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.

Effectiveness of dose-intensified salvage regimens versus standard-dose chemotherapy on 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 is deemed 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 χ2 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. SYSTEMATIC REVIEW REGISTRATION NUMBER: 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).

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.

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.

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.

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.

Anemia in inflammatory bowel disease outpatients: prevalence, risk factors, and etiology.

UNLABELLED: Anemia is common in inflammatory bowel disease (IBD). However, epidemiological studies of nonwestern IBD populations are limited and may be confounded by demographic, socioeconomic, and disease-related influences. This study evaluated the prevalence, risk factors, and etiology of anemia in Brazilian outpatients with IBD. METHODS: In this cross-sectional study, 100 Crohn's disease (CD) patients and 100 ulcerative colitis (UC) subjects were assessed. Anemia workup included complete blood count, ferritin, transferrin saturation, serum levels of folic acid and vitamin B12, and C-reactive protein (CRP) concentration. RESULTS: The overall prevalence of anemia in IBD was 21%. There was no significant difference in the prevalence of anemia between CD subjects (24%) and UC (18%). Moderate disease activity (OR: 3.48, 95% CI, 1.95-9.64, P = 0.002) and elevated CRP levels (OR: 1.8, 95% CI, 1.04-3.11, P = 0.02) were independently associated with anemia. The most common etiologies of anemia found in both groups were iron deficiency anemia (IDA; 10% on CD and 6% on UC) followed by the anemia of chronic disease (ACD; 6% for both groups). CONCLUSIONS: In Brazilian IBD outpatients, anemia is highly concurrent condition. Disease moderate activity as well as increased CRP was strongly associated with comorbid anemia. IDA and/or ACD were the most common etiologies.

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.

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 9.0g/dL (±1.4g/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.

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine.

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4 x 10(9)/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment due to liver toxicity, and one (16.6%) due to dyspepsia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

Increased levels of circulating endothelial progenitor cells in human T-cell lymphotropic virus type I carriers.

BACKGROUND AND AIMS: HTLV-I-transformed T cells secrete biologically active forms of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF). In addition, HTLV-I-transformed cells have a high capacity of adhesion to endothelial cells. METHODS: We measured the circulating endothelial progenitor cells (EPCs) and mature endothelial cells (MECs) by flow cytometry in 27 HTLV-I carriers in comparison to 30 healthy, age- and gender-matched subjects. All subjects had HTLV-I positivity confirmed by Western blot and/or polymerase chain reaction (PCR). The numbers of different subpopulations of EPCs and MECSs were evaluated by four-color flow cytometry using a panel of monoclonal antibodies. All reactions were done in duplicate to confirm reproducibility of the results. RESULTS: The median age of all 27 HTLV-I carriers enrolled in this study was 45 years (range: 27-65 years); 11 (41%) were male and 16 (59%) were female. The median age of the 30 healthy subjects in the control group was 45.5 years (range: 20-63 years); 11 (36.6%) were male and 19 (63.4%) were female. The number of EPCs was significantly higher in HTLV-I carriers (median 0.8288 cells/µL, range: 0.0920-3.3176 cells/µL) as compared to control group (median 0.4905 cells/µL, range: 0.0000-1.5660 cells/µL) (p = 0.035). In contrast, the median of the MECs in the HTLV-I carriers was 0.6380 cells/µL (range: 0.0473-5.7618 cells/µL) and 0.4950 cells/µL (range: 0.0000-4.0896 cells/µL) in the control group, with no statistical difference (p = 0.697). CONCLUSIONS: We demonstrated that EPCs, but not MECs, are increased in the peripheral blood of HTLV-I carriers.

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.

Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma.

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

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...