Yordanka Tirefort

Comparing Two Types of Rabbit ATG prior to Reduced Intensity Conditioning Allogeneic Hematopoietic SCT for Hematologic Malignancies

Different rabbit polyclonal antilymphocyte globulins (ATGs) are used in allogeneic hematopoietic stem cell transplantation (alloHSCT) to prevent graft-versus-host disease (GvHD). We compared 2 different ATGs in alloHSCT after reduced intensity conditioning (RIC) for hematological malignancies. We reviewed 30 alloHSCT for hematologic malignancies performed between 2007 and 2010 with fludarabine and i.v. busulfan as conditioning regimen. Patients alternatingly received Thymoglobulin or ATG-F. Median followup was 3.3 (2.5–4.5) years. Adverse events appeared to occur more frequently during Thymoglobulin infusion than during ATG-F infusion but without statistical significance (P = 0.14). There were also no differences in 3-year overall survival (OS), disease-free survival (DFS), relapse incidence, and transplant related mortality (TRM) in the Thymoglobulin versus ATG-F group: 45.7% versus 46.7%, 40% versus 33.7%, 40% versus 33.3%, and 20% versus 33.3%. The same held for graft failure, rejection, infectious complications, immune reconstitution, and acute or chronic GvHD. In patients transplanted for hematologic malignancies after RIC, the use of Thymoglobulin is comparable to that of ATG-F in all the aspects evaluated in the study. However due to the small number of patients in each group we cannot exclude a possible difference that may exist.

Outcome of hematopoietic stem cell transplantation is similar for patients with a partial in vitro T-cell-depleted graft compared with a non-T-cell-depleted graft when stratified by the refined disease risk index.

Comparisons of hematopoietic stem cell transplantation (HSCT) methods in retrospective studies are often hampered by the heterogeneity of comparison groups. The refined disease risk index (DRI) is a potentially interesting tool to compare HSCT protocols as it is based on the disease type and burden at transplant and stratifies patients into four prognostic groups for overall survival (OS). We included 265 patients with partial T-cell-depleted graft (TDEP) and 163 non-TDEP patients in a retrospective study and compared outcomes following stratification using the refined DRI. The 2-year OS rate for TDEP patients was 81.6, 60.9 and 43.3% for the low-, intermediate- and high-risk groups, respectively (P<0.001). For non-TDEP patients, the 2-year OS rate was 62.9, 48.8, 44.2 and 7.6% for the low-, intermediate-, high- and very-high-risk groups, respectively (P<0.001). There was no significant difference when comparing OS between TDEP and non-TDEP for the low-, intermediate- and high-risk groups, but TDEP patients had less acute GvHD grades II–IV. In conclusion, we confirm that the refined DRI is a valuable tool to compare the outcomes of different HSCT protocols. We demonstrate also that TDEP did not impact on the outcome of HSCT, but it did reduce the incidence of acute GvHD.

Complete and sustained remission of spondyloarthritis after allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 27 decembre 2014

Impact of T-cell depletion on outcome of patients undergoing allogeneic hematopoietic cell transplantation for myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are clonal stem cell disorders usually characterized by cytopenia and dysplasia. MDS are usually diagnosed during the sixth decade and are associated with reduced life expectancy, mainly related to transformation to acute leukemia, infections, or bleeding. Currently, the only potentially curative treatment for MDS is allogeneic hematopoietic stem cell transplantation (HSCT) [1–3]. However, HSCT is associated with significant morbidity and mortality mainly related to acute or chronic graft-vs.-host disease (aGvHD or cGvHD) [4, 5]. In the Geneva Stem Cell Transplant Center we use partial in vitro T-cell-depleted grafts usually for patients in complete remission at transplant to reduce GvHD incidence [6]. Indeed, partial T-cell depletion decreases the number of alloreactive donor T cells triggering GvHD. However, it is hypothesized that this strategy could increase relapse incidence (RI) and decrease overall survival (OS) due to the loss of the graft-vs.-leukemia effect mediated by donor lymphocytes. Impact of partial T-cell depletion was previously investigated in a cohort of patients, including heterogeneous diseases and results had shown no worsening of outcome for partially T-cell-depleted patients [7]. However, the impact of partial T-cell depletion was never specifically investigated for patients undergoing transplantation for MDS. In this retrospective study, we investigated patients allografted for a diagnosis of MDS over a 19 years’ period (from 01 January 1998 to 31 August 2016). Patients aged ≥18 years old at transplant time, who had a diagnosis of MDS according to the 2008 World Health Organization criteria, and who had a first HSCT were included. Patients with haploidentical transplantation, stem cell from identical twins, umbilical cord blood transplantation, or more than two human leukocyte antigen (HLA) locior allelemismatched unrelated donor (MMUD) transplantation were excluded. This study was approved by an ethics committee. Primary outcomes were comparison of 3-year OS, progression-free survival (PFS), GvHD-free/relapse-free survival (GRFS) [8], RI, and non-relapse mortality (NRM) between partially T-cell-depleted patients and non-T-celldepleted ones. Secondary outcomes were impact of partial T-cell depletion on grade 2–4 acute and chronic GvHD. Sixty-two patients were included. Forty-four percent were female, median age at transplant was 48 years (range: 18–70 years) with myeloablative conditioning for 66% and reduced intensity for 34%. Median time from diagnosis to HSCT was 7.5 months (range: 3–86 months). Peripheral blood stem cell (90%) or bone marrow (BM; 10%) grafts were from HLA-identical siblings (45%), HLA-matched unrelated donor (MUD; 42%), or MMUD (13%). Antithymocyte globulin was used for 56% of patients and partial T-cell depletion was performed for 52% of patients. Median follow-up was 4.6 years (range: 0–15). Patients’ characteristics and data on transplantation are shown in Table 1. Myeloablative conditioning usually consisted of cyclophosphamide (120 mg/kg) with either total body irradiation These authors contributed equally: Maude Raboud, Yan Beauverd.

FLT3-ITD mutations do not impact the outcome of patients allografted with partial T-cell depleted grafts for AML with normal cytogenetics in first complete remission

To the Editor Acute myeloid leukemia (AML) is by far the most frequent form of acute leukemia in adults. Usually, allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the best therapeutic option for patients in complete remission (CR) other than low-risk [defined as t(8:21), inv(16), mutated NPM1 without FLT3-ITD with normal cytogenetics, mutated CEBPA with normal cytogenetics] [1]. The outcome of patients suffering from AML with normal cytogenetics harboring internal tandem duplication of FLT3 gene (FLT3-ITD) is worse than that of patients suffering from AML with normal cytogenetics and FLT3 wild-type gene (FLT3-wt) [2], and allo-HSCT has shown to improve outcome when compared with chemotherapy alone for consolidation in retrospective studies [3,4]. The recent publication of the prospective AML 2003 trial has confirmed the impact of allo-HSCT for patients with FLT3-ITD in terms of overall survival and event-free survival [5], and current guidelines recommend allo-HSCT as consolidation therapy for FLT3-ITD AML patient [1,6]. However, allo-HSCT is impacted by considerable morbidity that is principally caused by acute and chronic graft-versus-host disease (GvHD) [7]. Partial T-cell depletion (pTCD) reduces the rate of GvHD [8] but may increase the relapse rate and impair survival by decreasing the graft-versus-leukemia effect. In the Geneva University Hospital, Stem Cell and Bone Marrow Transplant Centre, we perform in vitro partial T-cell depletion (pTCD) {alemtuzumab [CAMPATH-1H (Genzyme Corporation, Cambridge, MA)] ‘in the bag’ [9,10]} for patients in first CR at transplant time to reduce morbidity secondary to GvHD and improve quality of life. Recently, we have shown that pTCD does not hamper outcome [overall survival (OS), progression-free survival (PFS), and relapse incidence (RI)] when compared with non-pTCD grafts for hematological malignancies classified according to the disease risk index [11]. However, impact of pTCD in term of outcome for AML with normal cytogenetics with or without FLT3-ITD has never been investigated. In this retrospective study, we included all AML patients with normal cytogenetics transplanted with pTCD allografts in first hematologic CR between 2003 and 2013.Main objective was 5-year OS, PFS, and RI for FLT3-ITD and FLT3-wt patients. Secondary objectives were the impact of molecular CR at transplant (defined as absence of FLT3-ITD in bone

Excellent outcome with a high proportion of mixed chimerism in patients with severe aplastic anemia treated with partially T-cell-depleted peripheral hematopoietic stem cell transplants

Excellent outcome with a high proportion of mixed chimerism in patients with severe aplastic anemia treated with partially T-cell-depleted peripheral hematopoietic stem cell transplants

A rare case of primary cutaneous follicle centre lymphoma presenting as a giant tumour of the scalp and combined with JAK2V617F positive essential thrombocythaemia.

Primary cutaneous follicle centre lymphoma (PCFCL) is a rare cutaneous B cell lymphoma in middle-age adults with excellent prognosis. Here we present a case of a patient with a PCFCL in the form of a giant tumour of the scalp in combination with a myeloproliferative neoplasm, JAK2V617F positive essential thrombocythaemia. This case may be of interest because of the favourable outcome in spite of the large size of the PCFCL, the rare combination with essential thrombocythaemia and because it contributes to discussion on the role of JAK2 mutation in such patients.