COVID-19 does not impact on outcome of myeloma patients infected while undergoing autologous stem cell transplantation.

Here we report two cases of myeloma patients who became positive for SARS-CoV-2 infection during the acute phase of autologous stem cell transplant. Both patients were promptly treated with monoclonal antibodies and remdesivir, and, despite the profound neutropenia and lymphopenia, they did not develop respiratory failure and they remained paucisymptomatic during the entire period of aplasia. Neutrophil engraftment took place as expected and the patients were discharged quickly and did not experience adverse effects after discharge.

Prognostic Relevance of NPM1 and FLT3 Mutations in Acute Myeloid Leukaemia, Longterm Follow-Up-A Single Center Experience.

The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly NPM1 and FLT3-ITD mutations. The targeted drugs' availability has renewed interest in FLT3 mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15−74) carrying the FLT3 (ITD or TKD) and/or NPM1 mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the NPM1-mutated (CR 93.9%, p: 0.0001; survival 71% +/− 6, p: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, p: 0.0009), and the 3 years-relapse-free survival worse (24%, p: <0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the NPM1-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.

Allogeneic stem cell transplantation in patients with mantle cell lymphoma: results from the MANTLE-FIRST study on behalf of Fondazione Italiana Linfomi.

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.

Evans syndrome in adults: an observational multicenter study.

Evans syndrome (ES) is a rare condition, defined as the presence of 2 autoimmune cytopenias, most frequently autoimmune hemolytic anemia and immune thrombocytopenia (ITP) and rarely autoimmune neutropenia. ES can be classified as primary or secondary to various conditions, including lymphoproliferative disorders, other systemic autoimmune diseases, and primary immunodeficiencies, particularly in children. In adult ES, little is known about clinical features, disease associations, and outcomes. In this retrospective international study, we analyzed 116 adult patients followed at 13 European tertiary centers, focusing on treatment requirements, occurrence of complications, and death. ES was secondary to or associated with underlying conditions in 24 cases (21%), mainly other autoimmune diseases and hematologic neoplasms. Bleeding occurred in 42% of patients, mainly low grade and at ITP onset. Almost all patients received first-line treatment (steroids with or without intravenous immunoglobulin), and 23% needed early additional therapy for primary refractoriness. Additional therapy lines included rituximab, splenectomy, immunosuppressants, thrombopoietin receptor agonists, and others, with response rates >80%. However, a remarkable number of relapses occurred, requiring ≥3 therapy lines in 54% of cases. Infections and thrombotic complications occurred in 33% and 21% of patients, respectively, mainly grade ≥3, and correlated with the number of therapy lines. In addition to age, other factors negatively affecting survival were severe anemia at onset and occurrence of relapse, infection, and thrombosis. These data show that adult ES is often severe and marked by a relapsing clinical course and potentially fatal complications, pinpointing the need for high clinical awareness, prompt therapy, and anti-infectious/anti-thrombotic prophylaxis.

Clinical characteristics and risk factors for mortality in hematologic patients affected by COVID-19.

BACKGROUND: Patients with cancer are considered highly vulnerable to the recent coronavirus disease 2019 (COVID-19) pandemic. However, there are still few data on COVID-19 occurring in hematologic patients. METHODS: One hundred two patients with COVID-19 symptoms and a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 seen at 2 hematologic departments located in Lombardy, Italy, during March 2020 were studied. Risk factors for acquiring COVID-19 were analyzed by comparisons of patients with COVID-19 and the standard hematologic population managed at the same institutions in 2019. Thirty-day survival was compared with the survival of matched uninfected control patients with similar hematologic disorders and nonhematologic patients affected by COVID-19. RESULTS: Male sex was significantly more prevalent in patients with COVID-19. The infection occurred across all different types of hematologic disease; however, the risk of acquiring a COVID-19 infection was lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive-related treatments. The 30-day mortality rate was 39.2%, which was higher than the rates for nonhematologic patients with COVID-19 (23.5%; P = .02) and uninfected hematologic controls (3%; P < .001). The severity of the respiratory syndrome at presentation and active hematologic treatment were independently associated with a worse prognosis. Neither diagnosis nor disease status affected the prognosis. The worst prognosis was demonstrated among patients on active hematologic treatment and those with more severe respiratory syndrome at COVID-19 presentation. CONCLUSIONS: During the COVID-19 pandemic, patients should be advised to seek medical attention at the earliest signs of dyspnea and/or respiratory infection. Physicians should perform a risk-benefit analysis to determine the impact of temporarily deferring nonlifesaving treatments versus the risk of adverse outcomes associated with COVID-19. LAY SUMMARY: Coronavirus disease 2019 (COVID-19) infection occurs across all different types of hematologic disease; however, the risk of acquiring it is lower for patients with chronic myeloproliferative neoplasms, including chronic myeloid leukemia, and higher for patients with immune-mediated anemia on immunosuppressive treatment. The 30-day mortality rate is 39.2%, which is far higher than the rates for both uninfected hematologic controls (3%; P < .001) and nonhematologic patients with COVID-19 (23.5%; P = .02) despite matching for age, sex, comorbidities, and severity of disease. Variables independently associated with a worse prognosis are the severity of the respiratory syndrome at presentation and any type of active hematologic treatment. Neither diagnosis nor disease status influence the prognosis.

Transplant eligibility in elderly multiple myeloma patients: Prospective external validation of the international myeloma working group frailty score and comparison with clinical judgment and other comorbidity scores in unselected patients aged 65-75 years.

Autologous stem cell transplantation (ASCT) is feasible and effective in selected older patients with Multiple Myeloma, but specific criteria for evaluating ASCT eligibility in elderly patients are lacking. We evaluated 131 patients aged 65-75 considered for ASCT at our center: The Charlson Comorbidity Index (CCI), Hematopoietic cell transplantation comorbidity index (HCT-CI) and IMWG frailty score were obtained at diagnosis, but the intensity of treatment was left to physician's choice. The scores and age's impact on outcome was analyzed: 85 patients were judged transplant eligible, whereas 46 patients received a less intensive treatment (median follow up 27 months). No patients classified as frail had been considered eligible to ASCT with a worse outcome compared to fit and unfit patients (median PFS (progression free survival): 7.9 vs 32.9 and 29.6 months; P < .001). PFS was superior in the ASCT group (35.6 vs 19.9 months, P .013). In the ASCT group, PFS was better in patients aged 65-69 years than in patients ≥70 (51.5 vs 27.7 months, P.004). Indeed, in unfit patients aged ≥70 the PFS of the ASCT group was comparable to NO ASCT group (18 vs 27 months, P = .33) whereas in unfit patients aged 65-69 PFS was superior in the ASCT group: 43.3 vs 18.4 months, P .01. ISS III and impaired functional status independently affected PFS in a multivariate analysis (P .011 and P .006). While CCI and HCT-CI did not predict different outcome in ASCT patients, the IMWG frailty score would be of help in identifying unfit patients aged 70-75, whose outcome with ASCT selected by clinical judgment was no better than with less intensive treatments.

An increase in MYC copy number has a progressive negative prognostic impact in patients with diffuse large B-cell and high-grade lymphoma, who may benefit from intensified treatment regimens.

MYC translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of MYC have also been detected in these patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of MYC increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for MYC, BCL2, and BCL6 rearrangements. We enumerated the number of MYC copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of MYC translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with MYC copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of MYC extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of MYC had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with MYC translocation. The survival of patients with >4 copies, translocation or amplification of MYC seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence in situ hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of MYC.

Prognostic role of baseline 18F-FDG PET/CT metabolic parameters in mantle cell lymphoma.

OBJECTIVE: Mantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may predict treatment evaluation and prognosis in MCL. METHODS: We retrospectively enrolled 87 patients who underwent baseline 18F-FDG PET/CT and 85 end-of-treatment (eot) PET/CT. The baseline PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-liver SUVmax ratio (L-L SUV R), lesion-to-blood pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). EotPET/CT was visually interpreted according to the criteria of the Deauville 5-point scale (DC). Survival curves were plotted according to the Kaplan-Meier method. RESULTS: At a median follow-up of 40 months, relapse/progression occurred in 47 and death in 23 patients. Median PFS and OS were 30 and 41 months. Baseline MTV and TLG were significantly higher in patients with progressive metabolic response compared to complete/partial response group. EotPET/CT results using DC significantly correlated with PFS, not with OS. MTV and TLG were demonstrated to be independent prognostic factors for PFS; instead the other metabolic parameters were not related to outcome survival. Considering OS, no variable was significantly associated. CONCLUSIONS: EotPET/CT results (using DC), MTV and TLG were significantly correlated with response to treatment and PFS.