A Modified Post-Transplant Cyclophosphamide Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: A Multicenter Study.

We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg on days +3 and +5. The median age was 51 (range, 17-74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days.

Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation.

No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcomes and risk factors in 698 patients, treated with different strategies. The median overall survival from relapse was 4.

Different drug-resistant influenza A(H3N2) variants in two immunocompromised patients treated with oseltamivir during the 2011-2012 influenza season in Italy.

Background: Monitoring the emergence of drug-resistant influenza variants is crucial in influenza surveillance programs.

Objectives: Influenza A kinetics and the emergence of drug-resistant strains in hospitalized patients treated with oseltamivir were investigated.

Study Design: Sequential samples from oseltamivir-treated and -untreated hospitalized patients in the period November 2011 through April 2012 were analyzed.

Outcome of patients activating an unrelated donor search: the impact of transplant with reduced intensity conditioning in a large cohort of consecutive high-risk patients.

An unrelated donor (UD) search was submitted to the Italian Bone Marrow Donor Registry between February 2002 and December 2004, for 326 consecutive patients with hematological malignancies, eligible for a reduced intensity conditioning (RIC) UD transplant. Only two regimens were allowed: melphalan, alemtuzumab, fludarabine and total body irradiation of 200 cGy (regimen A) and thiotepa, cyclophosphamide, anti-thymocyte globulin (regimen B). The outcome of patients receiving an UD transplant (n=121) was compared with patients who did not find a donor (n=205), in a time dependent analysis, correcting for time to transplant.

Allogeneic stem cell transplantation in therapy-related acute myeloid leukemia and myelodysplastic syndromes: impact of patient characteristics and timing of transplant.

Patients with therapy-related acute myeloid leukemia (t-AML) and myelodysplastic syndromes (t-MDS) have poor survival and high non-relapse mortality (NRM) after allogeneic stem cell transplantation. This retrospective study assessed the transplant outcomes of 29 consecutive patients with t-AML (83%) or t-MDS (17%) treated with allogeneic transplantation. The median age of patients was 51 years.

Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines.

Since 2002, date of publication of the previous Italian Society of Haematology (SIE) practice guidelines for management of myelodysplastic syndromes (MDS), novel disease-modifying treatments have been introduced and the SIE commissioned an update. After a comprehensive review of the medical literature published since January 2001, the Expert Panel formulated recommendations for the management of adult and paediatric MDS, graded according to the available evidence. The major updates are: first-line hypomethylating agents in patients with INT2-high-risk disease; controlled use of first-line lenalidomide in low-INT1 risk transfusion-dependent patients with 5q deletion; deferasirox in low-INT1 patients with a relevant transfusional load; first-line high-dose ESA in low-INT1 patients with Hb <10 g/dl and endogenous EPO <500 U/l; allogeneic HSCT first-line therapy for INT2- and high-risk patients <65 years without severe co morbidities.

Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: delay of the transplant is associated with inferior survival.

Allogeneic stem cell transplantation (alloSCT) for patients with refractory anaemia may result in a 50% event-free survival, but the high non-relapse mortality (NRM) precludes a general application of this therapeutic modality. This study evaluated the impact of various pre-transplant variables, including disease duration, intensity of the conditioning regimen, type of donor and year of transplantation on outcome. The study population consisted of 374 patients; 244 were transplanted from human leucocyte antigen (HLA)-identical siblings and 130 patients from matched unrelated donors.

Isomorphic cutaneous graft-versus-host disease reaction after ultraviolet exposure: clinical, histological and direct immunofluorescence studies of four allo-transplanted patients.

Background: Acute and chronic graft-versus-host disease (GVHD) continues to be a major limitation to successful haematopoietic stem cell transplantation. If experimental studies and clinical observations could partially elucidate the pathophysiology of acute GVHD, the biology of chronic GVHD is still much less well understood.

Objectives: The aim of this study is to describe a peculiar photoinduced rash which triggered acute and then chronic lesions of GVHD in four allogenic haematopoietic-transplanted patients and discuss the possible aetiology and treatment.

HLA matching affects clinical outcome of adult patients undergoing haematopoietic SCT from unrelated donors: a study from the Gruppo Italiano Trapianto di Midollo Osseo and Italian Bone Marrow Donor Registry.

The importance of HLA donor-recipient matching in unrelated haematopoietic SCT (HSCT) is the subject of debate. In this retrospective study, we analyzed 805 adult patients from the Italian Registry receiving HSCT for a haematological malignancy from January 1999 to June 2006 and correlated the degree of HLA matching with transplant outcome. All patient-donor pairs had high-resolution typing at HLA-A, -B, -C, -DRB1 and -DQB1.

Long-term study on symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients.

From October 2004 through October 2006 a study was performed to evaluate the prevalence of human Metapneumovirus (hMPV) infection in adult hematopoietic stem cell transplant (HSCT) recipients. Sequential nasopharyngeal aspirates (NPA) were collected independently from respiratory symptoms and evaluated for hMPV-RNA by polymerase chain reaction (PCR) and sequence analysis. Results indicate epidemiological and molecular differences between the 2004-2005 and 2005-2006 periods and that hMPV seems not to symptomatically affect HSCT patients or cause late respiratory sequelae.

Bartonella-related pseudomembranous angiomatous papillomatosis of the oral cavity associated with allogeneic bone marrow transplantation and oral graft-versus-host disease.

Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Human infections due to Bartonella spp. are viewed as emerging diseases typical in, although not exclusive to, immunosuppressed patients, in particular those with AIDS, organ transplants and haematological malignancies.

Treatment of refractory chronic GVHD with rituximab: a GITMO study.

The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to induce significant clinical response in a proportion of patients with refractory chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age 48 years (22-61), receiving Rituximab for refractory cGVHD, assessed for clinical response and survival. Median duration of cGVHD before Rituximab was 23 months (range 2-116), the median number of failed treatment lines was 3 (range 1 to > or =6) and the median follow-up after Rituximab was 11 months (1-88).

Hematopoietic stem cell transplantation for adults with acute promyelocytic leukemia in the ATRA era: a survey of the European Cooperative Group for Blood and Marrow Transplantation.

We performed a survey of the European Cooperative Group for Blood and Marrow Transplantation to analyze the outcome of 625 acute promyelocytic leukemia (APL) patients transplanted with auto- or allogeneic-hematopoietic stem cell transplantation (autoHSCT, alloHSCT) after 1993, in first (CR1) or in second complete remission (CR2). Leukemia-free survival (LFS) at 5 years in CR1 was 69% for 149 patients autografted and 68% for 144 patients allografted, whereas in CR2, LFS was 51% in 195 autoHSCT and 59% in 137 alloHSCT recipients, respectively. In the group of autoHSCT for CR1 (n=149), higher relapse incidence (RI) was associated with shorter time from diagnosis to transplant (<7.

Risk factors and severe outcome in thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation.

Background: Thrombotic microangiopathy (TMA) has been described as severe complication after hematopoietic stem cell transplantation (HSCT). The principal aim of this study was to focus the incidence and the outcome of TMA in the era of more complex HSCTs.

Methods: We analyzed the role of some predicting factors for the incidence and the outcome of TMA after HSCT.

Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation.

This is an update of a randomized study on antithymocyte globulin (ATG; Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors. The median follow-up for surviving patients is 5.7 years.

Normal-looking skin in oncohaematological patients after allogenic bone marrow transplantation is not normal.

Background: Graft-versus-host-disease (GvHD) occurs in one-third or even half of bone marrow transplant (BMT) patients, involving three major target organs: gut, liver and skin.

Objectives: The histopathological and immunohistochemical features of normal-looking skin in oncohaematological patients on day 100 after BMT were studied to find a possible relationship between the histopathological findings and clinical variables (history or clinical evidence of GvHD, previous therapeutic regimens or infections).

Methods: Fifty-one Caucasian oncohaematological patients, who had had an allogenic BMT, had a biopsy taken from normal-looking skin in nonsun-exposed areas (buttocks or the lumbar region), around the 100th day after BMT.

Radiation recall dermatitis, panniculitis, and myositis following cyclophosphamide therapy: histopathologic findings of a patient affected by multiple myeloma.

Radiation recall dermatitis is one of the skin sequelae that may affect oncology patients. It occurs in a previously irradiated field, when subsequent chemotherapy is given. The eruption may be elicited by chemotherapy, even several months after radiotherapy.

Lack of dendritic cell mobilization into the peripheral blood of cancer patients following standard- or high-dose chemotherapy plus granulocyte-colony stimulating factor.

Background: Dendritic cells (DC), the most specialized antigen-presenting cells, can be detected in the peripheral blood (PB) and divided into two subsets of populations, DC1 and DC2, endowed with different functions. The aim of this study was to evaluate the effect on DC release and on their subsets of three regimens utilized to mobilize CD34+ cells into the PB in cancer patients and in normal CD34+ cell donors.

Patients And Methods: The mobilizing sequences were: standard-dose epirubicin+taxol+granulocyte-colony-stimulating factor (G-CSF; 15 patients with advanced breast cancer), high-dose cyclophosphamide (CTX)+G-CSF (10 patients with breast cancer patients and 7 with non-Hodgkin's lymphoma, NHL), and G-CSF alone (5 normal donors of CD34+ cells for allogeneic transplantation).

Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO).

One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P =.

Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation.

Purpose: Leukemic relapse is the most frequent cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (HSCT). To identify prognostic factors affecting the outcome of second HSCT, we performed a retrospective study on patients with acute leukemia (AL) undergoing second HSCT who reported to the Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation registry.

Patients And Methods: One hundred seventy patients who received second HSCTs for AL experienced relapse after first HSCTs were performed from 1978 to 1997.

A model for analysing the cost of autologous peripheral blood progenitor cell (PBPC) transplantation.

Data from autologous peripheral blood progenitor cell (PBPC) transplant recipients were used for cost analysis and modelling so as to link the main intervention procedures and clinical events to resource use and costs. This cohort consisted of 64 patients from 4 to 62 years old at transplantation (mean, 36.9 years) who underwent a first transplant between August 1994 and May 1997.

Adverse events occurring during bone marrow or peripheral blood progenitor cell infusion: analysis of 126 cases.

Bone marrow (BM) and/or peripheral blood progenitor cells (PBPC) given after high-dose chemo-radiotherapy are commonly cryopreserved. Re-infusion of the thawed product can cause cardiovascular and other complications. We compared two groups of adult patients receiving autologous BM or PBPC transplant to assess the incidence of adverse events occurring during infusion.

Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation.

Ninety-five patients undergoing an allogeneic bone marrow transplant (BMT) and developing acute graft-versus-host disease (aGvHD) were randomized to receive low-dose intravenous 6-methylprednisolone (6MPred; 2 mg/kg /d; n = 47) or high-dose 6MPred (10 mg/kg/d; n = 48) for 5 days, with subsequent tapering doses. On day 5 patients not responding or progressing on low-dose 6MPred could be switched to high-dose 6MPred. All patients, aged 1 to 55 years, were recipients of unmanipulated BMT from HLA identical sibling donors.