Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia: results of the BURKIMAB14 trial.

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).

RELINF: prospective epidemiological registry of lymphoid neoplasms in Spain. A project from the GELTAMO group.

Lymphomas are a large, heterogeneous group of neoplasms with well-defined characteristics, and this heterogeneity highlights the importance of epidemiological data. Knowledge of local epidemiology is essential to optimise resources, design clinical trials, and identify minority entities. Given there are few published epidemiological data on lymphoma in Spain, the Spanish Lymphoma and Autologous Bone Marrow Transplant Group created the RELINF project. The aim of this project is to determine the frequencies and distribution of lymphoid neoplasms in Spain and to analyse survival. We developed an online platform for the prospective collection of data on newly diagnosed cases of lymphoma in Spain between January 2014 and July 2018; 11,400 patients were registered. Diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) were the most frequent lymphomas in our series. Marginal B cell lymphoma frequency was higher than that reported in other studies, representing more than 11% of mature B cell lymphomas. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) was the most common subtype of T cell lymphoma, and NK/T cell lymphomas were more frequent than expected (5.4% of total). Hodgkin's lymphoma accounted for 12% of lymphoproliferative syndromes. Overall survival was greater than 90% at 2 years for indolent B cell lymphomas, and approximately 60% for DLBCL, somewhat lower than that previously reported. Survival was poor for PTCL-NOS and angioimmunoblastic T cell lymphoma, as expected; however, it was somewhat better than that in other studies for anaplastic large cell anaplastic lymphoma kinase lymphomas. This is the first prospective registry to report the frequencies, distribution, and survival of lymphomas in Spain. The frequencies and survival data we report here are globally consistent with that reported in other Western countries. These updated frequencies and survival statistics are necessary for developing appropriate management strategies for neoplasias in the Spanish population.

Percutaneous hepatic biopsy under propofol sedation. A safe and effective procedure.

INTRODUCTION: the percutaneous hepatic biopsy is a necessary procedure for the diagnosis of liver diseases which can cause complications and psychological discomfort for the patient. AIMS: to determine the safety profile of propofol in percutaneous hepatic biopsy, the complications of the technique per se and patients satisfaction once completed. METHODS: a retrospective observational study was performed via the acquisition of data of tolerance and perceived quality by the patients using a transversal survey. RESULTS: ninety-seven patients were included with an average propofol dose of 170.46 mg. Of the complications resulting from the sedation, there were six slight desaturations (6.2 %) resolved with a forehead maneuver (50 %) or cessation of the propofol infusion pump (50 %) and eleven hypotension episodes (11.3 %) resolved without intervention (82.82 %) or with fluid replacement (18.18 %). Of the complications resulting from the technique, there were three cases of early-onset pain (3.1 %) and one delayed (1.03 %); all were resolved with 1 g of intravenous paracetamol. All patients were discharged with oral tolerance and without the need for analgesia 24 hours after the procedure. General satisfaction, as well as psychological discomfort, were evaluated as "very good/excellent" in 100 % of the patients. DISCUSSION: propofol demonstrated a favorable safety profile in hepatic biopsy, aiding in the ultimate success of the procedure and tolerance for the patient. We propose the expansion of the use of sedation with propofol to this procedure.

Spanish online survey on informed consent for the performance of paracentesis. Do we have it? Do we use it?

INTRODUCTION: informed consent is necessary for invasive procedures as a document that guarantees the ethical health relationship and patient safety. AIMS: to analyze whether we have and use informed consent documents for paracentesis in our hospitals and to obtain data on the technique. METHODS: a descriptive observational study was performed during December 2019, via a cross-sectional survey disseminated through social networks, aimed at specialists and residents of gastroenterology. RESULTS: two hundred and three anonymous surveys were included (55.2 % gastroenterologist and 44.8 % residents) from 74 hospitals in 34 Spanish provinces. Ninety respondents (44.3 %) stated that they had the document in their centers. Of these, 29 (32.2 %) always provided it, 31 (34.4 %) provided it sometimes and 21 (23.3 %) never. Seventy-two professionals (35.5 %) answered that they did not have it and 41 (20.5 %) selected "unknown". Of these, 77 (68.1 %) considered it was necessary to create this document, 31 (27.4 %) did not think it was necessary and five (4.4 %) did not answer. With regards to the technique, 173 (85.2 %) performed paracentesis under direct visualization and 30 (14.8 %) were eco-guided on most occasions. One hundred and nine (53.7 %) always applied local anesthetic, 80 (39.4 %) sometimes and 14 (6.9 %) did not. One hundred and sixty-seven respondents (82.3 %) considered it to be a simple technique versus 36 (17.7 %) who thought that it was of intermediate complexity. In terms of risk, 150 (73.5 %) considered it was low and 52 (25.6 %), medium. Ninety-nine (48.8 %) experienced minor complications and 37 (18.2 %) experienced major complications. CONCLUSIONS: paracentesis is a common technique in digestive services and could be associated with complications, even though it is considered to be simple and safe. Due to the important intra- and inter-hospital variability that this technique presents, we consider standardized training in this technique is necessary, as well as the creation, spread and use of informed consents.

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group.

BACKGROUND: Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). METHODS: Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard-dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes. RESULTS: Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo-HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease-free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively). CONCLUSIONS: Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.

Comparing R-Bendamustine vs. R-CHOP Plus Maintenance Therapy as First-Line Systemic Treatment in Follicular Lymphoma: A Multicenter Retrospective GELTAMO Study.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and R-bendamustine (R-B) are the most common frontline treatment strategies for advanced-stage follicular lymphoma (FL). After R-CHOP induction therapy, using rituximab for maintenance therapy notably improves outcomes; however, whether this can be achieved by using the same approach after R-B therapy is still being determined. This retrospective analysis compared 476 FL patients from 17 GELTAMO centers who received R-based regimens followed by rituximab maintenance therapy for untreated advanced-stage FL. The complete response rate at the end of induction was higher with R-B and relapses were more frequent with R-CHOP. During induction, cytopenias were significantly more frequent with R-CHOP and so was the use of colony-stimulating factors. During maintenance therapy, R-B showed more neutropenia and infectious toxicity. After a median follow-up of 81 months (95% CI: 77-86), the 6-year rates of progression-free survival (PFS) were 79% (95% CI: 72-86) for R-bendamustine vs. 67% (95% CI: 61-73) for R-CHOP (p = 0.046), and 6-year overall survival (OS) values were 91% (95% CI: 86-96) for R-B vs. 91% (95% CI: 87-94) for R-CHOP (p = 0.49). In conclusion, R-B followed by rituximab maintenance therapy in patients with previously untreated FL resulted in significantly longer PFS than R-CHOP, with older patients also benefiting from this treatment without further toxicity. Adverse events during maintenance were more frequent with R-B without impacting mortality.

Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups.

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4-6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44-0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31-0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria.

Treatment patterns and outcomes of 2310 patients with secondary acute myeloid leukemia: a PETHEMA registry study.

Secondary acute myeloid leukemia (sAML) comprises a heterogeneous group of patients and is associated with poor overall survival (OS). We analyze the characteristics, treatment patterns, and outcomes of adult patients with sAML in the Programa Español de Tratamientos en Hematología (PETHEMA) registry. Overall, 6211 (72.9%) were de novo and 2310 (27.1%) had sAML, divided into myelodysplastic syndrome AML (MDS-AML, 44%), MDS/myeloproliferative AML (MDS/MPN-AML, 10%), MPN-AML (11%), therapy-related AML (t-AML, 25%), and antecedent neoplasia without prior chemotherapy/radiotherapy (neo-AML, 9%). Compared with de novo, patients with sAML were older (median age, 69 years), had more Eastern Cooperative Oncology Group ≥2 (35%) or high-risk cytogenetics (40%), less FMS-like tyrosine kinase 3 internal tandem duplication (11%), and nucleophosmin 1 (NPM1) mutations (21%) and received less intensive chemotherapy regimens (38%) (all P < .001). Median OS was higher for de novo than sAML (10.9 vs 5.6 months; P < .001) and shorter in sAML after hematologic disorder (MDS, MDS/MPN, or MPN) compared with t-AML and neo-AML (5.3 vs 6.1 vs 5.7 months, respectively; P = .04). After intensive chemotherapy, median OS was better among patients with de novo and neo-AML (17.2 and 14.6 months, respectively). No OS differences were observed after hypomethylating agents according to type of AML. sAML was an independent adverse prognostic factor for OS. We confirmed high prevalence and adverse features of sAML and established its independent adverse prognostic value. This trial was registered at www.clinicaltrials.gov as #NCT02607059.

Long-Term Outcomes After Autologous Versus Allogeneic Stem Cell Transplantation in Molecularly-Stratified Patients With Intermediate Cytogenetic Risk Acute Myeloid Leukemia: A PETHEMA Study.

Acute myeloid leukemia (AML) with intermediate risk cytogenetics (IRcyto) comprises a variety of biological entities with distinct mutational landscapes that translate into differential risks of relapse and prognosis. Optimal postremission therapy choice in this heterogeneous patient population is currently unsettled. In the current study, we compared outcomes in IRcyto AML recipients of autologous (autoSCT) (n = 312) or allogeneic stem cell transplantation (alloSCT) (n = 279) in first complete remission (CR1). Molecular risk was defined based on CEBPA, NPM1, and FLT3-ITD mutational status, per European LeukemiaNet 2017 criteria. Five-year overall survival (OS) in patients with favorable molecular risk (FRmol) was 62% (95% confidence interval [CI], 50-72) after autoSCT and 66% (95% CI, 41-83) after matched sibling donor (MSD) alloSCT (P = .68). For patients of intermediate molecular risk (IRmol), MSD alloSCT was associated with lower cumulative incidence of relapse (P < .001), as well as with increased nonrelapse mortality (P = .01), as compared to autoSCT. The 5-year OS was 47% (95% CI, 34-58) after autoSCT and 70% (95% CI, 59-79) after MSD alloSCT (P = .02) in this patient subgroup. In a propensity-score matched IRmol subcohort (n = 106), MSD alloSCT was associated with superior leukemia-free survival (hazard ratio [HR] 0.33, P = .004) and increased OS in patients alive 1 year after transplantation (HR 0.20, P = .004). These results indicate that, within IRcyto AML in CR1, autoSCT may be a valid option for FRmol patients, whereas MSD alloSCT should be the preferred postremission strategy in IRmol patients.

SEGHI Study: Defining the Best Surveillance Strategy in Hodgkin Lymphoma after First-Line Treatment.

The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action.

Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia.

About 25-35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18-60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia.

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.

Chemotherapy-induced nausea and vomiting in acute leukemia and stem cell transplant patients: results of a multicenter, observational study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the incidence and severity of chemotherapy-induced nausea and vomiting (CINV) in oncohematology in routine clinical practice, its impact on quality of life, and caregivers' perception of the extent of the problem. DESIGN AND METHODS: This was a multicenter, prospective, observational follow-up study including: (i) acute myeloid leukemia patients treated with moderately to highly emetogenic chemotherapy and (ii) hematopoietic stem cell transplant recipients, without reduced intensity conditioning. No exclusion criteria were applied. All patients received at least one 5-HT3 antagonist for emesis prophylaxis. Patients recorded emetic episodes and rated nausea daily. Quality of life was assessed through a validated functional living Index-Emesis questionnaire. A survey of caregivers' predictions of CINV was made and the predictions then compared with the observed CINV. RESULTS: One hundred consecutive transplant and 77 acute myeloid leukemia patients were studied. Transplant conditioning was the most important risk factor for CINV: complete response occurred in only 20% of transplant patients (vs. 47% for leukemia patients). Among patients with emesis, the mean percentage of days with emesis and the mean (+/-SD) total number of emetic episodes were 61% and 9.4+/-8.9 (transplant recipients), and 53.6% and 6.2+/-7.3 (leukemia patients), respectively. CINV control was lower in the delayed than in the acute phase. Antiemetic rescue therapy was ineffective. CINV had a deleterious effect on quality of life, especially among transplant recipients. Caregivers underestimated the incidence of delayed nausea and emesis in the transplant setting. INTERPRETATION AND CONCLUSIONS: Despite 5-HT3 antagonist prophylaxis, CINV remains a significant problem in oncohematology, especially in the delayed phase and in transplant recipients.