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Transfusion-associated iron overload may lead to increased risk of infection, but its role in myelofibrosis (MF) has been scarcely explored. We evaluated 106 consecutive patients with primary or secondary MF. Up to 38% of patients were transfusion-dependent (TD) with a median of 14 RBC units received. Median observation time was 36 months (range 3–203). Forty-five percent of patients experienced one or more infectious episodes for a total of 69 infectious events, 13 (19%) of which were severe. The 60-month cumulative incidence of infection was 64.1 ± 6.5%. TD patients showed a higher incidence of infection (HR = 2.13, p = 0.019). Transfusion burden was markedly greater in TD patients with infectious complication (median 24 RBC units vs 15 RBC units; p = 0.012). The 60-month overall survival was 40 ± 5.9%. Lower International Prognostic Scoring System (IPSS) risk (p < 0.0001) and ruxolitinib (p = 0.027) were significantly correlated with higher survival. This real-world study showed increased infections in patients with higher transfusion burden. It may therefore be interesting to further investigate the role of iron chelation in improving infection-free survival in MF patients.

Numerous prognostic indexes have been developed in hematological diseases based on patient characteristics and genetic or molecular assessment. However, less attention was paid to more accessible parameters, such as neutrophils, lymphocytes, monocytes, and platelet counts. Although many studies have defined the role of neutrophil-to-lymphocyte or platelet-to-lymphocyte in lymphoid malignancies, few applications exist for myeloid neoplasm or hematopoietic stem cell transplantation procedures. In this review, we synthesized literature data on the prognostic value of count blood cells in myeloid malignancies and hematopoietic stem cell transplantation in the context of classical prognostic factors and clinical outcomes.

Background: Cardiovascular adverse events (CV-AEs) are considered critical complications in chronic myeloid leukemia (CML) patients treated with second- and third-generation tyrosine kinase inhibitors (TKIs). The aim of our study was to assess the correlation between metabolic profiles and CV-AEs in CML patients treated with TKIs. Methods: We investigated 39 adult CML patients in chronic-phase (mean age 49 years, range 24–70 years), with no comorbidities evidenced at baseline, who were consecutively identified with CML and treated with imatinib, nilotinib, dasatinib, and ponatinib. All patients performed Gas-Chromatography-Mass-Spectrometry-based metabolomic analysis and were divided into two groups (with and without CV-AEs). Results: Ten CV-AEs were documented. Seven CV-AEs were rated as 3 according to the Common Toxicity Criteria, and one patient died of a dissecting aneurysm of the aorta. The patients’ samples were clearly separated into two groups after analysis and the main discriminant metabolites were tyrosine, lysine, glutamic acid, ornithine, 2-piperdinecarboxylic acid, citric acid, proline, phenylalanine, threonine, mannitol, leucine, serine, creatine, alanine, and 4-hydroxyproline, which were more abundant in the CV-AE group. Conversely, myristic acid, oxalic acid, arabitol, 4-deoxy rithronic acid, ribose, and elaidic acid were less represented in the CV-AE group. Conclusions: CML patients with CV-AEs show a different metabolic profile, suggesting probable mechanisms of endothelial damage.

We examined the association between serum ferritin (SF) levels and patient-reported functional aspects and symptoms, as measured by the EORTC QLQ-C30, in newly diagnosed patients with myelodysplastic syndromes (MDS). Analysis was conducted on 497 MDS patients who were classified in two groups based on the SF value of 1000 ng/mL. Clinically relevant differences of patient-reported functional and symptom scales were evaluated and classified as small, medium and large, based on established thresholds. Multivariable linear regression analysis was performed to account for potential confounding factors. Patients with SF of ≥ 1000 ng/mL reported statistically significant and clinically relevant worse outcomes across various health domains. Dyspnea was the symptom indicating the largest difference and mean scores of patients with higher and lower SF levels were 40 and 24.3, respectively (p = 0.005), indicating a large clinically relevant difference (Δ = 15.7). Further research is needed to better understand the relationship between SF levels and specific health-related quality of life domains.

Background Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs). Methods We investigated KIR gene frequencies, KIR haplotypes, and KIR-ligand combinations in a cohort of 135 patients with advanced-stage classic Hodgkin lymphoma and 221 healthy controls. We furthermore evaluated the correlation of KIR genes and KIR haplotypes with the achievement of negative iPET-2. Results In the cohort of patients, the 5-year overall survival and progression-free survival were 93.6 and 79 %, respectively. Homozygosity for KIR A haplotype and the HLA-C1 KIR ligand (KIR-AA/C1C1) was significantly higher in healthy controls (15.7 vs. 4.8 %, p  = 0.001). The KIR-AA genotype resulted to have a significant predictive power for achieving iPET-2 negativity ( p  = 0.039). Conclusions Homozygosity for KIR A haplotype offers protection against classic Hodgkin lymphoma. The association found for the KIR-AA genotype and achievement of negative iPET-2 suggests that KIR-AA could be used in clinical practice to enhance the chemosensitivity predictive power of iPET-2. Our results point to the possibility of adapting treatment strategies based on the combination of KIR biomarkers and PET scan.

The success of transplant procedures in patients with beta-thalassemia major (β-thalassemia) goes hand-in-hand with improvements in disease knowledge, better supportive care, discoveries in immunogenetics, increase in stem cell sources, and enhancement of conditioning regimens. The aim of this scoping review was to report the evolution of conditioning regimes for β-thalassemia hematopoietic stem cell transplantation. We performed a systematic search for all relevant articles published before July 2021, using the following Medical Subject Headings: “bone marrow transplantation”, “stem cell transplantation”, “allogeneic”, “thalassemia”, “β-thalassemia”, and “thalassemia major”. The final analysis included 52 studies, published between 1988 and 2021, out of 3877 records. The most common conditioning regimen was a combination of busulfan and cyclophosphamide, with successive dose adjustments or remodulation based on patient characteristics. Pre-transplant treatments, reductions in cyclophosphamide dosage, or the adoption of novel agents such as treosulphan all improved overall survival and thalassemia-free survival in transplant-related mortality high-risk patients. Conditioning regimes were modulated for those without a suitable fully matched sibling or unrelated donor, with encouraging results. Hematopoietic stem cell transplantation with haploidentical donors is currently available to virtually all patients with β-thalassemia. However, disparities in outcome are still present around the world. In developing and limited-resource countries, where most diagnoses are focused, transplants are not always available. Therefore, more efforts are needed to close this treatment gap.

Background: Off-target effects in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) are associated with cardiovascular toxicity. Hypertension represents an important cardiovascular complication and, if not appropriately managed, can contribute to developing thrombotic events. Third-generation TKI ponatinib is associated with hypertension development, and its use is more restricted than in the past. Few data are reported for second-generation TKI, nilotinib, dasatinib, and bosutinib. The aim of this article was to evaluate with a systematic review and meta-analysis the real incidence of hypertension in CML patients treated with second- or third-generation TKI. Methods: The PubMed database, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for studies published between January 1, 2000, and January 30, 2021; the following terms were entered in the database queries: Cardiovascular, Chronic Myeloid Leukemia, CML, Tyrosine kinases inhibitor, TKI, and Hypertension. The study was carried out according to the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) statement. Results: A pooled analysis of hypertension incidence was 10% for all new-generation TKI, with an even higher prevalence with ponatinib (17%). The comparison with the first-generation imatinib confirmed that nilotinib was associated with a significantly increased risk of hypertension (RR 2; 95% CI; 1.39-2.88, I 2 =0%, z=3.73, p=0.0002). The greatest risk was found with ponatinib (RR 9.21; 95% CI; 2.86-29.66, z=3.72, p=0.0002). Conclusion: Hypertension is a common cardiovascular complication in CML patients treated with second- or third-generation TKI.

Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity. A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate. KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.