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

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Research

Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Authors: Nicole Santoro, Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Fabio Ciceri, Zafer Gülbaş, He Huang, Boris Afanasyev, William Arcese, Depei Wu, Yener Koc, Johanna Tischer, Stella Santarone, Sebastian Giebel, Mohamad Mohty, Arnon Nagler

Published in: Journal of Hematology & Oncology | Issue 1/2017

Login to get access

Abstract

Background

Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors.

Methods

We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014.

Results

Median age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on anti-thymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II–IV acute-graft-versus-host-disease (GVHD) was 31%, grade III–IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS.

Conclusions

Unmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Jabbour E, O'Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer. 2015;121:2517–28.CrossRefPubMed
4.
Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman AV, Richards SM, et al. Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII/ECOG 2993 trial. Br J Haematol. 2012;157:463–71.CrossRefPubMedPubMedCentral
5.
Kantarjian HM, Thomas D, O'Brien S, Cortes J, Giles F, Jeha S, Bueso-Ramos CE, Pierce S, Shan J, Koller C, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788–801.CrossRefPubMed
6.
Gokbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Hüttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, et al. Outcome of relapsed adult acute lymphoblastic leukemia depends on reponse to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012;120:2032–41.CrossRefPubMed
7.
Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008;111:1827–33.CrossRefPubMed
8.
Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004;22:4075–86.CrossRefPubMed
9.
Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C, Falkenburg JH, Farge-Bancel D, Gennery A, Kröger N, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50:1037–56.CrossRefPubMed
10.
Gupta V, Richards S, Rowe J, Acute Leukemia Stem Cell Transplantation Trialists’ Collaborative Group. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta analysis. Blood. 2013;121:339–50.CrossRefPubMedPubMedCentral
11.
Oliansky DM, Larson RA, Weisdorf D, Dillon H, Ratko TA, Wall D, McCarthy Jr PL, Hahn T, et al. The role of cytotoxic therapy with hemopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence based review. Biol Blood Marrow Transplant. 2012;18:18–36.CrossRefPubMed
12.
Messori A, Fadda V, Maratea D, Trippoli S. Acute lymphoblastic leukemia in first complete remission: temporal trend of outcomes in studies comparing allogenic transplant with autologus transplant or chemotherapy. Ann Hematol. 2013;92:1221–8.CrossRefPubMed
13.
Ciurea SO, Bayraktar UD. “No donor”? Consider a haploidentical transplant. Blood Rev. 2015;29:63–70.CrossRefPubMed
14.
Tucunduva L, Ruggeri A, Sanz G, Furst S, Socié G, Michallet M, Arcese W, Milpied N, Yakoub-Agha I, Linkesch W, et al. Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2014;49:887–94.CrossRefPubMed
15.
Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, Duarte RF, Dufour C, Falkenburg JH, Farge-Bancel D, et al. Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant. 2015;50:476–82.CrossRefPubMedPubMedCentral
16.
Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:10–24.CrossRefPubMed
17.
Luznik L, O’Donnel PV, Fuchs EJ. Post transplantation cyclophosphamide for tolerance induction in HLA haploidentical BMT. Seminar Oncol. 2012;39:683–93.CrossRef
18.
Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19:117–22.CrossRefPubMed
19.
Di Bartolomeo P, Santarone S, De A, Picardi A, Cudillo L, Cerretti R, Adorno G, Angelini S, Andreani M, De Felice L, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:849–57.CrossRefPubMed
20.
Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Wu MQ, Wu DP, Huang XJ. Haploidentical versus matched-sibling transplant in adults with Philadelphia-negative high-risk acute lymphoblastic leukemia: a biologically phase III randomized study. Clin Cancer Res. 2016;22:3467–76.CrossRefPubMed
21.
Chang YJ, Huang XJ. Haploidentical stem cell transplantation: anti-thymocyte globulin-based experience. Semin Hematol. 2016;53:82–9.CrossRefPubMed
22.
Savani BN, Labopin M, Kröger N, Finke J, Ehninger G, Niederwieser D, Schwerdtfeger R, Bunjes D, Glass B, Socié G, et al. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT. Haematologica. 2016;101:773–80.CrossRefPubMedPubMedCentral
23.
Piemontese S, Ciceri F, Labopin M, Bacigalupo A, Huang H, Santarone S, Gorin NC, Koc Y, Wu D, Beelen D, et al. A survey of unmanipulated haploidentical hematopoietic stem cell transplantation in adult with acute leukemia. Leukemia. 2015;29:1069–75.CrossRefPubMed
24.
Piemontese S, Ciceri F, Labopin M, Arcese W, Kyrcz-Krzemien S, Santarone S, Huang H, Beelen D, Gorin NC, Craddock C, et al. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. J Hematol Oncol. 2017;10:24.CrossRefPubMedPubMedCentral
25.
Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, Blaise D, Bosi A, Huang H, Karakasis D, et al. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia. 2015;29:1891–900.CrossRefPubMed
26.
Srour SA, Milton DR, Bashey A, Karduss-Urueta A, Al Malki MM, Romee R, Solomon S, Nademanee A, Brown S, Slade M, et al. Haploidentical transplantation with post-transplantation cyclophosphamide for high-risk acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2017;23:318–24.CrossRefPubMed
27.
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.CrossRefPubMedPubMedCentral
28.
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.CrossRefPubMed
29.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus conference on aGvHD grading. Bone Marrow Transplant. 1995;15:825–8.PubMed
30.
Lee SJ, Vogelsang G, Flowers ME. Chronic graft versus host disease. Biol Blood Marrow Transplant. 2003;9:215–33.CrossRefPubMed
31.
Hoogard P. Frailty model for survival data. Lifetime Data Anal. 1995;1:255–73.CrossRef
32.
Andersen PK, Klein JP, Zhang MJ. Testing for center effects in multi-center survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–500.CrossRefPubMed
33.
Giebel S, Labopin M, Socié G, Beelen D, Beelen D, Browne P, Volin L, Kyrcz-Krzemien S, Yakoub-Agha I, Aljurf M, Wu D, et al. Improving results of allogeneic hematopoietic cell transplantation for adults with acute lymphoblastic leukemia in first complete remission: an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2017;102:139–49.CrossRefPubMedPubMedCentral
34.
Pavlů J, Labopin M, Zoellner AK, Sakellari I, Stelljes M, Finke J, Fanin R, Stuhler G, Afanasyev BV, Bloor AJ, et al. Allogeneic hematopoietic cell transplantation for primary refractory acute lymphoblastic leukemia: a report from the acute leukemia working party of the EBMT. Cancer. 2017. doi:10.​1002/​cncr.​30604. [Epub ahead of print].
35.
Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16:57–66.CrossRefPubMed
36.
Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gökbuget N, O’Brien S, Wang K, Wang T, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;25(375):740–53.CrossRef
37.
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17.CrossRefPubMedPubMedCentral
38.
Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28.CrossRefPubMed
39.
Rubio MT, Savani BN, Labopin M, Piemontese S, Polge E, Ciceri F, Bacigalupo A, Arcese W, Koc Y, Beelen D, et al. Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT. J Hematol Oncol. 2016;9:25.CrossRefPubMedPubMedCentral
40.
O'Donnell PV, Eapen M, Horowitz MM, Logan BR, DiGilio A, Brunstein C, Fuchs EJ, Flowers ME, Salit R, Raj K, et al. Comparable outcomes with marrow or peripheral blood as stem cell sources for hematopoietic cell transplantation from haploidentical donors after non-ablative conditioning: a matched-pair analysis. Bone Marrow Transplant. 2016;51:1599–601.CrossRefPubMed
41.
Castagna L, Crocchiolo R, Furst S, Bramanti S, El Cheikh J, Sarina B, Granata A, Mauro E, Faucher C, Mohty B, et al. Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2014;20:724–9.CrossRefPubMed
42.
Giebel S, Czyz A, Ottmann O, Baron F, Brissot E, Ciceri F, Cornelissen JJ, Esteve J, Gorin NC, Savani B, et al. 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. Cancer. 2016;122:2941–51.CrossRefPubMed
43.
Dhédin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, Thomas X, Chevallier P, Nguyen S, Coiteux V, et al. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015;125:2486–96.CrossRefPubMed
Metadata
Title
Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT
Authors
Nicole Santoro
Annalisa Ruggeri
Myriam Labopin
Andrea Bacigalupo
Fabio Ciceri
Zafer Gülbaş
He Huang
Boris Afanasyev
William Arcese
Depei Wu
Yener Koc
Johanna Tischer
Stella Santarone
Sebastian Giebel
Mohamad Mohty
Arnon Nagler
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0480-5

Other articles of this Issue 1/2017

Journal of Hematology & Oncology 1/2017 Go to the issue

Editorial

Recent advances in cancer immunotherapy

Research

EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth

Research

Single- or double-unit UCBT following RIC in adults with AL: a report from Eurocord, the ALWP and the CTIWP of the EBMT

Review

The cell cycle checkpoint inhibitors in the treatment of leukemias

Review

New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy

Research

Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China Continuation study
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