Functional iron deficiency was the most common cause of anaemia but was not associated with outcome. The only haematological parameter that was associated with outcome was hepcidin concentration, which is a novel finding and introduces further complexity into our understanding of the role of iron and its regulation by hepcidin. We propose that future research should target patients with elevated hepcidin.

hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLAmatched related and unrelated donor transplantation. Journal of Clinical Oncology, 31, 1310-1316. Blaise, D., F€ urst, S., Crocchiolo, R., El-Cheikh, J., Granata, A., Harbi, S., Bouabdallah, R., Devillier, R., Bramanti, S., Lemarie, C., Picard, C., Chabannon, C., Weiller, P.-J., Faucher, C., Mohty, B., Vey, N. & Castagna, L. (2015) Haploidentical T-cell replete transplantation with post-transplant cyclophosphamide for patients in or above the 6(th) decade of age compared with allogeneic hematopoietic stem cell transplantation from an HLA-matched related or unrelated donor. Cambier et al, 2008;Pieri et al, 2011). We present morphological, cytogenetic and molecular genetic data from a series of 23 patients with concurrent BCR-ABL1 rearrangement and JAK2 V617F mutation. To obtain more information on the biology of these rare cases, we furthermore analysed the mutational status of 25 other genes frequently mutated in myeloid disorders (Fig 1). A total of 27 907 patients with suspected myeloproliferative neoplasm (MPN) were analysed in parallel for BCR-ABL1, JAK2 V617F and MPL mutations at our institution between May 2005 and October 2014. BCR-ABL1 analysis was performed by reverse transcription polymerase chain reaction (RT-PCR) (Cross et al, 1994) and the JAK2 V617F mutation by a melting curve-based LightCycler assay (Schnittger et al, 2006). A total of 10 875 patients were diagnosed with a myeloproliferative neoplasm (JAK2 V617F n = 9134, BCR-ABL1 n = 1487 and MPL n = 254). From those 10 875, a total of 23 patients (0Á2%; 11 males, 12 females) were posi- 135British Journal of Haematology, 2017, 176, 131-143 tive for JAK2 V617F and BCR-ABL1. The median age was 72 years (range 46-80 years) at time of detection of the two aberrations.Eighteen patients had two or more sample time points available for follow-up analyses (median follow-up: 4 years, range: 5 months to 9 years). Per cent (%) BCR-ABL1/ABL1 expression and % JAK2 V617F mutation load were assessed by quantitative PCR.Of the 23 cases, 22 were analysed by next generation sequencing applying a pan-myeloid gene panel consisting of 25 genes (Fig 1). Either complete coding genes or hotspots were first amplified by a microdroplet-based assay (RainDance, Lexington, MA) and subsequently sequenced with a MiSeq instrument (Illumina, San Diego, CA). RUNX1 was sequenced on GS Junior system (Roche 454, Branford, CT). The median coverage per amplicon was 2215 reads (range 100-24 716). The lower limit of detection was set at a cutoff of 1Á5%. As far as possible, cases were further characterized with cytomorphology (n = 12) and chromosome banding analyses (n = 19) accompanied by interphase fluorescence in situ hybridization (FISH

LHD was superior to hepcidin and bone marrow iron stores in identifying patients with ACD and associated iron deficiency, which would potentially benefit from parenteral iron therapy.

Acute myeloid leukemias with ring sideroblasts show a unique molecular signature straddling secondary acute myeloid leukemia and de novo acute myeloid leukemia Ring sideroblasts (RS) are a distinct morphological feature present in myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and acute myeloid leukemia (AML). The International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) defines them as erythroblasts with a minimum of 5 siderotic granules covering at least one third of the circumference of the nucleus. Their presence ≥15% has been associated with mutations in the splicing factor 3B subunit 1 (SF3B1) in 64-83% of patients with refractory anemia with ring sideroblasts (RARS), 57-76% of patients with refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) and in 90% of RARS with thrombocytosis (RARS-T).1-5 Recently, the 2016 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemias has recognized the biological importance of SF3B1mut and the correlation with RS, classifying all MDS without excess blasts or 5q deletion into a category of their own.6 Mutations in SF3B1 are so frequently associated with RS 7 that the threshold at which MDS may be classified as bearing RS has been lowered from the classical 15% to 5% if SF3B1 mutations are demonstrated.6 Although the impact of SF3B1 mutations was initially associated with better outcomes in MDS, 1,7 this can be explained through a higher incidence in low-grade MDS and due to the lack of prognostic significance carried by the mutation itself.4 Recent studies have shown the incidence of SF3B1 in de novo AML is low.7,8 However the significance of RS and SF3B1mut in AML had not been assessed in a larger cohort. In an attempt to analyze whether RS could differentiate a subgroup of AML with different biological characteristics, we herein present the biological and clinical associations of RS and SF3B1 mutations in patients with AML (n=1857).From a total of 1857 AML patients (excluding those with cytogenetically defined entities according to WHO), bone marrow assessment revealed 473 (25%) with RS ≥1%, of which 290 (16% of all 1857 patients) had RS ≥5%, and 183 (10% of all 1857 patients) had ≥15% RS, indicating a lower incidence of RS in comparison to cohorts of MDS patients described in the literature (57% of cases showing RS ≥1%).9 This incidence was, however, significantly higher to that recently reported in AML patients (5%).7 It must be acknowledged, however, that especially in those cases with lower RS counts, other causes of RS, like alcohol consumption or drug toxicity, cannot be excluded.Next-generation sequencing (NGS) for a panmyeloid panel, gene scan and quantitative polymerase chain reaction (PCR) were performed in a subcohort of 340/473 patients (due to sample availability) for the detection of © Ferrata Storti Foundation

A 35-year-old woman presented with a widespread petechial rash and pancytopenia. She underwent simultaneous pancreas and kidney transplantation for type 1 diabetes 8 years previously followed by a renal transplant 1 year prior to presentation, and was taking tacrolimus as long-term immunosuppression. The full blood count showed haemoglobin 97 g/L, platelet count 2×109/L and neutrophil count 0.22×109/L. Peripheral blood film examination confirmed genuine thrombocytopenia in the absence of any haemolytic or malignant features. Serological testing identified autoantibodies against all three blood lineages, consistent with a diagnosis of autoimmune pancytopenia. Treatment with steroids, intravenous immunoglobulins, romiplostim and mycophenolate mofetil achieved only fleeting remissions. Blood counts eventually normalised following the administration of rituximab and a change from tacrolimus to ciclosporin immunosuppression. Cytopenias are a well-recognised complication of post-transplantation care but we believe this to be the first reported case of autoimmune pancytopenia following solid organ transplantation. In this case report, we discuss the approach to investigation of haematological abnormalities post-transplant and the rationale for, and outcome of, the management of this rare case.