-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1050 [CANCELED] Outcome of Children with B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) with Hypodiploidy or BCR-ABL1 Fusion Given Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): Results from the Prospective Forum Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Donor and Conditioning Regimen Selection
Hematology Disease Topics & Pathways:
Research, ALL, Biological therapies, clinical trials, Lymphoid Leukemias, Clinical Research, pediatric, Diseases, Therapies, Lymphoid Malignancies, Human, Study Population, Transplantation
Monday, December 11, 2023: 5:45 PM

Jochen Buechner, MD, PhD1*, Ulrike Poetschger2*, Paulina Kurzmann2*, Peter Bader, MD, PhD3, Jean-Hugues Dalle, MD, PhD4*, Akif Yesilipek, MD5*, Herbert Pichler, MD6*, Julia Palma, MD7*, Raquel Staciuk, MD8*, Petr Sedlacek, MD, PhD9*, Gergely Krivan, MD, PhD10*, Marianne Ifversen, MD11*, Tayfun Güngör, MD12*, Vassiliki Kitra Rousou13*, Krzysztof Kalwak, MD, PhD14*, Jacek Toporski15*, Peter J. Shaw, MBBS, FRACP, MA, MRCP16, Marleen Renard17*, Cristina Díaz De Heredia, MD18*, Toni Matic, MD19*, Marc Bierings, MD20, Peter Svec, MD, PhD21*, Roland Meisel, MD22*, Adriana Balduzzi23,24, Franco Locatelli, MD, PhD25, Christina Peters, MD26,27* and Jerry Stein, MD28,29*

1Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway
2St. Anna Children's Cancer Research Institute (CCRI), Vienna, Austria
3Division for Stem Cell Transplantation and Immunology, University Children's Hospital Frankfurt, Frankfurt, Germany
4Pediatric Hematology and Immunology Department, GHU APHP Nord - Université Paris Cité, Robert Debré Hospital, Paris, France
5Medical Park Antalya Hospital, Antalya, Turkey
6Children's Cancer Research Institute, St. Anna Children's Hospital, University Vienna, Vienna, Austria
7Hospital Luis Calvo Mackenna, Santiago, RM, CHL
8Hospital de Pediatría "Prof. Dr Juan P. Garrahan", Buenos Aires, Argentina
9Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague, Czech Republic
10Pediatric Hematology and Stem Cell Transplantation Department, National Institute of Hematology and Infectious Diseases, Central Hospital of Southern Pest, Budapest, Hungary
11Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
12University Children's Hospital, Zürich, Switzerland, Zürich, Switzerland
13Stem Cell Transplant Unit, Agia Sofia Children’s Hospital, Athens, Greece
14Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland
15Department Cell Therapy and Allogeneic Stem Cell Transplant (CAST), Karolinska University Hospital, Stockholm, Sweden
16The Children's Hospital at Westmead, Sydney, Australia
17University Hospital Leuven, Leuven, BEL
18Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca, Barcelona, Spain
19Department of Paediatrics, University Hospital Centre, Zagreb, Croatia
20Princess Máxima Center, University Hospital for Children, Utrecht, Netherlands
21Bone Marrow Transplantation Unit, Department of Pediatric Hematology and Oncology, National Institute of Children's Diseases, Comenius University, Bratislava, Slovakia
22Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
23Pediatric Hematopoietic Transplant Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy, School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy
24School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
25Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy
26St. Anna Children's Hospital, Vienna, Austria, Austria
27Children’s Cancer Research Institute, Vienna, Austria
28Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
29Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel


Hypodiploid karyotype (HYPO) and bcr-abl1 fusion (BCRABL) define high-risk BCP-ALL subtypes, with historically worse outcomes. Many front-line treatment protocols recommend allogeneic HSCT for these patients (pts), either in first complete remission (CR1) irrespective of response (adolescents/young adults with HYPO), if minimal residual disease (MRD) signals persist at specific time points (younger pts with HYPO and all pts with BCRABL), or following leukemic relapse.

We have assessed the outcomes of BCP-ALL pts aged 4 to 18 years (y) with either HYPO or BCRABL who participated in the phase III ALL SCT PED FORUM study (EudraCT: 2012-003032-22) and underwent HSCT from either a matched sibling (MSD) or matched unrelated donor (MUD).

Patients and Methods:

Between 2014 and January 2023, 741 evaluable BCP-ALL pts were enrolled in FORUM (Table 1). HYPO was present in 61 pts, BCRABL in 82 pts, and neither lesion in 598 pts (NEITHER). 43/61 (70%), 40/82 (49%) and 215/598 (36%) pts with HYPO, BCRABL and NEITHER were in CR1, respectively (p= n.s.). Prior to HSCT, 82 of 101 HYPO/BCRABL pts with available MRD data were MRD negative by PCR and/or flowcytometry (<10-4). Total body irradiation (TBI) + VP16 was administered to 42 and 50 pts in the HYPO and BCRABL groups, respectively, while 18 HYPO and 30 BCRABL pts received non-TBI conditioning (busulfan or treosulfan + fludarabine and thiotepa, as per study protocol). Randomization determined allocation to TBI/non-TBI treatment arms until randomization closure in 03/2019, while treatment in some pts was dictated by lack of access to TBI, or contraindication to TBI in individual pts. An MSD was available in 14 (23%) and 24 (29%) HYPO and BCRABL pts, respectively. Notably, 24 out of 143 pts (17%) with HYPO/BCRABL received immunotherapy before HSCT (blinatumomab, inotuzumab ozogamicin, and/or CAR-T cells). Post-HSCT, 14 out of 82 BCRABL pts (17%) received a tyrosine kinase inhibitor (TKI), either prophylactically or pre-emptively.


With a median follow-up of three years post-HSCT, the 5-y probabilities of overall survival (OS) for pts with HYPO, BCRABL and NEITHER were 0.79±0.06, 0.83±0.05, and 0.74±0.02 (p=n.s.), while those of event-free survival (EFS) were 0.73±0.06, 0.65±0.07, and 0.61±0.02, respectively (p=n.s.). The 5-y cumulative incidence of relapse (CIR) for HYPO/BCRABL and NEITHER pts was 0.21±0.04 and 0.29±0.02 (p=0.036), and 5-y non-relapse mortality (NRM) was nearly identical for these groups (0.07±0.2 and 0.08±0.1).

Among pts who received TBI, 5-y OS and EFS for HYPO, BCRABL, and NEITHER groups were 0.76±0.08 and 0.70±0.08, 0.89±0.05 and 0.70±0.10, and 0.80±0.03 and 0.71±0.03, respectively (p=n.s., Figure 1), while 5-y CIR and NRM post TBI were 0.15±0.06 and 0.11±0.05, 0.15±0.06 and 0.11±0.05, and 0.20±0.02 and 0.07±0.02, for the three groups, respectively (p=n.s.). The 3-y GvHD-free/relapse-free survival (GRFS) was similar between HYPO/BCRABL and NEITHER (0.60±0.06 and 0.58±0.03, respectively) and reached a plateau at 5-years (0.60±0.06 and 0.57±0.03, respectively). In subgroup analyses of pts in CR1 and >CR1, comparable outcomes were observed for HYPO, BCRABL, and NEITHER, hence results were not affected by the remission status.

BCRABL and NEITHER pts receiving non-TBI conditioning had inferior outcomes (5-y EFS of 0.56±0.10 and 0.47±0.04, respectively) with a high 5-y CIR (0.36±0.09 and 0.43±0.04, respectively) as compared to those who received TBI. Similar 5-y OS and EFS were seen in HYPO pts whether receiving TBI (0.76±0.8 and 0.70±0.08) or chemo conditioning (83±0.09 and 83±0.09). Rates of NRM and acute/chronic graft-versus-host disease were similar in pts receiving TBI/ non-TBI conditioning and in BCRABL/HYPO vs. NEITHER pts.

In multivariate analysis adjusted for CR status, conditioning and MRD, EFS did not differ between HYPO/BCRABL and NEITHER pts.


Children receiving HSCT for treatment of BCP-ALL with either hypodiploidy or bcr-abl1 fusion showed outcomes comparable to BCP-ALL pts without these genetic lesions. CIR and EFS reached plateaus beyond 3 y post-HSCT, indicating that approximately two-thirds of these pts can be cured by HSCT with low rates of treatment-related mortality. Pts with BCRABL achieved favorable outcomes without the need for long-term or lifelong TKI therapy.

Disclosures: Buechner: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bader: Neovii: Research Funding; Novartis: Consultancy, Research Funding; BMS: Research Funding; Medac: Consultancy, Patents & Royalties: medac, Research Funding. Dalle: Novartis, Orchard: Membership on an entity's Board of Directors or advisory committees, Other: speaker (symposia); blue bird bio, Incyte, Jazz Pharm. Medac, Sanofi, Vertex: Membership on an entity's Board of Directors or advisory committees. Pichler: Neovii: Other: Travel grants . Kalwak: medac: Speakers Bureau; Novartis: Speakers Bureau; Pierre Fabre: Other: travel grants, Speakers Bureau. Díaz De Heredia: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Speakers Bureau; Biotest: Consultancy; Prothya Biosolutions: Research Funding; Jazz Pharmaceuticals: Consultancy, Other: travel expenses. Meisel: Vertex: Consultancy, Research Funding, Speakers Bureau; CRISPR Therapeutics: Consultancy, Research Funding, Speakers Bureau; Miltenyi Biotech: Research Funding; Bluebird Bio: Consultancy, Speakers Bureau; CELGENE BMS: Consultancy, Research Funding, Speakers Bureau; Gilead/KITE: Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; medac: Consultancy, Research Funding, Speakers Bureau. Balduzzi: Novartis: Speakers Bureau; Agmen: Speakers Bureau; Medac: Speakers Bureau; Neovii: Speakers Bureau. Locatelli: Miltenyi, Jazz Pharm, Medac, Sobi, Gilead, BluebirdBio: Speakers Bureau; Bellicum, Amgen, Neovii, Novartis. Sanofi, SOBI, Vertex: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi, Vertex: Membership on an entity's Board of Directors or advisory committees. Peters: AOP Orphan Drugs, Jazz, Neovii: Other: Meeting/Travel grant; Riemser, Medac: Honoraria; Novartis, AMGEN: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; AMGEN, Neovii, Jazz: Research Funding.

<< Previous Abstract | Next Abstract
*signifies non-member of ASH