0000000000033706
AUTHOR
Dietger Niederwieser
Allogeneic Stem Cell Transplantation for Acquired Aplastic Anemia: Better Outcome with Bone Marrow as Compared to Peripheral Blood in HLA-Matched Sibling Donor Transplantation and Improved Outcome Over Time After Matched Unrelated Donor Transplantation. A Retrospective Analysis of Transplants Reported to the German Registry for Stem Cell Transplantation (DRST).
Abstract Abstract 876 Background: Transplantation of bone marrow (BM) from a HLA-matched sibling donor is an effective treatment for severe aplastic anemia (AA) with long-term survival in excess of 80%. In the recent years there were two trends in allogeneic stem cell transplantation (SCT) for AA: (1) increasing proportion of transplants performed from matched unrelated donors (MUD) and (2) increasing proportion of transplants using peripheral blood progenitor cells (PBSC) as stem cell source instead of BM. A similar switch to PBSC over BM grafts is reported in leukemia transplants. PBSC grafts for leukemia are associated with higher rates of chronic graft-versus-host disease (cGVHD). This …
P046 Deconstructing HLA-C mismatch in hematopoietic stem cell transplantation
Contrary to other HLA loci, allele vs antigen mismatches in HLA-C appear to differentially impact HSCT outcome. Aim of this study was to investigate the independent role of other factors characterizing a patient’s HLA-C non-shared allele, in HSCT outcome as well as their distribution in allele vs antigen mismatched cases. 288 9/10 HLA-C mismatched unrelated transplant pairs, were additionally genotyped by sequence based typing for rs9264942(C/T) and rs67384697(ins/del), which are considered surrogate markers of HLA-C expression levels. A proxy MFI model as previously described (Petersdorf et al., Blood 2014), was also implemented in the analysis. All patient non-shared alleles were characte…
Identification of NM23-H2 as a tumour-associated antigen in chronic myeloid leukaemia.
Therapeutic effects of haematopoietic stem cell transplantation are not limited to maximal chemoradiotherapy and subsequent bone marrow regeneration, but include specific as well as unspecific immune reactions known as graft-versus-leukaemia (GvL) effects. Specific immune reactions are likely to be particularly relevant to the long-term treatment of diseases, such as chronic myeloid leukaemia (CML), in which residual cells may remain quiescent and unresponsive to cytotoxic and molecular therapies for long periods of time. Specific GvL effects result from the expression on leukaemic cells of specific tumour-associated antigens (TAAs) in the context of HLA proteins. As human leukocyte antigen…
The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells.
BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-…
Donors with KIR-Bx Haplotypes Improve Outcome of Unrelated Hematopoietic Stem Cell Transplantation for Recipients with a Myeloid Malignant Disease and a C1 Ligand Phenotype
relapse, or transplant related mortality (TRM) (p1⁄40.2, p1⁄40.1, p1⁄40.08, respectively). To investigate why higher CPSS scores were associated with higher mortality, we performed analysis restricted to patients with relapse following HCT. Those with intermediate-2/high riskhadnearly two-fold increase in riskof death after relapse compared to thosewith low/intermediate1 CPSS scores. Corresponding rates for low/intermediate-1 risk groups,OSat1year, 3years, and5yearswere61%,48%, and44% respectivelyand for intermediate-2/high riskgroupswere 38%, 32%, and19%respectively.OSofpatientswho receivedpre-HCT treatment with hypomethylating agents, chemotherapy, or both was not different compared to th…
CD4 monoclonal antibody VIT4 in human alloimmune response in vitro and in vivo.
In the present report the immunosuppressive effects of the murine anti-human CD4 monoclonal antibody (mAb) VIT4 on human alloimmune response in vitro were analyzed. Moreover, the antibody was tested for its activity to prolong allograft survival in seven patients with steroid-refractory allograft rejection. VIT4 inhibited the proliferative response to alloantigens in the mixed lymphocyte reaction (MLR) in a dose-dependent manner. At concentrations of 1 and 10 micrograms/ml VIT4 blocked MLR by 55 +/- 11% and 77 +/- 1%, respectively. Also alloantigen-specific proliferation of in vitro- generated memory T cells was dose-dependently reduced to 23 +/- 1% at a VIT4 concentration of 100 micrograms…
P043 HLA-DPB matching and donor cytomegalovirus positive (CMV+) status: An “unconventional alliance” associated with a decreased relapse incidence in unrelated hematopoietic stem cell transplantation (UHSCT)
Aim While the role of HLA-DPB1 (DP) compatibility in uHSCT regarding graft versus host disease (GVHD)- and graft versus leukaemia (GVL)-effects has been extensively discussed, its interaction with donor CMV status (dCMV), remains elusive. The aim of this study was, to investigate the impact of dCMV status in DP matched (DPM) and mismatched (DPMM) uHSCT. Methods 1749 HSCT transplant (Tx) pairs were DP genotyped with an exon 2 amplicon based NGS approach in order to assess their DP matching status. CMV sero-status as well as clinical data were retrieved from the German Stem Cell Registry. Overall survival (OS), relapse incidence (RI) and chronic GvHD (cGvHD) were defined as endpoints, while s…
Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients: Results from the EBMT IDWP01 trial
The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly …
Improved relapse-free survival after autologous stem cell transplantation does not translate into better quality of life in chronic lymphocytic leukemia: Lessons from the randomized European Society for Blood and Marrow Transplantation-Intergroup study
Item does not contain fulltext In chronic lymphocytic leukemia (CLL) medical progress is driven by clinical studies with relapse-free survival (RFS) as the primary endpoint. The randomized EBMT-Intergroup trial compared high-dose therapy and autologous stem cell transplantation (ASCT) to observation and demonstrated a substantial improvement of RFS without showing improved overall survival for the transplant arm. Here we report quality of life (QoL) information of the first 3 years following randomization from that study. The main objective was to assess the impact of treatment on QoL over time. Two secondary analyses were performed to further investigate the impact of ASCT and relapse on Q…
Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia
We studied 128 patients with chronic myeloid leukemia (CML) relapsing after allogeneic stem cell transplantation (SCT). Disease at the time of treatment with Imatinib was in chronic phase (CP) in 51 patients, accelerated phase (AP) in 31 and blastic crisis (BC) in 46. Of the 51 patients in CP, 14 were in cytogenetic and two in molecular relapses. The median interval between relapse and Imatinib therapy was 5 months (0–65). A total of 50 patients had failed treatment with donor lymphocyte infusions prior to Imatinib. The overall hemato-logical response rate was 84% (98% for patients relapsing in CP). The complete cytogenetic response (CCR) was 58% for patients in CP, 48% for AP and 22% for p…
Relevance of the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) On Non-Relapse Related Mortality (NRM) in Patients with Acute Lymphoblastic Leukemia (ALL) Receiving Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in First Complete Remission: Results From the GMALL Study Group.
Abstract Abstract 3352 Poster Board III-240 Allogeneic HSCT is established as a potent curative therapy in adult patients with high risk ALL. However, due to transplant-related morbidity and lethality the gains in relapse prevention do not necessarily translate into survival advantages in the overall patient population. Defining the role of allogeneic HSCT in ALL patients in first complete remission (CR1) according to leukemia related risk factors, to transplant related risk factors (e.g. HLA matching, conditioning therapy and immunosuppressive treatment), and to comorbidity related risks, remains a major task for upcoming clinical trials. Several retrospective studies suggest that the HCT-…
A non-randomised trial of an art therapy intervention for patients with haematological malignancies to support post-traumatic growth
The aim of this study was to determine the effect of art therapy on post-traumatic growth in patients with haematological malignancies in a non-randomised trial ( n = 36, intervention group; n = 129, control group). Art therapy was administered over a period of 22 weeks in small groups. Post-traumatic growth was measured with the Stress-Related Growth Scale. After controlling for the effect of potential confounders, no difference in post-traumatic growth was observed between the intervention and control groups after 22 weeks. There was no evidence for an effect of weekly group sessions with art therapy on post-traumatic growth in patients with haematological malignancies.
Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial
Background: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. Methods: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18–70 years, had acute myeloid leukaemia in first or consecutive complete haematological remissi…
Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study.
BACKGROUND AND OBJECTIVES: This European Group for Blood and Marrow Transplantation (EBMT) multicentre randomized phase III study was designed to assess the safety and efficacy of CD34+ selection in newly diagnosed myeloma patients undergoing autologous transplantation. DESIGN AND METHODS: One hundred and eleven patients responsive to initial chemotherapy were randomized to receive CD34+ selected (arm A) or unselected PBPC (arm B) after conditioning with high-dose melphalan and TBI. ASO-PCR was used to assess purging efficacy and reinfused tumor load. Tumor load could be assessed in 59 patients. RESULTS: CD34+ selection gave a median tumor cell depletion of 2.2 logs (0.77-5.96). No tumor ce…
High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) Has a Significant but Transient Impact on Quality of Life: Lessons From the Chronic Lymphocytic Leukemia (CLL) ASCT Study by the CLL Subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation
Abstract Abstract 1989 Objective: High-dose therapy (HDT) and ASCT is the standard of care in a variety of hematologic malignancies. Whereas for some indications a survival advantage for HDT and ASCT has been demonstrated, a benefit only in terms of better progression-free survival has been shown for CLL. Because of this the quality of life (QoL) deserves particular attention. QoL assessment was a major focus of a randomized controlled EBMT-Intergroup trial on the value of HDT compared to observation in first or second remission of CLL (Michallet, Blood, 2011). Methods: 222 patients were enrolled into the study and allocated to either ASCT or observation. In the transplant arm, 72% received…
Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
Purpose This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day …
Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia
Contains fulltext : 218279.pdf (Publisher’s version ) (Open Access) Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (>/=0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 …
Biomarker Analysis in Patients (pts) with Steroid-Refractory Acute Graft-Vs-Host Disease (aGVHD) Treated with Ruxolitinib (RUX) or Best Available Therapy (BAT) in the Randomized, Phase 3 REACH2 Study
BACKGROUND aGVHD, a common complication of allogeneic stem cell transplant (alloSCT), is driven by proinflammatory cytokines and chemokines that activate the immune system, resulting in end-organ damage. Steroids are first-line treatment but up to 50% of pts are steroid refractory (SR), resulting in high mortality and morbidity. RUX, a JAK1/JAK2 inhibitor, inhibits cytokine-dependent activation of the JAK-STAT pathway and cell proliferation and differentiation, which prevents worsening of aGVHD and allows recovery. JAK pathway inhibition by RUX may also lead to modulation of proinflammatory cytokines and prognostic GVHD biomarkers. The phase 3 randomized REACH2 trial (NCT02913261) in SR aGV…
Randomized Study of Early versus Late Immunization with Pneumococcal Conjugate Vaccine after Allogeneic Stem Cell Transplantation
BACKGROUND: Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after trans…
Effects of stepped psychooncological care on referral to psychosocial services and emotional well-being in cancer patients: A cluster-randomized phase III trial
Objective Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. Methods In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and em…
Patient participation in the medical decision-making process in haemato-oncology - a qualitative study
Cancer patients are showing increased interest in shared decision-making. Patients with haematological illnesses, however, express considerably less desire for shared decision-making as compared with other oncological patient groups. The goal of the current project was to identify the reasons for the lower desire for shared decision-making among patients with haematological illness. We conducted qualitative, semi-structured interviews with 11 haematological patients (39-70 years old) after the beginning of therapy concerning the course and evaluation of medical shared decision-making. The patients were often overwhelmed by the complexity of the illness and the therapy and did not want to as…
OR26. Investigating the impact of patient’s non-shared HLA-C Allotype expression levels in A 9/10 Single HLA-C mismatched hematopoieticstem cell transplantationsetting using two different HLA-C Expression proxy models
Aim Petersdorf et al. reported in 2014 an association between patient high expressed HLA-C (C) allotypes and inferior HSCT outcome using an imputed C-expression model (Apps et al., 2013). This study aims at: a) examining the validity of Apps et al. model in Caucasians by using the same methodology in a sample of 400 healthy German blood donors. b) specifically investigating the effect of patient’s non-shared (PNS) C expression levels on outcome by applying C expression imputed data in a 9/10 HLA C-mismatched HSCT setting. Methods Buffy coats from 400 healthy German blood donors were tested by flow cytometry as previously described (Apps et al., 2013) in order to determine C expression on ly…
Comparison of Allogeneic Stem Cell Transplantation for Transformed Acute Myeloid Leukemia Derived from MDS, CMML or MPN. a Report of the Chronic Malignancies Working Party of EBMT
Abstract Introduction Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukemia (CMML) can progress to acute myeloid leukemia (transformed AML). The aim of this EBMT registry study was to compare 3 year outcome in patients with transformed AMLwho received allogeneic stem cell transplantation according to the primary disease. Patients and Methods Within the European Society of Blood and Marrow Transplantation (EBMT) registry, we found 4214 patients (female: 39%, male: 61%) with transformed acute myeloid leukemia, who received allogeneic stem cell transplantation between 2000 and 2014. The primary disease was MDS (n=3541), CMML (n=251) or MPN (n=4…
Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial
Abstract The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations. At a median follow-up of 60.7 months (95% CI, 55.0-70.8), the 5-year event-free survival (EFS) rate was significantly higher in patients treated with midostaurin than in those treated with placebo (45.2% vs 30.1%; P = .044). A trend toward improved …
Factors associated with non-participation and dropout among cancer patients in a cluster-randomised controlled trial
We investigated the impact of demographic and disease related factors on non-participation and dropout in a cluster-randomised behavioural trial in cancer patients with measurements taken between hospitalisation and 6 months thereafter. The percentages of non-participation and dropout were documented at each time point. Factors considered to be potentially related with non-participation and dropout were as follows: age, sex, marital status, education, income, employment status, tumour site and stage of disease. Of 1,338 eligible patients, 24% declined participation at baseline. Non-participation was higher in older patients (Odds Ratio [OR] 2.1, CI: 0.6-0.9) and those with advanced disease …
Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors-A Retrospective Study.
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: H…
AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION (AUTOHSCT) IN CLL: FIRST RESULTS OF AN EBMT RANDOMIZED TRIAL COMPARING AUTOTRANSPLANT VERSUS WAIT AND WATCH
Abstract Abstract 877 This phase-III randomized EBMT-intergroup trial studied the impact of a consolidating autoHSCT vs no consolidation for patients with CLL in Binet stage A progressive, B or C , in CR, nodular PR or VGPR after first or second line therapy. The primary objective was to show that autoHSCT increased the 5-year progression-free survival (PFS) by 30%. Although it had been calculated that 270 patients were to be randomized, the study was terminated by the steering committee in July 2007 due to poor accrual. Here we present a first analysis based on 69% of expected follow-up forms. Results: Between November 2001 and July 2007, 223 patients were enrolled (SFGM-TC/FCLLG n=98, MRC…
Increased age-associated mortality risk in HLA-mismatched hematopoietic stem cell transplantation.
We investigated a possible interaction between age-associated risk and HLA-mismatch associated risk on prognosis in different age categories of recipients of unrelated hematopoietic stem cell transplants (HSCT) (n=3019). Patients over 55 years of age transplanted with 8/10 donors showed a mortality risk of 2.27 (CI 1.70–3.03, P<0.001) and 3.48 (CI 2.49–4.86, P<0.001) when compared to 10/10 matched patients in the same age group and to 10/10 matched patients aged 18–35 years, respectively. Compared to 10/10 matched transplantations within each age category, the Hazards Ratio for 8/10 matched transplantation was 1.14, 1.40 and 2.27 in patients aged 18–35 years, 36–55 and above 55 years. Model…
Effect of interleukin-3 pretreatment on granulocyte/macrophage colony-stimulating factor induced mobilization of circulating haemopoietic progenitor cells.
Recombinant human colony stimulating factors (CSFs) as single agents are increasingly used for mobilizing peripheral blood progenitor cells (PBPCs) for stem cell transplantation. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers of subsequent administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on GM-CSF-induced mobilization of PB progenitors in patients who were potential candidates for autologous stem cell transplantation (n = 16). Patients were treated with GM-CSF at a dose of 5 micrograms/kg/d for 5 d and after a treatment free interval received another cycle of GM-CS…
Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside
Abstract Patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) and on interferon (IFN)-α-2c treatment for at least two months were entered in the present pilot study. IFN-α treatment was maintained identically and cytosine arabinoside (Ara-C) was added at monthly cycles of 10 mg/m 2 /day for ten days subcutaneously. In the case of a leukocyte nadir above 10 G/1, the Ara-C dose was increased to 20 mg/m 2 /day for 10 days per month. Ten of the eleven patients entered in this study were evaluable for toxicity and response. They received a total of 87 IFN-α/Ara-C cycles (3–14/patient). Five patients received 1–5 cycles with Ara-C dose intensification to 20 mg/m …
Immune Response to the 23-Valent Polysaccharide Pneumococcal Vaccine (PPV23) after the 7-Valent Conjugate Vaccine (PCV7) in Allogeneic Stem Cell Transplant (SCT) Recipients: Results of the EBMT IDWP01 Trial
Abstract Background: Pneumococcal infections are causes of death after SCT. The IDWP01 trial compared early (E) vs late (L) pneumococcal immunization after allogeneic SCT, starting either at 3, or at 9 months post-transplant with 3 doses of PCV7 given at 1 month intervals,. This study has shown that the early immunization was not inferior in the proportion of responders one month after the last PCV7 dose. In addition, all patients received one dose of PPV23 after the 3 doses of PCV7 at 12 months and 18 months in the E and L groups, respectively. The goal of this supplementary analysis was to look at the immune response to the PPV23 according to the time of its administration. Methods: 158 p…
An Immunogenic Peptide Derived from NM23-H2 Is Expressed on Bcr/abl+ Cells.
Abstract Objective: Most tumors express antigens which, when presented by MHC molecules, can be recognized by cytotoxic T-lymphocytes. These tumor-associated-antigens (TAA) are considered to be key determinants in the graft-versus-tumor effect after allogeneic hematopoietic cell transplantation (HCT) and are therefore potential candidates for tumor vaccination. Unfortunately only small numbers of TAA have been isolated to date. In this project we looked for immunogenic peptides presented by bcr/abl+ cells of an HLA-A32 CML patient. Methods: Leukemia-specific mixed lymphocyte leukemia cell cultures (MLLC) were generated by co-culturing irradiated bcr/abl+ cells from the patient with peripher…
Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n…
Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
Abstract The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for …