A Prospective Study of Hematologic Complications and Long-Term Survival of Italian Patients Affected by Shwachman-Diamond Syndrome - 06/02/20

Doi : 10.1016/j.jpeds.2019.12.041

Simone Cesaro, MD ^1,^⁎ , Anna Pegoraro, MD ¹, Laura Sainati, MD ², Vincenzina Lucidi, MD ³, Enza Montemitro, MD ³, Paola Corti, MD ⁴, Ugo Ramenghi, MD ⁵, Cristina Nasi, MD ⁶, Giuseppe Menna, MD ⁷, Marco Zecca, MD ⁸, Cesare Danesino, MD ⁹, Elena Nicolis, PhD ¹⁰, Francesco Pasquali, MD ¹¹, Sandra Perobelli, PhD ¹², Gloria Tridello, MSc ¹, Piero Farruggia, MD ¹³, Marco Cipolli, MD ¹²
¹ Pediatric Hematology and Oncology Unit, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
² Pediatric Hematology and Oncology Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy
³ Cystic Fibrosis Unit, Department of Specialized Pediatrics, “Bambino Gesù” Children's Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, Roma, Italy
⁴ Pediatric Hematology Oncology, Department of Pediatrics, University Milano-Bicocca, San Gerardo Hospital, Monza, Italy
⁵ Department of Pediatric and Public Health Sciences, University of Torino, Torino, Italy
⁶ Division of Pediatrics, Azienda Sanitaria ASL 17, Savigliano, Italy
⁷ Department of Pediatric Hemato-Oncology, Santobono-Pausilipon Hospital, Napoli, Italy
⁸ Pediatric Hematology and Oncology Unit, Deparment of Pediatrics, Istituto di Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
⁹ Department of Molecular Medicine, University of Pavia and Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy
¹⁰ L Transfusion Medicine and Immunology Unit, Department of Transfusion Medicine, Azienda Ospedaliera Universitaria Integrata Verona, Italy
¹¹ Medical Genetics, Department of Medicine and Surgery, University of Insubria, Varese, Italy
¹² Cystic Fibrosis Center, Department of Cardiovascular and Thoracic Surgery, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
¹³ Pediatric Hematology and Oncology Unit, Oncology Department, Azienda Ospedaliera di Rilieno Nazionale di Alta Specializzazione, Ospedale Civico, Palermo, Italy

^∗Reprint requests: Simone Cesaro, MD, Pediatric Hematology Oncology, Department of Mother and Child , Piazzale Aristide Stefani 1,37126, Verona, Italy.Pediatric Hematology OncologyOspedale Donna BambinoPiazzale Aristide Stefani 1,37126VeronaItaly

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Abstract

Objective

To describe the hematologic outcome and long-term survival of patients enrolled in the Shwachman-Diamond syndrome Italian Registry.

Study design

A retrospective and prospective study of patients recorded in the Shwachman-Diamond syndrome Italian Registry.

Results

The study population included 121 patients, 69 males and 52 females, diagnosed between 1999 and 2018. All patients had the clinical diagnosis confirmed by mutational analysis on the SBDS gene. During the study period, the incidence of SDS was 1 in 153 000 births. The median age of patients with SDS at diagnosis was 1.3 years (range, 0-35.6 years). At the first hematologic assessment, severe neutropenia was present in 25.8%, thrombocytopenia in 25.5%, and anemia in 4.6% of patients. A normal karyotype was found in 40 of 79 patients, assessed whereas the most frequent cytogenetic abnormalities were isochromosome 7 and interstitial deletion of the long arm of chromosome 20. The cumulative incidence of severe neutropenia, thrombocytopenia, and anemia at 30 years of age were 59.9%, 66.8%, and 20.2%, respectively. The 20-year cumulative incidence of myelodysplastic syndrome/leukemia and of bone marrow failure/severe cytopenia was 9.8% and 9.9%, respectively. Fifteen of 121 patients (12.4%) underwent allogeneic stem cell transplantation. Fifteen patients (12.4%) died; the probability of overall survival at 10 and 20 years was 95.7% and 87.4%, respectively.

Conclusions

Despite an improvement in survival, hematologic complications still cause death in patients with SDS. Further studies are needed to optimize type and modality of hematopoietic stem cell transplantation and to assess the long-term outcome in nontransplanted patients.

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Keywords : Shwachman-Diamond syndrome, leukemia, cytopenia, myelodysplastic syndrome, survival

Abbreviations : SDS, AML, EFS, HSCT, MDS, OS, RI-SDS