Monosomy 7 is the most common cytogenetic abnormality in pediatric myelodysplastic syndrome (MDS) and associated with a high risk of disease progression. However, in young children, spontaneous loss of monosomy 7 with concomitant hematologic recovery has been described, especially in the presence of germline mutations in SAMD9 and SAMD9L genes. Here, we report on our experience of close surveillance instead of upfront hematopoietic stem cell transplantation (HSCT) in seven patients diagnosed with SAMD9L syndrome and monosomy 7 at a median age of 0.6 years (range, 0.4-2.9). Within 14 months from diagnosis, three children experienced spontaneous hematological remission accompanied by a decrease in monosomy 7 clone size. Subclones with somatic SAMD9L mutations in cis were identified in five patients, three of whom attained hematological remission. Two patients acquired RUNX1 and EZH2 mutations during the observation period, of whom one progressed to myelodysplastic syndrome with excess of blasts (MDS-EB). Four patients underwent allogeneic HSCT at a median time of 26 months (range, 14-40) from diagnosis for MDSEB, necrotizing granulomatous lymphadenitis, persistent monosomy 7, and severe neutropenia. At last follow-up, six patients were alive, while one passed away due to transplant-related causes. These data confirm previous observations that monosomy 7 can be transient in young children with SAMD9L syndrome. However, they also indicate that delaying HSCT poses a substantial risk of severe infection and disease progression. Finally, surveillance of patients with SAMD9L syndrome and monosomy 7 is critical to define the evolving genetic landscape and to determine the appropriate timing of HSCT (clinicaltrials gov. Identifier: NCT00662090).

Department of Human Genetics Hannover Medical School Hannover

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology Hannover Medical School Hannover

Department of Pediatric Hematology and Oncology Klinikum Kassel Kassel Germany; Department of Pediatrics and Children's Cancer Research Center Klinikum rechts der Isar Technical University of Munich School of Medicine Munich

Department of Pediatric Hematology Oncology Aghia Sophia Children's Hospital Athens Greece

Department of Pediatric Hematology Oncology and Stem Cell Transplantation Ghent University Hospital Ghent

Department of Pediatric Hematology Oncology University Hospital Brussel Brussels

Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and Oncology Medical Center Faculty of Medicine University of Freiburg Freiburg

Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and Oncology Medical Center Faculty of Medicine University of Freiburg Freiburg Germany; Department of Hematology St Jude Children's Research Hospital Memphis TN

Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and Oncology Medical Center Faculty of Medicine University of Freiburg Freiburg Germany; German Cancer Consortium Partner Site Freiburg

Department of Pediatrics and Adolescent Medicine Division of Pediatric Hematology and Oncology Medical Center Faculty of Medicine University of Freiburg Freiburg Germany; Institute of Medical Bioinformatics and Systems Medicine Medical Center Faculty of Medicine University of Freiburg Freiburg

Division of Pediatric Hematology Oncology Department of Pediatrics and Adolescent Medicine Medical University of Graz Graz

Pediatrics and Adolescent Medicine University Medical Center Augsburg Augsburg

St Anna Children's Hospital Medical University of Vienna Department of Pediatrics and Adolescent Medicine Vienna Austria; St Anna Children's Cancer Research Institute Vienna

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ClinicalTrials.gov
NCT00662090