Effectiveness of dose-intensified salvage regimens versus standard-dose chemotherapy for progression-free survival in early progressed follicular lymphoma before autologous stem cell transplantation: a systematic review protocol.

OBJECTIVE: This review will evaluate the effectiveness of dose-intensified versus standard-dose salvage regimens on progression-free survival in early progressed follicular lymphoma before high-dose chemotherapy and autologous stem cell transplantation. INTRODUCTION: Despite the substantial advances in the management of follicular lymphoma, approximately 20% of patients experience progression of the disease within 2 years of induction therapy. These patients have worse outcomes, and autologous stem cell transplantation has been shown to improve outcomes in this context. Little is known about the optimal salvage regimen. INCLUSION CRITERIA: Studies must include patients ≥18 years old with early progressed follicular lymphoma who were submitted to autologous stem cell transplantation in subsequent remission. Clinical trials and observational studies will be included. METHODS: The search strategy will be carried out in MEDLINE (PubMed), Embase (Periódicos CAPES), Scopus, Web of Science, LiLACS, and the Cochrane Library. No date or language restrictions will be imposed. The recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis will be used. Studies should score at least 50% in accordance with the critical appraisal tool. Data will be pooled whenever possible using the random effects model. Heterogeneity will be assessed using the standard χ 2 and I2 tests. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in the meta-analysis. The GRADE approach will be used to rate certainty of evidence. REVIEW REGISTRATION: PROSPERO CRD42022373345.

COVID-19 in multiple myeloma patients: frequencies and risk factors for hospitalization, ventilatory support, intensive care admission and mortality -cooperative registry from the Grupo Brasileiro de Mieloma Multiplo (GBRAM) / COVID-19 in multiple myeloma patients: frequencies and risk factors for hospitalization, ventilatory support, intensive care admission and mortality ­cooperative registry from the Grupo Brasileiro de Mieloma Multiplo (GBRAM)

ABSTRACT Introduction: This study evaluated outcomes and risk factors for COVID-19 in 91 Brazilian multiple myeloma (MM) patients between April 2020 and January 2022. Results: Of the 91 MM patients diagnosed with COVID-19, 64% had comorbidities and 66% required hospitalization due to COVID-19, with 44% needing ventilatory support and 37% intensive care. Age (OR 2.02; 95%CI 1.02 - 7.7) and hypertension OR 4.5; 95%CI 1.3 - 15.5) were independently associated with hospitalization and certain MM therapies (corticosteroids and monoclonal drugs) were associated with ventilatory support (OR 4.3; 95%CI 1.3 - 14 and OR 5.7; 95%CI 1.8 - 18, respectively), while corticosteroids and immunomodulatory drugs were linked to ICU admission (OR 5.1; 95% CI 1.4 - 18 and OR 3.4; 95%CI 1.1 - 10, respectively). The overall mortality rate was 30%, with the highest rate observed in the ICU (73%). Additionally, the ECOG performance status was linked to increased mortality (OR 11.5; 95%CI 1.9 - 69). The MM treatment was delayed in 63% of patients who recovered from COVID-19. Conclusions: The findings highlight the need for preventing COVID-19 and prioritizing vaccination among MM patients, as they have high rates of severe outcomes in the event of COVID-19. It is also essential to monitor the potential clinical impacts of COVID-19 on MM patients in the long-term. Given the limited resources available in treating MM patients in Brazil during the COVID-19 pandemic, outcomes might be worse in this population.

COVID-19 in multiple myeloma patients: frequencies and risk factors for hospitalization, ventilatory support, intensive care admission and mortality -cooperative registry from the Grupo Brasileiro de Mieloma Multiplo (GBRAM).

INTRODUCTION: This study evaluated outcomes and risk factors for COVID-19 in 91 Brazilian multiple myeloma (MM) patients between April 2020 and January 2022. RESULTS: Of the 91 MM patients diagnosed with COVID-19, 64% had comorbidities and 66% required hospitalization due to COVID-19, with 44% needing ventilatory support and 37% intensive care. Age (OR 2.02; 95%CI 1.02 - 7.7) and hypertension OR 4.5; 95%CI 1.3 - 15.5) were independently associated with hospitalization and certain MM therapies (corticosteroids and monoclonal drugs) were associated with ventilatory support (OR 4.3; 95%CI 1.3 - 14 and OR 5.7; 95%CI 1.8 - 18, respectively), while corticosteroids and immunomodulatory drugs were linked to ICU admission (OR 5.1; 95% CI 1.4 - 18 and OR 3.4; 95%CI 1.1 - 10, respectively). The overall mortality rate was 30%, with the highest rate observed in the ICU (73%). Additionally, the ECOG performance status was linked to increased mortality (OR 11.5; 95%CI 1.9 - 69). The MM treatment was delayed in 63% of patients who recovered from COVID-19. CONCLUSIONS: The findings highlight the need for preventing COVID-19 and prioritizing vaccination among MM patients, as they have high rates of severe outcomes in the event of COVID-19. It is also essential to monitor the potential clinical impacts of COVID-19 on MM patients in the long-term. Given the limited resources available in treating MM patients in Brazil during the COVID-19 pandemic, outcomes might be worse in this population.

Vírus Epstein-Barr associado ao Linfoma de Hodgkin clássico: um estudo de casos / Epstein-Barr virus associated with classical Hodgkin lymphoma: a case study

Introdução: A expressão da positividade do vírus Epstein-Barr nas células de Reed-Sternberg/Hodgkin e o impacto dessa relação na sobrevida do Linfoma de Hodgkin clássico (LHc) permanecem controversos. Objetivo: Avaliar a presença de Epstein Baar Vírus (EBV) em pacientes com LHc, associando com características anatomopatológicas e clínicas. Materiais e Métodos: Para determinar a presença de EBV, a partir de um material de biópsia de tecidual foi realizada analise por hibridização para RNA codificado para EBV (EBER) e imuno-histoquímica para proteína de membrana latente viral (LMP-1) de uma amostra de demanda de pacientes com diagnóstico entre janeiro de 2009 e janeiro de 2015. As características clínicas avaliadas foram as que compõem o Escore Prognóstico Internacional para estadiamento avançado e os fatores de risco desfavoráveis instituídos pelo Grupo Alemão de Estudos em Hodgkin para estadiamento limitado. Posteriormente, tais características foram relacionadas com a situação do vírus nas células tumorais. Resultados: Foram avaliadas as lâminas de biópsia de 29 pacientes com diagnóstico de Linfoma de Hodgkin. Em relação as características histológicas, o subtipo histológico de celularidade mista apresentou associação estatística com EBV positivo (p= 0,02). Além disso, a presença de EBV foi mais comum em pacientes com 45 anos ou mais (p= 0,07). Embora sem significância estatística, houve uma tendência de melhor sobrevida livre de eventos (p= 0,07), para os pacientes EBV positivo. Conclusão: O subtipo histológico de celularidade mista, apresentou uma relação estatisticamente significativa com a presença de EBV nas células tumorais, em conformidade com a literatura. São necessários estudo com maior número de casos para que se possa entender melhor a relação entre a presença de EBV e o prognóstico do LHc em nosso meio.

Introduction: The expression of Epstein-Barr virus positivity in Reed-Sternberg/Hodgkin cells and the impact of this relationship on survival in classical Hodgkin Lymphoma (cHL) remain controversial. Objective: To evaluate the presence of Epstein Baar Virus (EBV) in patients with cHL, associating it with anatomopathological and clinical characteristics.Materials and Methods: To determine the presence of EBV, analysis was carried out using a tissue biopsy material by hybridization for EBV-encoded RNA (EBER) and immunohistochemistry for viral latent membrane protein (LMP-1) from a demand sample of patients diagnosed between January 2009 and January 2015. The clinical characteristics evaluated were those that make up the International Prognostic Score for advanced stage and the unfavorable risk factors established by the German Hodgkin Study Group for limited stage. Subsequently, these characteristics were related to the status of the virus in tumor cells. Results: Biopsy slides from 29 patients diagnosed with Hodgkin's Lymphoma were evaluated. Regarding histological characteristics, the histological subtype of mixed cellularity showed a statistical association with positive EBV (p= 0.02). Furthermore, the presence of EBV was more common in patients aged 45 years or older (p= 0.07). Although not statistically significant, there was a trend towards better event-free survival (p= 0.07) for EBV positive patients. Conclusion: The histological subtype of mixed cellularity showed a statistically significant relationship with the presence of EBV in tumor cells, in accordance with the literature. Studies with a larger number of cases are needed to better understand the relationship between the presence of EBV and the prognosis of cHL in our country.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation

ABSTRACT Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p = 0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

Nursing documentation for chemotherapy in a university hospital's bone marrow transplant unit: a best practice implementation project.

AIM: The aim of this evidence implementation project was to improve the documentation of chemotherapy administration by nursing staff in a bone marrow transplant unit, to improve patient care and safety, as well as meet the legal and educational responsibilities of the nursing staff. METHODS: This evidence implementation project used the Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback framework for the design and development of an evidence-based audit and feedback change project. A baseline audit was conducted to assess current practices against best practice and identify areas requiring improvement. Next, the project team reflected on the results of the audit to develop and implement strategies for documentation improvement. Lastly, a follow-up audit was conducted to assess changes in practice improvement. RESULTS: The baseline audit results revealed practice areas requiring improvement; facilitators of and barriers to nursing documentation and practice improvement were identified. A checklist, educational session, Nursing Documentation Guidelines for Chemotherapy Administration, was implemented to improve nursing documentation. The follow-up audit demonstrated improved adherence across all audit criteria. CONCLUSION: The checklist implemented for nursing documentation and education contributed to improved practices. To promote additional improvements, nurses will continue to utilize the tools developed and receive continued education through formal training and staff meetings. Future auditing is planned to ensure sustainability.

Superiority of the triple combination of bortezomib, cyclophosphamide and dexamethasone versus cyclophosphamide, thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma, eligible for transplantation.

BACKGROUND: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature. METHODS: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma. RESULTS: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p=0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens. CONCLUSION: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM.

Safety and feasibility of inspiratory muscle training for hospitalized patients undergoing hematopoietic stem cell transplantation: a randomized controlled study.

PURPOSE: Patients undergoing hematopoietic stem cell transplantation (HSCT) usually experienced respiratory muscle weakness. Inspiratory muscle training (IMT) at HSCT has not been studied yet. Thus, it is important to evaluate the safety, feasibility, and preliminary effectiveness of IMT for hospitalized patients undergoing HSCT with an unstable and acute clinical condition. METHODS: This is a randomized controlled feasibility study. Thirty-one hospitalized patients undergoing HSCT were randomized to the conventional physical rehabilitation (CON) or to the IMT group (conventional physical rehabilitation + IMT). IMT was carried out at 40% of maximal inspiratory pressure (MIP), 5 sessions weekly, 10-20 min/session. Primary outcomes were safety and feasibility (recruitment, adherence, and attrition rates) of IMT. Secondary outcomes were respiratory strength, respiratory rate, oxygen saturation, and frequency of patients with oxygen desaturation, bleeding, dyspnea, and acute pulmonary edema. RESULTS: Patients were allocated to the IMT (N = 15; 43.6 years) or to the CON group (N = 16; 46.6 years). The recruitment rate was 100%, the adherence rate was 91%, and attrition was 13% to IMT. Two events were observed in 126 IMT sessions (1.5%). MIP increased in the IMT group (P < 0.01). No differences were observed in respiratory rate and oxygen saturation between groups. Trends to negative outcomes were observed in the CON in comparison to IMT group for a need of oxygen therapy (18% vs. 6%), bleeding (12% vs. 6%), dyspnea (25% vs. 13%), and acute pulmonary edema (6% vs. 0%). CONCLUSIONS: IMT is safe, feasible, and improves the inspiratory muscle strength in hospitalized patients undergoing HSCT. TRIAL REGISTRATION: Clinical trial registration: NCT03373526.

Functional Capacity Change Impacts the Quality of Life of Hospitalized Patients Undergoing Hematopoietic Stem Cell Transplantation.

OBJECTIVE: The aim of the study was to compare the quality of life (QOL) of patients undergoing hematopoietic stem cell transplantation who improved their functional capacity during hospitalization (increased functional capacity group) with that of patients who maintained or decreased functional capacity during hospitalization (decreased functional capacity group). DESIGN: This observational, longitudinal study included 27 hospitalized patients undergoing hematopoietic stem cell transplantation. Patients were divided into increased functional capacity group (16 patients) and decreased functional capacity group (11 patients). Functional capacity (6-min step test), peripheral muscle strength (sit-to-stand test and handgrip strength), and QOL (European Organization for Research and Treatment of Cancer) were assessed at admission and at hospital discharge. RESULTS: Increased functional capacity patients had increased functional capacity and peripheral muscle strength of the lower and upper limbs at hospital discharge (P < 0.01, <0.01, and 0.02, respectively). The patients in the increased functional capacity group demonstrated an increase in global health and reduced symptoms at discharge (P = 0.02 and 0.03, respectively). No significant differences were observed between groups in the functional domain. CONCLUSIONS: Patients undergoing hematopoietic stem cell transplantation, who have improved functional capacity at discharge, also experience an improved QOL, with no such improvement noted among patients who have stable or reduced functional capacity. We recommend that the treatment protocol for hospitalized patients undergoing hematopoietic stem cell transplantation include an exercise program aimed at improving functional capacity.

Supplementation with concentrated milk protein in patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: The aim of this study was to analyze the influence of dietary supplementation with whey protein concentrate (WPC) in the incidence of oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Patients were supplemented with a daily intake of WPC delivering 50% of the daily protein requirements (DPR) according to the Dietary Reference Intakes and classified later based on the amount of ingested supplement until OM median onset. RESULTS: We evaluated 73 patients. Forty-three were part of the historical control and 30 were supplemented with WPC. The OM had a mean duration of 5.3 d (SD 4.5), ranging from the day of the infusion of stem cells until the 17th day after infusion and a median of 5 d after infusion. OM duration was influenced by the conditioning protocol (P < 0.01) and WPC (P = 0.01). Patients who consumed the WPC in an amount ≥40% of DPR had a 35% reduction in duration of OM, and the incidence of OM grades 3 and 4 was 11 times smaller. Body mass index, serum albumin, and adverse reactions, such as diarrhea, nausea and vomiting, dysphagia, dry mouth and drooling, showed no statistically significant differences. CONCLUSION: WPC intake ≥40% of DPR helped to reduce the severity and duration of OM. The use of WPC in patients undergoing HSCT was shown to be safe, encouraging new studies in this population to assess its action mechanism.

Herpes zoster after autologous hematopoietic stem cell transplantation

ABSTRACT Background: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. Methods: A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. Results: Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value = 0.002). There were no significant differences for the other variables analyzed. Conclusion: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

Herpes zoster after autologous hematopoietic stem cell transplantation.

BACKGROUND: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. METHODS: A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. RESULTS: Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value=0.002). There were no significant differences for the other variables analyzed. CONCLUSION: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

Transfusion practices in a neonatal intensive care unit in a city in Brazil

OBJECTIVE: Newborn infants are the most heavily transfused population inside intensive care units. The hemoglobin level used to indicate the need of transfusions is not well established. The aim of this study was to evaluate transfusional practices in newborns in the neonatal intensive care units of one specific city. METHODS: Red blood cell transfusion practices of all transfused newborns in all five of the neonatal intensive care units of the city were analyzed. Data are reported as descriptive statistics, including numbers and percentages and means and standard deviation. Univariate analysis, followed by stepwise logistic regression was performed in respect to transfusional data and outcomes. RESULTS: A total of 949 patients were admitted to the intensive care units during the 12-month study period with 20.9% receiving at least one transfusion, most (62.4%) of whom received more than one transfusion. The mean number of transfusions per infant was 2.7 ± 2.16; in the liberal transfusion group the mean number was 1.59 ± 1.63 and in the restrictive group it was 1.08 ± 1.51. The mean hemoglobin and hematocrit levels were 9.0 g/dL (±1.4 g/dL) and 27.4% (±4.3%), respectively. The most common indications for blood transfusions were sepsis and prematurity. CONCLUSION: This study shows that the characteristics and the transfusion practices for newborns admitted in the neonatal intensive care units of Juiz de Fora are similar to recent pubications. There was no significant reduction in the number of transfusions per child in the restrictive group compared to the liberal group. Restrictive transfusions are an independent risk factor for peri-intraventricular hemorrhages and death...

Allogeneic hematopoietic stem cell transplantation in mycosis fungoides.

Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.

Allogeneic hematopoietic stem cell transplantation in mycosis fungoides / Transplante alogenico de celulas-tronco hematopoieticas em micose fungoide

Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.

Micose Fungoide é tipicamente uma doença indolente em estágios iniciais. No entanto, aproximadamente 30% dos pacientes têm doença avançada na apresentação e 20% irão desenvolvê-la em algum momento. Esses pacientes têm um pior prognóstico com uma sobrevida média de dois a quatro anos. A única possibilidade de cura é o transplante alogênico de células-tronco hematopoiéticas. Relatamos o caso de uma paciente com micose fungoide em estágio avançado (IIB), refratária às opções terapêuticas e que foi submetida a um transplante alogênico de células-tronco hematopoiéticas. A paciente permanece em remissão completa 19 meses após o procedimento. O transplante alogênico é capaz de mudar a história natural da micose fungoide e deve ser considerado em pacientes com doença avançada e refratária aos tratamentos disponíveis.