Outcome of relapsed/refractory acute promyelocytic leukaemia in children, adolescents and young adult patients — a 25‐year Italian experience

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A retrospective study of paroxysmal nocturnal hemoglobinuria in pediatric and adolescent patients

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease, especially in children, characterized by intravascular hemolysis, thrombotic events, serious infections and bone marrow failure. We describe 16 patients who were diagnosed with PNH in childhood or adolescence. The time interval between the onset of symptoms and the PNH diagnosis and its treatment were compared in patients with classic PNH versus PNH associated with bone marrow disorder (PNH/BMD). A greater delay in diagnosis was observed in classic PNH compared to PNH/BMD patients. The first group of patients had higher levels of LDH, total bilirubin and absolute reticulocyte count and a bigger PNH clone size compared to PNH/BMD patients; also thrombotic events were observed only in the classic form of PNH. Conversely, PNH/BMD patients showed lower median levels of platelets. Apart from standard supportive measures, four patients with classic PNH received eculizumab whereas four patients with PNH/BMD underwent hematopoietic stem cell transplantation. Our series confirm that the most frequent presentation of PNH in the pediatric-adolescent age is PNH/BMD. The delay between the onset of symptoms and PNH diagnosis is relevant principally in the classic form. Moreover, our study showed that any case of unexpected thrombosis represents a criterium to perform a PNH screening

Diagnosis and management of neutropenia in children: The approach of the Study Group on Neutropenia and Marrow Failure Syndromes of the Pediatric Italian Hemato-Oncology Association (Associazione Italiana Emato-Oncologia Pediatrica - AIEOP)

Neutropenia refers to a group of diseases characterized by a reduction in neutrophil levels below the recommended age threshold. The present study aimed to review the diagnosis and management of neutropenia, including a diagnostic toolkit and candidate underlying genes. This study also aimed to review the progress toward the definition of autoimmune and idiopathic neutropenia rising in infancy or in late childhood but without remission, and provide suggestions for efficient diagnostics, including indications for the bone marrow and genetic testing. The management and treatment protocols for common and unique presentations are also reviewed, providing evidence tailored to a single patient

Somatic, hematologic phenotype, long-term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology\u2013Oncology)

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. (C) 2016 Wiley Periodicals, Inc

Screening for SARS-CoV-2 infection in pediatric oncology patients during the epidemic peak in Italy

Results of a prospective screening for SARS-COV-2 in pediatric patients with hematological and oncological disease

Pediatric IgG4-related lymphadenopathy: A rare condition associated with autoimmunity and lymphoproliferative disorders

gG4-related disease (IgG4-RD) is a clinical-pathological entity defined by the presence of tissue-based tumor lesions, histologically featuring a dense lymphoplasmacytic infiltrate with numerous IgG4-positive plasma cells (IgG4/IgG ratio >40%). Serum IgG4 concentration is often elevate

Prognostic Role of Minimal Disseminated Disease and NOTCH1/FBXW7 Mutational Status in Children with Lymphoblastic Lymphoma: The AIEOP Experience

NOTCH1/FBXW7 (N/F) mutational status at diagnosis is employed for T-cell lymphoblastic lymphoma (T-LBL) patients' stratification in the international protocol LBL 2018. Our aim was to validate the prognostic role of Minimal Disseminated Disease (MDD) alone and in combination with N/F mutational status in a large retrospective series of LBL pediatric patients. MDD was analyzed in 132 bone marrow and/or peripheral blood samples by flow cytometry. Mutations in N/F genes were analyzed on 58 T-LBL tumor biopsies. Using the previously established cut-off of 3%, the four-year progression-free survival (PFS) was 57% for stage I-III patients with MDD ≥ 3% versus 80% for patients with MDD inferior to cut-off (p = 0.068). We found a significant worsening in the four-year PFS for nonmutated (51 ± 12%) compared to mutated patients (100%, p = 0.0013). Combining MDD and N/F mutational status in a subgroup of available cases, we found a statistically significant difference in the four-year PFS for different risk groups (p = 0.0012). Overall, our results demonstrate that N/F mutational status has a more relevant prognostic value than MDD at diagnosis. However, the combination of N/F mutations with MDD analysis could identify patients with very aggressive disease, which might benefit from a more intensive treatment

Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP)

Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3/million inhabitants/year, in Europe, but higher in East Asia. Survival in severe aplastic anemia (SAA) has markedly improved in the past 2 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. In SAA hematopoietic stem cell transplant (HSCT) from a matched sibling donor (MSD) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary, evidence-based document issued by a group of pediatric hematologists was discussed, modified and approved during a series of "Consensus Conferences" according to procedures previously validated by the AIEOP Board. The guidelines highlight the importance of referring pediatric patients with AA to pediatric centers with long experience in diagnosis, differential diagnosis, management, supportive care and follow-up of AA