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Purpose Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. Methods This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin’s lymphoma. Eighty-one patients participated. Results Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. Conclusion NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT.

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.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive, heterogeneous neoplasm where prognostication and therapeutic decision are challenging. The available prognostic tools are not able to identify all patients refractory to treatment. MicroRNAs, small RNAs frequently deregulated in cancer, stably circulate in biofluids, representing interesting candidates for non-invasive biomarkers. Here we validated serum miR-22, an evolutionarily conserved microRNA, as a prognostic/predictive biomarker in DLBCL. Moreover, we found that its expression and release from DLBCL cells are related to therapy response and adversely affect cell proliferation. These results suggest that miR-22 is a promising complementary or even independent non-invasive biomarker for DLBCL management.

Background: JACIE (Joint Accreditation Committee ISCTEurope & EBMT) standards define continuous training as a requirement for nurses working in accredited transplant units. Obtaining continuous education can be difficult, so our center decided to implement their own accredited training course. Since 2008 a specific training course, accredited by regular authorities, free of charges in the workplace and held by staff nurses, has been organized. Through all these years, the structure has been modified according to the needs and opinions of the attending nurses. Currently, it consisted of 10 sessions that take place through the year;each session was held at two or three different times (depending on the availability of the speaker), and so nurses from all shifts could attend. At the beginning of the pandemic caused by SARS-COVID 2, in March 2020, we had to suspend the program and reconsider how we could maintain the educational sessions. Methods: From June to November we reinitiated the course. Now, several options were offered to participate: (a) in person, since in our country meetings were restricted to ten people, with previous registration required, (b) synchronously through the Zoom platform, and (c) deferred, as all sessions were recorded so nurses were able to access through the internal training platform of our center. To justify attendance and get the accreditation, when the session was viewed in a delayed manner through the platform, three questions about the viewed session were required to be answered. The course has been accredited by our national system of accreditation. Results: 91 nurses participated in the course. 63.8% of the attendance was virtual. At the end of the course, a satisfaction survey was carried out among the participants. The average score of the questions was 9,25. The lowest score was 8,57 and, the highest, 9,53. There was also a final question in an open format to make comments and suggestions for future editions. Conclusions: Offering quality and up-to-date training to nurses in hematological transplantation wards is one of the JACIE's standards that sometimes is difficult to achieve due to the difficulty of combining nursing schedules and shifts, and the lack of economic resources. The appearance of the pandemic has been an added challenge in order to be able to maintain continuous training as it was established in our center. It was not easy initially to organize it, but it helped us that our center already had a training platform, the availability of online streaming platforms and our background in offering training courses. The high participation and satisfaction of the attendance nurses encourage us to explore and continue new training formats for highly specialized nurses.

Several kinds of stress promote the formation of three-stranded RNA:DNA hybrids called R-loops. Insufficient clearance of these structures promotes genomic instability and DNA damage, which ultimately contribute to the establishment of cancer phenotypes. Paraspeckle assemblies participate in R-loop resolution and preserve genome stability, however, the main determinants of this mechanism are still unknown. This study finds that in Multiple Myeloma (MM), AATF/Che-1 (Che-1), an RNA-binding protein fundamental to transcription regulation, interacts with paraspeckles via the lncRNA NEAT1_2 (NEAT1) and directly localizes on R-loops. We systematically show that depletion of Che-1 produces a marked accumulation of RNA:DNA hybrids. We provide evidence that such failure to resolve R-loops causes sustained activation of a systemic inflammatory response characterized by an interferon (IFN) gene expression signature. Furthermore, elevated levels of R-loops and of mRNA for paraspeckle genes in patient cells are linearly correlated with Multiple Myeloma progression. Moreover, increased interferon gene expression signature in patients is associated with markedly poor prognosis. Taken together, our study indicates that Che-1/NEAT1 cooperation prevents excessive inflammatory signaling in Multiple Myeloma by facilitating the clearance of R-loops. Further studies on different cancer types are needed to test if this mechanism is ubiquitously conserved and fundamental for cell homeostasis.

Simple Summary IDH1/2 mutations are a common event in acute myeloid leukemia (AML) and represent a therapeutic target. We designed the GIMEMA AML1516 observational protocol to examine the prevalence of IDH1/2 mutations and the associations between IDH mutations and clinico-biological parameters in a cohort of Italian patients affected by AML. By analyzing 284 consecutive adult AML patients, we confirmed that IDH1 and IDH2 mutations are frequently detected-14% and 18%, respectively-at diagnosis. IDH1/2 mutations were significantly associated with an inferior performance status and non-complex karyotype when compared to IDH1/2-WT. With regards to the outcome, in the subset of IDH1/2-mutated patients the rate of complete remission achievement was 60.5% and overall survival at 2 years was 44.5%: these percentages did not significantly differ from IDH1/2-WT patients. However, given the availability of IDH1/2 inhibitors, it is important to recognize IDH1/2-mutated cases up-front to offer patients the most appropriate therapeutic strategy. IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19-86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors.

Background Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose. Methods Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher’ exact test and the Mann–Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively. Results At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p p p p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed. Conclusions BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).

Flow cytometry is a highly sensitive and specific approach for discriminating between normal and clonal plasma cells in multiple myeloma. Uniform response criteria after treatment have been established by the International Myeloma Working Group and the EuroFlow Group; however, the way in which flow cytometry data are reported has suffered from no collaborative or multicentre efforts. This study, involving 8 expert laboratories and 12 clinical hematology units of the Lazio region in Italy, aims to produce a uniform and shared report among the various Centres. From the pre-analytical phase to sample processing, data acquisition, analysis, and evaluation of the potential limitations and pitfalls of the entire process, the study reaches a final conclusion shared by laboratories and clinicians according to the most updated principles and recommendations. The aim was to identify the necessary data to be included in the clinical report by using multiple-choice questionnaires at every single stage of the process. An agreement of more than 75% of the laboratories was considered mandatory for the data to be included in the report. By ensuring the operational autonomy of each laboratory, this study provides a clear report that limits subjective interpretations and highlights possible bias in the process, better supporting clinical decision-making.

Takezaki et al. analyzed the outcome of 57 patients with indolent lymphomas treated with Bendamustine plus Rituximab (BR) according to the number of cycles received, showing that patients who discontinued BR after four cycles had similar outcomes compared to patients who received five or six cycles. Considering the similarities but also the differences between indolent lymphomas and chronic lymphocytic leukemia (CLL), we enriched the results obtained with a cohort of CLL patients treated with BR starting from the experience of the Lazio region group on CLL. Out of 115 patients, 97 (84%) received 4-6 cycles of BR, while 18 (16%) received 1-3 cycles. The outcome of the group of patients who received at least 4 cycles was superior in terms of response rate (ORR 96% vs. ORR 83%, p = 0.041; CR 58% vs. CR 28%, p = 0.052 respectively) and PFS [median PFS 52.6 (40.3-64.9) versus 26.2 (19.3-33.0) months, p 0.001]. The number of patients undergoing 4 cycles of BR (4-cycles group) and 5-6 cycles (over-4-cycles group) was 9 and 88, respectively. Compared to analysis conducted by the Japanese group in indolent lymphomas, in CLL we did not observe any difference between the outcome of the 4-cycles group and the over-4-cycles group in terms of ORR (89% vs. 97%, p = 0.268) and in survival [median PFS 40.8 (13.7-67.8) versus 52.6 (38.7-66.5) months, p = 0.117]. Moreover, we observed that patients who achieved a clinical CR showed overlapping outcomes with patients who received more than 4 cycles [CR vs. non-CR median PFS not reached vs. 11.0 months; over-4-cycles group median PFS 52.6 months (40.3-64.9); p 0.001]. Nowadays chemoimmunotherapy with BR is reserved to fit elderly CLL patients, and there are many chemo-free treatment options available; therefore, discontinuation after 4 cycles may be permissible in patients who obtained a CR in order to limit toxicity as much as possible.

A matched-pair analysis of transplant-related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling (n = 58) or haploidentical related donor (n = 58). The 2 patient series were matched with 9 variables: period of transplant, patient and donor age, sex, diagnosis, disease phase, conditioning regimen, donor-recipient sex, and cytomegalovirus (CMV) status combinations. As graft-versus-host disease (GVHD) prophylaxis, all patients received the standard cyclosporine and methotrexate association with the addition of anti-thymocyte globulins, mycophenolate mofetil, and basiliximab in haploidentical, unmanipulated bone marrow recipients. Anti-infectious management, transfusion policy, and supportive care were identical for all patients. By comparing the 2 patient series, no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD, transplant-related mortality, and relapse. With a median follow-up of 3.5 years, the 5-year disease-free survival was 37% ± 6% and 36% ± 6% for HLA identical sibling and haploidentical recipients, respectively. The results of transplant from HLA identical siblings and haploidentical donors are comparable. Regardless of the HLA matching, other factors known to affect the transplant outcomes, such as donor-recipient age, sex, and CMV status combinations, might drive the search for the best donor.

Cerebrospinal fluid (CSF) flow cytometry has a crucial role in the diagnosis of leptomeningeal disease in onco-hematology. This report describes the flow cytometry characterization of 138 CSF samples from patients affected by non-Hodgkin lymphoma, negative for disease infiltration. The aim was to focus on the CSF non-neoplastic population, to compare the cellular composition of the CSF with paired peripheral blood samples and to document the feasibility of flow cytometry in hypocellular samples. Despite the extremely low cell count (1 cell/µl, range 1.0–35) the study was successfully conducted in 95% of the samples. T lymphocytes were the most abundant subset in CSF (77%; range 20–100%) with a predominance of CD4-positive over CD8-positive T cells (CD4/CD8 ratio = 2) together with a minority of monocytes (15%; range 0–70%). No B cells were identified in 90% of samples. Of relevance, a normal, non-clonal B-cell population was documented in 5/7 (71%) patients with primary central nervous system lymphoma at diagnosis (pp

7511 Background: Zandelisib, a PI3Kδ inhibitor with high target-binding affinity, is administered by intermittent dosing (ID) on days 1-7 of 28-day cycles to potentially enable regulatory T-cell repopulation and lower the risk of immune adverse events (irAEs) seen with continuous PI3Kδ inhibition. In a phase 1b study in 37 patients (pts) with R/R FL, zandelisib daily for two 28-day cycles for tumor debulking then on ID achieved an overall response rate (ORR) of 87% (78% single agent and 95% with rituximab) with < 10% irAEs (Pagel et al. ICML 2021; #113). We conducted the TIDAL study to further evaluate zandelisib in R/R indolent lymphomas (NCT03768505). Methods: Eligible pts ≥18 years with FL Grade I-IIIA, progressive disease after ≥2 prior therapies, and no prior PI3K inhibitor, gave consent and received zandelisib 60 mg daily for 2 cycles then on ID. Not reported here are an arm randomizing pts to zandelisib daily continuously, closed to enrollment early, and an actively enrolling arm in R/R marginal zone lymphoma (MZL). The planned FL sample size was 120 pts on ID, with the primary efficacy population (PEP) pre-defined as the first 91 pts treated. The primary efficacy endpoint was ORR by the Lugano criteria in the PEP as assessed by independent review and analyzed after a minimum 6-month follow-up. Results: 121 FL pts were enrolled. In the PEP (N = 91), the median number of prior therapies was 3 (range 2-8), 21 pts (23%) had received prior stem cell transplant, 42 (46%) had disease refractory to last therapy, 31 (34%) had tumors ≥5 cm, and 51 (56%) were POD24. Overall response rate was 70.3% (n = 64) (95% CI 59.8-79.5%) and complete response rate was 35.2% (n = 32) (95% CI 25.4-45.9%). Responses occurred early with 87.5% (n = 56) of responses observed at the end of Cycle 2 and 75% (n = 24) of CRs at the end of Cycle 4. The data are still immature to estimate accurately the duration of response (DOR). With a median follow-up of 9.4 months (range 0.8-24) for all 121 pts, 12 pts (9.9%) discontinued therapy due to any drug-related AE. Grade 3 AEs of special interest (AESI) were diarrhea in 6 pts (5%), colitis in 2 (1.7%), rash in 4 (3.3%), stomatitis in 3 (2.5%), and 1 (0.8%) each for AST and ALT elevation, and non-infectious pneumonitis. Grade 3 AESIs primarily (15 of 18, 83%) occurred in cycles 1-3, during daily dosing. Conclusions: Zandelisib on ID achieved high ORR and CR rate in heavily pretreated FL pts, and was associated with < 10% of discontinuations due to drug-related AEs and grade 3 AESI, results comparable to the Phase 1b study. Longer follow-up is needed to estimate median DOR. This profile supports evaluation of zandelisib alone and in combination in various B-cell malignancies, both in relapsed disease and earlier lines of therapy. Zandelisib plus rituximab vs chemoimmunotherapy is being studied in the phase 3 trial COASTAL in R/R FL and MZL (NCT 04745832). Clinical trial information: NCT03768505.

PurposePrevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy (MD-CT). While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use with MD-CT administered for mobilization of hematopoietic stem cells prior to ASCT. MethodsThis multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during MD-CT being given for mobilization of stem cells prior to ASCT in patients with relapsed-refractory aggressive non-Hodgkin’s lymphoma. Eighty-one patients participated. ResultsResponse rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of MD-CT through 48 hours after). NEPA was well tolerated with no treatment-related adverse events reported. ConclusionNEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing MD-CT for mobilization of hematopoietic stem cells prior to ASCT.

In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.

Bacterial bloodstream infection (BSI) represents a significant complication in hematologic patients. However, factors leading to BSI and progression to end-organ disease and death are understood only partially. The study analyzes host and microbial risk factors and assesses their impact on BSI development and mortality. A total of 96 patients with hematological malignancies and BSI were included in the study. Host-associated risk factors and all causes of mortality were analyzed by multivariable logistic regression at 30 days after BSI onset of the first neutropenic episode. The multidrug-resistant profile and biofilm production of bacterial isolates from primary BSI were included in the analysis. Median age was 60 years. The underlying diagnoses were acute leukemia (55%), lymphoma (31%), and myeloma (14%). A total of 96 bacterial isolates were isolated from BSIs. Escherichia coli was the most common isolate (29.2%). Multidrug-resistant bacteria caused 10.4% of bacteremia episodes. Weak biofilm producers (WBPs) were significantly (P

BEAM conditioning regimen (Carmustine, Etoposide, Cytarabine and Melphalan) is the currently standard for lymphoma patients undergoing an autologous hematopoietic stem cell transplant (ASCT) [1–2]....

Multiple myeloma (MM) is a hematologic malignancy produced by a clonal expansion of plasma cells and characterized by abnormal production and secretion of monoclonal antibodies. This pathology exhibits an enormous heterogeneity resulting not only from genetic alterations but also from several epigenetic dysregulations. Here we provide evidence that Che-1/AATF (Che-1), an interactor of RNA polymerase II, promotes MM proliferation by affecting chromatin structure and sustaining global gene expression. We found that Che-1 depletion leads to a reduction of “active chromatin” by inducing a global decrease of histone acetylation. In this context, Che-1 directly interacts with histones and displaces histone deacetylase class I members from them. Strikingly, transgenic mice expressing human Che-1 in plasma cells develop MM with clinical features resembling those observed in the human disease. Finally, Che-1 downregulation decreases BRD4 chromatin accumulation to further sensitize MM cells to bromodomain and external domain inhibitors. These findings identify Che-1 as a promising target for MM therapy, alone or in combination with bromodomain and external domain inhibitors.

Background and Aims: In cancer patients, a common complication during chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). For this reason, we decided to conduct a phase II prospective study on 33 patients with multiple myeloma at first diagnosis, to evaluate whether a nutraceutical compound given for 6 months during bortezomib (BTZ) treatment succeeded in preventing the onset of neurotoxicity. Methods: Neurological evaluation, electroneurography, and functional and quality of life (QoL) scales were performed at baseline and after 6 months. We administered a tablet containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C 60 mg, and vitamin E 10 mg bid for 6 months. Results: Concerning the 25 patients who completed the study, at 6-month follow-up, 10 patients had no neurotoxicity (NCI-CTCAE [National Cancer Institute-Common Terminology Criteria for Adverse Events] = 0), while 13 progressed to NCI-CTCAE grade 1, 1 had NCI-CTCAE grade 1 with pain, and 1 experienced a NCI-CTCAE grade 2. Painful symptoms were reported only in 2 patients, and we observed stability on functional and QoL scales in all patients. None of the 25 patients stopped chemotherapy due to neurotoxicity. Conclusions: Our data seem to indicate that the co-administration of a neuroprotective agent during BTZ treatment can prevent the appearance/worsening of symptoms related to CIPN, avoiding the interruption of BTZ and maintaining valuable functional autonomy to allow normal daily activities. We believe that prevention remains the mainstay to preserve QoL in this particular patient population, and that future studies with a larger patient population are needed.

BACKGROUND Randomized trials comparing chemomobilization efficiency between lenograstim and biosimilar filgrastim are lacking. Our previous retrospective study suggested that lenograstim could be more effective than biosimilar filgrastim when used at the same conventional dosage (5 µg/kg) only in lymphoma patients undergoing peripheral blood stem cell mobilization. We planned a prospective randomized study comparing lenograstim 5 µg/kg with biosimilar filgrastim 10 µg/kg to verify the hypothesis of lenograstim superiority even at half the dosage (stress test). Herein we report data after enrolling 60% of planned patients. STUDY DESIGN AND METHODS From October 2014 to November 2017, a total of 42 of 70 planned patients with lymphoma were randomly assigned to receive lenograstim 5 µg/kg (21) or biosimilar filgrastim 10 µg/kg (21). Patients were stratified according to treatment line at the time of mobilization (1 or ≥2). Primary endpoint was the rate of achievement of the CD34+ cell collection target dose (≥ 4 × 106 /kg). An improvement by 23% was expected to validate the hypothesis of lenograstim superiority. RESULTS The two cohorts were balanced for all the baseline features. We observed an identical rate of patients able to reach the targeted CD34+ cell dose and of mobilization failures (90.4 and 4.8% in both cohorts) and a perfect equivalence in any of the secondary collection outcomes. The hypothesis of lenograstim superiority was not corroborated at interim analysis. CONCLUSION Lenograstim at conventional dosage has failed to demonstrate its superiority over biosimilar filgrastim at double the dosage at interim analysis in their first head-to-head trial.

Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant-related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T-cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High-dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first-line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high-risk patients.

BACKGROUND From 2011 to 2014, a total of 71% of the 3834 patients with hematologic malignancies successfully identified a matched unrelated donor (MUD) through the Italian Bone Marrow Donor Registry (IBMDR), corresponding to a transplant efficiency of 62%. STUDY DESIGN AND METHODS From 2006, the Rome Transplant Network (RTN) followed a hierarchical selection strategy for the alternative donor search: first MUD, second cord blood, and third haploidentical donor. Using a low-resolution HLA, a preliminary query (PQ) was performed in all cases with assignment of good or poor score if more or less than 10 MUDs were identified in Bone Marrow Donors Worldwide. Herein we assessed the utility of PQ and of high-resolution (HR) HLA from the start of the search. Moreover, we compared the donor identification and the transplant efficiency between IBMDR and RTN. RESULTS At RTN 79% of 417 patients met a good PQ with a 50% MUD identification versus 12.5% with poor PQ. Our policy led to 78 and 74% of alternative donor identification and transplant efficiency, respectively, higher than IBMDR data equal to 71% (p = 0.007) and 62% (p

Pulmonary complications are a relevant clinical issue in patients with hematologic malignancies. However, the causative agent of lung infiltrates (LI) remains often undetected [1]. Although convent...

High-dose melphalan (HDMel) is the most common conditioning chemotherapy regimen for autologous stem cell transplantation (SCT) in patients affected by multiple myeloma (MM). No consensus exists for the emetogenicity or prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in this regimen. Data on the incidence and efficacy/safety of CINV prophylaxis among patients affected by MM undergoing autologous SCT with the HDMel regimen was extracted from electronic databases and analyzed. Eleven studies involving multiple CINV prophylaxis regimens were identified and included. No consensus on HDMel emetogenicity was reached, but most studies summarized the emetogenicity as moderate-high risk. An aprepitant-based three-drug regimen (aprepitant + serotonin receptor antagonist (5HT3RA) + dexamethasone) showed better efficacy than a two-drug regimen (5HT3RA + dexamethasone) for CINV prevention without increasing the frequency in adverse events. The aprepitant-based three-drug regimen should be the regimen of choice for CINV prophylaxis for MM patients undergoing autologous SCT with HDMel conditioning.

Bronchoalveolar lavage (BAL) is recommended for diagnosing lung infiltrates (LI) in patients with hematologic malignancy (HM). Prospective data on the impact of BAL on survival are still lacking. We conducted a prospective observational study on patients who performed BAL for LI among 3055 HM patients hospitalized from January to September 2018. The BAL was performed in 145 out of 434 patients who developed LI, at a median time of four days from LI detection. The median age was 60 (1-83). Most patients had an acute myeloid leukemia/myelodisplastic syndrome (81), followed by lymphoma (41), acute lymphoblastic leukemia (27), and other types of HM (36). A putative causal agent was detected in 111 cases (76%), and in 89 cases (61%) the BAL results provided guidance to antimicrobial treatment. We observed a significantly improved outcome of LI at day +30 in patients who could receive a BAL-driven antimicrobial treatment (improvement/resolution rate: 71% vs 55%; P = .04). Moreover, we observed a significantly improved outcome in 120-day overall survival (120d-OS) (78% vs 59%; P = .009) and 120-day attributable mortality (120d-AM) (11% vs 30%; P = 0.003) for patients who could receive a BAL-driven treatment. The multivariate analysis showed that BAL-driven antimicrobial treatment was significantly associated with better 120d-OS and lower 120d-AM. We did not observe any severe adverse events. In conclusion BAL allows detection of a putative agent of LI in about 75% of cases, it is feasible and well tolerated in most cases, demonstrating that a BAL-driven antimicrobial treatment allows improvement of clinical outcome and survival.