continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cord blood banks has significantly increased the odds of finding a suitable HLA matched donor.

Pregnancy outcome following hematopoietic cell transplantation for thalassemia major.

The aim of this study was to investigate the methods of conception and delivery, as well as the course and outcome of 42 pregnancies occurring in 15 female patients (27 pregnancies) and partners of 8 male patients (15 pregnancies) with β-thalassemia major who were successfully treated with allogeneic hematopoietic cell transplantation (HCT). Most pregnancies (n=21) were achieved with spontaneous conception in female patients. There were two miscarriages.

Rare case of disseminated fusariosis in a young patient with graft vs. host disease following an allogeneic transplant.

infection is a severe fungal infection caused by fungi of the genus . It most commonly occurs in immunocompromised patients with malignant hematological comorbidities or secondary to hematopoietic stem cell transplant. The classical route of contamination is through inhalation but infection may also occur through contiguity with a skin lesion.

First report of pediatric hematopoietic stem cell transplantation activities in the eastern mediterranean region from 1984 to 2011: on behalf of the pediatric cancer working committee of the eastern mediterranean blood and marrow transplantation group.

To describe the hematopoietic stem cell transplantation (HSCT) activities for children in the Eastern Mediterranean (EM) region, data on transplants performed for children less than 18 years of age between 1984 and 2011 in eight EM countries (Egypt, Iran, Jordan, Lebanon, Oman, Pakistan, Saudi Arabia and Tunisia) were collected. A total of 5187 transplants were performed, of which 4513 (87%) were allogeneic and 674 (13%) were autologous. Overall, the indications for transplantation were malignant diseases in 1736 (38.

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients.

We studied telomere length in 32 CML patients who discontinued imatinib after achieving complete molecular remission and 32 age-sex-matched controls. The relative telomere length (RTL) was determined by q-PCR as the telomere to single copy gene (36B4) ratio normalized to a reference sample (K-562 DNA). Age-corrected RTL (acRTL) was also obtained.

Hematopoietic, Mesenchymal, and Immune Cells Are More Enhanced in Bone Marrow than in Peripheral Blood from Granulocyte Colony-Stimulating Factor Primed Healthy Donors.

The use of granulocyte colony-stimulating factor (G-CSF) primed bone marrow (G-BM) has been recently considered as an alternative to mobilized hematopoietic stem cells from peripheral blood (G-PB), especially in the haploidentical transplant setting. The purpose of this study was to compare the effect of in vivo G-CSF priming on BM and PB hematopoietic, mesenchymal (MSC), and immune cells. Forty healthy donors undergoing BM harvest for haploidentical transplant were given subcutaneous recombinant human G-CSF for 7 days.

Translation, Cross-Cultural Adaptation, and Validation of the Lee Chronic Graft-versus-Host Disease Symptom Scale in a Brazilian Population.

The Lee Chronic Graft-versus-Host Disease (GVHD) Symptom Scale is a patient-reported instrument developed and validated in English to measure the symptoms and functional impact of cGVHD. This tool has not yet been validated in a Latin American population, however. The Brazil-Seattle Chronic GVHD Consortium conducted a multicenter study at 5 Brazilian institutions to validate the Lee cGVHD Symptom Scale in adults with cGVHD.

The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma.

Background: Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs).

Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.

Background: Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses.

Methods And Findings: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls.

Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial.

Background: The standard busulfan-cyclophosphamide myeloablative conditioning regimen is associated with substantial non-relapse mortality in patients older than 40 years with acute myeloid leukaemia who are undergoing allogeneic stem-cell transplantation. Because the combination of busulfan plus fludarabine has been proposed to reduce non-relapse mortality, we aimed to compare this treatment with busulfan plus cyclophosphamide as a preparative regimen in these patients.

Methods: We did an open-label, multicentre, randomised, phase 3 trial for patients with acute myeloid leukaemia at 25 hospital transplant centres in Italy and one in Israel.

Long-term outcome and prognostic factors of second allogeneic hematopoietic stem cell transplant for acute leukemia in patients with a median follow-up of ⩾10 years.

Second allogeneic hematopoietic stem cell transplantation (HSCT2) is a frequently used treatment option for relapse of acute leukemia after first allogeneic transplantation. Remission can be induced in selected patients, but data on long-term outcome and finally cure are limited. To estimate the long-term results of HSCT2, we retrospectively analyzed the course of 286 patients receiving myeloablative HSCT2 between 1985 and 2000, with a median follow-up of 11.

Killer immunoglobulin-like receptors can predict TKI treatment-free remission in chronic myeloid leukemia patients.

Several factors are predictive of treatment-free remission (TFR) in chronic myeloid leukemia (CML), but few data exist on the role of natural killer (NK) cells and their killer-cell immunoglobulin-like receptors (KIRs). KIR and human leukocyte antigen (HLA) genotypes were investigated in 36 CML patients who discontinued tyrosine kinase inhibitor (TKI) treatment after achieving deep molecular response (MR(4.5)).

The surgery of the long-term central venous accesses in oncology.

The implantation of Long-Term Central Venous Catheters (LTCVC) in cancer patients has been essential to conduct the oncological treatments of today. The complexity of the protocols requires accuracy on the management of such devices in order to keep them long-functioning. The article focuses on such subject from an oncological perspective, pointing out threats of the disease to the central venous system (CVS) and the ways to face them successfully.