Оценка показателей питания перед трансплантацией в качестве прогнозов пневмонии и смертности у многих пациентов с миеломой после аутологической трансплантации стволовых клеток.

Introduction

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal plasma-cell proliferation, leading to bone marrow failure, bone lesions, and immune deficiency [ 1 ]. Among current treatments, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a cornerstone for eligible patients [ 2 ]. However, ASCT carries substantial infectious risk; pneumonia is a leading early post-transplant cause of morbidity and mortality [ 3 , 4 ].

The development of pneumonia after ASCT is closely linked to immune competence and nutritional reserves. Protein–calorie malnutrition compromises innate and adaptive immunity—reducing mucosal barrier integrity, phagocytic activity, and lymphocyte proliferation—and thereby increases susceptibility to bacterial, viral, and fungal pneumonia [ 5 ]. Conditioning regimens used in ASCT (high-dose chemotherapy, prolonged neutropenia, mucosal injury) also weaken host defenses. Accordingly, objective pre-transplant nutritional indices may help anticipate post-transplant infection risk.

Recent studies highlight the prognostic use of the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI) in MM patients undergoing ASCT. For example, in 59 MM patients, higher pre-transplant CONUT was independently associated with delayed neutrophil engraftment and increased oral mucositis [ 6 ]. Lower PNI correlates with higher mortality in community-acquired pneumonia [ 7 ], and GNRI is a potential prognostic marker in aspiration pneumonia among older adults [ 8 ]. Despite these data, the role of these indices in predicting post-transplant pneumonia and survival in ASCT for MM remains underexplored.

Prognostic systems such as the International Staging System (ISS) and the Revised ISS (R-ISS) estimate survival by incorporating albumin, β2-microglobulin, and cytogenetic findings [ 5 , 9 , 10 ]. Because malnutrition is linked to higher infection risk, poorer treatment tolerance, and worse survival [ 11 ], nutritional screening scores—especially CONUT—are increasingly used to assess nutritional status and infection risk [ 12 ]. In this context, we examined whether CONUT, GNRI, and PNI predict post-transplant pneumonia and 1-year mortality in MM patients undergoing ASCT.

Materials and methods

In this retrospective, single center study, a total of 286 patients who underwent autologous stem cell transplantation secondary to the diagnosis of multiple myeloma between 2013 and 2023 were analyzed. Clinical information of the patients, additional diseases, laboratory values, chest radiographs, thorax computed tomography results, pathology results, treatments given, prognosis and death information were recorded retrospectively.

Subjects

Autologous hematopoietic stem cells were collected from the patients themselves via peripheral blood apheresis at the Department of Hematology, University of Health Sciences, Ankara Oncology Training and Research Hospital (Ankara, Türkiye). No organs or tissues were obtained from prisoners or other vulnerable populations.

Pre-transplant assessment and laboratory variables

All laboratory variables used to compute GNRI, PNI, and CONUT were collected during the routine pre-transplant evaluation within 7–14 days before stem-cell infusion; peri-engraftment or post-conditioning results were not considered. Treatment and supportive-care protocols were standardized with no patient-level variability. Antibacterial, antiviral, antifungal, and Pneumocystis jirovecii prophylaxis, as well as G-CSF support, were applied uniformly.

Inclusion criteria for the study

The following were included in the study:

Patients over the age of 18 who were diagnosed with multiple myeloma and underwent autologous stem cell transplantation.

Exclusion criteria for the study

The following were excluded from the study:

Patients under 18 years of age. Patients with multiple malignancies. Patients whose researched criteria could not be accessed from the patient file or computer environment.

Measurements

Pre-transplant nutritional status was assessed using three objective indices: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) score. These indices were calculated using standard formulas derived from laboratory and clinical data obtained prior to transplantation.

CONUT is a nutritional grading method based on blood test results, including total albumin (Alb), lymphocyte count (T-Lymph) and cholesterol (T-Cho) [ 10 ]. Decreases in T-Lymph and T-Cho are assigned 0, 1, 2 and 3 points, and a decrease in Alb is assigned 0, 2, 4 and 6 points according to the severity. The overall score is divided into four categories: normal (CONUT: 0–1), mild malnutrition (CONUT: 2–4), moderate malnutrition (CONUT: 5–8) and severe malnutrition (CONUT: >9). Higher scores suggest lower nutritional status.

Serum albumin and lymphocyte percentage are checked to calculate the PNI. PNI was calculated as follows: (10 × serum albumin (g/dL)) + (0.005 × total lymphocyte value) and grouped as PNI value ≥ 50: normal, PNI value 45–50: mild malnutrition, PNI value 40–45: moderate to severe malnutrition, PNI value < 40: severe malnutrition [ 10 ].

The geriatric nutritional index (GNRI) was calculated from serum albumin and body mass index (BMI) using the following formula: GNRI = 14.89 × serum albumin (g/dL) + 41.7 × (current body weight/ideal body weight). Patients were divided into four groups according to the GNRI: G0 (no risk, >98), G1 (low risk, 92–98), G2 (intermediate risk, 82–91) and G3 (high risk, < 82) [ 11 ].

Patients were stratified into two groups based on the development of pneumonia within the first year post-transplantation and survival status at one year.

Statistical analysis

Data analysis was performed using IBM SPSS 15.0 (SPSS Inc., Chicago, IL, USA) package program. Descriptive statistics were shown as mean ± standard deviation for variables with normal distribution, median (min – max) for variables with abnormal distribution, and nominal variables as number of cases and (%). When the number of groups was two, the significance of the difference in terms of means between groups was investigated using the t test, and the significance of the difference in terms of median values ​​was investigated using the Mann Whitney test. When the number of groups was more than two, the significance of the difference in terms of means between groups was investigated using the ANOVA analysis of variance test, and the significance of the difference in terms of median values ​​was investigated using the Kruskal Wallis test. Nominal variables were evaluated using Pearson Chi-Square or Fisher’s Exact test. When investigating the relationship between continuous variables, the Spearman correlation test was used when the distribution was not normal, and the Pearson correlation test was used when it was normal. The results were considered statistically significant for p < 0.05.

Results

In our cohort, 35 patients (12.2%) developed pneumonia within one year after autologous stem cell transplantation. Among patients without pneumonia, 60.2% were male and 39.8% were female, whereas among those with pneumonia, 54.3% were male and 45.7% were female. No statistically significant difference was found between the two groups. The mean age at the time of transplantation was significantly higher in patients who developed pneumonia compared to those who did not (Table 1 ).

Table 1 Comparison of demographic and anthropometric characteristics between patients with and without pneumonia PNEUMONIA ABSENT PNEUMONIA TOTAL χ²/Z; p N/Mean ± SD %/Min–Max N/Mean ± SD %/Min–Max N/Mean ± SD %/Min–Max SEX Male 151 60.2% 19 54.3% 170 59.4% 0.440; 0.507 Female 100 39.8% 16 45.7% 116 40.6% AGE AT TRANSPLANT 55.6 ± 8.8 26.0–75.0 59.3 ± 6.3 46.0–75.0 56.1 ± 8.6 26.0–75.0 2.243; 0.025 HEIGHT (cm) 167.1 ± 9.4 145.0–191.0 165.2 ± 10.5 148.0–185.0 166.9 ± 9.5 145.0–191.0 1.046; 0.296 WEIGHT (kg) 78.3 ± 13.7 46.0–133.0 77.5 ± 12.3 51.0–100.0 78.2 ± 13.5 46.0–133.0 0.200; 0.842 BMI 27.6 ± 4.4 17.0–43.0 28.0 ± 3.9 20.0–36.0 27.6 ± 4.3 17.0–43.0 0.504; 0.614 BMI Body mass index

With regard to the distribution of pneumonia types, bacterial pneumonia was the most frequently observed, accounting for 48.6% of the cases ( n = 17). Fungal and bacterial co-infections were identified in 6 patients (17.1%), while viral pneumonia and viral–bacterial co-infections were noted in 3 (8.6%) and 2 (5.7%) patients, respectively.

The median GNRI was 86.14 ± 11.47 in patients without pneumonia and 87.98 ± 13.57 in those with pneumonia. The median PNI was 89.63 ± 7.22 in the non-pneumonia group and 88.67 ± 7.73 in the pneumonia group. The median Controlling Nutritional Status (CONUT) score was 2.39 ± 1.68 for patients without pneumonia and 2.20 ± 1.37 for those with pneumonia. None of these differences was statistically significant (Table 2 ).

Adjusted analyses: “GNRI, PNI, and CONUT were not associated with 1-year pneumonia in univariable analyses (all p > 0.10); accordingly, these indices were not advanced to multivariable modelling.

Table 2 Comparison of nutritional indices between patients with and without pneumonia Variable PNEUMONIA ABSENT Mean ± SD (Min–Max) PNEUMONIA Mean ± SD (Min–Max) TOTAL Mean ± SD (Min–Max) Z; p PNI 89.63 ± 7.22 (67.00–114.00) 88.67 ± 7.73 (74.50–104.80) 89.51 ± 7.27 (67.00–114.00) 0.684; 0.494 GNRI 86.14 ± 11.47 (71.10–146.35) 87.98 ± 13.57 (74.71–136.70) 86.37 ± 11.74 (71.10–146.35) 0.498; 0.618 CONUT 2.39 ± 1.68 (0.00–10.00) 2.20 ± 1.37 (0.00–5.00) 2.36 ± 1.64 (0.00–10.00) 0.117; 0.907 PNI Prognostic Nutritional Index, GNRI Geriatric Nutritional Risk Index, CONUT Controlling Nutritional Status

Furthermore, no statistically significant difference was observed in the distribution of patients with and without pneumonia across CONUT categories. The incidence of pneumonia did not differ significantly among CONUT-defined nutritional status groups (normal, mild, moderate, and severe malnutrition) (χ² = 1.562; p = 0.668) (Table 3 ).

Table 3 Distribution of CONUT score categories according to pneumonia status CONUT PNEUMONIA ABSENT PNEUMONIA TOTAL χ²; p n (%) n (%) n (%) NORMAL 69 (27.5%) 7 (20.0%) 76 (26.6%) 1.562; 0.668 MILD 162 (64.5%) 26 (74.3%) 188 (65.7%) MODERATE 17 (6.8%) 2 (5.7%) 19 (6.6%) SEVERE 3 (1.2%) 0 (0.0%) 3 (1.0%)

Within one year after autologous stem cell transplantation, 6.6% of the patients ( n = 19) had died, while 93.4% ( n = 267) were still alive. Among the deaths, 10.52% were attributed to pneumonia (Table 4 ).

Table 4 One-year mortality after ASCT and pneumonia-related mortality among deceased patients Variable Category N % 1-year mortality after ASCT Yes 19 6.6% No 267 93.4% Mortality due to pneumonia Yes 2 0.7% No 284 99.3% ASCT Autologous Stem Cell Transplantation

The relationship between nutritional indices and one-year survival was evaluated. The mean PNI value was 91.07 ± 7.83 in patients who died within one year after autologous stem cell transplantation, and 89.40 ± 7.24 in those who survived; however, this difference was not statistically significant (Z = 1.003; p = 0.316). Similarly, there was no significant difference in GNRI values between deceased (90.18 ± 18.27) and surviving patients (86.09 ± 11.13) (Z = 0.258; p = 0.797). CONUT scores were also comparable between patients who died (3.00 ± 2.00) and those who survived (2.32 ± 1.61) (Z = 1.763; p = 0.078) (Table 5 ).

Table 5 Comparison of nutritional indices by one-year post-transplant mortality status Variable Mortality (+) Mean ± SD (Min–Max) Mortality (–) Mean ± SD (Min–Max) Total Mean ± SD (Min–Max) Z; p PNI 91.07 ± 7.83 (74.50–105.00) 89.40 ± 7.24 (67.00–114.00) 89.51 ± 7.27 (67.00–114.00) 1.003; 0.316 GNRI 90.18 ± 18.27 (77.97–145.21) 86.09 ± 11.13 (71.10–146.35) 86.37 ± 11.74 (71.10–146.35) 0.258; 0.797 CONUT 3.00 ± 2.00 (0.00–9.00) 2.32 ± 1.61 (0.00–10.00) 2.36 ± 1.64 (0.00–10.00) 1.763; 0.078 PNI Prognostic Nutritional Index, GNRI Geriatric Nutritional Risk Index, CONUT Controlling Nutritional Status

Discussion

Patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) are at high risk for infectious complications owing to persistent neutropenia, disruption of mucosal barriers, and profound immunosuppression; pneumonia remains a leading cause of post-transplant morbidity and mortality [ 13 ]. Prior studies have linked pre-transplant malnutrition with adverse outcomes, including higher infection rates [ 4 ]. Because ASCT is a cornerstone therapy, infections—particularly pneumonia—continue to contribute substantially to post-transplant morbidity and mortality. Pre-transplant nutritional status may influence immunologic recovery and the risk of post-transplant infection. Accordingly, this study evaluated whether pre-transplant nutritional indices (PNI, GNRI, CONUT) predict post-transplant pneumonia in multiple myeloma.

Contrary to earlier reports, we observed no significant association between these indices and post-transplant outcomes. This discrepancy may reflect the profound immunosuppression induced by ASCT, which can override the prognostic value of baseline nutritional status [ 14 , 15 ]. For example, Brotelle et al. (2018) reported that pre-transplant hypoalbuminemia (albumin < 3.5 g/dL) independently conferred a 2.1-fold higher risk of bacterial pneumonia within 100 days post-ASCT [ 16 ] whereas in our cohort serum albumin did not differ significantly between patients with and without pneumonia.

GNRI, originally developed for older adults, has been applied in oncology and transplantation. A retrospective study in multiple myeloma reported baseline GNRI as an independent predictor of overall survival [ 17 ], suggesting nutritional status may inform survival; in contrast, we found no association between GNRI and one-year mortality, implying that its predictive value may differ for post-transplant complications such as pneumonia.

The CONUT score predicts prognosis across several cancers, but its relevance in multiple myeloma remains uncertain. While a study reported shorter median overall survival with high versus low CONUT scores in MM [ 17 ], we detected no statistically significant association between CONUT and one-year mortality.

Beyond infection and mortality, CONUT may indicate non-infectious complications. In a retrospective series of 59 MM patients undergoing ASCT, higher pre-transplant CONUT scores were independently associated with delayed neutrophil engraftment and a higher incidence of oral mucositis [ 6 ].

Matsukawa et al. evaluated GNRI, PNI, and CONUT in lymphoma and found low GNRI and high CONUT independently associated with poor outcomes, whereas PNI was not [ 18 ]. Similarly, in our study PNI was not associated with one-year mortality in MM after ASCT. Collectively, these data suggest that although nutritional indices may carry prognostic information in certain malignancies, their predictive power for post-transplant complications in MM appears limited, underscoring the need for more specific biomarkers.

A study of 74 MM patients identified PNI and CONUT as independent prognostic factors for elderly patients in both univariate and multivariate analyses [ 19 ]. In our cohort, however, neither PNI nor CONUT was an independent prognostic factor. Notably, mean transplant age was significantly higher among patients who developed pneumonia, consistent with age being a well-established risk factor for post-ASCT infections. This highlights age as a critical determinant for risk stratification and prevention; while nutritional indices may offer some insight, age appears to be a more reliable predictor of post-transplant outcomes in MM and supports age-adjusted post-ASCT care.

Overall, we found no significant relationship between pre-transplant nutritional indices (CONUT, PNI, GNRI) and post-transplant pneumonia or one-year mortality in MM patients undergoing ASCT. Several factors may account for the lack of association: the profound immunosuppressive effects of ASCT, dynamic laboratory changes during conditioning that may mask baseline signals, and other post-transplant determinants—such as immune reconstitution, graft-versus-host disease (GVHD), and prophylactic antibiotics—that may exert stronger influences on infection risk. Further research is warranted to delineate these interactions and to test combined models that better predict post-transplant outcomes.

Conclusion

To the best of our knowledge, this is the first study in the literature to comprehensively evaluate the predictive role of pre-transplant nutritional indices (PNI, GNRI, CONUT) for post-transplant pneumonia and 1-year mortality in multiple myeloma patients undergoing ASCT. Our findings suggest that these indices are not significantly associated with post-transplant infectious complications or survival outcomes. This lack of association may be attributed to the dynamic changes in laboratory parameters during conditioning regimens, which may reduce the reliability of baseline nutritional indices. These results highlight the need for more comprehensive, possibly functional or immune-based markers to improve risk stratification in this population.

Publisher’s Note

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Acknowledgements

The authors thank all the patients who participated in this study.

Authors’ contributions

D.Y, E.S.A. and O.D.B. conceptualized the present study and wrote the manuscript; D.K, T.D and O.D.B. collected, analyzed, and interpreted the data. O.D.B., E.S.A. and M.S.D. were responsible for drafting the manuscript; the manuscript was reviewed by all authors. All authors have read and agreed to the published version of the manuscript.

Funding

The present study was supported by the University of Health Sciences, Ankara Oncology Training and Research Hospital Ethics Committee (No: 2024-05/66).

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The writers are responsible for all aspects of the writing, including ensuring that any concerns about the work’s quality or credibility are thoroughly investigated and resolved. University of Health Sciences, Ankara Oncology Training and Research Hospital Ethics Committee approved this study (No: 2024-05/66). Written informed consent to participate was obtained from all participants prior to their inclusion in the study. This research was carried out in conjunction with the Helsinki Declaration (as revised in 2013).

Competing interests

The authors declare no competing interests.

Conflict of interest

There are no conflicts of interest.

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