Glucose transporter protein-1 GLUT-1 is expressed on some solid tumors and plasma cells.In this prospective study, we aimed the effect of serum GLUT-1 levels on leucocyte and thrombocyte engraftment in multiple myeloma (MM) patients during autologous stem cell transplantation. The fifty-one patients with MM included in the study. GLUT-1 levels at autologous stem cell harvest of patients with myeloma were determined by ELISA. The results analyzed with SPSS for Windows version 19.0 module. A total of 51 patients (25 males, 26 females, mean age 58 ± 9 years) were evaluated. 26 patients were in complete remission and 25 had a very good response. The mean GLUT-1 level was 7.3 ± 2.3 ng / mL (min. 3.48-max.13.87). CD 34 was 5.2 x 106 / kg. Mean neutrophil engraftment time was 15.6 ± 4.1 / day and mean platelet engraftment time was 18.6 ± 5.2 / day. There was a positive correlation between GLUT-1 level and neutrophil engraftment (p=0,004) and no correlation with thrombocyte engraftment. Pretransplant GLUT-1 levels are high in myeloma patients with partial remission and neutrophil engraftment is delayed at these patients whereas GLUT-1 level is low in myeloma patients with complete remission and posttransplantation neutrophil engraftment occurs early. And there was positive correlation with GLUT-1 levels in patients with partial remission according to complete remission (p<0,001). This study showed that GLUT-1 level is related to neutrophil engraftment and also a complete or partial remission rate.

Yavasoglu I, Akkaya E, Asici O, Firat O, Ergin F, et al. (2020) The Effect of GLUT-1 Levels on Leukocyte and Platelet Engraftment in Myeloma Patients at Autologous Stem Cell Transplantation, a Prospective Multicenter Study. J Hematol Transfus 7(1): 1084.

• Glucose transporter protein-1
• Engraftment
• Multiple myeloma
• Autologous stem cell transplantation

Glucose transporter (GLUT) members are membrane proteins that regulate the movement of glucose between extracellular and intracellular compartments. Glucose is required for the metabolism of mammalian cells [1]. GLUT-1 is found in erythrocytes, brain, kidney, colon, and placenta. It is an insulin independent glucose carrier and provides glucose transport to the brain [2]. In humans, it is encoded by the SLC2A1 gene [3]. There have been many previous studies on glucose transporter protein family members. In these studies, the relationship of GLUT 1 with breast, esophagus, etc. has been demonstrated in many cancer types [1,4].

In another study, therapies for GLUT-1, GLUT-4, GLUT-8, GLUT-11, which are members of the glucose transporter protein family, were investigated in MM [5]. MM is a malignancy of terminally differentiated plasma cells, and patients typically present with bone marrow infiltration of clonal plasma cells and monoclonal protein in the serum and/or urine [6].

With the introduction of immunomodulatory drugs (lenalidomide, pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), there have been significant changes in the induction therapy of patients. However, autologous stem cell-supported high-dose melphalan therapy is recommended as the standard treatment for patients under 65 years of age or older than 65 years of age with good performance [6,7]. Indicators related to myeloma engraftment insufficiency are limited although age and amount of CD 34 as an indicator help us to determine. Biomarkers as indicators are very limited [8].

In this prospective study, we aimed to investigate the relationship between GLUT-1 and neutrophil and platelet engraftment in patients with MM who underwent autologous stem cell transplantation.

Stem cell products of 51 patients from two transplant centers were investigated. Patients with diabetes mellitus and body mass index ≥ 30 were excluded from the study.

The conditioning regimen was 200 mg/m2 melphalan in all patients. The patients were treated with an average of 6 cycles of bortezomib, cyclophosphamide, and dexamethasone; and then their transplant was performed, they were all transplantnaive before. The response criteria were evaluated according to the International Myeloma Working Group [9]. GLUT-1 levels in stem cell products of 51 patients in two bone marrow transplant centers were determined by the ELISA test. Mean values were obtained in patients who had 2 products. Human GLUT-1 (Glucose Transporter-1), ELISA Kit (catalog: E-EL-H1822), was used for GLUT-1 test and the Sandwich-ELISA method was used as the method. The optical density (OD), of the DAR 800 Absorbance Microplate Reader was measured spectrophotometrically at a wavelength of 450 nm ± 2 nm.

All data were entered into SPSS version 19.0 for Windows and statistical analysis was performed. Descriptive data were displayed as mean ± standard deviation, median, minimum, maximum, and percentage values. Pearson correlation test was used to comparing variables of patients and determine the correlation between neutrophil-platelet engraftment, response and GLUT 1 level. Adnan Menderes University Medical Faculty Clinical Research Ethics Committee approval was obtained for the study (2018/1049)

A total of 51 patients (25 males, 26 females, mean age 58 ± 9) were evaluated. 26 patients were in complete remission and 25 had a very good response.

The mean GLUT-1 level was 7.3 ± 2.3 ng / mL (min. 3.48- max.13.87). CD 34 was 5.2 x 106 / kg. Mean neutrophil engraftment time was 15.6 ± 4.1 / day and mean platelet engraftment time was 18.6 ± 5.2 / day. Blood glucose was 105 ± 12 mg/dl. There was a positive correlation (p=0.004) between neutrophil engraftment and GLUT-1 level, although no correlation was detected with platelet engraftment. Correlation was in patients with a very good partial response (p<0,001). This was independent of the amount of CD 34. There were no patients with engraftment insufficiency.

We found a correlation between GLUT-1 and neutrophil engraftment. Engrafman is the placement of lymphohematopoietic cells in the recipient and the production of new blood cells after transplantation.

Ensuring engraftment is an indicator for the assessment of graft function in the early post-transplant period and is achieved by the following criteria: Neutrophil engraftment: The first day when the number of neutrophils is> 500 / mm³ for 3 consecutive days. Platelet engraftment: The first day of platelet counts> 20 000 / mm³ for 3 consecutive days and > 50 000mm³ for 7 days without platelet supplementation. Engraftment time is 7-21 days after transplantation. Engraftment delay and engraftment failure are the terms of when exceeding 21 days and 40 days after transplantation respectively [10].

Cancer cells are known to use glucose. The same data applies to the MM. (11,12) The human GLUT gene family (solute carrier family 2A [SLC2A]), consists of 14 members encoding integral membrane proteins capable of ATP-independence[5]. GLUT-1 and GLUT-4 are highly selective in glucose transport. GLUT 4 is located at the plasma membrane [11].

In contrast, GLUT-1 which is the more ubiquitously expressed isoform, is constitutively localized to the plasma membrane, facilitating basal glucose transport. GLUT-1 activity is critical for the normal function of several cell types including erythrocytes, neurons, and endothelial cells thereby accounting for the transport of glucose across the blood-brain barrier [11- 14]. GLUT-1 is high in many cancers, but it is also known to be expressed at erythrocytes, neurons, endothelium. This creates a restriction upon the target of treatment. Therefore, experimental studies that antagonize GLUT-4 MM have been performed [11,12].

In the MM cell line study by Shanmugam et al, GLUT-1 expression was shown in the plasma membrane [15]. In another study, it was shown that histone deacetylase inhibition affects GLUT proteins and decreases glucose uptake in OPM2 cells [16]. Again, there was a positive correlation between GLUT-1 overexpression and histone deacetylase inhibition in non-small cell lung cancer. GLUT-1 was specifically selected for its effect on glucose metabolism. For example, GLUT-8 is more important in fructose metabolism [17].

Based on our knowledge, our study was the first to reveal the relationship between GLUT-1 and MM in vivo. The elevation of GLUT-1 may have an effect on engraftment as it shows disease activity.

Both disease activity and engraftment determinants can be considered as biomarkers. In non-nucleated platelets, glucose metabolism contributes to thrombosis. GLUT-1 and GLUT-3 knockout experimental study showed decreased thrombotic effect [15].

In this study, it can be claimed that the GLUT effect in platelets is important, but studies are limited. In our study, we did not see any effect on platelet engraftment. Since the determination of erythrocyte engraftment was not standardized, we could not search it in our study.

The lack of numbers, a single induction regimen and not evaluating different types of GLUT were the limitations of the study.

In conclusion, GLUT-1 level is elevated in patients with very good responses to MM before transplantation and neutrophil engraftment is delayed in these patients. In contrast, complete response myeloma patients have low GLUT-1 levels and neutrophil engraftment becomes earlier.

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