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[Effects of Pre-Transplant CONUT and Post-Transplant MRD on Prognosis of Patients with Multiple Myeloma after Auto-HSCT]
Xiong, Y. Y., Zhou, Q., Chen, L., Yu, W., Zhang, H. B., Chen, J. B.
Zhongguo shi yan xue ye xue za zhi. 2024;32(1):146-154
Abstract
OBJECTIVE To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT). METHODS The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group (n=62) and High-CONUT group (n=17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve. RESULTS The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group (P <0.01), but CR rate did not(P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective. CONCLUSION The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.
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Effects of Korean red ginseng on T-cell repopulation after autologous hematopoietic stem cell transplantation in childhood cancer patients
Hong, K. T., Kang, Y. J., Choi, J. Y., Yun, Y. J., Chang, I. M., Shin, H. Y., Kang, H. J., Lee, W. W.
Journal of ginseng research. 2024;48(1):68-76
Abstract
BACKGROUND Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. METHODS This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. RESULTS All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4(+) T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4(+) EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28(-) subset was ameliorated. CONCLUSIONS These findings suggest that KRG promotes the repopulation of CD4(+) EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.
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Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study
Mizutani, Y., Kawamoto, S., Takahashi, M., Doi, H., Wakida, K., Tabuchi, S., Tanda, M., Soga, A., Chijiki, R., Takakura, H., et al
Internal medicine (Tokyo, Japan). 2023
Abstract
Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.
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No Effect of Vitamin C Administration on Neutrophil Recovery in Autologous Stem Cell Transplantation for Myeloma or Lymphoma: A Blinded, Randomized Placebo-Controlled Trial
van Gorkom, G. N. Y., Boerenkamp, L. S., Gijsbers, Blmg, van Ojik, H. H., Wodzig, Wkwh, Wieten, L., Van Elssen, Chmj, Bos, G. M. J.
Nutrients. 2022;14(22)
Abstract
Vitamin C is an important micronutrient for various immune cells. It increases phagocytic cell function and is necessary for T and natural killer (NK) cell development. Patients in need of an autologous hematopoietic stem cell transplantation (HSCT) are often vitamin C-depleted. We therefore hypothesized that vitamin C supplementation could improve immune recovery in autologous HSCT patients. This blinded, placebo-controlled trial included 44 patients randomized to receive vitamin C or a placebo. The following outcome measures used were clinical and immunological parameters, among others: time to neutrophil recovery, serum, and intracellular vitamin C values. Twenty-one patients received vitamin C, and 23 received a placebo. The time to neutrophil recovery did not differ between the two groups at 11.2 days (p = 0.96). There were no differences in hospitalization time (19.7 vs. 19.1 days, p = 0.80), the incidence of neutropenic fever (57% vs. 78%, p = 0.20), or 3-month overall survival (90.5% vs. 100%, p = 0.13). Bacteremia seemed to occur less in the vitamin C group (10% vs. 35%, p = 0.07). Our study shows no benefit from vitamin C supplementation on neutrophil recovery and hospitalization, despite possible lower rates of bacteremia in the vitamin C group. Therefore, we do not advise vitamin C supplementation in this treatment group.
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Nutrition support use and clinical outcomes in patients with multiple myeloma undergoing autologous stem cell transplant
Kuypers, J., Simmance, N., Quach, H., Hastie, K., Kiss, N.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2022
Abstract
PURPOSE Malnutrition is associated with worse outcomes post-haematopoietic stem cell transplantation, with nutrition support recommended for people who are malnourished or have prolonged inadequate energy intake. We investigated associations between nutritional status, nutrition support type and clinical outcomes in adults with multiple myeloma post stem cell transplantation. METHODS Medical records (2015-2020) were reviewed to retrieve demographics, anthropometry, dietary data, nutrition support type (enteral/oral versus parenteral), and clinical outcomes (engraftment time, infection, length of stay, weight changes). Relationships were examined using linear regression modelling and Fisher's exact test. RESULTS One hundred thirteen participants were included (61% male; median age 62 years). Fifteen participants (13%) received parenteral and 98 (87%) received enteral/oral nutrition support. Parenteral nutrition was associated with shorter platelet engraftment time by 2.7 days (p = 0.036) and a longer hospital stay by 6.1 days (p < 0.001). Nutrition support was not associated with neutrophil engraftment time (p = 0.365). Inadequate energy intake for ≥ 7 days was not associated with any clinical outcomes (p > 0.05). CONCLUSIONS Participants who received parenteral nutrition reached platelet engraftment sooner but were in hospital longer. Inadequate energy intake for ≥ 7 days did not impact clinical outcomes. Multi-site prospective studies are warranted to confirm results.
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Effect of vitamin C on immune reconstitution after bone marrow transplantation
Urbalejo-Ceniceros, V. I., Rocha-González, H. I., Acosta-Maldonado, B. L., Valero-Saldaña, L. M., Hernández-Alcantara, A. E., Pérez-Camargo, D. A.
International Journal of Clinical Pharmacology and Therapeutics. 2022;60(9):384-391
Abstract
BACKGROUND Vitamin C is an essential nutrient for the adequate function and maturation of the immune system. In vitro studies show that the development, proliferation, and functioning of T cells requires vitamin C, especially for natural killer (NK) cells. Their deficiency during the acute phase post-transplantation could cause greater morbidity and mortality in these patients. A prospective clinical trial using high-dose vitamin C was performed to determine if vitamin C supplementation improves reconstitution of NK lymphocytes after hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS We enrolled 24 patients who underwent autologous HSCT for multiple myeloma and lymphoma. Patients were randomized to receive standard treatment or standard treatment plus 20 g vitamin C once daily (1 - 10 days) and 500 mg twice daily (11 - 100 days) after transplantation. RESULTS NK and CD3(+) lymphocytes showed an increase from days +30 to +100 only in the vitamin C-treated group. Patients in the vitamin C group had a lower frequency of infections. No severe adverse events were reported. CONCLUSION Our results suggest that high-dose vitamin C supplementation is an effective and safe therapeutic option to decrease the frequency of infections and enhance immune reconstitution after HSCT.
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The nutrition risk index is associated with bacteraemia within 30 days after autologous stem cell transplantation in patients with multiple myeloma
Garzon Herazo, J. R., Mauricio Munoz Velandia, O., Solano, J. C., Molina Pimienta, L., Figueroa Lemus, W. J.
Transplant infectious disease : an official journal of the Transplantation Society. 2020;:e13302
Abstract
OBJECTIVES To assess whether the nutrition risk index (NRI) is associated with the risk of bacteraemia within the first days after autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). MATERIALS AND METHODS Retrospective cohort study of adult patients with MM taken to ASCT at the Hospital Universitario San Ignacio (Bogota, Colombia) between 2005 and 2019. The outcome of interest was the incidence of bacteraemia at 30 days. Multivariate analysis was used to identify if the NRI was associated with bacteraemia, controlling by different confounding variables. RESULTS 124 patients with a median age of 58.5 years, (IQR 54 - 64) were included. 47.1% were in stage ISS III. 36.0% had moderate or severe malnourishment (NRI <97.5). 11.2% presented bacteraemia in the first 30 days after transplantation. In the univariate analysis, the NRI <97.5 was associated with bacteraemia (OR 1.88; 95% CI 1.30 - 2.72, p = 0.001), however this association was not significant in the multivariate analysis, unlike the presence mucositis (OR 11.59; 95% CI 1.9-68.3, <0.01), one or more previous lines of therapy (OR 12.0; 95% CI 2.1 - 67.4; p <0.01) and duration of aplasia (OR 1.70; 95% CI 1.2-2.4, p <0.01) CONCLUSIONS Patients with moderate or severe malnourishment have a higher incidence of bacteraemia in the 30 days post ASCT in patients with MM. Additional risk factors associated with bacteraemia include the presence of mucositis, one or more previous lines of therapy, and the duration of aplasia.
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Reduced survival after autologous stem cell transplantation in myeloma and lymphoma patients with low vitamin D serum levels
Eicher, F., Mansouri Taleghani, B., Schild, C., Bacher, U., Pabst, T.
Hematological oncology. 2020
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Abstract
High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is applied for consolidation in myeloma and relapsing lymphoma patients. Vitamin D (VitD) exerts effects during hematopoietic stem cell proliferation, differentiation and interactions with the immune system. VitD deficiency is frequent in patients with hematological malignancies, but its prognostic relevance after ASCT remains unclear. We investigated the effect of VitD serum levels in patients with lymphomas and myeloma at ASCT on progression-free (PFS) and overall survival (OS). The cohort (n = 183) was divided in two groups: 81 (44%) had VitD levels >52 nmol/L and 102 (56%) ≤52 nmol/L at ASCT. VitD levels >52 nmol/L were associated with better PFS (P = 0.0194) and OS (P = 0.011). Similarly, when evaluating myeloma patients alone, patients with lower VitD levels (≤52 nmol/L) had inferior PFS (P = 0.0412) and OS (P = 0.049). Finally, the multivariate analysis was consistent that varying VitD levels were significantly associated with OS (P = 0.0167), also when stratifying patients in groups with VitD levels > vs ≤52 nmol/L (P = 0.0421). Our data suggest that reduced serum VitD levels in myeloma and lymphoma patients undergoing HDCT/ASCT are associated with inferior outcome. Optimizing VitD levels before ASCT may be warranted. This article is protected by copyright. All rights reserved.
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Effect of malnutrition-driven nutritional support protocol on clinical outcomes in autologous stem cell transplantation patients
Lazarow, H., Singer, R., Compher, C., Gilmar, C., Kucharczuk, C. R., Mangan, P., Salam, K., Cunningham, K., Stadtmauer, E. A., Landsburg, D. J.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020
Abstract
PURPOSE Poor nutrition status in patients receiving high-dose chemotherapy and autologous stem cell transplant (ASCT) has been associated with inferior clinical outcomes. We aim to determine whether a malnutrition-driven nutritional support protocol can improve these outcomes. METHODS In this prospective cohort study, we assessed adults for malnutrition who were consecutively admitted for ASCT between October 2017 and March 2019 (n = 251), and provided enteral or parenteral nutrition (EN/PN) to patients who were malnourished early in the transplantation admission. We compared their clinical outcomes with those of a historical cohort admitted between May 2016 and October 2017 (n = 257) for whom nutrition assessment and initiation of EN/PN were not protocol-driven. RESULTS Patients receiving ASCT during the intervention period experienced decreased odds of prolonged hospital stay (p = 0.023), central line-associated bloodstream infection (p = 0.015), mucosal barrier injury (p = 0.037), and high weight loss (p = 0.002), in a multivariate analysis as compared with those receiving ASCT during the control period. Outcomes for ICU transfer, deconditioning on discharge, time to platelet engraftment, and unplanned 30-day hospital readmission did not differ significantly between groups. CONCLUSION A malnutrition-driven nutritional support protocol may improve outcomes for ASCT patients.
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Nutritional status as a predictor of adverse events and survival in pediatric autologous stem cell transplant
Kranjcec, I., Matijašic, N., Mašic, M., Švigir, A., Jakovljevic, G., Bolanca, A.
Pediatric hematology and oncology. 2020;:1-15
Abstract
Nutritional status is recognized as an independent and modifiable risk factor of outcome in stem cell transplant. Our research aim was to evaluate the impact of body mass index (BMI) and serum albumin on the prevalence of adverse events and survival in autologous transplant in children. A retrospective study was conducted of autologous transplants performed between 2006 and 2017 in the Children's Hospital Zagreb, Croatia. Nutritional status was assessed at the times of diagnosis, procedure, and discharge using BMI (underweight, normal, obese) and serum albumin (grades 1-4). Adverse events (fever, gastrointestinal toxicity, electrolyte disturbances, dysglycemia) and outcome (3-year, relapse, mortality) were documented. Seventy-seven children (54.5% males, mean age 7.9?years) underwent autologous transplant, mostly for neuroblastoma. In terms of BMI and albumin, which showed significant positive correlation at diagnosis (p?=?0.026) and transplant (p?=?0.016), most participants were well nourished. Average post-transplant weight loss was 4%. Major toxicities were severe mucositis (72.7%) and hypophosphatemia (31.2%). Relapse and mortality rates were 35.1% and 42.9%, respectively. Hypokalemia (p?=?0.041) and hypomagnesemia (p?=?0.044) were more prevalent in the underweight group, while obese children experienced significantly less severe mucositis (p?=?0.016) and hypophosphatemia (p?=?0.038). There was no significant difference regarding outcome among children of different nutritional status, although undernourished children tended to have lower relapse and mortality rates. In conclusion, underweight children are significantly more prone to severe electrolyte disorders and mucositis, and although statistical significance was not reached, are more likely to survive.