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1. Treatment patterns and clinical outcomes of asciminib in a real-world multiresistant chronic myeloid leukemia patient population

Author

Kockerols, Camille C.B., Janssen, Jeroen J.W.M., Blijlevens, Nicole M.A., Klein, Saskia K., van Hussen-Daenen, Laura G.M., van Gorkom, Gwendolyn G.Y., Smit, Willem M., van Balen, Peter, Biemond, Bart J., Cruijsen, Marjan J., Corsten, Maarten F., te Boekhorst, Peter A.W., Koene, Harry R., van Sluis, Geerte L., Cornelissen, Jan J., Westerweel, Peter E., Hematology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Clinical Haematology, AII - Inflammatory diseases, CCA - Cancer Treatment and Quality of Life, Interne Geneeskunde, MUMC+: MA Hematologie (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy

Subjects
Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], All institutes and research themes of the Radboud University Medical Center, Hematology, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 291291.pdf (Publisher’s version ) (Open Access)

Published
2022

2. Comparison of Dynamic International Prognostic Scoring System and MYelofibrosis SECondary to PV and ET Prognostic Model for Prediction of Outcome in Polycythemia Vera and Essential Thrombocythemia Myelofibrosis after Allogeneic Stem Cell Transplantation

Author

Gagelmann, Nico, Eikema, Diderik-Jan, de Wreede, Liesbeth C, Koster, Linda, Wolschke, Christine, Arnold, Renate, Kanz, Lothar, McQuaker, Grant, Marchand, Tony, Socié, Gerard, Bourhis, Jean Henri, Mohty, Mohamad, Cornelissen, Jan J, Chevallier, Patrice, Bernasconi, Paolo, Stelljes, Matthias, Rohrlich, Pierre-Simon, Fanin, Renato, Finke, Jürgen, Maertens, Johan, Blaise, Didier, Itälä-Remes, Maija, Labussière-Wallet, Hélène, Robin, Marie, McLornan, Donal, Chalandon, Yves, Yakoub-Agha, Ibrahim, Kröger, Nicolaus, CMWP of the European Society for Blood and Marrow Transplantation, Hematology, and Medical Oncology

Subjects
Adult, medicine.medical_specialty, Essential thrombocythemia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, Internal medicine, Humans, Transplantation, Homologous, Medicine, Allogeneic stem cell transplantation, Secondary myelofibrosis, Hematology, Transplantation, Myelofibrosis, Polycythemia Vera, Survival analysis, Aged, ddc:616, Framingham Risk Score, business.industry, Hematopoietic Stem Cell Transplantation, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Treatment Outcome, Primary Myelofibrosis, International Prognostic Scoring System, 030220 oncology & carcinogenesis, Cohort, business, Thrombocythemia, Essential, 030215 immunology
Abstract

We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P = .78). Overall, the DIPSS was not significantly predictive of outcome (P = .28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P = .05), whereas groups with intermediate 2 and high risk showed no significant difference (P = .44). Assessment of prognostic utility yielded a C-index of .575 (95% CI, .502 to .648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of .636 (95% CI, .563 to .708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P = .04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P = .01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification. ispartof: Biol Blood Marrow Transplant vol:25 issue:6 pages:e204-e208 ispartof: location:United States status: published

Published
2019

3. Additional file 1 of Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

Author

Dholaria, Bhagirathbhai, Labopin, Myriam, Sanz, Jaime, Ruggeri, Annalisa, Cornelissen, Jan, Labussière-Wallet, Hélène, Blaise, Didier, Forcade, Edouard, Chevallier, Patrice, Grassi, Anna, Zubarovskaya, Ludmila, Kuball, Jürgen, Ceballos, Patrice, Ciceri, Fabio, Baron, Frederic, Bipin N. Savani, Nagler, Arnon, and Mohty, Mohamad

Abstract

Additional file 1. Supplementary material.

Published
2021
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4. Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations

Author

Geneugelijk, Kirsten, Thus, Kirsten A., Van Deutekom, Hanneke W.M., Calis, Jorg J.A., Borst, Eric, Keşmir, Can, Oudshoorn, Machteld, Van Der Holt, Bronno, Meijer, Ellen, Zeerleder, Sacha, De Groot, Marco R., Von Dem Borne, Peter A., Schaap, Nicolaas, Cornelissen, Jan, Kuball, Jürgen, Spierings, Eric, Sub Theoretical Biology & Bioinformatics, Sub Theoretical Biology, Theoretical Biology and Bioinformatics, AII - Inflammatory diseases, Hematology, CCA - Cancer biology and immunology, Sub Theoretical Biology & Bioinformatics, Sub Theoretical Biology, Theoretical Biology and Bioinformatics, Clinical Haematology, ACS - Pulmonary hypertension & thrombosis, and Faculteit Medische Wetenschappen/UMCG

Subjects
Male, 0301 basic medicine, Oncology, HLA mismatch, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Disease, Epitope, Epitopes, MOLECULES, 0302 clinical medicine, HLA Antigens, VERSUS-HOST-DISEASE, Immunology and Allergy, Child, Original Research, UNRELATED-DONOR, biology, Non-permissible mismatch, Hematopoietic Stem Cell Transplantation, HSCT-hematopoietic stem cell transplant, Middle Aged, HLA, HLA-DPB1, HISTOCHECK, Child, Preschool, PIRCHE, Cohort, Female, DETERMINES NONPERMISSIVE MISMATCHES, Antibody, Unrelated Donors, Adult, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, HSCT—hematopoietic stem cell transplant, Adolescent, Immunology, Human leukocyte antigen, ACUTE GVHD, Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Transplantation Immunology, Internal medicine, medicine, Journal Article, Humans, Aged, Proportional Hazards Models, business.industry, Infant, CLASS-I MISMATCHES, HLA Mismatch, Transplantation, 030104 developmental biology, ANTIBODIES, biology.protein, lcsh:RC581-607, business, RECIPIENT, 030215 immunology
Abstract

HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA. We retrospectively scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II (PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease. These patients were divided into low and high PIRCHE-I and PIRCHE-II groups, based on their PIRCHE scores, and compared using multivariate statistical analysis methods. The high PIRCHE-II group had a significantly impaired OS compared to the low PIRCHE-II group and the 10/10 reference group (HR: 1.86, 95%-CI: 1.02-3.40; and HR: 2.65, 95%-CI: 1.53-4.60, respectively). Overall, PIRCHE-II seem to have a more prominent effect on OS than PIRCHE- I. This impaired OS is probably due to an increased risk for severe acute graft-vs.-host disease. These data suggest that high PIRCHE-II scores may be used to identify non-permissible HLA mismatches within single HLA-mismatched hematopoietic stem-cell transplantations.

Published
2019

5. Richtlijn Acute promyelocytenleukemie (APL): richtlijnen voor diagnostiek en behandeling

Author

Huls, G, Löwenberg, Bob, van de Loosdrecht, AA, Janssen, JJWM, Jongen - Lavrencic, Mojca, Raaijmakers, Marc, Wouters, Bas, van den Borne, P, Kuball, J, Biemond, B, van Gelder, M, van der Velden, WJFM, de Weerdt, O, Marwijk Kooy, R, Klein, S, Ammatuna, Emanuele, Poel, M, van Rhenen, A, Jong, JJM, Valk, Peter, van der Reijden, B, Cornelissen, Jan, Vellenga, E, Ossenkoppele, G, and Hematology

Published
2019

7. Additional file 1: of Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author

PoirĂŠ, Xavier, Labopin, Myriam, Maertens, Johan, Yakoub-Agha, Ibrahim, Blaise, Didier, Ifrah, Norbert, GĂŠrard SociĂŠ, Gedde-Dhal, Tobias, Schaap, Nicolaas, Cornelissen, Jan, StĂŠphane Vigouroux, Sanz, Jaime, Michaux, Lucienne, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon

Abstract

Table S1. (DOCX 13 kb)

Published
2017
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9. Additional file 1: of Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

Author

Saraceni, Francesco, Labopin, Myriam, Norbert-Claude Gorin, Blaise, Didier, Tabrizi, Reza, Volin, Liisa, Cornelissen, Jan, Jean-Yves Cahn, Chevallier, Patrice, Craddock, Charles, Depei Wu, Huynh, Anne, Arcese, William, Mohty, Mohamad, and Nagler, Arnon

Abstract

Listing all EBMT members. (DOCX 17 kb)

Published
2016
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10. PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay (R) in 201 patients with haematological disease suspected for invasive aspergillosis

Author

Chong, Ga-Lai, van der Beek, MT, von dem Borne, Pavd, Boelens, J, Steel, E, Kampinga, GA, Span, L F R, Lagrou, K, Maertens, JA, Dingemans, GJH, Gaajetaan, GR, van Tegelen, DWE, Cornelissen, Jan, Vonk, Alieke, Rijnders, Bart, Internal Medicine, Hematology, and Medical Microbiology & Infectious Diseases

Published
2016

11. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation

Author

Schmid, C, Labopin, M, Socie, G, Daguindau, E, Volin, L, Huynh, A, Bourhis, J H, Milpied, N, Cornelissen, Jan, Chevallier, P, Maertens, J, Jindra, P, Blaise, D, Lenhoff, S, Ifrah, N, Baron, F, Ciceri, F, Gorin, C, Savani, B, Giebel, S, Polge, E, Esteve, J, Nagler, A, Mohty, M, Acute Leukemia Party, Europ, Hematology, Schmid, C, Labopin, M, Socie, G, Daguindau, E, Volin, L, Huynh, A, Bourhis, Jh, Milpied, N, Cornelissen, J, Chevallier, P, Maertens, J, Jindra, P, Blaise, D, Lenhoff, S, Ifrah, N, Baron, F, Ciceri, Fabio, Gorin, C, Savani, B, Giebel, S, Polge, E, Esteve, J, Nagler, A, and Mohty, M.

Subjects
Adult, Male, medicine.medical_specialty, NPM1, Genotype, medicine.medical_treatment, Immunology, Graft vs Host Disease, Hematopoietic stem cell transplantation, Biology, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, Enhancer binding, medicine, Humans, Transplantation, Homologous, Survival rate, Neoplasm Staging, Retrospective Studies, Hematology, Remission Induction, Hematopoietic Stem Cell Transplantation, Induction chemotherapy, Cell Biology, Middle Aged, Prognosis, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, fms-Like Tyrosine Kinase 3, Tandem Repeat Sequences, 030220 oncology & carcinogenesis, Fms-Like Tyrosine Kinase 3, Cytogenetic Analysis, Female, Nucleophosmin, 030215 immunology, Follow-Up Studies
Abstract

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) can be subdivided by molecular mutations. However, data on the influence of combinations of different aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) is limited. Therefore, we performed a retrospective registry analysis on 702 adults with CN-AML undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. 2y-OS from HSCT was 81±5% in NPM1(mut)/FLT3(wt) (n=68), 75±3% in NPM1(wt)/FLT3(wt) (n=290), 66±3% in NPM1(mut)/FLT3-ITD (n=269) and 54±7% in NPM1(wt)/FLT3-ITD (n=75; p=0.003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) (n=13, 2y-OS:100%), and with a triple negative genotype (n=138, 2y-OS:77±3%). In a Cox-model of predefined factors, older age, presence of FLT3-ITD and >1 course of chemotherapy to reach CR were associated with inferior outcome. 2y-OS/LFS were 88±3%/79±4% in patients without any, 77±2%/73±3% with one, and 53±4%/50±4 with>=2 risk factors (p=0.002 for LFS, p=0.003 for OS). Hence, FLT3-ITD proofed to be the decisive molecular marker for outcome after HSCT for CN-AML in CR1, regardless of NPM1 mutational status, variations of transplant protocols, or development of GvHD. Age, FLT3-ITD and response to induction chemotherapy allow for a prognostic risk classification. (Less)

Published
2015

14. Flow Cytometric Differential of Leukocyte Populations in Normal Bone Marrow: Influence of Peripheral Blood Contamination

Author

Brooimans, Rik, Kraan, Jaco, Putten, Wim, Cornelissen, Jan, Löwenberg, Bob, Gratama, Jan willem, Medical Oncology, and Hematology

Abstract

Background: Availability of immunophenotypic reference values for the various leukocyte populations distributed in bone marrow may be helpful to recognize abnormal bone marrow development and, therefore, useful as first screening of individuals with suspected hematological malignancies or other hematopoietic disorders. Methods: A single tube four-color staining panel (CD66abce/CD14/CD45/CD34) together with a predefined gating strategy was utilized to immunologically differentiate the distribution of the major leukocyte populations in bone marrow aspirates of healthy donors. The sample-blood erythrocyte ratio was applied to assess the amount of blood contamination of marrow and account for this in the marrow value estimates. Results: The frequency of the major leukocyte populations in bone marrow of 134 normal donors were for granulocytes: mean, 69.4%; SD, 10.3%; monocytes: mean, 4.7%; SD, 2.3%; lymphocytes: mean, 18.3%; SD, 8.7%. The frequency of the immature cell population that included precursor cells of each of the cell lineages among other cell types were mean 5.0%; Sd 2.2%. The mean percentage of CD34 positive cells was 1.5%; SD 0.7%. Our results showed further that the frequency of cell populations, of which the presence is restricted to the bone marrow (e.g., CD34+ progenitor cells), is influenced by the degree of peripheral blood admixture. Between the total immature cells and purity of the bone marrow, there was a significant positive correlation demonstrated, whereas a negative correlation was found between the percentages of both lymphocytes as monocytes and the purity of the bone marrow. Conclusions: With a single tube-staining panel, we obtained reference values for flow cytometric assessment of all relevant leukocyte populations present in bone marrow that can be used as a frame of reference for better recognition of individuals with abnormal hematopoiesis. In addition, we have demonstrated the influence of the degree of peripheral blood admixture in the bone marrow aspirates on those reference values.(C) 2008 Clinical Cytometry Society

Published
2009

28. Progress in allogeneic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983-93 and 1994-98 at European Group for Blood and Marrow Transplantation centres

Author

Gahrton, G, Svensson, H, Cavo, M, Apperley, J, Bacigalupo, A, Björkstrand, B, Bladé, J, Cornelissen, Jan, de Laurenzi, A, Facon, T, Ljungman, P, Michallet, M, Niederwieser, D, Powles, R, Reiffers, J, Russell, NH, Samson, D, Schaefer, UW, Schattenberg, A, Tura, S, Verdonck, LF, Vernant, JP, Willemze, R, Volin, L, EBMT, GROUP, and Hematology

Published
2001

29. Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrosopective registry study from the European Group for Blood and Marrow

Author

Björkstrand, B, Svensson, H, Goldschmidt, HMJ, Ljungman, P, Apperley, J, Mandelli, F, Marcus, R, Boogaerts, MA, Alegre, A, Remes, K, Cornelissen, Jan, Bladé, J, Lenhoff, S, Iriondo, A, Carlson, K, Volin, L, Littlewood, T, Goldstone, AH, San miguel, JF, Schattenberg, A, Gahrton, G, EBMT, GROUP, and Hematology

Published
2001

30. Prognostic Value Of Five-Group Cytogenetic Risk Classification In Patients With MDS After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study Of The Chronic Malignancies Working Party Of The EBMT

Author

Christian Koenecke, Goehring, Gudrun, Wreede, Liesbeth, Biezen, Anja, Scheid, Christof, Volin, Liisa, Maertens, Johan, Finke, Juergen, Schaap, Nicolaas P. M., Robin, Marie, Passweg, Jakob R., Cornelissen, Jan J., Beelen, Dietrich, Heuser, Michael, Witte, Theo, and Kroeger, Nicolaus

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Abstract

Introduction The only curative treatment approach for patients with myelodysplastic syndromes (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), but disease relapse after transplantation is a major concern. Predictors for disease outcome after HSCT are limited. However, unfavorable cytogenetic abnormalities have been shown to serve as predictors for MDS-relapse after transplantation. Similar to the data available in MDS-patients not undergoing HSCT (Schanz et al. J Clin Oncol 2012), there is evidence that the novel 5-group cytogenetic classification has a better predictive value for outcome after HSCT than standard IPSS cytogenetics (Deeg et al. Blood 2012). The aim of this large multicentric, international study was to retrospectively determine the impact of the new 5-group cytogenetic MDS classification on outcome after HSCT. Patients and Methods Patients were selected from the EBMT database who had received HSCT for the treatment of MDS between 1982 and 2010 and for whom sufficient cytogenetic information was available. In total, 903 patients were included into the study. At time of HSCT, 97 (10.7%) patients had untreated MDS, 218 (24.1%) patients had advanced MDS or AML evolving from MDS in complete remission, and 227 (25.1%) patients were not in remission after treatment (in 12.3% information on stage of the disease was not available). Median time between diagnosis and transplant was 6.6 months (range 0.2-359.3). Matched related donor HSCT was performed in 574 patients (63.6%), and matched unrelated donor HSCT in 329 patients (36.4%). Bone marrow (35.4%) or peripheral blood (64.6%) served as stem cell graft. Myeloablative preparative regimens were used in 582 patients (64.5%), and a non-myeloablative regimen was given to 320 patients (35.4%). Impact of cytogenetic classification was analyzed in uni- and multivariate models regarding overall survival (OS) and relapse free survival (RFS) after HSCT. Predictive performance of the 2 classifications was compared by means of the cross-validated log partial likelihood. Results Estimated 5-year RFS and OS were 32% and 36% respectively. According to the 5-group cytogenetic classification 19 (2.1%) patients had very good risk cytogenetics, 204 (22.6%) normal risk cytogenetics, 438 (48.5%) intermediate risk cytogenetics, 178 (19.7%) poor risk cytogenetics, and 64 (7.1%) very poor risk cytogenetics. Good, intermediate, and poor risk cytogenetics according to IPSS were found in 192 (38.0%), 500 (40.2%), and 211 (23.7%) patients, respectively. In univariate analysis 5-group cytogenetic information was found to be strongly associated with OS and RFS (OS: log-rank test P Further clinicopathologic factors showed a significant impact on impaired OS and RFS: Disease status at HSCT (RA/RARS no pretreatment; RAEB(t)/sAML in CR; RAEB(t)/sAML not in CR, RAEB(t)/sAML untreated) (OS: P In multivariate analysis, statistically significant predictors for RFS and OS at HSCT were 5-group cytogenetics, IPSS-cytogenetics, disease status and patient's age. Using 5-group cytogenetics classification, patients with poor risk [(RFS: P=.001, HR=1.40 (95% CI: 1.15-1.71); OS: P=.003, HR=1.38 (95% CI: 1.12-1.70)] or very poor risk cytogenetics [(RFS: P When comparing the predictive performance of a series of 3 models both for OS and for RFS – (1) with only classical risk factors, (2) these extended with IPSS cytogenetics, (3) extended with 5-group classification instead-, the model with 5-group cytogenetics performed best. Conclusion In this international, multicentric analysis we confirm that MDS patients with poor and very poor risk cytogenetics had significantly worse RFS and OS after HSCT than patients in the other risk groups of the 5-group cytogenetic classifier. New therapeutic strategies to prevent relapse after HSCT in patients with poor or very poor cytogenetics are urgently needed. Disclosures: No relevant conflicts of interest to declare.

Published
2013

33. Tumortherapie

Author

Bruaset, I, Levendag, Peter, Vriens, JPM, Planting, AST, Cornelissen, Jan, Kalk, W., Freihofer, H.P.M., Visch, L.L., Radiation Oncology, Medical Oncology, and Hematology

Published
1999

41. Allogeneic Transplantation for Acute Myeloid Leukemia with Monosomy 7 or Deletion 7q: a Study from the Acute Leukemia Working Party (ALWP) of the EBMT

Author

Poire, Xavier, Labopin, Myriam, Polge, Emmanuelle, Volin, Liisa, Finke, Jurgen, Ganser, Arnold, Didier Blaise, Yakoub-Agha, Ibrahim, Beelen, Dietrich, Milpied, Noel, Ledoux, Marie-Pierre, Socie, Gerard, Niederwieser, Dietger, Michallet, Mauricette, Maertens, Johan, Cornelissen, Jan, Craddock, Charles, Mohty, Mohamad, Esteve, Jordi, and Nagler, Arnon

Subjects
Medizin

42. The Prognostic Impact of the Donor/Recipient CMV Serostatus in Patients with Different Chronic Hematological Disorders after Allogeneic Hematopoietic Stem Cell Transplantation: A Report from the Infectious Diseases Working Party of EBMT

Author

Schmidt-Hieber, Martin, Tridello, Gloria, Mikulska, Malgorzata, Knelange, Nina, Blaise, Didier, Socie, Gerard, Volin, Liisa, Nicolaas Schaap, Fegueux, Nathalie, Ljungman, Per, Yakoub-Agha, Ibrahim, Milpied, Noel, Maertens, Johan, Chevallier, Patrice, Passweg, Jakob R., Cornelissen, Jan J., Russell, Nigel H., Craddock, Charles, Bourhis, Jean-Henri, Lamy, Thierry, Remenyi, Peter, Cahn, Jean-Yves, Michallet, Mauricette, Montoto, Silvia, Kroger, Nicolaus, Glass, Bertram, and Styczynski, Jan

44. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

Author

Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J

Subjects
hemic and lymphatic diseases, 610 Medizin und Gesundheit, 3. Good health
Abstract

Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.

46. The Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: An Analysis By the EBMT Complications and Quality of Life WP

Author

Jagasia, Madan, Greinix, Hildegard T., Beohou, Eric, Werf, Steffie, Niederwieser, Dietger, Meijer, Ellen, Chevallier, Patrice, Sengeloev, Henrik, Blaise, Didier, Petersen, Eefke, Cornelissen, Jan J., Ehninger, Gerhard, Gribben, John G., Caballero, Dolores, Beguin, Yves, Michael Hallek, Jindra, Pavel, Fanin, Renato, Delage, Jeremy, Schoemans, Helene, Gedde-Dahl, Tobias, Nicolaus, Kroger, Basak, Grzegorz, and Duarte, Rafael F.

48. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Robin Foà, Elena Paravichnikova, Sebastian Giebel, Anita W. Rijneveld, Hervé Dombret, Frédéric Baron, David I. Marks, Adele K Fielding, Mohamad Mohty, Jordi Esteve, Fabio Ciceri, Arnon Nagler, Sabina Chiaretti, Helene Hallböök, Norbert Claude Gorin, Michael Doubek, Jan J. Cornelissen, Dieter Hoelzer, Nicola Gökbuget, Bipin N. Savani, Ulla Wartiovaara-Kautto, Christoph Schmid, Nicolas Boissel, Josep-Maria Ribera, Hematology, Giebel, Sebastian, Marks, David I., Boissel, Nicola, Baron, Frederic, Chiaretti, Sabina, Ciceri, Fabio, Cornelissen, Jan J., Doubek, Michael, Esteve, Jordi, Fielding, Adele, Foa, Robin, Gorin, Norbert-Claude, Gökbuget, Nicola, Hallböök, Helene, Hoelzer, Dieter, Paravichnikova, Elena, Ribera, Josep-Maria, Savani, Bipin, Rijneveld, Anita W., Schmid, Christoph, Wartiovaara-Kautto, Ulla, Mohty, Mohamad, Nagler, Arnon, and Dombret, Hervé

Subjects
Male, Pediatrics, medicine.medical_specialty, Allogeneic transplantation, Transplantation Conditioning, Cyclophosphamide, medicine.medical_treatment, Hematopoietic stem cell transplantation, Philadelphia chromosome, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Humans, Prospective Studies, Acute leukemia, Transplantation, business.industry, Remission Induction, Hematopoietic Stem Cell Transplantation, Hematology, Total body irradiation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Minimal residual disease, Europe, 030220 oncology & carcinogenesis, Adult Acute Lymphoblastic Leukemia, Female, business, 030215 immunology, medicine.drug
Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is a standard of care for adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) and high risk of relapse. However, the stratification systems vary among study groups. Inadequate response at the level of minimal residual disease is the most commonly accepted factor indicating the need for alloHSCT. In this consensus paper on behalf of the European Working Group for AdultAcute Lymphoblastic Leukemia and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize available evidence and reflect current clinical practice in major European study groups regarding both indications for HSCT and particular aspects of the procedure including the choice of donor, source of stem cells and conditioning. Finally, we propose recommendations for daily clinical practice as well as for planning of prospective trials.

Published
2019

49. Use of Tyrosine Kinase Inhibitors to Prevent Relapse After Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Position Statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Jordi Esteve, Arnon Nagler, Fabio Ciceri, Sebastian Giebel, Norbert Claude Gorin, Jan J. Cornelissen, Bipin N. Savani, Oliver G. Ottmann, Frédéric Baron, Christoph Schmid, Eolia Brissot, Anna Czyż, Mohamad Mohty, Giebel, Sebastian, Czyz, Anna, Ottmann, Oliver, Baron, Frederic, Brissot, Eolia, Ciceri, Fabio, Cornelissen, Jan J., Esteve, Jordi, Gorin, Norbert Claude, Savani, Bipin, Schmid, Christoph, Mohty, Mohamad, Nagler, Arnon, and Hematology

Subjects
Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Dasatinib, Tyrosine kinase inhibitor, Hematopoietic stem cell transplantation, Philadelphia chromosome, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, medicine, Humans, Philadelphia Chromosome, Intensive care medicine, Protein Kinase Inhibitors, Societies, Medical, Acute leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Cancer, Imatinib, Recommendation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Nilotinib, medicine.disease, R1, respiratory tract diseases, 030220 oncology & carcinogenesis, Allogeneic hematopoietic stem cell transplantation, Neoplasm Recurrence, Local, business, 030215 immunology, medicine.drug
Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL). The introduction of tyrosine kinase inhibitors (TKIs) to first-line therapy has improved overall outcomes; however, a significant proportion of patients still relapse after alloHSCT. Posttransplant TKI maintenance was demonstrated to reduce the risk of relapse in a large retrospective study and, therefore, should be considered a valuable option. This consensus paper, written on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, presents an overview of clinical studies on the use of TKIs after alloHSCT and proposes practical recommendations regarding the choice of TKI, treatment timing, and dosage. It is hoped that these recommendations will become the state of art in this field and, more importantly, lead to a reduction of Ph-positive ALL relapse after alloHSCT. Cancer 2016;122:2941-2951. © 2016 American Cancer Society.

Published
2016

50. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Author

Christophe Picard, Cécile Macquin, Sergi Querol, Catherine Paillard, Katharina Fleischhauer, Gaëlle Giacometti, Bronno van der Holt, Ibrahim Yakoub-Agha, Wassila Ilias, Anne Cesbron, Myriam Labopin, Masao Ota, Jorge Sierra, Fabio Ciceri, Dominique Charron, Ryad Tamouza, Régis Peffault de Latour, Xavier Lafarge, Katia Gagne, Seiamak Bahram, Myriam Maumy-Bertrand, Meiggie Untrau, Pascale Loiseau, Raphael Carapito, Jürgen Kuball, Bruno Lioure, Frans H.J. Claas, Noel Milpied, Antoine Toubert, Jan J. Cornelissen, Irina Kotova, Philippe Moreau, Eric Spierings, Mauricette Michallet, Arnon Nagler, Annette Schmitt-Graeff, Angélique Pichot, Petya Apostolova, Mohamad Mohty, Aurore Morlon, Myriam Labalette, Nicolas Jung, Didier Blaise, Yoshihiko Katsuyama, Hidetoshi Inoko, A. Parissiadis, Frédéric Bertrand, Marius Kwemou, Sandra Michel, Machteld Oudshoorn, Gérard Socié, Robert Zeiser, Peter A. von dem Borne, Valérie Dubois, Luca Vago, Carapito, Raphael, Jung, Nicola, Kwemou, Mariu, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, Van Der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, Von Dem Borne, Peter A., Kuball, Jürgen, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, De Latour, Régis Peffault, Blaise, Didier, Cornelissen, Jan J., Yakoub Agha, Ibrahim, Claas, Fran, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, Bahram, Seiamak, inconnu, Inconnu, Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'Etudes et de recherches en Statistiques et Développement (LERSTAD), Université Gaston Bergé Sénégal, Laboratoire d'Acoustique Environnementale (IFSTTAR/AME/LAE), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Lyon-PRES Université Nantes Angers Le Mans (UNAM), Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Etablissement Français du Sang [Nantes], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne (PRISME-GSPE), Centre National de la Recherche Scientifique (CNRS), Centre de Transfusion Sanguine Aquitaine-Limousin (CTS AQUITAINE-LIMOUSIN), Centre de Transfusion Sanguine, Ospedale San Raffaele, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Barcelona Cord Blood Bank, Agrosystèmes tropicaux (ASTRO), Institut National de la Recherche Agronomique (INRA), Chaim Sheba Medical Center [Ramat Gan, Israel], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Université Paris Diderot - Paris 7 (UPD7), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigations Biomédicales-Hématologie, Oncologie et Greffes (CIB-HOG), Hôpital St Louis, Assistance Publique des Hôpitaux de Paris (AP-HP), Centre d'Investigations Biomédicales-Hématologie, Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), ALWP-EBMT & Département d'hématologie et de thérapie cellulaire [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Hematology, Institut de Recherche Mathématique Avancée ( IRMA ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Mathématiques et Modélisation d'Evry ( LaMME ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -ENSIIE-Centre National de la Recherche Scientifique ( CNRS ), laboratoire d'Etudes et de recherches en Statistiques et Développement ( LERSTAD ), Laboratoire d'Acoustique Environnementale ( IFSTTAR/AME/LAE ), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ) -Université de Lyon-PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire d'Histoire des Sciences et de Philosophie - Archives Henri Poincaré ( LHSP ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des interactions ioniques et moléculaires ( PIIM ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Functional Genomics and Cancer, Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne ( PRISME-GSPE ), Centre National de la Recherche Scientifique ( CNRS ), Centre de Transfusion Sanguine Aquitaine-Limousin ( CTS AQUITAINE-LIMOUSIN ), Géographie de l'environnement ( GEODE ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse - Jean Jaurès ( UT2J ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Agrosystèmes tropicaux ( ASTRO ), Institut National de la Recherche Agronomique ( INRA ), Hospices Civils de Lyon ( HCL ), IFR Saint-Louis, institut d'hématologie ( ISLIH ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC University medical Centre / Daniel den Hoed Cancer centre, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Laboratoire de Mathématiques et Modélisation d'Evry, PRES Université Nantes Angers Le Mans (UNAM)-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-ENSIIE-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Graft vs Host Disease, Hematopoietic stem cell transplantation, Biochemistry, Linkage Disequilibrium, immune system diseases, HLA Antigens, Cytotoxic T cell, Child, ComputingMilieux_MISCELLANEOUS, HLA-DQB1, biology, Histocompatibility Testing, Incidence, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, 3. Good health, surgical procedures, operative, NK Cell Lectin-Like Receptor Subfamily K, Child, Preschool, Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, Adolescent, Immunology, Human leukocyte antigen, 03 medical and health sciences, MHC class I, medicine, Journal Article, Humans, Aged, Retrospective Studies, Transplantation, [ SDV ] Life Sciences [q-bio], Histocompatibility Antigens Class I, Infant, Newborn, Infant, Cell Biology, medicine.disease, Histocompatibility, stomatognathic diseases, 030104 developmental biology, Graft-versus-host disease, Chronic Disease, biology.protein
Abstract

Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B. Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.

Published
2016

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