Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2018

Open Access 01-12-2018 | Research

Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC

Authors: Florent Malard, Myriam Labopin, Christina Cho, Didier Blaise, Esperanza B. Papadopoulos, Jakob Passweg, Richard O’Reilly, Edouard Forcade, Molly Maloy, Liisa Volin, Hugo Castro-Malaspina, Yosr Hicheri, Ann A. Jakubowski, Corentin Orvain, Sergio Giralt, Mohamad Mohty, Arnon Nagler, Miguel-Angel Perales

Published in: Journal of Hematology & Oncology | Issue 1/2018

Login to get access

Abstract

Background

Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT).

Methods

We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors.

Results

Two-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p = 0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p = 0.02; HR 15.1 (95% CI 5.3–42.2), p < 0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p = 0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p = 0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p = 0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p = 0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p = 0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p = 0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p = 0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p = 0.04).

Conclusions

These data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.
Appendix
Available only for authorised users
Literature
1.
Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136–52.CrossRef
2.
Sengsayadeth S, Savani BN, Blaise D, Malard F, Nagler A, Mohty M. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission - a review from the Acute Leukemia Working Party of the EBMT. Haematologica. 2015;100:859–69.CrossRef
3.
Malard F, Chevallier P, Guillaume T, Delaunay J, Rialland F, Harousseau JL, Moreau P, Mechinaud F, Milpied N, Mohty M. Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a single-institution’s three decade experience. Biol Blood Marrow Transplant. 2014;20:1217–23.CrossRef
4.
Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, Petersdorf EW, Pereira SE, Nash RA, Mielcarek M, Fero ML, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117:3214–9.CrossRef
5.
Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Couban S, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487–96.CrossRef
6.
Arai S, Arora M, Wang T, Spellman SR, He W, Couriel DR, Urbano-Ispizua A, Cutler CS, Bacigalupo AA, Battiwalla M, et al. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2015;21:266–74.CrossRef
7.
Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Barbanti M, Sacchi N, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98:2942–7.CrossRef
8.
Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T, Heim DA, Schwerdtfeger R, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64.CrossRef
9.
Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, Gallagher G, Kerr H, Kuruvilla J, Lee SJ, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164–73.CrossRef
10.
Kroger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, Nagler A, Selleri C, Risitano A, Messina G, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med. 2016;374:43–53.CrossRef
11.
Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, et al. 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. Biol Blood Marrow Transplant. 2006;12:560–5.CrossRef
12.
Soiffer RJ, Kim HT, McGuirk J, Horwitz ME, Johnston L, Patnaik MM, Rybka W, Artz A, Porter DL, Shea TC, et al. Prospective, randomized, double-blind, phase iii clinical trial of anti-T-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017. https://​doi.​org/​10.​1200/​JCO.​2017.​75.​8177.CrossRef
13.
14.
Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000;96:2419–25.PubMed
15.
Devine SM, Carter S, Soiffer RJ, Pasquini MC, Hari PN, Stein A, Lazarus HM, Linker C, Stadtmauer EA, Alyea EP 3rd, et al. Low risk of chronic graft-versus-host disease and relapse associated with T cell-depleted peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission: results of the blood and marrow transplant clinical trials network protocol 0303. Biol Blood Marrow Transplant. 2011;17:1343–51.CrossRef
16.
Papadopoulos EB, Carabasi MH, Castro-Malaspina H, Childs BH, Mackinnon S, Boulad F, Gillio AP, Kernan NA, Small TN, Szabolcs P, et al. T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. Blood. 1998;91:1083–90.PubMed
17.
Jakubowski AA, Small TN, Kernan NA, Castro-Malaspina H, Collins N, Koehne G, Hsu KC, Perales MA, Papanicolaou G, van den Brink MR, et al. T cell-depleted unrelated donor stem cell transplantation provides favorable disease-free survival for adults with hematologic malignancies. Biol Blood Marrow Transplant. 2011;17:1335–42.CrossRef
18.
Jakubowski AA, Petrlik E, Maloy M, Hilden P, Papadopoulos E, Young JW, Boulad F, Castro-Malaspina H, Tamari R, Dahi PB, et al. T cell depletion as an alternative approach for patients 55 years or older undergoing allogeneic stem cell transplantation as curative therapy for hematologic malignancies. Biol Blood Marrow Transplant. 2017;23:1685–94.CrossRef
19.
Pasquini MC, Devine S, Mendizabal A, Baden LR, Wingard JR, Lazarus HM, Appelbaum FR, Keever-Taylor CA, Horowitz MM, Carter S, et al. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. J Clin Oncol. 2012;30:3194–201.CrossRef
20.
Jakubowski AA, Small TN, Young JW, Kernan NA, Castro-Malaspina H, Hsu KC, Perales MA, Collins N, Cisek C, Chiu M, et al. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood. 2007;110:4552–9.CrossRef
21.
Bayraktar UD, de Lima M, Saliba RM, Maloy M, Castro-Malaspina HR, Chen J, Rondon G, Chiattone A, Jakubowski AA, Boulad F, et al. Ex vivo T cell-depleted versus unmodified allografts in patients with acute myeloid leukemia in first complete remission. Biol Blood Marrow Transplant. 2013;19:898–903.CrossRef
22.
Keever-Taylor CA, Devine SM, Soiffer RJ, Mendizabal A, Carter S, Pasquini MC, Hari PN, Stein A, Lazarus HM, Linker C, et al. Characteristics of CliniMACS(R) system CD34-enriched T cell-depleted grafts in a multicenter trial for acute myeloid leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303. Biol Blood Marrow Transplant. 2012;18:690–7.CrossRef
23.
Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.CrossRef
24.
Peric Z, Cahu X, Chevallier P, Brissot E, Malard F, Guillaume T, Delaunay J, Ayari S, Dubruille V, Le Gouill S, et al. Features of Epstein-Barr virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation. Leukemia. 2011;25:932–8.CrossRef
25.
Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016;51:610–1.CrossRef
26.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.
27.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.CrossRef
28.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi MS, Storb R, Thomas ED. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.CrossRef
29.
Wagner JE, Thompson JS, Carter SL, Kernan NA, Unrelated Donor Marrow Transplantation Trial. Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): a multi-centre, randomised phase II-III trial. Lancet. 2005;366:733–41.CrossRef
30.
Goldberg JD, Zheng J, Ratan R, Small TN, Lai KC, Boulad F, Castro-Malaspina H, Giralt SA, Jakubowski AA, Kernan NA, et al. Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant. Leuk Lymphoma. 2017;58:1859–71.CrossRef
31.
Kosuri S, Adrianzen Herrera D, Scordo M, Shah GL, Cho C, Devlin SM, Maloy MA, Nieves J, Borrill T, Carlow DC, et al. The impact of toxicities on first-year outcomes after ex vivo CD34(+)-selected allogeneic hematopoietic cell transplantation in adults with hematologic malignancies. Biol Blood Marrow Transplant. 2017;23:2004–11.CrossRef
32.
Scordo M, Shah GL, Kosuri S, Herrera DA, Cho C, Devlin SM, Maloy MA, Nieves J, Borrill T, Avecilla ST, et al. Effects of late toxicities on outcomes in long-term survivors of ex-vivo CD34(+)-selected allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2018;24:133–41.CrossRef
33.
Shah GL, Scordo M, Kosuri S, Herrera DA, Cho C, Devlin SM, Borrill T, Carlow DC, Avecilla ST, Meagher RC, et al. Impact of toxicity on survival for older adult patients after CD34(+) selected allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2018;24:142–9.CrossRef
34.
Cho C, Hsu M, Barba P, Maloy MA, Avecilla ST, Barker JN, Castro-Malaspina H, Giralt SA, Jakubowski AA, Koehne G, et al. Long-term prognosis for 1-year relapse-free survivors of CD34+ cell-selected allogeneic hematopoietic stem cell transplantation: a landmark analysis. Bone Marrow Transplant. 2017;52:1629–36.CrossRef
35.
Huang YT, Kim SJ, Lee YJ, Burack D, Nichols P, Maloy M, Perales MA, Giralt SA, Jakubowski AA, Papanicolaou GA. Co-infections by double-stranded DNA viruses after ex vivo T cell-depleted, CD34(+) selected hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2017;23:1759–66.CrossRef
36.
Huang YT, Neofytos D, Foldi J, Kim SJ, Maloy M, Chung D, Castro-Malaspina H, Giralt SA, Papadopoulos E, Perales MA, et al. Cytomegalovirus infection after CD34(+)-selected hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:1480–6.CrossRef
37.
Storek J, Mohty M, Boelens JJ. Rabbit anti-T cell globulin in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21:959–70.CrossRef
38.
Barba P, Martino R, Zhou Q, Cho C, Castro-Malaspina H, Devlin S, Esquirol A, Giralt S, Jakubowski AA, Caballero D, et al. cd34+ selection vs. reduced-intensity conditioning and unmodified graft for allogeneic hematopoietic cell transplantation in patients with AML and MDS > 50 years. Biol Blood Marrow Transplant. 2018;24:964–72.
39.
Ayuk F, Diyachenko G, Zabelina T, Wolschke C, Fehse B, Bacher U, Erttmann R, Kroger N, Zander AR. Comparison of two doses of antithymocyte globulin in patients undergoing matched unrelated donor allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:913–9.CrossRef
40.
Locatelli F, Bernardo ME, Bertaina A, Rognoni C, Comoli P, Rovelli A, Pession A, Fagioli F, Favre C, Lanino E, et al. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:1126–36.CrossRef
41.
Admiraal R, Nierkens S, de Witte MA, Petersen EJ, Fleurke GJ, Verrest L, Belitser SV, Bredius RGM, Raymakers RAP, Knibbe CAJ, et al. Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a multicentre, retrospective, pharmacodynamic cohort analysis. Lancet Haematol. 2017;4:e183–91.CrossRef
Metadata
Title
Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC
Authors
Florent Malard
Myriam Labopin
Christina Cho
Didier Blaise
Esperanza B. Papadopoulos
Jakob Passweg
Richard O’Reilly
Edouard Forcade
Molly Maloy
Liisa Volin
Hugo Castro-Malaspina
Yosr Hicheri
Ann A. Jakubowski
Corentin Orvain
Sergio Giralt
Mohamad Mohty
Arnon Nagler
Miguel-Angel Perales
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2018
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-018-0668-3

Other articles of this Issue 1/2018

Journal of Hematology & Oncology 1/2018 Go to the issue

Case report

Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma

Correction

Correction to: Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel

Research

MET alterations detected in blood-derived circulating tumor DNA correlate with bone metastases and poor prognosis

Research

PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse

Research

Exosomes released by hepatocarcinoma cells endow adipocytes with tumor-promoting properties

Review

T cell senescence and CAR-T cell exhaustion in hematological malignancies
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits