Federica Quaglia

Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes.

The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

BACKGROUND Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. METHODS We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. FINDINGS Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses. Overall, all 31 (100%, 89-100) patients responded to therapy with a significant decrease in all epistaxis parameters (p<0·0001 for frequency, intensity, and duration). A response was achieved by 25 (81%) patients at 50 mg/day of thalidomide, five (16%) patients at 100 mg/day, and one (3%) patient at 150 mg/day. Patients had only non-serious, grade 1 adverse effects, the most common of which were constipation (21 patients), drowsiness (six patients), and peripheral oedema (eight patients). One patient died a month after the end of treatment, but this was not deemed to be related to treatment. INTERPRETATION Low-dose thalidomide seems to be safe and effective for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia. Our findings should be validated by further studies with larger patient populations, longer follow-up, and that also assess the benefit for quality of life. FUNDING Telethon Foundation.

Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia.

Graphical abstract

Pure red cell aplasia caused by parvovirus B19 in a heart transplant recipient

A case of parvovirus B19‐induced pure red cell aplasia occurring in a heart transplant recipient is reported. The diagnosis of this rare but clinically important complication can be suspected on the basis of the pathognomonic morphological features of the bone marrow.

A case of feverish neutropenia

A case of feverish benign neutropenia occurring in a diabetic patient receiving pregabalin for peripheral neuropathy is reported. Although pregabalin‐induced neutropenia is very rare, it is important to keep in mind that this drug like other anticonvulsants used for neuropathic pain, can cause severe neutropenia.

Su di un caso di aplasia eritroblastica pura

L’aplasia eritroblastica pura rappresenta una patologia rara, caratterizzata da anemia normocromica/normocitica o normocromica/macrocitica, reticolocitopenia marcata ed ipoplasia o aplasia eritroblastica isolata a livello midollare. I precursori granulocitari ed i megacariociti mostrano invece in genere normali caratteristiche di maturazione. Le diverse forme di tale patologia sono attualmente classificate come condizioni congenite ed acquisite. In base alle indagini sierologiche ed al quadro midollare del caso riportato abbiamo posto diagnosi di aplasia eritroblastica pura acquisita ed intrapreso terapia steroidea con progressiva normalizzazione dell’esame emocromocitometrico.

Definizione degli aspetti displastici nelle sindromi mielodisplastiche: proposta di un pannello morfologico standardizzato

Le sindromi mielodisplastiche rappresentano un disordine oncoematologico complesso caratterizzato da una clinica eterogenea associata ad aumentato rischio di evoluzione in leucemia acuta mieloide. In assenza di marcatori biologici specifici per tale patologia, la diagnosi risulta ad oggi sostanzialmente di tipo morfologico. Il principale scopo del nostro lavoro consiste nell’elaborazione di un pannello morfologico dotato di parametri di specificita, sensibilita e valore prognostico associati sia a ciascun tipo di alterazione displastica, sia alla percentuale di displasia in toto per ciascuna linea cellulare midollare. Il pannello morfologico da noi elaborato potrebbe essere inserito, accanto ai parametri attualmente in uso, in nuovi sistemi di score prognostici al fine di migliorare la gestione clinico-terapeutica dei pazienti affetti da sindromi mielodisplastiche.

Due casi di amiloidosi linfonodale

We report two cases of amyloidosis lymph nodes involvement. In the first case amyloidosis affects only mediastinal lymph nodes, which represents an extremely rare manifestation of the disease. The second patient presented with widespread lymphadenopathy. Even after many years, in both cases, no other organs were involved by disease. The two cases show a rare manifestation of the disease with relative benign course. At present the molecular mechanisms that cause the deposition of amyloid fibrils in specific target tissues are not known.

Embolie polmonari recidivanti in paziente con trait falcemico misconosciuto

Sickle cell trait occurs in approximately 300 million people worldwide, with the highest prevalence of approximately 30% to 40% in sub-Saharan Africa. If people with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, genetic risk factors for venous thromboembolism (VTE) in the black population are poorly understood; in fact common genetic risk factors for VTE in Caucasian people rarely are found among blacks. We report the case of a young Cameroonian man with multiple episodes of thromboembolism, the last of which occurred when he was 36 years old. The major identifiable risk factor for recurrent venous thrombosis was the presence of sickle cell trait.