Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Congenital Amegakaryocytic Thrombocytopenia, a PDWP/EBMT Study

Aldebert, Clemence

Oral and Poster Abstracts
904. Outcomes Research—Non-Malignant Conditions: Poster III

Biological therapies, Bone Marrow Failure Syndromes, Inherited Marrow Failure Syndromes, Diseases, Therapies, Transplantation

Clemence Aldebert¹^*, Mony Fahd, MD MSc²^*, Jacques-Emmanuel Galimard, PhD³^*, Ibrahim A. Ghemlas, MD⁴^*, Marco Zecca, MD⁵^*, Juliana Silva, MD⁶^*, Alexander Mohseny⁷^*, Alphan Kupesiz, MD⁸^*, Rose-Marie Hamladji, MD, PhD⁹^*, Nuno Miranda¹⁰^*, Tayfun Gungor¹¹^*, Robert F Wynn, MRCP, MD, FRCPath¹², Pietro Merli, MD¹³^*, Mikael Sundin, MD, PhD¹⁴, Maura Faraci, MD¹⁵^*, Cristina Díaz-de-Heredia, MD, PhD¹⁶^*, Birgit Burkhardt, MD, PhD¹⁷^*, Victoria Bordon, MD, PhD¹⁸^*, Charlotte Jubert, MD¹⁹^*, Peter Bader, MD, PhD²⁰, Marianne Ifversen, MD, PhD²¹^*, Concepcion Herrera Arroyo, MD²²^*, Natalia Maximova²³^*, Susana Riesco²⁴^*, Jerry Stein, MD²⁵^*, Arnaud Dalissier, PhD²⁶^*, Franco Locatelli, Prof., MD, PhD²⁷, Krzysztof Kalwak, MD, PhD²⁸^*, Jean-Hugues Dalle, MD, PhD¹ and Selim Corbacioglu, MD²⁹

¹Pediatric Hematology and Immunology Department, Robert Debré Hospital , GHU APHP Nord - Université Paris Cité, Paris, France
²Pediatric Hematology and Immunology Department, Robert-Debré Hospital, GH APHP Nord Université de Paris, Paris, France
³EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
⁴Department of Pediatric Hematology-Oncology, King Faisal Specialist Hospital & Research Center, Saudi Arabia, Riyadh, Saudi Arabia
⁵Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
⁶Bone Marrow Transplant Department, Great Ormond Street Hospital, London, United Kingdom
⁷Division of stem cell transplantation, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, Netherlands
⁸Pediatric Hematology, Akdeniz University Medical School, Antalya, TUR
⁹Service Hématologie Greffe de Moëlle, Centre Pierre Et Marie Curie, Alger, Algeria
¹⁰BMT, Instituto Portugues de Oncologia, Lisboa, PRT
¹¹Division of Stem Cell Transplantation, The Hospital of the Eleonore Fondation,University Children`s Hospital, ZüRich, Switzerland
¹²Department of Paediatric Haematology, Bone Marrow Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom
¹³Department of Pediatric Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
¹⁴Division Pediatric Hematology, Immunology and HCT, Pediatric Hematology, Immunology and HCT Section, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Division of Pediatrics, CLINTEC, Karolinska Institutet, Stockholm, Sweden
¹⁵Unità di Trapianto di Cellule Staminali Emopoietiche - Department of Hematology, Oncology and Hematopoietic Stem Cell Transplantion, IRCSS, Istituto Giannina Gaslini, Genova, Italy
¹⁶Pediatric Oncology and Hematology Department, Hospital Universitari Vall d’Hebron Vall d’Hebron, Barcelona, Spain
¹⁷Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany
¹⁸Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium
¹⁹Hematology Pediatrics, CHU Bordeaux, Bordeaux Cedex, France
²⁰Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, University Children's Hospital Frankfurt, Frankfurt, Germany
²¹Department of Paediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet,, Copenhagen, Denmark
²²Department of Hematology, Reina Sofia University Hospital / University of Cordoba, Cordoba, Spain
²³Bone Marrow Transplant Center, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy
²⁴Department of Pediatrics, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain
²⁵Department for Hemato-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
²⁶EBMT Paris Study Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
²⁷Department of Pediatric Hematology/Oncology, Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
²⁸Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland
²⁹Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany

Background:

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited bone marrow failure syndrome, which is characterized by a severe thrombocytopenia at birth without predictive stigmata and by a risk for progression into aplastic anemia and myeloid malignancy. CAMT is caused by a mutation of the thrombopoietin (THPO) receptor, c-Mpl. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only potentially curative treatment option. The outcomes of transplanted patient for CAMT have not been well described.

Design/Method

We conducted an EBMT (European Society for Blood and Marrow Transplantation) registry-based retrospective study in patients diagnosed with CAMT receiving an allogeneic HSCT.

Results

66 patients with CAMT could be included which were transplanted between 1998 and 2020. Median age at diagnosis was 1.3 years (0.1-2.8). The mutation was identified in 18 patients and absent in 7 patients. For the remaining patients, the genetic testing was not performed. The median age at transplant was 3.2 years (0.3-13). The median year of transplant is 2013. Bone marrow (BM) was the main stem cell source (59%) followed by peripheral blood (PB) (27%) and cord blood (CB (12%)) with 1 BM+CB from the same donor. The predominant donor type was HLA-matched (65% with matched-sibling donor (MSD) 34.8%, unrelated donor (UD) 10/10 22.7%, matched other relative 4.5% and umbilical cord blood (UCB) 6/6 3%)), followed by UD < 10/10 (15.1%), then the UCB< 6/6 (9%) then haploidentical (7.5%) and UD missing HLA (3%). The most frequently used conditioning regimen included busulphan and cyclophosphamide in 30% of cases, followed by the busulfan-fludarabine (14%) and treosulfan-fluradarabine-thiotepa (14%). Considering death and second transplant as competing event, platelet recovery (>= 20 000/mm³) occurred in 69.8% (95% confidence interval [CI] 56.6-79.7%) at day 60 and 71.4% (95% [CI] 58.2-81.1%) at day 180. Grade II-IV acute graft-versus-host disease (GvHD) was 20% (95% CI 11.3-30.5%), grade III-IV was 3.1% (95% CI 0.6-9.6%), and the 6-year cumulative incidence (CI) of chronic GvHD was 14.3% (95% CI 6.9-24.3%). The 6y-CI was 17.2% (95% [CI] 9.1-27.5%). Six-year overall survival (OS) was 85.6% (95% [CI] 74-92.3%) with a transplant related mortality of 8.0% (95% [CI] 2.9-16.6%). 6y-GVHD/-graft failure-free survival was 65.7% (95% [CI] 52.6-76%). OS was significantly lower after CB transplantation (6y OS: 37.5% with 95% [CI] 8.7-64.4%) than after BM (6y OS: 95% [CI] 81.5-98.7%) or PB (6y OS: 88.9% 95% [CI] 62.4-97.1%) transplantation (p<0.001).

Conclusion:

This study demonstrates that HSCT, the only available potentially curative option, has an acceptable 6-year overall survival and an acceptable rate of chronic GvHD. While the number of patients in such a rare disease does not allow to perform multivariable analyses, we can confirm that OS is better with the use of BM as the main stem cell source compared to the CB.

Disclosures: Merli: JAZZ Pharmaceuticals: Honoraria; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees. Díaz-de-Heredia: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: meeting and travel expenses ; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: meeting and travel expenses ; Biotest: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: meeting and travel expenses ; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: meeting and travel expenses . Bader: Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Research Funding; Neovii: Research Funding; Riemser: Research Funding, Speakers Bureau; Medac: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Miltenyi: Speakers Bureau. Locatelli: NEOVII: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MILTENYI: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MEDAC: Speakers Bureau; TAKEDA: Speakers Bureau; GILEAD: Speakers Bureau; NOVARTIS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Membership on an entity's Board of Directors or advisory committees; SOBI: Speakers Bureau; BLUEBIRD BIO: Speakers Bureau; PFIZER: Membership on an entity's Board of Directors or advisory committees; JAZZ PHARMACEUTICALS: Speakers Bureau; AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dalle: Novartis: Honoraria; Vertex: Honoraria; Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Orchard: Honoraria; Medac: Honoraria; Teva: Current equity holder in private company.

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4895 Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Congenital Amegakaryocytic Thrombocytopenia, a PDWP/EBMT Study