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Summary: In recent years, the surprising progress made in other areas of hematology (advances in the understanding of leukemogenesis, improved transplant techniques) has been conspicuously absent in the management of hematologic emergencies. And yet, every step toward greater knowledge, every new treatment option will be of little value unless we are able to manage the acute complications of hematologic diseases. These complications are better defined as hematologic emergencies, and they are characterized by a high rate of mortality. This review is based on a search of the literature that was initially confined to articles published in the journal Hematology from 2000 to 2009. The search was then extended to the Cochrane Library and to Pub Med in February 2010 with the following Keywords emergencies; urgencies; hematology. The same key words were employed in a search of the archives of Blood and the New England Journal of Medicine from 2000 to 2010. The results confirm that hematologic emergencies can be caused by hematologic malignancies as well as by non-neoplastic hematologic diseases. Within the former category; this review examines the causes; manifestations; treatment and prevention of disseminated intravascular coagulation; superior vena caval syndrome; spinal cord compression; tumor lysis syndrome; hyperleukocytosis; and hypercalcemia. We also review emergency situations associated with non-neoplatic haematological diseases; such as thrombotic thrombocytopenic purpura; drug-induced hemolytic anemia; and acute sickle-cell crisis. [Copyright &y& Elsevier]

Aims: Bone marrow (BM) stem cells improve cardiac function and outcome after acute ST-segment elevation myocardial infarction (MI). In this randomized controlled trial, the effects of intracoronary transfer of autologous BM cells on left ventricular ejection fraction (LVEF) and volumes (2D-echo and resting SPECT), stroke volume [impedance cardiography (ICG)], autonomic control [heart rate variability (HRV)], baroreflex sensitivity (BRS), and exercise tolerance (cardiopulmonary exercise test) were assessed in post-MI patients. Exercise stress SPECT was also performed. [ABSTRACT FROM PUBLISHER]

Purpose: Because an etiologic role for hepatitis C virus in non-Hodgkin's B-cell lymphoma has been suggested by several reports, we assessed the prevalence of hepatitis C virus infection in patients with non-Hodgkin's B lymphoma and in controls, and evaluated the influence of viral infection on histologic and clinical features of the lymphoma patients.Patients and Methods: We prospectively investigated 175 consecutive patients with non-Hodgkin's lymphoma and 350 controls for serologic and molecular markers of hepatitis C virus infection. Controls were selected from inpatients (n = 175) and outpatients (n = 175) cared for at our hospital. Patients with lymphoma who had hepatitis C virus infection were tested for mixed cryoglobulinemia. Aminotransferase levels were measured in all lymphoma patients at baseline and during and after chemotherapy.Results: Hepatitis C virus prevalence in patients with non-Hodgkin's lymphoma was significantly greater than in control subjects (37% vs 9%, P = 0.0001). Among patients with lymphoma, viral infection was associated with older mean (+/-standard deviation) age (67 +/- 14 vs 61 +/- 8 years, P = 0.001), and women (41 of 87, 47%) were more likely than men (24 of 88, 27%) to have evidence of hepatitis C infection (P = 0.006). Thirteen of the 20 cases of immunocytoma were associated with hepatitis C virus infection, which was also more common in patients with orbital and conjunctival localization of lymphoma. Patients with mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach were less likely to have evidence of hepatitis C infection. Mixed cryoglobulinemia was much more common in patients with hepatitis C virus infection (14 of 65 vs 1 of 110, P = 0.0001); it was not associated with the histologic type of lymphoma. Patients with and without hepatitis C virus infection underwent similar chemotherapy regimens and had no differences in response to chemotherapy or in overall and disease-free survival. Hepatic toxicity from chemotherapy was seen only in patients with hepatitis C virus infection, although all but one of these patients were able to complete their planned treatment.Conclusion: These findings suggest that the hepatitis C virus may have a role as an etiologic agent in non-Hodgkin's B-cell lymphoma. Some clinical and pathologic features of the disease are associated with hepatitis C virus infection, but the virus does not seem to affect prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: The therapeutic landscape of Chronic Lymphocytic Leukemia (CLL) has dramatically changed in recent years, with a shift from chemoimmunotherapy towards many new targeted agents, such as Bruton Tyrosine Kinase inhibitors (BTKi) and anti-BCL-2. We now need an accurate re-definition of prognostic/predictive parameters to support clinicians in choosing the more appropriate option. This review explores recent advances in the molecular biology of chronic lymphocytic leukemia, with the aim of identifying the most important biomarkers to define prognosis and to guide first-line and second-line treatment. Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in Western countries. In recent years, there have been important advances in the knowledge of molecular alterations that underlie the disease's pathogenesis. Very heterogeneous prognostic subgroups have been identified by the mutational status of immunoglobulin heavy variable genes (IGVH), FISH analysis and molecular evaluation of TP53 mutations. Next-generation sequencing (NGS) technologies have provided a deeper characterization of the genomic and epigenomic landscape of CLL. New therapeutic targets have led to a progressive reduction of traditional chemoimmunotherapy in favor of specific biological agents. Furthermore, in the latest clinical trials, the minimal residual disease (MRD) has emerged as a potent marker of outcome and a guide to treatment duration. This review focuses on recent insights into the understanding of CLL biology. We also consider the translation of these findings into the development of risk-adapted and targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

The role of allogeneic stem cell transplantation (allo-SCT) in mantle cell lymphoma (MCL) is uncertain, even more in the era of bruton's tyrosine kinase inhibitors (BTKi) and chimeric antigen receptor T-cells. We retrospectively analyzed 55 patients who underwent allo-SCT for MCL relapsed or refractory (r/r) after rituximab and high-dose cytarabine within the MANTLE-FIRST project. With a median follow-up of 3.7 years, non-relapse mortality (NRM), progression-free survival, and overall survival were 23%, 53%, and 56%, respectively. NRM was significantly higher in the case of acute graft-versus-host disease, > 2 prior lines of therapy, age > 60 years. The outcome was similar for patients with early (≤24 months) and late progression of disease. The use of BTKi as a bridge to allo-SCT did not increase the toxicity and allowed a good control of disease. Our real-life experience confirms that allo-SCT still represents an option in MCL patients, especially if young and early-relapsed. [ABSTRACT FROM AUTHOR]

Presents a study that investigated the use of rituximab in combination with interferon-alpha in the treatment of two patients with relapsed and refractory diffuse large b-cell non-Hodgkin's lymphoma. Background on rituximab; Medical history of the patients; Analysis of the effectiveness of rituximab.

Summary: Little is known of the course of COVID‐19 and the antibody response to infection or vaccination in patients with hairy‐cell leukaemia (HCL). Among a total of 58 HCL cases we studied in these regards, 37 unvaccinated patients, mostly enjoying a relatively long period free from anti‐leukaemic treatment, developed COVID‐19 between March 2020 and December 2021 with a usually favourable outcome (fatality rate: 5/37, 14%); however, active leukaemia, older age and more comorbidities were associated with a worse course. Postinfection (n = 11 cases) and postvaccination (n = 28) seroconversion consistently developed, except after recent anti‐CD20 or venetoclax therapy, correlating with perivaccine B‐cell count. Vaccination appeared to protect from severe COVID‐19 in 11 patients with breakthrough infection. [ABSTRACT FROM AUTHOR]

Objectives: Early chimerism analysis is important to assess engraftment in allogeneic hematopoietic stem cell transplantations. Methods: We retrospectively investigated the impact of T‐cell chimerism at day 30 in bone marrow on acute graft‐versus‐host disease (aGVHD), relapse, and overall survival in 142 adult allo‐transplanted patients. Results: The majority of patients (89%) received myeloablative conditioning and 90% have undergone T‐cell replete donor graft. At day 30, 103 patients showed T‐complete chimerism with prevalence in haploidentical transplants, whereas 39 cases had CD3+ mixed chimerism, including 30 patients transplanted with HLA identical donors, and 21 with T‐cell donors<90%. T‐cell chimerism at day 30 was weakly inversely related to aGVHD grades II–IV (p =.078) with no cases of grades III–IV aGVHD in patients with CD3+ <95%. Mixed T‐cell chimerism did not impact on relapse (p =.448) and five of the seven patients who relapsed had T‐cell chimerism ≤90%. Older age and active disease at transplant had a statistically significant negative effect on overall survival (p =.01 and p =.0001, respectively), whereas mixed CD3+ chimerism did not. Conclusions: T lymphocyte chimerism analysis at day +30 in bone marrow could identify allo‐transplanted patients at major risk of aGVHD grades III–IV (CD3+ donors >95%) mainly post‐myeloablative conditioning regimen. [ABSTRACT FROM AUTHOR]

Background: A central venous catheter (CVC) currently represents the most frequently adopted intravenous line for patients undergoing infusional chemotherapy and/or high-dose chemotherapy with hematopoietic stem-cell transplantation and parenteral nutrition. CVC insertion represents a risk for pneumothorax, nerve or arterial punctures. The aim of this prospective observational study was to explore the safety and efficacy of CVC insertion under ultrasound (US) guidance and to confirm its utility in clinical practice in cancer patients. Methods: Consecutive adult patients attending the oncology-hematology department were eligible if they had solid or hematologic malignancies and required CVC insertion. Four types of possible complication were defined a priore: mechanical, thrombotic, infection and malfunctioning. The patient was placed in Trendelenburg's position, a 7.5 MHZ puncturing US probe was placed in the supraclavicular site and a 16-gauge needle was advanced under real-time US guidance into the last portion of internal jugular vein. The Seldinger technique was used to place the catheter, which was advanced into the superior vena cava until insertion into right atrium. Within two hours after each procedure, an upright chest X-ray and ultrasound scanning were carried out to confirm the CVC position and to rule out a pneumotorax. CVC-related infections, symptomatic vein thrombosis and malfunctioning were recorded. Results: From December 2000 to January 2009, 1,978 CVC insertional procedures were applied to 1,660 consecutive patients. The procedure was performed 580 times in patients with hematologic malignancies and 1,398 times those with solid tumors. A single-needle puncture of the vein was performed on 1,948 of 1,978 procedures (98.48%); only eighteen attempts among 1,978 failed (0.9%). No pneumotorax, no major bleeding, and no nerve puncture were reported; four cases (0.2%) showed self-limiting hematomas. The mean lifespan of CVC was 189.7 +/- 18.6 days (range 7-701). Symptomatic deep-vein thrombosis of the upper limbs developed in 48 patients (2.42%). Catheter-related infections occurred in 197 (9.96%) of the catheters inserted. They were successfully treated with antibiotics and only in 48 (2.9%) patients definitive CVC removal was required for infection and/or thrombosis or malfunctioning. [ABSTRACT FROM AUTHOR]

Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies before vaccinations and 2–6 weeks after the administration of the second vaccine dose. Primary end-point: seropositivity rate. Secondary end-points: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. Between 20th March 2021 and 12th June 2021, 293 consecutive patients with cancer-solid tumours underwent a program of COVID-19 vaccinations; of these, 2 patients refused vaccination, 13 patients did not receive the second dose of the vaccine because of cancer progression, and 21 patients had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28–86), 66.15% with metastatic disease. Primary end-point: seropositivity rate in patients was 75.88% versus 100% in the control group. Secondary end-points: no Grade 3–4 side-effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group; male sex and active anticancer therapy influenced negative seroconversion. BNT162b2 or messenger RNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile. • Patients with cancer are at great risk of serious complications and death from coronavirus disease (COVID-19). • 257 patients with cancer vaccinated against COVID-19, 75.88% showed seroconversion. • 219 of the 257 patients (85.21%) were on active anticancer treatment. • No Grade 3–4 side-effects were reported. • Male sex and active anticancer treatment negatively influence serologic response. [ABSTRACT FROM AUTHOR]

Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients. However, CLL patients sensitive to lenalidomide clearly show a peculiar gene expression profile in leukemic cells. The most up-regulated gene (fold change =  +23 in R vs. NR) is Wnt inhibitor SHISA homolog 3 (SHISA3). SHISA3highCLL are characterized by a restrained activation of Wnt signaling and sensibility to lenalidomide-induced apoptosis. In conclusion, SHISA3 is a candidate gene for the identification of CLL patients who will benefit of lenalidomide treatment as single agent. [ABSTRACT FROM AUTHOR]

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R–B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12–71 months). Toxicity was moderate, mainly grades 1 and 2. R–B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs. [ABSTRACT FROM AUTHOR]

Survival rates for elderly Hodgkin Lymphoma ( HL) have not improved substantially in recent years, mainly because of a lack of prospective randomized studies, due to difficulties in enrolling patients. Between 2002 and 2006, 54 untreated HL patients, aged between 65 and 80 years and considered 'non-frail' according to a comprehensive geriatric evaluation, were enrolled into a phase III randomized trial to compare a reduced-intensity regimen (vinblastine, cyclophosphamide, procarbazine, prednisone, etoposide, mitoxantrone, bleomycin; VEPEMB) with standard ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Primary endpoint was progression-free survival ( PFS). Seventeen patients were in early stage (I- IIA), while 37 were advanced stage. Median age was 72 years and median follow-up was 76 months. Five-year PFS rates were 48% vs. 70% [adjusted Hazard ratio ( HR) = 2·19, 95% confidence interval ( CI) = 0·94-5·10, P = 0·068] and 5-year overall survival ( OS) rates were 63% vs. 77% (adjusted HR = 1·67, 95% CI = 0·69-4·03, P = 0·254) for VEPEMB compared to ABVD. Overall treatment-related mortality was 4%. World Health Organization grade 4 cardiac and lung toxicity occurred in four patients treated with ABVD versus no cases in the VEPEMB arm. Standard ABVD regimen resulted in better PFS and OS than the VEPEMB, although the differences were not statistically significant. The low toxicity of both treatments was probably attributable to stringent selection of patients based on a Comprehensive Geriatric Assessment that excluded frail patients. [ABSTRACT FROM AUTHOR]

Background In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes ( MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. Methods The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Results Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10-20 mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event ( AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966 ng/mL to 1475 ng/mL ( P < 0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12 months, respectively. Conclusions Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence. [ABSTRACT FROM AUTHOR]

The endothelin axis, comprising endothelins (ET-1, ET-2 and ET-3) and their receptors (ETAR and ETBR), has emerged as relevant player in tumor growth and metastasis. Here, we investigated the involvement of ET-1/ETAR axis in chronic lymphocytic leukemia (CLL). CLL cells expressed higher levels of ET-1 and ETA receptor as compared to normal B cells. ET-1 peptide stimulated phosphoinositide-3-kinase and mitogen-activated protein kinase signaling pathways, improved survival and promoted proliferation of leukemic cells throughout ETAR triggering. Moreover, the blockade of ETAR by the selective antagonist BQ-123 inhibited the survival advantage acquired by CLL cells in contact with endothelial layers. We also found that blocking ETAR via BQ-123 interferes with ERK phosphorylation and CLL pro-survival effect mediated by B-cell receptor (BCR) activation. The pro-apoptotic effect of phosphoinositide-3-kinase δ inhibitor idelalisib and mitogen-activated protein kinase inhibitor PD98059 was decreased by the addition of ET-1 peptide. Then, ET-1 also reduced the cytotoxic effect of fludarabine on CLL cells cultured alone or co-cultured on endothelial layers. ETAR blockade by BQ-123 inhibited the ET-1-mediated protection against drug-induced apoptosis. Lastly, higher plasma levels of big ET-1 were detected in patients (n = 151) with unfavourable prognostic factors and shorter time to first treatment. In conclusion, our data describe for the first time a role of ET-1/ETAR signaling in CLL pathobiology. ET-1 mediates survival, drug-resistance, and growth signals in CLL cells that can be blocked by ETAR inhibition. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary central nervous system (CNS) lymphoma. The open, randomized phase two trial was conducted in 24 centers in six countries, and involved 79 patients ages 18 to 75 yeas with non-Hodgkin lymphoma exclusively localized into the CNS, cranial nerves or eyes. The patients were randomly assigned by computer to receive four courses of either methotrexate on day one, or methotrexate on day one combined with cytarabine twice a day on days two to three. Main variable measured was complete remission rate following chemotherapy. Interpretation of the research findings indicate the efficacy of the drug.

Abstract: Background: Bisphosphonates are commonly used as standard care in the management of patients with advanced-stage cancer involving bone. There has recently been growing concern that the use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ). Methods: Between 2001 and 2005, five patients with ONJ associated with pamidronate and zoledronate therapy were diagnosed at our department. The patients had breast cancer, renal carcinoma, mesothelioma, and multiple myeloma, all involving bone. The literature was reviewed. Results: The duration of bisphosphonate therapy before presentation of ONJ ranged from 21 to 36 months. The lesions were localized to the mandible (n =3) and maxilla (n =2). All of the patients presented with pain and exposed bone; in two of them, symptoms began after tooth extraction. A review of the literature through March 2006 identified more than 250 reported cases of ONJ. Conclusions: The findings in our patients, combined with the literature review, suggest that: (1) the most common clinical presentation of ONJ is pain and exposed bone of the mandible or maxilla; (2) for patients who develop ONJ, conservative, non-surgical treatment is strongly recommended; (3) clinical dental examination and a panoramic jaw radiograph should be performed before patients begin bisphosphonate therapy; (4) dental treatment and other oral procedures should be completed before initiating bisphosphonate therapy; (5) patients should be informed and instructed on the importance of maintaining good oral hygiene and having regular dental assessment; and (6) the medical community needs to be aware of the association between bisphosphonate usage and ONJ so that unnecessary and harmful surgical procedures can be avoided. [Copyright &y& Elsevier]

The article discusses a study on the safety profile and clinical activity of rituximab in combination with fludarabine and cyclophosphamide in patients with recurrent follicular lymphoma (FL). The study involved 54 patients with recurrent FL who were administered with rituximab at a dose of 375 mg/m² following the first course of fludarabine and cyclophosphamide treatment. It cites that the combination therapy showed significant antilymphoma activity, excellent clinical complete response (CR) and molecular response rates.

The article provides information on a study which evaluated the impact of evolving therapy including the introduction of rituximab on follicular lymphoma patients. The study made use of data from the consecutive Gruppo Italiano Studio Linfomi (GISL) trials between 1988 and 2004 which enrolled 438 advanced-stage follicular lymphoma patients. Patients enrolled in the trial received anthracycline- and/or fludarabine-based regimens. From the said trial, the overall survival (OS), failure-free survival (FFS) and survival after recurrence (SAR) were analyzed.

A 41-year-old man with advanced Waldenström’s macroglobulinemia (WM) associated with the hyperviscosity syndrome, massive splenomegaly and with IgM concentration of 10 g/dl, was treated in January 1984 with plasmapheresis, systemic chemotherapy (M2 protocol) and splenic radiotherapy. He rapidly improved and was discharged 1 month later. Fourteen months later he underwent splenectomy since a mild splenomegaly persisted though the normalization of bone marrow, peripheral blood and electrophoresis with an IgM concentration of 140 mg/dl. However, at this time immunofixation and immunoelectrophoresis showed a small IgM-κ monoclonal component. The histological and immunohistochemical analysis showed minimal splenic involvement by WM. Two months after splenectomy, immunofixation and immunoelectrophoresis showed no monoclonal component. The spleen was the probable site of minimal residual disease. The patient was treated with monthly chlorambucil and prednisone for 2 years. Subsequently clinical and laboratory tests persisted within normal limits. The last control performed in January 2002 showed that the patient was in good health; bone marrow examination (aspiration, biopsy with immunohistochemical analysis) and immunofixation persisted normally. This interesting case report, with advanced WM, alive, in good health and without signs of disease 18 years from diagnosis, is presented here and the role of splenectomy is debated.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Simple Summary: The interest in using Machine-Learning (ML) techniques in clinical research is growing. We applied ML to build up a novel prognostic model from patients affected with Mantle Cell Lymphoma (MCL) enrolled in a phase III open-labeled, randomized clinical trial from the Fondazione Italiana Linfomi (FIL)—MCL0208. This is the first application of ML in a prospective clinical trial on MCL lymphoma. We applied a novel ML pipeline to a large cohort of patients for which several clinical variables have been collected at baseline, and assessed their prognostic value based on overall survival. We validated it on two independent data series provided by European MCL Network. Due to its flexibility, we believe that ML would be of tremendous help in the development of a novel MCL prognostic score aimed at re-defining risk stratification. Background: Multicenter clinical trials are producing growing amounts of clinical data. Machine Learning (ML) might facilitate the discovery of novel tools for prognostication and disease-stratification. Taking advantage of a systematic collection of multiple variables, we developed a model derived from data collected on 300 patients with mantle cell lymphoma (MCL) from the Fondazione Italiana Linfomi-MCL0208 phase III trial (NCT02354313). Methods: We developed a score with a clustering algorithm applied to clinical variables. The candidate score was correlated to overall survival (OS) and validated in two independent data series from the European MCL Network (NCT00209222, NCT00209209); Results: Three groups of patients were significantly discriminated: Low, Intermediate (Int), and High risk (High). Seven discriminants were identified by a feature reduction approach: albumin, Ki-67, lactate dehydrogenase, lymphocytes, platelets, bone marrow infiltration, and B-symptoms. Accordingly, patients in the Int and High groups had shorter OS rates than those in the Low and Int groups, respectively (Int→Low, HR: 3.1, 95% CI: 1.0–9.6; High→Int, HR: 2.3, 95% CI: 1.5–4.7). Based on the 7 markers, we defined the engineered MCL international prognostic index (eMIPI), which was validated and confirmed in two independent cohorts; Conclusions: We developed and validated a ML-based prognostic model for MCL. Even when currently limited to baseline predictors, our approach has high scalability potential. [ABSTRACT FROM AUTHOR]

The article focuses on the GIMEMA MDS0306 study conducted to evaluate the long-term follow-up of myelodysplastic syndromes (MDS) patients treated with deferasirox regarding their safety profile and transfusion independence. The study found that out of 22 patients who continued deferasirox in the observational phase, 6 achieved transfusion independence.

Background: Allogeneic stem cell transplantation from haploidentical donor using an unmanipulated graft and post-transplantation cyclophosphamide (PT-Cy) is growing. Haploidentical transplantation with PT-Cy showed a major activity in Hodgkin lymphoma (HL), reducing the relapse incidence. The most important predictive factor of survival and toxicity was disease status before transplantation, which was better in patients with well controlled disease.Methods: We included 198 HL in complete (CR) or partial remission (PR) before transplantation. Sixty-five patients were transplanted from haploidentical donor and 133 from a HLA identical donor (both sibling and unrelated donors). Survival analysis was defined according to the EBMT criteria. Survival curves were generated by using Kaplan-Meier method and differences between groups were compared by the log rank test or by the log rank test for trend when appropriated.Results: The PFS, OS, and RI were significantly better in patients in CR compared to PR (55% vs 29% p = 0.001, 74% vs 55% p = 0.03, 27% vs 55% p <  0.001, respectively). The 2-year PFS was significantly better for HAPLO than HLA-id (63% vs 37%, p = 0.03), without difference in OS. The 1-year NRM was not different. The 2-year relapse incidence (RI) was lower in the HAPLO group (24% vs 44%, p = 0.008). Patients in CR receiving haplo HSCT showed higher 2-year PFS and lower 2-year RI than those allografted with HLA-id donor (75% vs 47%, p <  0.001 and 11% vs 34%, p < 0.001, respectively). In multivariate analysis, donor type and disease status before transplantation were independent predictors of PFS as well as they predict the risk of relapse. Disease status at transplantation and age were independently associated to OS.Conclusions: Nonetheless this is a retrospective study, limiting the wide applicability of results, data from this analysis suggest that HLA mismatch can induce a strong graft versus lymphoma effect leading to an enhanced PFS. [ABSTRACT FROM AUTHOR]

Lenalidomide is an IMID immunomodulatory agent clinically active in patients with chronic lymphocytic leukemia (CLL). We evaluated the activity of lenalidomide inside an in vitro coculture system of endothelial and CLL cells. Lenalidomide was able to inhibit CLL survival advantage mediated by endothelial contact. Moreover, the marked increase of in vitro angiogenesis determined by CLL-derived conditioned media was reduced by lenalidomide. We also analyzed peripheral blood collected from 27 patients with relapsed or refractory CLL being treated with lenalidomide within a phase II trial. Plasma levels of VEGF and THBS-1 decreased, whereas Ang2 and Ang increased during treatment. Patients who respond to lenalidomide showed a more pronounced decrease of VEGF and bFGF than did patients with stable or progressive disease (p = 0.007 and p = 0.005). Furthermore, lenalidomide reduced circulating endothelial cells and endothelial progenitors by increasing the percentage of apoptotic cells. Conversely, for six matched bone marrow biopsies available before and after treatment, we did not detect any modification in vessel density, suggesting a possible mechanism of vessel normalization rather than regression. In conclusion, our study provides further evidence that the anti-CLL effect of lenalidomide is mediated through the alteration of microenvironmental elements, implying the modulation of several angiogenesis-related factors and disruption of CLL crosstalk with endothelial cells. [ABSTRACT FROM AUTHOR]

Focuses on effects of use of clinical trial results, adopted by health administrators in reducing health costs, on medical care of patients. Removal of availability of certain medical products from health services; Problem for physicians in selection of a treatment; Need for the medical community to counter the practice of the administrators.