Low-dose radiotherapy (2×2 g) versus low doses and rituximab in the treatment of marginal zone b-cell lymphoma previously untreated.

Radiotherapy (RT)is considered the treatment of choice in patients with Extra-nodal marginal zone lymphoma (EMZL) at early stage, but the presence of late toxicities has been limited the acceptance. Recently, low doses of RT LDR) (2 x 2 Gy) and the use of limited fields has been observed that retain the efficacy but eliminate toxicities; rituximab is considered as a single agent useful in these setting of patients. Thus, we conducted a open label study to evaluate the use of LDR compared with LDR and rituximab, in a large number of patients without previous treatment. METHODS: Patients with pathological diagnosis or(EMZL)), stage I, without previous treatment, were allocated in a proportion 1:1 to received LDR) that were compared with a group that received LDR and rituximab. RESULTS: One hundred and fourteen patients were recruit ; overall response rate and complete response were : 58(98.3%) and 54 (96.4 %)in patients whose respectively in LDR that were no statistical different to the observed in the LDR + R arm: 53 (96.3%) and 51 (92.75 %) respectively. Actuarial curves at 5-years show that progression-free survival in LDR arm were: 98.4% (95% Confidence interval (CI): 93%-108%) and OS were 97.2% (95%CI: 92%-110%), that did no show statistical difference with the LDR-R arm: 96.4% (95%CI: 90%-110%), and 98.5%(95%CI:92%-107%) respectively. Univariate analysis did not show any statistical differences in the analysis of prognostic factors. Acute and late toxicities were not observed. CONCLUSION: We conclude that LDR will be considered as the treatment of choice in patients with EMZL, in early stage, localized in head and neck anatomical sites; because response and outcome were excellent, without any toxicity, addition of rituximab did not improve results and outcome.

Biology of SARS-CoV-2: Towards understanding and treating COVID-19. / Biología del SARS-CoV-2: hacia el entendimiento y tratamiento de COVID-19.

During the last two decades, three different epidemics, caused by three different coronaviruses, have affected humankind. The most recent, known as COVID-19, has caused in only five months, more than 340,000 deaths worldwide. Knowing the biology of coronavirus is key, not just to face the current pandemic, but to prepare ourselves for future epidemics. With this in mind, this article is focused on the biology of coronaviruses emphasizing SARS-CoV-2, the agent that causes COVID-19. This is a comprehensive review article, which covers different topics, from the biology and taxonomy of viruses, to the molecular biology of SARS-CoV-2, its mechanisms of action, and the immune response this virus elicits. We have also addressed clinical aspects of COVID-19, its methods of detection, treatment, and vaccines.

Durante las últimas dos décadas, tres epidemias de gran magnitud, causadas por tres distintos tipos de coronavirus, han impactado a la humanidad. La más reciente, conocida como COVID-19, ha provocado en tan solo cinco meses, más de 340 000 muertes en todo el mundo. Conocer la biología de los coronavirus es fundamental, tanto para enfrentar la pandemia actual, como para prepararnos para futuras epidemias. En este contexto, el presente artículo está enfocado en la biología de los coronavirus con énfasis en el SARS-CoV-2, agente causal de COVID-19. La temática que se incluye es muy amplia, abarca desde la biología general de los virus y su taxonomía, hasta aspectos muy puntuales de la biología molecular de SARS-CoV-2, así como de sus mecanismos de acción y la respuesta inmune. También presentamos distintos aspectos clínicos de COVID-19, de los métodos para su detección y algunos enfoques terapéuticos, incluyendo tratamientos antivirales y vacunas.

Retracted article: Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era.

Statement of Retraction: Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era We, the Editor[s] and Publisher of Hematology, have retracted the following article: Avilès, A, Nambo, M-J, Calva, A, et al. Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era. Hematology. 2019;24:507-511; DOI: 10.1080/10245332.2018.1423880 The above article has been retracted as a result of concerns regarding the data upon which the presented research has been based. After re-examination and several independent expert reviews the consensus is that the data and results are not reliable and therefore the article must be retracted. The authors have agreed with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted".

Primary gastric diffuse large B-cell lymphoma: The role of dose-dense chemotherapy.

OBJECTIVE: To assess if the use of a dose-dense regimen of chemotherapy can improve the prognosis in patients with primary gastric diffuse large B-cell lymphoma in early stages (I-II) but associated with worse prognostic factors. METHODS: One hundred and eight consecutive patients with primary gastric diffuse large B-cell lymphoma in early stages (I-II) with high serum levels of lactic dehydrogenase and beta 2 microglobulin (more than >2 of normal levels), which were associated with a worse prognostic outcome, were treated with a dose-dense chemotherapy: CHOP with increased doses of cyclophosphamide and doxorubicin, was administered every 14 days (instead of 21 days). The end points of this study were to improve outcome measured from progression-free survival and overall survival and to evaluate acute toxicities. RESULTS: Complete response was achieved in 85 patients (78%). Actuarial curves at five years show that progression-free survival was 82% and overall survival was 85%. Hematological toxicities were severe, but no death-related treatment was observed. CONCLUSIONS: We considered that in this setting of patients, the use of a dose-dense regimen could be of benefit because it improves outcome and toxicities were well controlled.

Treatment of Early Stages Hodgkin Lymphoma During Pregnancy.

BACKGROUND: To assess maternal and fetal outcome of women and newborns who received chemotherapy during pregnancy to treat Hodgkin lymphoma (HL)in early stages (IA, IIA), we performed a retrospective analysis of a cohort of 44 pregnant women with HL and early stages, diagnosed and treated between 1988 to 2013, at a tertiary reference cancer center. METHODS: We analyzed data on HL characteristics and treatment, with a particular attention to maternal and fetal complications; in children, we performed a longer follow-up to detect any anomaly in physical development, scholar performance, psychological, cardiac, neurological function, and intelligence tests. RESULTS: Median age was 29.4 (range 21-37) years; Most patients were stage IIA (86%), had M a bulky mediastinal disease (78%) and 60% had > 3 nodal sites involved; thus these patients were considered to have a not favorable condition. Abortion was refused when it was proposed. All patients received chemotherapy during pregnancy; ABVD (adryamicin, bleomycin, vinblastine, and dacarbazine) at standard doses and schedule, even during the first trimester. Radiotherapy, when indicated, was administered after delivery in 39 patients. No obstetrical complications were observed, delivery occurred between 33 to 36 weeks in 10 cases (22%); and >37 weeks in 34 cases (87%). Four newborns were low-weight: 2012 g median (range 1750 - 2350 g). No clinical malformations were observed, and development of newborns was physiological without evidence of cardiac and neurological damage, behavior, intelligence, and scholar attendance were normal. At median follow-up range of 120.4 (48-299) months, the progression-free survival and overall survival of patients were 95% and 93%respectively. CONCLUSION: Combined chemotherapy, as initial therapy appears to be the best approach in this setting of patients, with an excellent outcome to both mothers and children. If radiotherapy is necessary, it could be administered after delivery.

Prolonged Use of Zoledronic Acid (4 Years) Did Not Improve Outcome in Multiple Myeloma Patients.

BACKGROUND: Bisphosphonates, especially zoledronic acid (ZA), show antitumor effects in multiple myeloma (MM) and other neoplasms. The standard time for ZA administration has been 2 years. However, with improvement in overall survival (OS) in MM with new agents, it unclear whether ZA could be administered for a prolonged time to improve OS. PATIENTS AND METHODS: A total of 170 patients with untreated, symptomatic MM were randomly divided into a group to receive ZA for 4 years, with a control group to receive ZA for 2 years. All patients were treated with the same induction therapy and stem-cell transplantation. RESULTS: Actuarial curves at 5 years, showed that progression-free survival was 75% (95% confidence interval [CI], 64%-82%) and OS was 68% (95% CI, 60%-76%) in the 4-year group, which was not statistically significantly different compared with the control group: 72% (95% CI, 62%-78%) and 68% (95% CI, 60%-75%; P = .67). However, the 4-year group showed reduced skeletal events (21% occurrence rate); this was statistically significant compared with the control group: 43% (P < .001). CONCLUSION: Although ZA did not improve OS in patients with MM; it continued to be useful to reduce skeletal events, and thus improve better quality of life for patients.

Speckle-Tracking Echocardiography to Detect Cardiac Toxicity in Children Who Received Anthracyclines During Pregnancy.

Cardiac toxicities remain a possible risk to fetuses that received anthracyclines during pregnancy. The introduction of new echocardiographic techniques will improve the detection of early cardiac damage. Thus, we began a observational study using speckle-tracking echocardiography (STE) in children who had received anthracyclines during pregnancy, including the first trimester. From 2009 to 2013, we performed STE on patients > 5 years old, whose mothers had received anthracyclines during pregnancy. Siblings or cousins of equivalent age and gender were used as the control group. A total of 90 children fulfilled the entry criteria. Our results with STE were normal in all echocardiography parameters and did not show any differences when compared with the findings from the control group. We consider that the use of anthracyclines during pregnancy does not produce cardiac damage in newborns and can be safely administered, because no cardiac toxicity was evident in these children and it is of benefit to the mother.

Nasal NK/T-Cell Lymphoma. A Comparative Analysis of a Mexican Population with the Other Populations of Latin-America.

Nasal natural killer/T-cell lymphoma (nasal NKTCL), is a rare presentation of extranodal lymphoma in North-America and Europe, but in some countries, as China and Korea, nasal NKTCL occurred in 20 to 46 % of T-cell lymphomas. Some studies, analyzing the incidence in Latin-America, observed some differences between the various populations. However, this comparison included Argentina and Chile, Peru, and other Latin-America but not the Mexico. Thus, we performed a retrospective analysis of the patients diagnosed and treated as nasal, NKTCL, in our institution that is an academic tertiary national reference hospital of Mexico. From 1988 to 2014, we diagnosed and treated 14,816 cases of non-Hodgkin's lymphoma, 10,957 (73%) were of B-cell histology and 3822 (26%) were of T-cell histology. Nasal, NKTCL, was the most frequent of the T-cell histology: 40%. We compared our results with those of other countries and observed that nasal, NKTCL have a small number of cases in North-America, and in some countries of Latin-America, as Argentina, Brazil, and Chile. However, the number of NKTCL cases found in Mexico was similar to that found in Guatemala and Peru, and also in China and Korea. Our study suggests that this neoplasm could have a racial basis, but environmental factors should also be considered.

Rituximab as consolidation therapy did not improve outcome in patients with diffuse large B-cell lymphoma at complete response after dose-dense chemotherapy (CHOP-14).

The authors started a clinical trial to assess the efficacy and toxicity of rituximab (R) as consolidation in patients with diffuse large B-cell lymphoma, with poor prognostic factors, who were in complete response (CR) after dose-dense chemotherapy (CHOP-14). Four hundred sixty-five untreated patients, with advanced stages (III and IV), older (median age >60 years old), and high clinical risk, were treated with dose-dense CHOP-14 (cyclophosphamide 1500 mg/m(2), i.v., day 1; vincristine 2 mg, i.v., standard dose, day 1; epirubicin 120 mg/m(2), i.v., day 1; and prednisone 60 mg/m(2), p.o., days 1-5) every 14 days for six cycles. If CR was achieved, the patients were allocated to receive R (375 mg/m(2), days 1, 8, 15, and 22) at 3 and 9 months after chemotherapy. Three hundred twenty-five patients achieved CR (70%) and were allocated to receive R (151 patients) or not (174 patients). Actuarial curves at 5 years showed that progression-free survival (PFS) was 51% (95% confidence interval [CI]: 44%-58%) in the R group and 53% (95% CI: 47%-59%) in the observation group (p=0.8). Overall survival (OS) was 65% (95% CI: 58%-71%) and 66% (95% CI: 59%-72%), respectively (p=0.78). Late toxicities were more frequent in the R group. The authors showed that the use of R as a consolidation treatment was not useful to improve PFS and OS and toxicity secondary to R was frequent. They did not recommend the use of R as consolidation in this patient setting.

Interferon and low doses of methotrexate versus interferon and retinoids in the treatment of refractory/relapsed cutaneous T-cell lymphoma.

OBJECTIVES: Treatment of refractory/relapsed cutaneous T-cell lymphoma (CTCL) remains controversial, most studies included a few patients with a short follow-up. Previously, we performed two small studies employing interferon alpha 2b (IFN) combined with low doses of methotrexate (MTX) or retinoids. Thus, we conducted an open-label clinical trial to assess the benefit and toxicity of the two mentioned regimens in a large number of patients with a longer follow-up of the treatment of refractory/relapsed CTCL. PATIENTS AND METHODS: Three-hundred and seventy-seven patients with refractory/relapsed, pathologically confirmed, CTCL, with advanced stages and at least treated with two previous effective regimens in CTCL, were randomized to receive IFN and low doses of MTX compared with IFN and all trans-retinoid acid during 6 months; if a complete response (CR) was not achieved, treatment was continued until 12 months in both arms. At this time, if patient achieves CR, MTX or retinoid was stopped, and the patient continues to receive IFN until progression disease or toxicity. One-hundred and eight patients received IFN for more than 5 years. RESULTS: Toxicity was minimal and well tolerated, no patients needed to modify the administration of IFN secondary to toxicity. The overall complete response was achieved 80% in both arms. Actuarial curves at 5 years showed that progression-free survival was 60% in the IFN/MTX group and 62% in the IFN/retinoids group (P = 0.8) that were not statistically different and overall survival (OS) rates were 70 and 67%, respectively (P = 0.03). DISCUSSION: Both present schedules showed good tolerance and an excellent OS at 5 years, which is better than the other, more expensive and toxic, regimens. Considering the indolent course of CTCL, we suggested that those regimens, mentioned in this paper, will be regarded as the standard therapy, for patients of this setting. CONCLUSION: The use of IFN and retinoids or low dose of cytotoxic drugs will be preferred in patients with refractory/relapse CTCL, because OS is good and toxicity is minimal.

Combined therapy in untreated patients improves outcome in nasal NK/T lymphoma: results of a clinical trial.

Nasal NK/T-cell lymphoma is a rare presentation of T-cell lymphoma in USA and in Europe, but is the most common presentation in Latin America. The lymphoma is associated with a worse prognosis even in the early stage. Until now, a better treatment has not been determined. We performed a prospective, open-label, controlled clinical trial to assess the efficacy and toxicity of the most common treatment options. We treated 427 patients, of whom 109 patients received radiotherapy (RT), 116 patients received chemotherapy (C), and 202 patients received combined therapy (CT), which were balanced according to stage and prognostic factors. Complete response was achieved in 91 % (95 % confidence interval CI 88-102 %) in CT arm 69 % (95 % CI 61-75 %) in RT arm; and 59 % (95 % CI 48-64 %) in C arm (p < 0.01). A progression-free disease was 91 % (95 % CI 83-96 %); 78 % (95 % CI 69-86 %); and 40 % (95 % CI 32-46 %), respectively (p < 0.01). Actuarial curves of overall survival at 5 years were as follows: 86 % (95 % CI 81-90 %), for CT; 64 % (95 % CI 59-70 %) for RT; and 45 % (95 % CI 39-51 %) for C (p < 0.001). Toxicity was mild and well tolerated. To our knowledge, this is the first controlled clinical trial, with a large number of patients and longer follow-up. Thus, we conclude that CT is the best therapeutic option in this setting of patients.

Central nervous system prophylaxis in patients with aggressive diffuse large B cell lymphoma: an analysis of 3,258 patients in a single center.

Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive or did not receive prophylaxis was not statistically significant: 49 % versus 53 % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised.

Rituximab in the treatment of diffuse large B-cell lymphoma primary of the lung.

Diffuse large B-cell lymphoma primary of lung (DLBCL-PL) is a rare presentation of extranodal lymphoma, in most cases chemotherapy-based anthracyclines: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the treatment, with excellent outcome. The addition of rituximab to CHOP (R-CHOP) has been considered the gold standard in the treatment of nodal DLBCL. Thus, we assess in a large number of cases of DLBCL-PL whether the use of R-CHOP could improve survival in this setting of patients. Forty-two patients with DLBCL-PL, stage IE, age 65 years or younger, were treated with standard R-CHOP, no consolidation radiotherapy or maintenance therapy were considered. They were matched with patients who received CHOP alone to assess efficacy and toxicity. Complete response was observed in 35 patients (83%), and 7 patients were considered failure (16%). The study has a median follow-up of 42.8 months. Actuarial curves at 5 years showed that progression-free survival was 88 % and overall survival was 70 %. The results were not statistically different when compared retrospectively with patients who received CHOP alone. Treatment was well tolerated. The addition of rituximab to chemotherapy did not improve outcome in patients with DLBCL-PL.

Hematological malignancies and pregnancy: treat or no treat during first trimester.

Treatment of hematological malignancies (HM) during pregnancy remain unsolved, although the use of chemotherapy during second and third trimester has been accepted because of the low rate of toxicities, the use of cytotoxic drugs during first trimester is generally forbidden. Most of the concerns are related to congenital abnormalities and development, but long-term follow-up of these children are not available. From 1975 to 2008, we diagnosed and treated 15,750 cases of HM, and 143 female patients were pregnant during this time that were treated with combined chemotherapy. In our study, we present the long-term follow-up (the median follow-up was 22.4 years with a range of 3.8-32.0 years) of 54 newborns, whose mothers received chemotherapy during the first trimester of pregnancy with an intent-to-cure HM. Physical and neurological development were carefully assessed, and cardiac and chromosomal studies were performed until the age of 20 years to evaluate late toxicities. The obstetrical development of pregnancy was normal, chemotherapy was used at doses and schedules used in normal patients. Low-weight birth was the most frequent finding. No congenital abnormalities were detected. Physical, psychological and neurological developments were normal. Education and academic degree were according to the economical and social factors. Cardiac function and chromosomal examination were normal. No neoplasm or acute leukemia has been observed in these children. Forty-three mothers are alive and disease-free and can be considered cured. The use of cytotoxic drugs during the first trimester to treat HM seems to be beneficial to both the mother and fetus, and chemotherapy during the first trimester can be considered if the cure of the patient is the goal.

Randomized clinical trial to assess the efficacy of radiotherapy in primary mediastinal large B-lymphoma.

PURPOSE: We developed a controlled clinical trial to assess the efficacy and toxicity of adjuvant-involved field radiotherapy (IFRT) in patients with primary mediastinal B-cell lymphoma that achieved complete response after the patients were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP-14). METHODS AND MATERIALS: Between January 2001 and June 2004, 124 consecutive patients who were in complete remission after dose dense chemotherapy and rituximab administration (R-CHOP14) were randomly assigned to received IFRT (30 Gy). Sixty-three patients received IFR, and 61 patients did not (control group). RESULTS: The study aimed to include 182 patients in each arm but was closed prematurely because in a security analysis (June 2004), progression and early relapse were more frequent in patients that did not received IFRT. Patients were followed until March 2009, at which point actuarial curves at 10 years showed that progression free-survival was 72% in patients who received IFR and 20% in the control group (p < 0.001), overall survival was 72% and 31%, respectively (p < 0.001). Acute toxicity was mild and well tolerated. DISCUSSION: Adjuvant radiotherapy to sites of bulky disease was the only difference to have an improvement in outcome in our patients; the use of rituximab during induction did not improve complete response rates and did affect overall survival; patients who received rituximab but not IFRT had a worse prognosis. CONCLUSIONS: The use of IFRT in patients with primary mediastinal B-cell lymphoma who achieved complete response remain as the best treatment available, even in patients that received rituximab during induction.

The role of genotype in 104 cases of diffuse large B-cell lymphoma primary of breast.

OBJECTIVES: To analyze the role of genotype in patients with diffuse large B-cell lymphoma primary of breast (DLBCL-PB) treated with chemotherapy or immunochemotherapy. METHODS: We carried out a retrospective analysis in 104 patients with DLBCL-PB who were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or immunochemotherapy: R-CHOP (adding rituximab) and also carried out an analysis of genotype, studied with immunohistochemistry, as a prognostic factor. RESULTS: Seventy-seven percent of patients showed the non-GCB (germinal center B) genotype. Patients treated with CHOP had a complete response of 70%; actuarial curves at 5 years showed that disease-free survival was 66 % and overall survival was 52% and that it was not statistically different than patients treated with R-CHOP: 78%, 61%, and 53%, respectively. When genotype was analyzed to assess the impact in prognosis, no statistical differences were observed. Patients treated with R-CHOP and non-GCB genotype have a complete response of 77%, disease-free survival of 56%, and overall survival of 66% that were not statistically different than patients with GCB: 80%, 60%, and 60% respectively, (P: 0.81, 0.5, and 0.66, respectively). CONCLUSIONS: We confirm that the non-GCB genotype is most frequent in DLBCL-PB, but the addition of rituximab did not improve outcome in primary breast lymphoma with non-GCB phenotype.