Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges.

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes.

Sarcopenia does not impact the outcome of patients with Multiple Mieloma consolidated with autologous Hematopoietic Stem Cell Transplantation.

Sarcopenia has been associated with chronic diseases and cancer. Aim of this study was to evaluate sarcopenia in Multiple Myeloma patients undergoing autologous stem cell trans-plantation. In 68 eligible patients' measurement of skeletal muscle area (cm2) on computed tomography scans at the level of the L3 vertebra (L3-SMI) was performed. 37(54%) patients were categorized as sarcopenic: 26 males with L3-SMI values < 52.4 cm2/m2, and 11 women with L3-SMI values < 38.9 cm2/m2. The majority of sarcopenic patients included were older than 60 years (69%, p=0.0005), and with BMI <25 (75%; p=0.0000). A significant association was found between sarcopenia and Sorror score value > 1 (p=0.02). The Kaplan Meyer curve showed a median OS of 73.5 months for non-sarcopenic patients vs. 86.5 months for sarcopenic patients, suggesting that sarcopenia is not an independent prognostic factor in this cohort of patients.

Fluorodeoxyglucose-Positron Emission Tomography in Relapsed/Refractory Hodgkin Lymphoma: A Practical Approach.

BACKGROUND: Positron emission tomography (PET) with the use of 18F-fluorodeoxyglucose (FDG), implemented with low-dosage computer tomography, is to be considered as the most important evolution of imaging in the management and assessment of classical Hodgkin lymphoma patients. SUMMARY: According to Lugano response criteria, FDG-PET is mandatory to define metabolic response to frontline therapy and moreover it is important in the definition of nonresponders or refractory disease patients. Refractory disease is reported in about 15% of patients, with some variations based on the choice of first-line chemotherapy, and particularly in advanced stages, up to 40% eventually relapse within 3 years. KEY MESSAGES: The aim of this review was to highlight a practical way to use FDG-PET in the subset of HL, with some notes of its use in first-line patients, and particularly centered on relapsed or refractory setting with a final focus of the evaluation of response by FDG-PET in the new treatment era of immunocheckpoint inhibitors.

Role of CD68 in the tumor immune microenvironment in Hodgkin's lymphoma.

INTRODUCTION: Despite the high rate of cure in classical Hodgkin Lymphoma (cHL), some patients experienced a refractory disease, sometimes, hardly curable. In the pathogenesis of cHL, Reed Sternberg Cells (HRSC), which represent only less than 1% of tumor cells, are not the only protagonist; in fact, the role of tumor microenvironment is essential in survival, tumor growth, and progression of the disease due to the interaction between immune cells, chemokines, and cytokines. AREAS COVERED: In this review, the current significant literature was discussed. Many studies demonstrated the role of macrophages CD68+ as 'protumor', especially in supporting HRSC survival through cell-to-cell and paracrine interactions. Increased infiltration of CD68 macrophages correlate with a poor prognosis. This review examines the interaction between CD68 macrophages, HRSC and cHL milieu, and the consequent clinical impact, providing an up-do-date portrait of these immune cells with possible translational and therapeutic applications. EXPERT OPINION: We can suggest that a high baseline CD68 macrophages in cHL patients could contribute to the identification of high-risk patients and help clinicians to choose the best treatment, in the context of refractory disease. A macrophage target strategy in association with chemotherapy or biological therapy could represent a promising approach for future studies and investigations.

Neuroradiology of acute pathologies in adults with hematologic malignancies: a pictorial review.

Hematopoietic and lymphoid tumors are a heterogeneous group of diseases including lymphomas, multiple myeloma (MM), and leukemias. These diseases are associated with systemic involvement and various clinical presentations including acute neurological deficits. Adult patients with hematologic malignancies (HM) are at risk for developing a wide array of acute conditions involving the nervous system. HM in adults may present as tumoral masses responsible for mass effect, possibly resulting in acute neurological signs and symptoms caused by tumor growth with compression of central nervous system (CNS) structures. Moreover, as result of the hematologic disease itself or due to systemic treatments, hematologic patients are at risk for vascular pathologies, such as ischemic, thrombotic, and hemorrhagic disorders due to the abnormal coagulation status. The onset of these disorders is often with acute neurologic signs or symptoms. Lastly, it is well known that patients with HM can have impaired function of the immune system. Thus, CNS involvement due to immune-related diseases such as mycotic, parasitic, bacterial, and viral infections linked to immunodeficiency, together with immune reconstitution inflammatory syndrome, are frequently seen in hematologic patients. Knowledge of the etiology and expected CNS imaging findings in patients with HM is of great importance to reach a fast and correct diagnosis and guide treatment choices. In this manuscript, we review the computed tomography (CT) and magnetic resonance findings of these conditions which can be related to the disease itself and/or to their treatments.

Exploratory Genome-Wide Association Analysis to Identify Pharmacogenetic Determinants of Response to R-CHOP in Diffuse Large B-Cell Lymphoma.

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaïve DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 × 10-8) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response.

Effects of ABVD chemotherapy on ovarian function: epidemiology, hormonal dosages and ultrasound morphologic analyses in 270 patients with Hodgkin's disease.

Introduction: Classical Hodgkin Lymphoma (HL) is a lymphoproliferative disease typically diagnosed in the young. The excellent results obtained with current treatment lead to long survival with age-related complications affecting patients' survival and quality of life. One issue affecting HL patients is infertility. This problem can be easily overcome in males with seminal liquid cryopreservation, however, in females it is more complex either in terms of the quality of the cryopreserved material or the patients' age at diagnosis. Moreover, not all chemo- or radio-therapies have the same negative impact on fertility.The main objectives of this study was to collect epidemiological information on HL patients involved in fertility preservation counseling and to analyze the impact of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the standard treatment for HL, on ovarian function, hormonal levels and ovarian and uterine tissue morphologies. Patterns of fertility preservation were also reported. Methods: Data were obtained from 270 female patients at HL onset who were interested in fertility counseling prior to therapy initiation. Each patient was assessed at HL diagnosis for levels of Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), and 17ß-oestradiol (17ß-oe), with additional assessments at 6 and 12 months after chemotherapy. Patients were evaluated with ultrasound scans to study the number of ovarian follicles and the degree of uterine thickness at the same timepoints. Results: The average patient AMH level showed a statistically significant reduction at 6 months after chemotherapy (p=0.05) and by the 12 month time point returned to near pre-chemotherapy values. FSH and 17ß-oe levels did not significantly vary throughout the study period. ABVD chemotherapy was associated with a significant reduction of both ovarian follicles and endometrial thickness at the 6 month time point followed by a recovery at the 12 time point in both ovaries. Different results were observed when patients changed treatment to a more intensive one. Discussion: Based on the results from the hormonal measurements and the follicle echography, it appears that the toxic effect of ABVD on fertility is transient, whereas, in contrast, more intensive therapies may potentially be more harmful and long-lasting.

Impact of Pretransplant Salvage Therapies on Outcome of Hodgkin Lymphoma Patients Performing Allogeneic Transplant.

BACKGROUND: Allogeneic transplant is an effective salvage therapy in patients with Hodgkin lymphoma (HL) relapsed or refractory (R/R) to previous treatments. In recent years, immunotherapies (conjugated antibody and checkpoint inhibitors [CPI]) showed interesting results and were used as bridge therapies to allotransplant. AIM: The aim of this retrospective study in Lazio region was to evaluate the impact of these new therapies on outcome after allogeneic hematopoietic stem cell transplantation (allo-SCT) in comparison with standard chemotherapies used in the past. METHODS: We selected all consecutive patients with diagnosis of HL transplanted in four hematology transplant units, and we collected data obtained from patients' records concerning all the treatments before allo-SCT. RESULTS: A total of 56 patients were enrolled in this study. All patients underwent allo-SCT for R/R HL. Seventeen patients (30%) received chemotherapy prior to allo-SCT (group B); they were treated between 2008 and 2015; and 39 patients (70%) received brentuximab vedotin (BV), CPI, or both before allo-SCT as a bridge to transplant (group A); they were treated between 2012 and 2020. Twenty-five patients were treated with BV alone, 2 with CPI alone, and 12 first with BV and then with CPI. No patient received concomitant BV and CPI. At 5 years from allo-SCT, overall survival (OS) was 59% and progression-free survival (PFS) was 65%. No statistical differences in OS or PFS were observed between patients in groups A and B. Relapse was significantly associated with a lower survival. The only factor associated with a reduced risk of relapse was development of any grade acute graft versus host disease (GVHD) (p > 0.02). CONCLUSIONS: This regional real-world experience shows the changes that have taken place in the last 10 years in R/R HL using new drugs to render a patient eligible for allo-SCT. This strategy appears to guarantee an impressive disease control with an increased risk of complications, for example, aGVHD, that appear to nullify this advantage at least in part.

Identification of Predictive Factors for Overall Survival and Response during Hypomethylating Treatment in Very Elderly (≥75 Years) Acute Myeloid Leukemia Patients: A Multicenter Real-Life Experience.

Elderly patients represent the most challenging and hard-to-treat patient population due to dismal characteristics of the disease, such as secondary-acute myeloid leukemia (AML), enrichment of unfavorable molecular genes (TP53) and comorbidities. We conducted a multicentric retrospective study to evaluate activity and safety in a real-life setting of hypomethylating drugs (HMAs) in patients older than 75 years with AML. Between September 2010 and December 2021, 220 patients were treated, 164 (74.5%) received AZAcitidine and 56 DECitabine; most patients (57.8%), received more than four cycles of HMAs. The best response obtained was CR in 51 patients (23.2%), PR in 23 (10.5%) and SD in 45 (20.5%); overall transfusion independence was obtained in 47 patients (34%), after a median of 3.5 months. The median OS (mOs) was 8 months (95% CI 5.9-10.2), with 1- and 2-years OS of 39.4% (95% CI 32.7-46) and 17.4% (95% CI 11.7-23.1), respectively; similar mOS was observed according to HMA treatment (AZA 8.3 vs. DEC 7.8 months, p = 0.810). A subset of 57 long survivors (44 in AZA group and 13 in DEC group) received at least 12 cycles of HMAs, their mOS was 24.3 months. In multivariate analysis, age (≥80), Charlson comorbidity index (≥3), creatinine clearance and the type of best response (≥PR) during treatment maintained independent significance in predicting survival. Infectious complications, most frequently pneumonia (35) and septic shock (12), were lethal in 49 patients (22.2%). Our data show that HMAs have similar efficacy compared to pivotal trials and are well tolerated in a setting of very elderly patients with several co-comorbidities.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV.

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy.

Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.

Corrigendum: Portrait of Italian Cardio-Oncology: Results of a Nationwide Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Survey.

[This corrects the article DOI: 10.3389/fcvm.2021.677544.].

Obinutuzumab does not improve complete methabolic response but does not compromise mobilization or engraftment of autologous peripheral blood stem cells in diffuse large B cell lymphoma: Results from a fondazione italiana linfomi prospective phase II study (the GIOTTO study).

Salvage immunochemotherapy and transplant consolidation is the standard treatment for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We tested a combination of Obinutuzumab and DHAP for treating R/R DLBCL. The primary end point was the rate of complete metabolic response (CMR). Secondary end points were stem cell mobilization, stem cell engraftment, overall survival, and feasibility. In this prospective, phase-2, single-arm trial (EudraCT 2014-004014-17) patients received the standard three doses of Obinutuzumab for the first cycle, and then one dose. Patients with CMR were consolidated with an autologous stem cell transplantation (ASCT). An interim analysis was provided after the first 29 patients to confirm the initial null hypothesis that at least 10/29 patients would achieve CMR. Among the 29 patients evaluated for the first stage only six patients (6/29, 21%) achieved CMR, thus, study enrollment was stopped. Nine patients exhibited extra-hematologic toxicities ≥ grade 3. Among the 19 patients that started stem cell mobilization, one failed (5%) and 18 achieved mobilization (95%). Of these 18 patients, nine were reinfused. Mobilization was observed in 16 patients (89%) after one or two apheresis rounds. The mean number of CD34 + cells mobilized was 5.8 × 106 /Kg (median: 5.5, IQR: 5-6.75). The mean number of reinfused CD34 + cells in the nine patients was 4.1 × 106 /Kg (median: 4.1, IQR: 3.5-5). Obinutuzumab combined with DHAP did not compromise stem cell mobilization or engraftment after ASCT in patients with DLBCL. However, Obinutuzumab + DHAP provided a lower CMR rate than expected.

Physicians' Perceptions of Clinical Utility of a Digital Health Tool for Electronic Patient-Reported Outcome Monitoring in Real-Life Hematology Practice. Evidence From the GIMEMA-ALLIANCE Platform.

Digital health tools are increasingly being used in cancer care and may include electronic patient-reported outcome (ePRO) monitoring systems. We examined physicians' perceptions of usability and clinical utility of a digital health tool (GIMEMA-ALLIANCE platform) for ePRO monitoring in the real-life practice of patients with hematologic malignancies. This tool allows for the collection and assessment of ePROs with real-time graphical presentation of results to medical staff. Based on a predefined algorithm, automated alerts are sent to medical staff. Participating hematologists completed an online survey on their experience with the platform. Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) agreed to enter the platform and had a median age of 57 years. Twenty-three hematologists with a median age of 42 years and an average of 17 years of experience in clinical practice were surveyed. All hematologists agreed or strongly agreed that the platform was easy to use, and 87%, agreed or strongly agreed that ePROs data were useful to enhance communication with their patients. The majority of physicians (78%) accessed the platform at least once per month to consult the symptom and health status profile of their patients. The frequency of access was independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). In conclusion, our preliminary results support the clinical utility, from the perspective of the treating hematologist, of integrating ePROs into the routine cancer care of patients with hematologic malignancies.

Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT.

Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.

Brentuximab Vedotin and Bendamustine Produce Long-Term Clinical Benefit in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter Real-Life Experience.

BACKGROUND: Patients with relapsed or refractory classical Hodgkin lymphoma (R/R cHL) have limited opportunities for curative therapy. High-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) produces cure rates of 50% to 60%. Patients relapsing after, or ineligible for HDT-ASCT have limited therapeutic options and long-term remission is uncommon. Furthermore, few patients are candidate to allogeneic stem cell transplantation (AlSCT), a potentially curative approach. The combination of brentuximab vedotin and bendamustine (BVB) is a promising treatment for patients with R/R cHL, regardless of SCT eligibility. PATIENTS AND METHODS: We conducted a real-life study of BVB in 41 patients with R/R cHL after failure of ≥ 1 therapy including ASCT, AlSCT, or BV. RESULTS: Among 40 patients evaluable for efficacy, the overall response rate and complete response (CR) rate were 75% and 50%, respectively. No significant differences were observed between patients with primary refractory and relapsed disease, previously treated with ≤ 2 and ≥ 3 lines of therapy, or BV-exposed and BV-naïve. After a median follow-up of 38 months, the median progression free survival (PFS) for the entire population is 26 months; PFS is not reached, 10.5 months, and 4 months for patients achieving CR, partial response and no response, respectively (P < .0001). BVB was well tolerated and no grade 4 toxicity or new safety signals were observed. The most common treatment-emergent adverse events were infections. CONCLUSION: Our experience supports the efficacy and tolerability of the BVB combination in R/R cHL as a bridge to SCT, or as a definitive therapy for SCT-ineligible patients. Larger comparative studies testing BVB against standards of care are warranted in both settings.

A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin's lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.