The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of ...intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and Burkitt (n=80) lymphoma at clinical risk of central nervous system disease and having had pre-treatment cerebrospinal fluid were analyzed by flow cytometry and cytology. Spinal fluid involvement was detected by flow cytometry alone (occult) in 33 (13%) diffuse large B-cell and 9 (11%) Burkitt lymphoma patients, and detected by cytology in 11 (4.5%) and 5 (6%) patients, respectively. Diffuse large B-cell lymphoma with occult spinal fluid involvement had poorer survival (P=0.0001) and freedom from central nervous system relapse (P<0.0001) compared to negative cases. Burkitt lymphoma with occult spinal fluid involvement had an inferior freedom from central nervous system relapse (P=0.026) but not survival. The amount of intrathecal chemotherapy was quantitatively associated with survival in diffuse large B-cell lymphoma with (P=0.02) and without (P=0.001) occult spinal fluid involvement. However, progression of systemic disease and not control of central nervous system disease was the principal cause of treatment failure. In diffuse large B-cell lymphoma, systemic rituximab was associated with improved freedom from central nervous system relapse (P=0.003) but not with survival. Our results suggest that patients at risk of central nervous system disease should be evaluated by flow cytometry and that intrathecal prophylaxis/therapy is beneficial.
The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients ...diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans' algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (
< 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (
< 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.
Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of ...corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.
Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. ...Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell–associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.
•Increased levels of sCD19 protein in the CSF are associated with CNS disease in DLBCL and BL patients at risk of CNS lymphoma.•Presence of lymphoma cells by FCM and/or increased CSF sCD19 levels are related with a poorer EFS and/or OS in DLBCL and BL patients.
Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation ...(alloSCT) could be a potentially curative option for these patients, but it has not been widely explored.
We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival.
A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6).
Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL.
Preliminary data on the use of autologous stem cell transplantation (ASCT) as a salvage therapy for peripheral T-cell lymphoma (PTCL) indicate that the results are similar to those obtained in ...aggressive B-cell lymphomas. The aim of our study was to analyze outcomes of a large series of patients with PTCL with a prolonged follow-up who received ASCT as salvage therapy.
Between 1990 and 2004, 123 patients in this situation were registered in the GELTAMO database. The median age at transplantation was 43.5 years; in 91% of patients the disease was chemosensitive.
Seventy-three percent of the patients achieved complete remission, 11% partial remission and the procedure failed in 16%. At a median follow-up of 61 months, the 5-year overall and progression-free survival rates were 45% and 34%, respectively. The presence of more than one factor of the adjusted International Prognostic Index (a-IPI) and a high beta2-microglobulin at transplantation were identified as adverse prognostic factors for both overall and progression-free survival and allowed the population to be stratified into three distinct risk groups.
Our data show that approximately one third of patients with PTCL in the salvage setting may enjoy prolonged survival following ASCT, provided they are transplanted in a chemosensitive disease state. The a-IPI and beta2-microglobulin level predict the outcome after ASCT in relapsing/refractory PTCL.
1 Complejo Hospitalario de Zamora
2 Hospital Marqués de Valdecilla, Santander
3 Hospital Duran i Reynals, LHospitalet de Llobregat
4 Hospital La Paz, Madrid
5 Hospital Juan Canalejo, La Coruña
6 ...Hospital Germans Trias i Pujol, Badalona
7 Hospital Dr. Peset, Valencia
8 Hospital del Mar, Barcelona
9 Hospital Clínico de Madrid
10 Hospital Universitario de Salamanca
11 Hospital Universitario de Getafe
12 Hospital Severo Ochoa, Leganés
13 Hospital General de Castellón
14 Hospital Virgen del Puerto, Plasencia
15 Hospital General de Jerez, Jerez de la Frontera
16 Hospital Carlos Haya, Málaga
17 Hospital Doce de Octubre, Madrid, Spain
Correspondence: Alejandro Martín, MD, PhD, Department of Hematology, Complejo Hospitalario de Zamora, Avenida de Requejo 35, Zamora 49022, Spain. E-mail: amartingar{at}aehh.org
Background: The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP).
Design and Methods: We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP.
Results: Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) ( p <0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6–84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p <0.0001) and overall survival (38% v 67% at 3 years, p =0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2–3.3, p =0.008) and overall survival (RR: 2.2; 95% CI: 1.3–3.9, p =0.004).
Conclusions: R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.
Key words: R-ESHAP, salvage therapy, diffuse large B-cell lymphoma, rituximab.
Background
Consensus is lacking regarding the optimal salvage therapy for patients with follicular lymphoma who relapse after or are refractory to immunochemotherapy.
Methods
This phase II trial ...evaluated the efficacy and safety of response‐adapted therapy with rituximab, bendamustine, mitoxantrone, and dexamethasone (RBMD) in follicular lymphoma patients who relapsed after or were refractory to first‐line immunochemotherapy. Sixty patients received three treatment cycles, and depending on their response received an additional one (complete/unconfirmed complete response) or three (partial response) cycles. Patients who responded to induction received rituximab maintenance therapy for 2 years.
Results
Thirty‐three (55%) and 42 (70%) patients achieved complete/unconfirmed complete response after three cycles and on completing induction therapy (4‐6 cycles), respectively (final overall response rate, 88.3%). Median progression‐free survival was 56.4 months (median follow‐up, 28.3 months; 95% CI, 15.6‐51.2). Overall survival was not reached. Progression‐free survival did not differ between patients who received four vs six cycles (P = .6665), nor between patients who did/did not receive rituximab maintenance after first‐line therapy (P = .5790). Median progression‐free survival in the 10 refractory patients was 25.5 months (95% CI, 0.6‐N/A) and was longer in patients who had shown progression of disease after 24 months of first‐line therapy (median, 56.4 months; 95% CI, 19.8‐56.4) than in those who showed early progression (median, 42.31 months; 95% CI, 24.41–NA) (P = .4258). Thirty‐six (60%) patients had grade 3/4 neutropenia. Grade 3/4 febrile neutropenia and infection were recorded during induction (4/60 6.7% and 5/60 8.3% patients, respectively) and maintenance (2/43 4.5% and 4/43 9.1% patients, respectively).
Conclusions
This response‐adapted treatment with RBMD followed by rituximab maintenance is an effective and well‐tolerated salvage treatment for relapsed/refractory follicular lymphoma following first‐line immunochemotherapy.
Clinical trial registration
ClinicalTrials.gov # NCT01133158.
RBMD using a response‐adapted strategy followed by rituximab maintenance is an effective and safe salvage treatment for relapsed/refractory follicular lymphoma following first‐line immunochemotherapy, thereby improving tolerability without compromising efficacy.
Purpose
To analyze using Pentacam
®
, the corneal and anterior chamber changes following periocular botulinum toxin injection in patients with facial dystonia.
Methods
Prospective study that included ...patients with facial dystonia that were going to receive a periocular botulinum toxin injection for the first time or six months or more after the previous injection. A Pentacam
®
examination was carried out in all patients before and 4 weeks after the injection.
Results
Thirty-one eyes were included. Twenty-two had a diagnosis of blepharospasm and nine of hemifacial spasm. Analysis of corneal and anterior chamber parameters revealed a significant decrease in iridocorneal angle after botulinum toxin injection (from 35 ± 10º to 33.8 ± 9.7º,
p
= 0.022). No other corneal or anterior chamber parameters changed significantly after the injection.
Conclusions
Periocular botulinum toxin injection causes narrowing of the iridocorneal angle.
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