Search

Therapy for relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (aB-NHL) post autologous stem cell transplantation (ASCT) or in elderly patients can be challenging. In this single-center, single-arm, phase II clinical study, we investigated the efficacy of ibrutinib (560 mg once daily) in combination with bendamustine and rituximab (IBR) given for six 28-day cycles in their standard dose, to patients with R/R aB-NHL who were either transplant ineligible in first or second relapse or post-ASCT for second relapse. The primary endpoint was overall response rate (ORR). Fifty-six patients (54% male, median age 69.7 years) were included. ORR was 49.1% among 55 patients treated with ≥ 1 cycle of IBR and 69.4% among 36 patients treated with ≥ 3 cycles. Patients with relapsed disease had significantly higher ORR compared to those with refractory disease (72.3% vs. 37.8%, p = 0.024). Median overall survival (OS) was 11.6 months (95% CI, 7.1-22.3) and median progression-free survival was 5.3 months (95% CI, 2.5-7.4). Patients with complete and partial responses had significantly longer median OS compared to those with stable and progressive disease (28.1 vs. 5.2 months, p < 0.0001). Adverse events included thrombocytopenia (19.6%), anemia (16.1%), neutropenia (7.1%), fatigue (35.7%), diarrhea (28.6%) and nausea (28.6%). At the first efficacy evaluation 8 patients were referred to transplantation, and 3 more were referred during follow-up. These data indicate that the IBR regimen is a safe and effective treatment option that can also be used for bridging to transplantation in patients with R/R aB-NHL.Trial Registration: ClinicalTrials.gov: NCT02747732., (© 2024 John Wiley & Sons Ltd.)

The COVID-19 pandemic continues to pose challenges to the treatment of hemato-oncology patients. Emergence of COVID-19 variants, availability of vaccine boosters and antiviral treatments could impact their outcome. We retrospectively studied patients with hematologic malignancies and confirmed COVID-19 during the Omicron outbreak. Of 116 evaluated patients, 16% developed severe or critical COVID-19. Diagnosis of chronic lymphocytic leukemia (CLL) was significantly associated with severe COVID-19 (p = 0.01). The vaccine effectiveness was related to the timing of the vaccine, with patients who received a mRNA vaccine within 7-90 days prior to COVID-19 being less likely to develop severe disease compared to all other patients (p = 0.019). There was no correlation between disease severity and antiviral therapies. Importantly, 45% of patients undergoing active hematological treatment had to interrupt their treatment due to COVID-19. In conclusion, patients with hematologic malignancies are at a considerable risk for severe COVID-19 during the Omicron outbreak, with patients with CLL being the most vulnerable. mRNA vaccines have the potential to protect hematological patients from severe COVID-19 if administered within the previous 3 months. Hematological treatment interruption is a frequent adverse outcome of COVID-19 infection., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia. In this retrospective multicenter study, 68 SP patients were included. Compared to solitary extramedullary plasmacytoma (SEP), patients with solitary bone plasmacytoma (SBP) were younger (57.3 vs. 70.9 years, p  = 0.031), had larger plasmacytoma (median: 5.4 vs. 3 cm, p  = 0.007) and higher median involved free light chain level (61 vs. 25.8 mg/L, p  = 0.056). 92.6% of patients were treated by radiotherapy and 11.8% received systemic anti-myeloma treatment. With a median follow-up of 42 months, 45.6% of patients progressed (8.8% - recurrent SP, 36.8% - active myeloma). The median PFS was 58 months and the median OS has not been reached (10-year OS: 84.8%). Patients who received also anti-myeloma treatment had longer PFS compared to those who did not (median not reached vs. 48 months, p  = 0.056). In conclusion, SBP and SEP appear to be different diseases. Radiotherapy is the cornerstone in the SP treatment. A large prospective trial is needed to evaluate the impact of adding systemic anti-myeloma treatment to local radiotherapy.

Background and Objectives: The COVID-19 pandemic has led to a growing interest in hospital-at-home programmes, including home transfusion services. We studied whether the pandemic had influenced patients' perception of home transfusions., Materials and Methods: We conducted a survey among haematology patients who receive transfusions in the hospital day care facility. Patients were asked about the burden of day care transfusions and whether they would prefer receiving home transfusions. The survey was conducted during the COVID-19 pandemic, and the results were compared with a survey performed before the pandemic (baseline)., Results: Sixty patients were included in the COVID-19 cohort and 31 patients in the baseline cohort. There was a non-significant decrease in the proportion of patients willing to receive home transfusions during the pandemic compared with baseline (35% vs. 47%, respectively, p = 0.28). More patients in the COVID-19 cohort were afraid to receive home transfusions (60% compared with 48% at baseline, p = 0.29), and fewer patients believed that hospital transfusion impaired their quality of life (19% compared with 36% at baseline, p = 0.09). These unexpected results may be partly attributed to the shorter time needed to arrive at the hospital during the pandemic and a greater fear of having transfusion-related adverse effects at home., Conclusions: Our results show that the pandemic did not increase the willingness of patients to receive home transfusions, with a non-significant drift towards refusal of home transfusions. Patients' opinions should be taken into consideration when planning for future home transfusion services, by creating a comprehensive approach to patients' needs., (© 2022 International Society of Blood Transfusion.)

This national Israeli multicenter retrospective study aimed to characterize the clinical course of COVID-19 infection among patients with hematological malignancies, with special emphasis on treatment efficacy and outcome. Clinical and laboratory data from haemato-oncological patients diagnosed with COVID-19 from 16 medical centers were centrally reported. Multivariate regression analyses were used to determine variables associated with severe disease, hospitalization, and mortality. In total, 313 patients were included: 103 (35.7%) developed severe/critical respiratory infection, 178 (61.4%) were hospitalized, and 60 (20.0%) died. Age > 70 years was associated with severe/critical disease ( p  = 0.036) and mortality ( p  = 0.023), hypertension with severe/critical disease ( p  = 0.046) and hospitalization ( p  = 0.001), active haemato-oncological treatment with hospitalization ( p  = 0.009), and remdesivir treatment was associated with decreased mortality ( p  = 0.021). Convalescent plasma, enoxaparin, and corticosteroids resulted in no clinical benefit. In conclusion, COVID-19 infection seems particularly severe in patients with hematological malignancies, and of all examined therapies, remdesivir appears to be the most effective.

Patients with hematologic malignancies have an increased risk of severe COVID-19 infection. Vaccination against COVID-19 is especially important in these patients, but whether they develop an immune response following vaccination is unknown. We studied serologic responses to the BNT162b2 vaccine in this population. A lower proportion of patients were seropositive following vaccination (75%) than in a comparison group (99%; p < 0.001), and median (interquartile range [IQR]) antibody titers in patients were lower (90 [12.4-185.5] and 173 [133-232] AU/ml, respectively; p < 0.001). Older age, higher lactate dehydrogenase, and number of treatment lines correlated with lower seropositivity likelihood and antibody titers, while absolute lymphocyte count, globulin level, and time from last treatment to vaccination correlated with higher seropositivity likelihood and antibody titers. Chronic lymphocytic leukemia patients had the lowest seropositivity rate followed by indolent lymphoma. Patients recently treated with chemo-immunotherapy, anti-CD20 antibodies, BCL2, BTK or JAK2 inhibitors had significantly less seropositive responses and lower median (IQR) antibody titers (29%, 1.9 [1.9-12] AU/ml; 0%, 1.9 [1.9-1.9] AU/ml; 25%, 1.9 [1.9-25] AU/ml; 40%, 1.9 [1.9-92.8] AU/ml; and 42%, 10.9 [5.7-66.4] AU/ml, respectively; p < 0.001). Serological response to BNT162b2 vaccine in patients with hematologic malignancies is considerably impaired, and they could remain at risk for severe COVID-19 infection and death., (© 2021 Wiley Periodicals LLC.)

Background: In December 2020 the Israeli Health Ministry began a mass vaccination campaign with the BNT162b2 vaccine. This was an important step in overcoming the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic. Autoimmune phenomenon have been described after receiving vaccinations., Patients/methods: Here we describe a case series of patients who developed acquired Thrombotic Thrombocytopenic Purpura, a rare autoimmune disease, within several days of receiving the BNT162b2 vaccine., Conclusions: A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity should be evaluated in patients with history of aTTP before and after any vaccination, especially the SARS-CoV-2 vaccination, and immunosuppression treatment should be considered before vaccination in cases of low ADAMTS13 activity. Patients should be closely monitored after the vaccine for clinical situation and laboratory data. Post vaccination thrombocytopenia assessment should include immune thrombocytopenic purpura, vaccine-induced immune thrombotic thrombocytopenia and acquired thrombotic thrombocytopenic purpura., (© 2021 International Society on Thrombosis and Haemostasis.)

Introduction: The myeloproliferative neoplasms (MPN) are clonal diseases that confer an increased risk of thrombohemorrhagic complications. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease associated with an increased thrombotic risk. Small PNH clones are prevalent in aplastic anemia and myelodysplastic syndrome patients, but their prevalence in MPN patients is unknown., Patients and Methods: Consecutive patients with MPN followed up at a single center were recruited. PNH clones were analyzed in erythrocytes and white blood cells by flow cytometry., Results: PNH clones were detected in 2% of patients and were more common in JAK2 V617F positive patients. We could not detect any differences in clinical manifestations or complications in patients either with or without PNH clones because of the small patient numbers., Conclusion: The prevalence of PNH clones in MPN is similar to that described in myelodysplastic syndromes. Whether PNH clones influence MPN phenotype and complications should be studied prospectively in larger patient cohorts and over long-term follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.

Introduction: Azacitidine (AZA) dose reduction is a common practice in cytopenic patients. However, a correlation between AZA dose and infection complications has never been studied., Patients and Methods: Higher-risk patients with myelodysplastic syndrome or acute myeloid leukemia treated with AZA in 18 Israeli hospitals between the years 2008 and 2011 were included in a former national survey. To reveal the effect of AZA dosage on infection risk we limited our analysis to the infection rate after the first AZA dose alone. We excluded subsequent cycles of AZA from the analysis, because infectious events during these cycles might be related to other cofactors such as disease response to AZA therapy., Results: After the first AZA cycle, infectious events were more frequent after doses of 75 mg/m(2) for 7 days than 75 mg/m(2) for 5 days (36/106 [34%] and 10/67 [14.9%], respectively; P = .008), regardless of the patient's age. Of the 46 recorded infectious events, the causative pathogen was identified as bacterial in 25 (54.3%) and as viral or fungal in 2 (4.3%) and 2 (4.3%) cases, respectively. No pathogen was identified in 17 (37%) cases. Infections were significantly more prevalent among patients who presented with platelet counts < 20,000 (43.6% vs. 23.6%; P = .012) and poor risk cytogenetics (40.7% vs. 19.8%; P = .008)., Conclusion: Reduction of AZA dose might decrease infection rate and therefore should be considered in patients with high infection risk., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hypomethylating agents have become the standard therapy for patients with high-risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA-treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high-risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29-92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 10⁹/L and neutrophil count below 0.5 × 10⁹/L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered., (Copyright © 2012 Wiley Periodicals, Inc.)