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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, typically presenting with systemic symptoms and mediastinal involvement. Leukemia cutis (LC) and renal infiltration are rare, especially at disease onset. A 27-year-old man presented with a solitary scalp lesion without systemic symptoms or hematologic abnormalities. Histopathology revealed a blastoid lymphoid infiltrate with a T-ALL immunophenotype. Two weeks later, laboratory tests showed leukocytosis, lymphocytosis, and renal dysfunction. Imaging revealed a large mediastinal mass, scalp soft tissue involvement, and bilateral renal infiltration. Bone marrow biopsy confirmed T-ALL with a mature phenotype. FISH identified TRAD:NKX2 rearrangement and CDKN2AB deletion. The patient received three cycles of pediatric-inspired chemotherapy, achieving complete molecular remission and resolution of extramedullary disease. He subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling. Post-transplant complications included febrile neutropenia and mucositis. On day +100, he remained in minimal residual disease (MRD)-negative remission. This case illustrates a rare presentation of T-ALL with isolated skin involvement and renal infiltration at diagnosis, highlighting the importance of early biopsy and immunophenotyping of atypical skin lesions. Intensive chemotherapy followed by HSCT represents a viable strategy for young adults with high-risk T-ALL and extramedullary disease.

Langerhans cell sarcoma (LCS) is a rare and aggressive neoplasm characterized by a clonal proliferation of Langerhans cells (LCs), with multi-organ involvement and poor prognosis. Diagnostic challenges arise from its rarity and overlapping features with Langerhans cell histiocytosis (LCH), requiring immunophenotypic and histological analysis for differentiation. This case report discusses a 67-year-old male with multi-organ LCS involvement. Diagnosis was confirmed via liver biopsy and genetic analysis, revealing a MAP2K1 mutation. Treatment with subcutaneous cladribine and dexamethasone resulted in significant clinical and radiological improvement, despite hematological toxicity due to an underlying myelodysplastic neoplasm (MDS). This case proves the potential efficacy of cladribine for disseminated LCS and highlights the necessity for further research into optimal therapeutic approaches for this rare malignancy.

Background Philadelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leukemia (ALL), as well as in rare cases of acute myeloid leukemias (AML). Most patients with CML harbor either the e13a2 or the e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. Moreover, several atypical BCR-ABL1 transcripts, beside the most common e1a2, e13a2 and e14a2, have been described, mainly in patients with CML. However, ALL and de novo AML may also carry BCR-ABL1 atypical transcripts which will confer a poor prognosis. Case presentation A 78-years old male was admitted at our hospital with clinical and laboratory features allowing to make the diagnosis of AML. No evidence of a preceding CML (splenomegaly or basophilia) was found. The karyotype on G-banded metaphases was 46,XY, t(9;22)(q34;q11). While the molecular analysis was ongoing, the patient started treatment based on hydroxyurea followed by 5-aza-2′-deoxycytidine. The molecular biology analysis revealed the simultaneous presence of the common p190 e1a2 and the rare e6a2 isoforms. Because of persistent pancytopenia and presence of blasts, according to the molecular data, he was then switched to tyrosine kinase inhibitors (TKIs) treatment. Nevertheless, after 2 months, the patient was still refractory to second line treatment dying because of a pulmonary infection. Conclusion The atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR-ABL1 transcripts may help to establish optimal treatment approaches on these aggressive BCR-ABL1 phenotypes in different setting of patients.

Extranodal involvement of non-Hodgkin lymphoma (NHL) has been reported in 20–40% of patients and has been typically observed in the skin, bones, gastrointestinal tract, liver and brain. Cardiac involvement has been reported in up to 20% of autopsy cases of patients with NHL and accounts for about 2% of all cardiac malignancies. Here, we report a peculiar case of a secondary cardiac diffuse large B-cell lymphoma (DLBCL), occurring with an abrupt hemodynamic instability, characterized by a sudden ventricular tachycardia and cardiogenic shock. The patient promptly started the first cycle of chemotherapy and was admitted to the cardiac intensive care unit (CICU) of our institution to prevent potential cardiovascular complications during treatment. We applied a fractionated treatment approach, progressively reaching standard doses, to decrease the risk of early death and ensure a successful management.

Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. NCT02088840.

The mammalian target of rapamycin (mTOR) is a central processor of intra- and extracellular signals, regulating many fundamental cellular processes such as metabolism, growth, proliferation, and survival. Strong evidences have indicated that mTOR dysregulation is deeply implicated in leukemogenesis. This has led to growing interest in the development of modulators of its activity for leukemia treatment. This review intends to provide an outline of the principal biological and molecular functions of mTOR. We summarize the current understanding of how mTOR interacts with microRNAs, with components of cell metabolism, and with controllers of apoptotic machinery. Lastly, from a clinical/translational perspective, we recapitulate the therapeutic results in leukemia, obtained by using mTOR inhibitors as single agents and in combination with other compounds.

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) represent a challenging problem after SCT. A retrospective survey (January 2010 to July 2013) involving 52 Italian centers was performed to assess the epidemiology and the prognostic factors of CRKp infections in auto- and allo-SCT. Cases of CRKp infection were reported in 53.4% of centers. CRKp infections were documented in 25 auto-SCTs and 87 allo-SCTs, with an incidence of 0.4% (from 0.1% in 2010 to 0.7% in 2013) and 2% (from 0.4% in 2010 to 2.9% in 2013), respectively. A CRKp colonization documented before or after transplant was followed by an infection in 25.8% of auto-SCT and 39.2% of allo-SCT patients. The infection-related mortality rates were 16% and 64.4%, respectively. A pre-transplant CRKp infection (hazard ratio (HR) 0.33, 95% confidence intervals (CIs) 0.15–0.74; P =0.007) and a not CRKp-targeted first-line treatment (HR 2.67, 95% CI 1.43–4.99; P =0.002) were independent factors associated with an increased mortality in allo-SCT patients who developed a CRKp infection. Our study shows challenging findings of CRKp infections in SCT patients in Italy particularly after allo-SCT. The detection of carriers and the definition of early therapeutic strategies represent critical aspects of the management of CRKp infections after SCT.

A real-life study on CPX-351 and the standard arm (‘7 + 3’) of the CPX-351 registrative trial in adults with secondary Acute Myeloid Leukemia were compared by an unanchored Matching-adjusted indirect comparison (MAIC), in order to evaluate the efficacy and toxicity of CPX-351. Results of this study are important to confirm the role of CPX-351 in significantly improving survival and remission rates compared with ‘7 + 3’ with a good safety profile in AML patients with high-risk features, a target group traditionally with a very poor prognosis. Moreover, this pilot analysis underlines the potentiality of the statistical method to compare studies with strong differences.