Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an ...antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.
Background
Few studies have explored the impact of cutaneous T‐cell lymphoma (CTCL) on health‐related quality of life (HRQoL) and compared it to other patients with cancer.
Objectives
The primary ...objective of the study was to assess the QoL of patients diagnosed with the mycosis fungoides (MF) and Sézary syndrome (SS) types of CTCL in Spain.
Methods
A cross‐sectional observational study was completed recruiting adult patients with MF and SS, exploring the European Organisation for Research and Treatment of Cancer‐Core Quality of Life Questionnaire, version 3 (EORTC‐QLQ‐C30v3) and Skindex‐29 HRQoL and itching intensity.
Results
A total of 141 patients 81 males (57.4%) and mean age of 63.6 years (95% CI: 61.4–65.7), were included. EORTC‐QLQ‐C30 global health status showed worse scores in CTCL patients compared to healthy population (p < 0.05) and did not differ from other patients with cancer. The physical and role functioning of CTCL patients were better than other patients with cancer (p < 0.05) but worse than healthy population (p < 0.05). The social functioning was similar to other patients with cancer but worse than healthy (p < 0.05). In the global health status, better scores were observed with aging (p = 0.023) and worse scores in patients with Eastern Cooperative Oncology Group (ECOG)‐1 versus ECOG‐0 (p = 0.01). The Skindex‐29 global score was 28.5 (95% CI: 24.8–32.3), being worst at higher clinical stage (p < 0.05) and at higher pruritus intensity (p < 0.001) and better for older patients (p < 0.001). More itching was related to female sex (p = 0.016), younger patients (p = 0.035), higher ECOG (p < 0.05) and higher m‐SWAT scores (p = 0.006).
Conclusions
These results allow mapping HRQoL affectation in CTCL patients. Global health status in MF/SS was like other patients with cancer and worse than the age‐matched healthy population. The highest impact in Skindex‐29 and EORTC‐QLQ‐C30 was associated with young age, ECOG, pruritus and disease stage.
Burkitt lymphoma (BL) is highly FDG‐avid even though its usefulness in the management of these patients is still controversial.
Aim
We analyzed the role of positron emission tomography/computerized ...tomography (PET/CT) in staging newly diagnosed patients with BL and evaluating disease after first‐line chemotherapy.
Methods
Fifty‐two PET/CTs were performed in 32 patients (20 at diagnosis, 27 after treatment, five to monitor residual disease). Involved areas were retrospectively compared with those observed in contrast‐enhanced CT.
Results
Discrepancies were found in 64.7% of patients for whom results of both tests at diagnosis were available (n = 17), most of them involving extranodal sites. Regarding response assessment, discrepancies were observed in 38% of patients with both tests (5/13): residual masses detected by CT with negative PET/CT. Of 27 patients with post‐treatment PET/CT, 22 were in complete remission whereas one true‐positive and four false‐positive lesions (two nodal and two extranodal) were detected. With a median follow‐up of 27 months, 22 patients with negative PET/CT did not relapse. Thus, negative predictive value (NPV) was 100%. With respect to positive predictive value (PPV), one of five patients with positive assays after treatment died due to progression while the remaining four had false‐positive lesions. Nevertheless, for these four patients, mean SUVmax at nodal sites was 4.1 vs. 14.9 at diagnosis, while mean SUVmax at extranodal sites was 3.8 vs. 12.1. Thus, with a cutoff value for SUVmax <66% of that observed at diagnosis, PPV was also 100%.
Conclusion
More accurate staging can be achieved using PET/CT. NPV reaches 100%, and using a ΔSUV <66%, a high PPV is also observed.
Follicular lymphoma (FL) is the most frequent indolent lymphoma. Some patients (10%-15%) experience histologic transformation (HT) to a more aggressive lymphoma, usually diffuse large B-cell lymphoma ...(DLBCL). This study aimed to validate and improve a genetic risk model to predict HT at diagnosis.We collected mutational data from diagnosis biopsies of 64 FL patients. We combined them with the data from a previously published cohort (total n = 104; 62 from nontransformed and 42 from patients who did transform to DLBCL). This combined cohort was used to develop a nomogram to estimate the risk of HT. Prognostic mutated genes and clinical variables were assessed using Cox regression analysis to generate a risk model. The model was internally validated by bootstrapping and externally validated in an independent cohort. Its performance was evaluated using a concordance index and a calibration curve.
The clinicogenetic nomogram included the mutational status of 3 genes (HIST1HE1, KMT2D, and TNFSR14) and high-risk Follicular Lymphoma International Prognostic Index and predicted HT with a concordance index of 0.746. Patients were classified as being at low or high risk of transformation. The probability HT function at 24 months was 0.90 in the low-risk group vs 0.51 in the high-risk group and, at 60 months, 0.71 vs 0.15, respectively. In the external validation cohort, the probability HT function in the low-risk group was 0.86 vs 0.54 in the high-risk group at 24 months, and 0.71 vs 0.32 at 60 months. The concordance index in the external cohort was 0.552. In conclusion, we propose a clinicogenetic risk model to predict FL HT to DLBLC, combining genetic alterations in HIST1H1E, KMT2D, and TNFRSF14 genes and clinical features (Follicular Lymphoma International Prognostic Index) at diagnosis. This model could improve the management of FL patients and allow treatment strategies that would prevent or delay transformation.
Fludarabine‐based regimens are highly effective as first‐line therapy in patients with follicular lymphoma. Nevertheless, noticeable haematological toxicity has been reported using fludarabine‐based ...regimens.
Aim
To analyse the combination of low‐dose oral fludarabine and cyclophosphamide plus rituximab (FCR) as induction therapy, followed by rituximab as maintenance therapy.
Methods
We retrospectively analysed 73 patients diagnosed with low‐grade follicular lymphoma treated with two different schemes: attenuated oral (AO) and standard intravenous (SIV) FCR.
Results
Overall response rate (ORR) was 95% (complete response rate, CRR 79.5%, partial response, PR 15.4%). CRR was 84.6% in AO vs. 61.9% in SIV (P = 0.058). 44.4% of patients underwent maintenance therapy. Grade 3–4 toxicities included neutropenia: 65.4%; anaemia: 39.7%; thrombocytopenia: five patients; infectious complications: six patients. There were no treatment‐related deaths. 6.8% had a secondary malignancy. Progression‐free survival (PFS) was 84.6% at 12 yr. The following variables influenced PFS in multivariate analysis: Hb < 12 g/dL HR 4.7 (95% CI 1.18–18.6), response after induction HR 4.9 (95% CI 1.01–24) for PR vs. CR and HR 21.27 (95% CI 4.33–104) for SD/DP vs. CR. OS was 83.1% at 12 yr. The following variables significantly influenced OS in multivariate analysis: not receiving rituximab as maintenance therapy (HR 10.7 (95% CI 1.4–82.5), increased levels of β2‐microglobulin HR 5.2 (95% CI 1.16–23.7).
Conclusions
FCR allowed us to obtain a high response rate, which translated into promising progression free and overall survival with an acceptable and manageable toxicity profile, especially with the attenuated oral scheme.
Abstract 1740
Patients with hematologic malignancies are likely to be at an increased risk for influenza infection. A few small series have documented seasonal influenza outbreaks among such ...patients, demonstrating the susceptibility of immunocompromised populations. These limited reports suggest that cancer patients are at a high risk for acquisition of influenza in both the community and health care settings. In April 2009, Mexico reported Influenza A virus outbreak. The virus was recognized as a novel known as Influenza A/pandemic 2009/H1N1 or 2009 H1N1 Influenza A. At present, there is scarce information on the clinical course of influenza A virus infection in hematologic patients.
To analyze the clinical course and laboratory characteristics of a cohort of hematologic patients diagnosed with influenza virus H1N1.
Prospective study in five centers in Andalucia and Extremadura (Spain), in hematologic patients who developed an influenza H1N1 virus infection in the winter of 2009. Clinical characteristics, laboratory, radiological findings and clinical course were collected and analyzed. Diagnosis of the infection was made by viral isolation determined by PCR in pharyngal or nasal samples or both. Patients were followed during at least one month after diagnosis of infection. Non-normal distribution data were expressed as median values (range). Chi-square test or Fisher exact test were used to compare differences between groups of categorical data. Differences were considered statistically significant for p-values <0.05. All statistical analyses were performed using SPSS 17.0 software (Chicago, IL).
A total of twenty-nine patients entered the study between September and December 2009. One patient had been vaccinated against influenza H1N1 virus. Fifty per cent were female, with a median age of 40 years (3-78). Hematolgic diseases were: acute leukemia (24.1%), multiple myeloma 13.8%, non-hodgkin lymphomas 17.2%, Hodgkin lymphoma 20.7%, chronic lymphocytic leukemia 10.3%, myelodysplastic syndrome 3.4%, hemoglobinopathies 6.9% and other hematologic diseases 3.4%. Twelve (41.4%) patients were hematopoietic stem cell recipients: allogeneic (58.3%), most of them from identical sibling (85.7%) and peripheral blood source (91.7%) and autologous (41.7%). Lymphopenia was observed in 72.4% cases and neutropenia in 27.6% cases. The median days between the initial symptoms and diagnosis was 2 days (0-7). Most patients were in an outpatient basis (82.2%) and only 8 patients (27.6%) were hospitalized for these reason. Thirteen patients (44.8%) presented radiologic findings: interstitial changes (54.5%) and alveolar condensation (45.5%). 28 patients received treatment with oseltamivir, most of them at 75 mg/12 h, during a median of 5 days (1-21) and 21 patients received simultaneously another antimicrobial therapy. Six patients (20.7%) needed mechanical ventilation. At the end of the follow up the global mortality was 20.7% (6 cases) being three death (10.3) caused by influenza A H1N1 virus infection. There was an increase risk of mortality in patients who had pneumonia at the beginning of the infection (9.5% vs 50%, p=0.033), suffered a respiratory co-infection (8% vs 60%, p=0.008), developed respiratory complications (0 vs 46.1%, p=0.005), progressed to pneumonia during the infection (4.7% vs 71.4%, p=0.001) or required mechanical ventilation (8% vs 66.7%, p=0.008). There were no differences in the evolution of HSCT recipients.
Respiratory co-infection, pneumonia at the beginning or during the infection and mechanical ventilation showed a relationship with fatal clinical course of influenza A/H1N1 virus infection in haematologic patients.
No relevant conflicts of interest to declare.
The use of PET in patients with marginal zone B cell lymphoma (MZL) is controversial because of variability of fluorodeoxyglucose (FDG) avidity. We analyzed 40 PET/CT in 25 consecutive patients to ...compare its performance with CT at staging and as a first-line response assessment. Sensitivity of PET/CT and CT was 96 and 76%. Mean standard uptake value was 6.1, 6.9 and 3.4 (p = 0.3) in nodal, extranodal and splenic subtypes, respectively. Of 17 patients (extranodal: n = 9; nodal: n = 6; splenic subtype: n = 2) with both imaging tests available at diagnosis, 8 (47%) had more involved areas with PET/CT than with CT, 75% of which were extranodal lesions. PET/CT resulted in upstaging of five patients although treatment of only two of them was changed. Responses of 15 patients with post-treatment PET/CT were the following: 9 negative and 6 positive of which 3 were isolated residual lesions. Progression was documented in two of these three patients. Response was also assessed by CT in 11 patients. Discrepancies were found in three: Two were in complete remission by CT while PET/CT detected localized residual disease; another patient was in partial remission by CT, whereas PET/CT showed only one positive lesion. Two of these three patients relapsed. Patients with negative post-treatment PET/CT did not relapse. With a median follow-up of 50 months (10-152 months), 3-year overall survival was 100 and 80% for patients with negative and positive post-treatment PET/CT (p = 0.2). Three-year disease-free survival was 86%; the negative predictive value (NPV) was 100%, and the positive predictive value (PPV) was 83.3%. Although a larger number of patients will be required to further confirm these data, we can conclude that PET/CT is a useful imaging tool for both staging and response assessment in patients with nodal and extranodal MZL as a result of its high sensitivity, NPV and PPV.
Summary
The aim of this study was to characterize timing, kinetic, and magnitude of CMV‐specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV ...replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV‐specific T‐cell response was measured in blood, while CMV viral load and chimerism were determined by real‐time PCR. Patients that reconstituted CMV‐specific T‐cell response within 6 weeks after Allo‐SCT showed a more robust immune response (CD8+: 0.7 cells/μl vs. 0.3/μl; P‐value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P‐value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P‐value = 0.04), and better overall survival (72%; CI: 0.53–0.96 vs. 42% CI: 0.24–0.71; P‐value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant‐related mortality than nonviremic patients after 1 year (33% CI: 0.15–0.52 vs. 0% CI: 0.05–0.34; P‐value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV‐positive serostatus (P‐value = 0.02) and acquiring CMV‐specific T‐cell response after 6 weeks post‐transplantation (P‐value = 0.009). In conclusion, timing of acquiring a positive CMV‐specific T‐cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.
Abstract 1281
Cytomegalovirus (CMV) end-organ disease is a serious complication after allogeneic stem cell transplantation (Allo-SCT). The quality of the post-transplant immune reconstitution plays a ...crucial role in the development of both, post-transplant infections and relapse of the underlying disease, two of the main factors conditioning post-transplant mortality and hence final survival. The relationship between viral replication and CMV specific immune reconstitution has not been completely unveiled. This knowledge would allow identifying patients at risk for developing CMV disease and eventually improving their clinical management.
to analyze the relationship between CMV replication and specific CMV immune reconstitution and the potential influence of this relationship in main clinical outcomes.
A prospective study of consecutive recipients of Allo-SCT was performed from June 2008 through December 2009 at a single institution. Blood samples were collected from one week before transplant, weekly during the first three months after transplant, every other week from month three to six and monthly from month seven to complete one year of follow up. CMV viral load was determined by real time PCR and CMV-specific T cell response was determined by flow cytometry with surface markers and intracellular cytokine staining. The percentage of activated CD4+, CD8+ and CD3+ T cells expressing CD69 were considered positive when IFN-'Y cytokine secretion was over 0.25%. Chimerism of the isolated CD8+ T cell subpopulation was determined by PCR. CD69 expression and cytokine secretion were compared in both CD4+ and CD8+ T cells between the different time points and both subsets of patients by the Wilcoxon test. CMV viral load reduction without treatment administration was compared by Wilcoxon test. Differences were considered statistically significant for p-values < 0.05. All statistical analyses were performed using SPSS 16.0 software (Chicago, IL).
Twenty-six patients were enrolled in the study with a median age of 33 years (range:15-61). We identified two groups of patients. A first group of 18 (69.2%) patients developed CMV infection and acquired CMV-specific T cell response by median week 8 (range:1-22; Figure 1A). The decline in the incidence of CMV replication episodes correlated with the acquisition of CMV-specific T cell response (Linear regresion r2=0.781, Pearson correlation p=0.01). A second group of 8 patients (30.8%) never developed CMV infection after the transplant, with a median value of 2 weeks (range:1-7; Figure 1B). The time of the acquisition of CMV-specific T cell response for the group with viremia and for the non-viremic group (week 2 vs. week 8) was statistically different (p= 0.01). Fifteen per cent of the patients (n=4) developed end-organ disease. Three out of five patients with end-organ disease developed replication CMV episodes over 10,000 copies/ml, while only 1 out of 13 patients with no end-organ disease developed viral loads under 10,000 copies/ml (p=0.04). The percentage of positive CD8+ T cells expressing IFN-γ in the patients that developed disease tended to be lower than in the patients that did not develop disease (median percentage of IFN-g positive CD8 T cells 0.3 vs. 0.5, respectively). The chimerism of the CD8+ T cells subpopulation after acquiring the specific immune response was of complete donor origin for all the patients.
Developing donor-derived T-cell mediated CMV-specific immune response within the following two weeks after the transplant is inversely associated with the development CMV infection. The level of CMV viral load may predict end-organ disease. The use of a tool to determine T-cell mediated CMV-specific immune response in the clinical practice may help to improve the management of these patients, avoiding unnecessary treatments, and predicting clinical outcomes.
Display omitted
No relevant conflicts of interest to declare.
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