Autoimmune hemolytic anemia (AIHA) is an uncommon disease of childhood caused by the premature destruction of erythrocytes by autoantibodies. In this rare disease both diagnostic criteria and therapeutic approaches are not well standardized. The Red Cell Working Group of the Pediatric Italian Hematogy and Oncology Association (AIEOP) developed specific recommendations to help Physicians for AIHA management. The document is available on the AIEOP website since November 1st 2013. The Italian Pediatric AIHA Group began an observational, retrospective and prospective study in order to monitor the management of children with AIHA diagnosed from 2010 to 2018, and to assess whether the availability of AIEOP recommendations had an impact on the clinical management of such patients in AIEOP Centers. We collected a national cohort of 159 children with AIHA from 21 AIEOP Centers; 48 patients were diagnosed before November 2013 and 111 patients after that date. Gender was 56% males and 44% females; median age at diagnosis was 47 months, with 11.9% under 12 months of age; 8.2% of children were born prematurely and 3.9% showed congenital malformations. 23.2 % of patients had a familiar history of immunological, hematological or oncological diseases. The median hemoglobin level at diagnosis was 6.1 gr/dL. Table 1 reports the distribution of our cases, according to the different type of autoantibodies. The comparison between the retrospective and prospective study did not reveal significative differences in clinical and biological presentation. The cold IgM forms were mainly post infective (38.4%) or primary forms (53.8%), only one patient had a secondary form due to a primitive immunodeficiency. These patients did not develop other diseases during follow up (median follow up: 28,6 months). The preliminary results of treatment and follow up of the 146 patients with warm antibody AIHA revealed the following: The treatment with conventional dose of steroids (median dose 2 mg/Kg, range 0.7- 3.5 mg/Kg) was started in 94.4% of patients, in 53% of cases on the same day of diagnosis. A high number of children used additional treatment: red blood cell transfusions (51.4%), high dose Prednisolone (59.7%), high dose i.v. Immunoglobulin (49.7%) and Plasma Exchange (1.4%). 9.5% of patients, with poor responsive disease, needed alternative drugs during the first four weeks of therapy. Response criteria were so defined: a complete response was defined as the achievement of an Hb concentration greater than or equal to the lower normal limit for age with no signs of haemolysis, i.e. normal reticulocyte count and bilirubine concentration. A partial response was defined as an increase of Hb >2 g/dL without the Hb concentration reaching a normal value for the patient age and no response as an increase of Hb< 2 g/dL and/or dependence on transfusion. A complete response was reached by 62.5%, 79.3%, 85.1% at 3, 4, 6 weeks respectively. 14.9% of patients had either a partial response or a resistant disease at 6 weeks. IgG/IgG+C3d positivity was a negative prognostic factor, as compared to positivity to C3d only, with the need of a second line treatment (prevalently Mabthera or Mycophenolate Mofetil) in 31.7% vs 0, respectively (p 0.009). Currently 6.1% of the patients were lost to follow up, 1.3% died, 55,8% are in Complete Response without events and 21.9% of the patients are still on treatment . At the last follow up, in the whole "cohort" of warm AIHA, 58% have a Primary form, 15.7% an isolated post infective form and 27.7% a Secondary form (56% Evans Syndrome). The management of the patients diagnosed after November 2013 was mostly in agreement with our recommendations, whose comprehensive therapeutic algorithm is reported in table 2, with prolonged steroid tapering in order to extend the treatment for at least 6 months. The most important difference between the retrospective and prospective study was the duration of first line treatment: 6 months or more, for steroid dependence, in 71.6% of patients in the prospective study versus 52.3% of the retrospective (p 0.031) and, more importantly, the percentage of relapsed patients: 8.3% in the prospective study versus 29.8% of the retrospective (p 0.001), these data need a longer follow up (median follow up: 24 months in the prospective study versus 63 in the retrospective) Disclosures Colombatti: Global Blood Therapeutics: Consultancy; Novartis: Consultancy; AddMedica: Consultancy.
Background: Hypereosinophilia in children can be primary or secondary. Numerous malignant diseases can cause hypereosinophilia, but it is seldom caused by acute lymphoblastic leukemia (ALL). In the event of protracted hypereosinophilia, it is extremely important to make a correct differential diagnosis. Case presentation: We present the case of an 11-year-old boy of Moroccan origin with ALL with hypereosinophilic onset (eosinophils in peripheral blood, 10,000/µL) in the absence of other signs of neoplastic disease, and compare this case with 61 similar cases in the literature. Following hospital admission, the patient initially presented with headache-caused nocturnal awakenings, evening fever, and cough, and he also lost approximately 7 kg in weight in a month not associated with sweating or itching. We first performed bone marrow aspiration, which showed an increase in eosinophils without cellular morphological abnormalities, and bone marrow immunophenotyping showed that 4.5% of cells had a phenotype compatible with lymphoid blasts. A lumbar puncture was negative. Given the poor marrow involvement, it was necessary to repeat a new bone marrow aspiration two days later, which showed an increase in blasts to 14%. A concomitant bone marrow biopsy showed an infiltration of blasts typical of B-cell ALL equal to 20–30% with associated hypereosinophilia. Cytogenetic analysis showed an hyperdiploid karyotype: 53–55, XY, +X, add(1)(q21q25), +4, +9, +10, +14, +2, +1, +21/46, XY. Conclusions: ALL is one of the possible causes of persistent hypereosinophilia. In patients with ALL and hypereosinophilia, peripheral hypereosinophilia can precede the appearance of blasts. Due to the negative prognosis and the increased risk of complications in these patients, bone marrow aspiration and biopsy are recommended if common causes of secondary hypereosinophilia are excluded.
Objectives HbS/β+ patients’ presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/β+ patients, with genotype‐phenotype correlation, in order to offer guidance for clinical management of such patients. Methods Retrospective cohort study of HbS/β+ patients among 15 AIEOP Centres. Results A total of 41 molecularly confirmed S/β+ patients were enrolled (1‐55 years, median 10.9) and classified on β+ mutation: IVS‐I‐110, IVS‐I‐6, promoter, and “others.” Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS‐I‐110 group presented the lowest median age at first SCD‐related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS‐I‐6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers. Conclusions HbS/β+ is not always a mild disease. Patients with IVS‐I‐110 mutation could benefit from a standard of care like SS and S/β° patients. Standardization of treatment is needed.
Introduction: The spread of Covid-19 has worsened the prognosis of oncology patients, interrupting or delaying life-saving therapies and contextually increasing the risk of severe SARS-CoV-2 infections. Acute lymphoblastic leukemia (ALL) is the most frequent cancer in pediatric age and the management of this disease with concomitant SARS-COV-2 infection represents a challenging situation.Case presentation: We present the case of a 6-year-old female newly diagnosed with ALL during a documented SARS-CoV-2 infection. Our patient was admitted 20 days after SARS-CoV-2 detection for evening-rise fever. Laboratory testing showed severe neutropenia while chest x-ray detected moderate pulmonary involvement. Acute lymphoblastic leukemia diagnosis was made through morphological and molecular analysis on bone marrow aspirate. Given the stability of the blood count and clinical conditions, antiviral therapy with Remdesivir and Convalescent Plasma was started before antileukemic treatment, obtaining a rapid resolution of the infection.Conclusion: In our experience, the treatment with Remdesivir and Convalescent Plasma led to a rapid resolution of Sars-Cov-2 infection. Our case did not present any adverse event to the therapy. Thus, this treatment could be considered in patients with malignancies, in order to accelerate the resolution of the infection and begin immunosuppressive treatment safely. Further studies are required to confirm this hypothesis.
Background NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated.Methodology and Principal FindingsBone marrow samples from 145 patients with myelodysplastic syndromes (MDS) and AML were included in this study. Cytogenetically 43 cases had isolated 5q-, 84 cases had 5q- plus other changes and 18 cases had complex karyotype without 5q deletion. FISH and direct sequencing investigated the NPM1 gene. NPM1 deletion was an uncommon event in the “5q- syndrome” but occurred in over 40% of cases with high risk MDS/AML with complex karyotypes and 5q loss. It originated from large 5q chromosome deletions. Simultaneous exon 12 mutations were never found. NPM1 gene status was related to the pattern of complex cytogenetic aberrations. NPM1 haploinsufficiency was significantly associated with monosomies (p<0.001) and gross chromosomal rearrangements, i.e., markers, rings, and double minutes (p<0.001), while NPM1 disomy was associated with structural changes (p = 0.013). Interestingly, in complex karyotypes with 5q- TP53 deletion and/or mutations are not specifically associated with NPM1 deletion.Conclusions and Significance NPM1/5q35 deletion is a consistent event in MDS/AML with a 5q-/-5 in complex karyotypes. NPM1 deletion and NPM1 exon 12 mutations appear to be mutually exclusive and are associated with two distinct cytogenetic subsets of MDS and AML.
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