Childhood polycythemia vera and essential thrombocythemia: Does their pathogenesis overlap with that of adult patients?

[No abstract available

Long-term follow-up of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in children and adolescents managed at a single institution over a 20-year period

Chronic myeloid leukaemia (CML) is rare in childhood. In our Institution we managed 30 consecutive Ph+CML patients aged <18 years, according to our adults’ guidelines. Patients with HLA-identical related donor (RD) underwent stem cell transplant (SCT). Since 1989, patients without RD were systematically treated with -interferon (IFN) (median dosage: 6 MU/day). Of 18/19 evaluable patients, 17 (94.5%) achieved haematologic response (HR), 11/17 (65%) cytogenetic response (CyR), complete (CCyR) in 4 (23.5%). Three patients remain in CCyR, 2 achieved BCR-ABL transcript disappearance. Of 13 patients without CCyR, 5 underwent SCT, 4 switched to STI571, 4 progressed. All patients receiving STI571 in chronic phase (CP) obtained sustained CCyR and 3 a persistent molecular response. 8-year survival among IFN-treated patients, censored or not for subsequent therapies, is 62% and 63%. Overall, 13/30 patients underwent SCT: 5 HLA-identical-RD, 5 matched unrelated donor, 2 mismatched-RD, 1 unrelated mismatched umbilical cord blood. Eight allotransplanted patients (6/6 in 1st CP) are in cytogenetic and molecular remission with 8-year survival of 61% from SCT and 69% from diagnosis. In our 20-year experience, the use of IFN in children without matched RD led to prolonged cytogenetic and molecular responses and long-term survival, without impairing the outcome of subsequent SCT

Twenty years of the Italian Fanconi Anemia Registry: where we stand and what remains to be learned

The natural history of Fanconi anemia remains hard to establish because of its rarity and its heterogeneous clinical presentation; since 1994, the Italian Fanconi Anemia Registry has collected clinical, epidemiological and genetic data of Italian Fanconi Anemia patients. This registry includes 180 patients with a confirmed diagnosis of Fanconi anemia who have either been enrolled prospectively, at diagnosis, or later on. After enrollment, follow-up data were periodically collected to assess the clinical course, possible complications and long-term survival; the median follow up was 15.6 years. The main goal of the study was to describe the natural history of Fanconi anemia, focusing on the following variables: family history, disease presentation, development of hematological manifestations, development of malignancies, occurrence of hematopoietic stem cell transplantation and survival. Typical morphological and/or hematological abnormalities and/or growth retardation were the most common manifestations at diagnosis; the majority of patients (77%) exhibited hematological abnormalities at the initial presentation, and almost all (96%) eventually developed hematological manifestations. More than half of the patients (57%) underwent a bone-marrow transplant. The occurrence of cancer was quite rare at diagnosis, whereas the cumulative incidence of malignancies at 10, 20 and 30 years was 5%, 8% and 22%, respectively, for hematological cancers and 1%, 15% and 32%, respectively, for solid tumors. Overall survival at 10, 20 and 30 years were 88%, 56% and 37%, respectively; the main causes of death were cancer, complications of the hematological presentation and complications of transplantation. These data clearly confirm the detrimental outcome of Fanconi anemia, with no major improvement in the past decades

A new severity score index for phenotypic classification and evaluation of responses to treatment in type I Gaucher disease

Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment.The \u201cGaucher Disease Severity Score Index Type I\u201d(GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods. Siix specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available. It is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment

Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187

Successful Management of a Chronic Refractory Leg Ulcer in an Adolescent with Sickle Cell Anemia

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by a wide range of clinical manifestations. Chronic leg ulcers are a disabling complication with repercussions on the quality of life. We report the case of a 14-year-old girl with a diagnosis of SCD who developed a chronic leg ulcer that was successfully treated with a multi-disciplinary approach, including local and systemic therapies. The role of different treatments, in particular low molecular weight heparin, in the refractory chronic leg ulcer healing process will be discussed. </p

Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis.

Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL(Ser505Asn) mutation could be underestimated. DESIGN AND METHODS: We extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL(Ser505Asn) mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis. RESULTS: Fifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy

Mast cell disorders, melanoma and pancreatic carcinoma: from a clinical observation to a brief review of the literature.

Mastocytosis can be associated with other clonal or non-clonal hematologic diseases as well as a variety of non-hematologic malignancies. A 75-year-old Caucasian male patient was referred to us with a 5-month history of neutrophilic leukocytosis and mild splenomegaly. He had developed a cutaneous melanoma sixteen years ago. According to the clinical and pathological features, a final diagnosis of systemic mastocytosis was established. The patient started treatment with interferon-α at a dose of 3 MIU/day, combined with low doses of prednisone. We observed a rapid disappearance of symptoms. Unfortunately, after 3 months a diagnosis of pancreatic adenocarcinoma was established. A review of the literature suggests that mastocytes could have a pivotal role in several malignancies. Different chemokines, mitogenic factors, chemical mediators of inflammation, and specific gene mutations could explain the association between mastocytosis and other hematologic and non-hematologic disorders. </p