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Comparison of single and double autologous stem cell transplantation in multiple myeloma patients

  • Umit Yavuz Malkan , Haluk Demiroglu , Yahya Buyukasik , Ayse Karatas , Elifcan Aladag and Hakan Goker EMAIL logo
Published/Copyright: January 27, 2021
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Open Medicine
From the journal Open Medicine Volume 16 Issue 1

Abstract

Background

Autologous stem cell transplantation (ASCT) is one of the standard treatments of choice for eligible multiple myeloma (MM) patients. Herein, we aimed to analyze MM patients at our center and compare the clinical outcomes of single and double ASCT patients.

Materials and methods

Patients who were diagnosed as having MM and had undergone single or double ASCT in our clinic between the years 2003 and 2020 were retrospectively examined.

Results

In this study, the median time of second ASCT is approximately 3.6 years from the first ASCT. Overall survival (OS) duration of the single and double transplanted groups was 4,011 ± 266 vs 3,526 ± 326 days, respectively (p: 0.33). Progression-free survival (PFS) duration of the single and double transplanted groups was 2,344 ± 228 vs 685 ± 120 days, respectively (p: 0.22). Disease assessment after ASCT stable or progressive disease, partial remission, and very good partial or complete remission (CR) in single and double ASCT groups was 62/44/105 and 8/4/5, respectively (p: 0.22).

Conclusion

The present study points out that the second ASCT treatment option for MM patients may not be effective as suggested, especially in the era of novel MM drugs, since our results come from the past data that novel drugs were not exist. In conclusion, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates, and the novel anti-myeloma drugs might decrease the need for a second transplant.

Keywords: second autologous stem cell transplantation; multiple myeloma

1 Introduction

Multiple myeloma (MM) is the second most common hematological malignancy, and autologous stem cell transplantation (ASCT) is the standard treatment of choice for eligible MM patients [1]. High-dose chemotherapy and ASCT have greatly changed the clinical course of MM [2,3]. Although high-dose therapy with ASCT is not curative, progression-free survival (PFS) and overall survival (OS) are prolonged compared to the standard-dose myeloma treatments alone. The median OS of MM patients is now ranging between 6 and 10 years with the help of novel agents [4].

Treatment choices for relapsed MM after an ASCT are a second ASCT, nonmyeloablative allogeneic hematopoietic cell transplant (HCT) as part of a clinical trial, and treatment with salvage chemotherapy. ASCT remains to be one of the main treatment options for MM. Many studies tried to find the best way of this procedure to maximize the benefit for the patients. There is a need for further studies regarding ASCT in MM patients. Herein, we aimed to analyze MM patients at our center and compare the clinical outcomes of single and double ASCT patients.

2 Patients and method

2.1 Study design and data collection

This study has been designed retrospectively. The patients who were diagnosed as having MM and had undergone ASCT in our hematology clinic between the years 2003 and 2020 were examined. Demographic data, transplantation data, and posttransplantation updates of the patients were obtained from the hospital database. Patients’ age, gender, dates of diagnosis–relapse–transplantation–exitus, M-protein types and levels, International Staging System (ISS) stage, Eastern Cooperative Oncology Group (ECOG) score, hemoglobin, sedimentation, calcium, uric acid, creatinine, albumin, β2-microglobulin, vitamin D levels, cytogenetic analyses, treatments, conditioning regimens, and disease status before ASCT and after treatment were noted.

All of the ethical considerations had been strictly followed by the Declaration of Helsinki 1964. As a standard care/action of the hospitals of the Hacettepe Medical School, it has been recognized from the patient records that all of the studied patients had given informed consent at the time of hospitalization and before the administration of chemotherapy and other relevant diagnostic/therapeutic standard of care.

2.2 Patients and disease characteristics

The patients who were aged ≥18 years, at the time of MM diagnosis, and underwent ASCT procedure were included in this study. Some of the patients had only one ASCT, whereas some other group of patients had double ASCT. The second ASCT was performed in eligible patients who had elevated serum or urine M-protein levels, elevated bone marrow atypical plasma cell ratio, the occurrence of new lytic bone lesions or plasmacytoma, and any other evidence of clinical progression or relapse. There were 17 patients in the double ASCT group and 211 patients in the single ASCT group. All of the patients who were double transplanted had relapsed before their second ASCT. All of the single or double ASCT patients were in ECOG 1 performance status before the procedure. There was no significant comorbidity from concomitant severe diseases in any patient. All patients underwent ASCT after receiving four to eight courses of induction chemotherapy. They received bortezomib/cyclophosphamide/dexamethasone, bortezomib/dexamethasone, vincristine, doxorubicin, and dexamethasone, and bortezomib/thalidomide/dexamethasone as induction therapy. Patients who underwent double ASCT also received proteasome inhibitors and immunomodulatory agents before the second ASCT. The preparative regimen for single or double ASCT patients was melphalan 200 mg/m2. The patients did not receive total body irradiation. There was no difference of preparation between the two groups. We did not give maintenance treatment after the transplantation procedure. No patient was given interferon. Responses were determined according to the International Myeloma Working Group response criteria. Cytogenetic data were available only for a minority of patients and were not considered in this analysis.

2.3 Statistical analysis

The primary endpoint of the study is the OS duration. OS was calculated from the start date of the first therapy to death for any cause. PFS duration was calculated from the transplantation date (second transplantation date was taken for double transplanted patients) to relapse or progression date. The patients who did not die and those who did not relapse or die in remission at the last follow-up were censored at this time for OS and PFS computations, respectively. Transplantation-related mortality (TRM) included any death occurring within 90 days and attributable to high-dose therapy.

The SPSS software version 25 (SPSS Inc., Chicago, IL, USA) was used for analyses. Continuous and categorical data were compared using the t-test and chi-square test, respectively. The variables were investigated using analytical methods (the Kolmogorov–Smirnov/Shapiro–Wilk’s tests) to determine whether they are normally distributed or not. One-way analysis of variance was used to compare parameters using means and standard deviations for normally distributed variables. The Kruskal–Wallis test was used to compare parameters for non-normally distributed variables. Survival analyses were done using the Kaplan–Meier test. Multivariate analysis of predictors of survival was performed using the Cox regression test. Parameters with p values ≤0.15 in univariate tests were included in the multivariate analysis. The p values <0.05 were considered statistically significant.

3 Results

The baseline characteristics of the patients in the two groups are similar except gender and serum β2-microglobulin level (Table 1). Disease assessment after ASCT stable or progressive disease, partial remission (PR), and very good partial or complete remission (CR) in single and double ASCT groups was 62/44/105 and 8/4/5, respectively (p: 0.22). Among the double transplanted patients, five were transplanted within one year after the first transplant. The median duration between the first and second transplants was 1,322 (414–4,242) days in double ASCT patients. OS duration of the single and double transplanted groups was 4,011 ± 266 vs 3,526 ± 326 days, respectively (p: 0.33). There was no statistically significant difference between the OS duration of single and double ASCT patients (Figure 1). Only four patients had died from TRM in the single ASCT group, whereas no patients had died from TRM in the double ASCT group. The PFS duration of the single and double transplanted groups was 2,344 ± 228 vs 685 ± 120 days, respectively (p: 0.22). There was no statistically significant difference between the PFS duration of single and double ASCT patients (Figure 2). The factors that are related to the OS of double ASCT patients were analyzed. In univariate analysis, serum calcium levels and IgA-type M-protein were found to be related to the OS of double ASCT patients. The mean OS time was 3,660 days [95% confidence interval; 2,997–4,323 days] in patients who had calcium levels <10 mg/dL, whereas it was 2,454 days [95% confidence interval; 2,152–2,786 days] in patients who had calcium levels of 10 g/dL or above (p: 0.09). The mean OS time was 1,856 days [95% confidence interval; 1,741–1,985 days] in patients who had IgA-type M-protein, whereas it was 2,729 days [95% confidence interval; 1,031–4,427 days] in patients who had IgG-type M-protein and 2,047 days [95% confidence interval; 1,473–2,621 days] in patients who had kappa/lambda light-chain M-protein (p: 0.06). However, this relationship was not found in multivariate analysis (p > 0.9 for serum calcium and IgA-type M-protein). In univariate analysis, serum uric acid levels and β2-microglobulin were found to be related to the PFS of double ASCT patients. The mean PFS time was 576 days [95% confidence interval; 34–1,118 days] in patients who had serum uric acid level <5 mg/dL, whereas it was 186 days [95% confidence interval; 35–371 days] in patients who had serum uric acid levels of 5 mg/dL or above (p: 0.04). The mean PFS time was 844 days [95% confidence interval; 533–1,156 days] in patients who had β2-microglobulin <3 mg/L, whereas it was 325 days [95% confidence interval; 148–501 days] in patients who had β2-microglobulin of 3 mg/dL or above (p: 0.07). However, this relationship was not found in multivariate analysis (p > 0.35 for uric acid and β2-microglobulin).

Table 1

The baseline characteristics of the patients in the single and double ASCT groups

Parameters Single ASCT (N:211) Double ASCT (N:17) p value
Age (years) 55 (34–76) 54 (42–65) 0.56
Gender (F/M) 91/120 3/14 0.04
M-protein type (IgA/IgG/light-chain disease/IgD/IgE/nonsecretory) 39/114/50/4/1/3 3/9/5/0/0/0 0.97
Disease assessment before ASCT (SD or PD/PR/VGPR or CR) 20/122/69 4/7/6 0.16
Disease last assessment (SD or PD/PR/VGPR or CR) 62/44/105 8/4/5 0.22
Serum M-protein (mg/dL) 3,140 (26–72,700) 3,940 (1,000–17,100) 0.97
Exitus/alive 51/160 4/13 0.95
ISS (I/II/III) 80/52/47 11/6/0 0.05
Bone lesion at diagnosis (N/Y) 69/142 3/14 0.19
β2-microglobulin (mg/L) 4.91 2.88 <0.001
Serum vitamin D (ng/mL) 18.8 (5.0–78.4) 19.8 (9.1–39.0) 0.87
Serum hemoglobin (g/dL) 11.2 (3.0–16.6) 11.3 (6.1–14.2) 0.99
Sedimentation (mm/h) 55 (2–144) 53.5 (2–147) 0.88
Serum calcium (mg/dL) 9.5 (6.8–18.4) 9.6 (5.8–13.6) 0.82
Serum uric acid (mg/dL) 5.9 (2.3–17.2) 5.0 (2.1–14.6) 0.19
Serum creatinine (mg/dL) 0.98 (0.40–13.81) 0.92 (0.72–2.64) 0.31
Serum albumin (mg/dL) 3.9 (2.3–5.0) 3.9 (2.3–4.8) 0.78

The significance of bold value is p < 0.05.

Y: Yes; N: No; SD: stable disease; PD: progressive disease; PR: partial remission; VGPR: very good partial remission; CR: complete remission.

Figure 1 There is no statistically significant overall survival duration difference between the single and double transplanted groups (4,011 ± 266 vs 3,526 ± 326 days, respectively, p: 0.33).
Figure 1

There is no statistically significant overall survival duration difference between the single and double transplanted groups (4,011 ± 266 vs 3,526 ± 326 days, respectively, p: 0.33).

Figure 2 There is no statistically significant progression-free survival duration difference between the single and double transplanted groups (2,344 ± 228 vs 685 ± 120 days, respectively, p: 0.22).
Figure 2

There is no statistically significant progression-free survival duration difference between the single and double transplanted groups (2,344 ± 228 vs 685 ± 120 days, respectively, p: 0.22).

4 Discussion

Treatment options for relapsed MM after an ASCT include a second ASCT, nonmyeloablative allogeneic HCT as part of a clinical trial, and treatment with salvage chemotherapy. ASCT remains to be one of the main treatment options for MM. Many studies tried to find the best way of this procedure to maximize the benefit for the patients. In general, a second ASCT is not recommended for cases that relapse within 12–18 months (if no maintenance therapy was given) of the first, since the PFS following the second ASCT will most likely be even shorter than the benefit seen with the first transplant [5]. Similarly in the present study, the median duration between the first and second ASCT was 1,322 days in double ASCT patients. In the cases that were given lenalidomide maintenance, a second ASCT is not considered if the relapse occurs within 36 months of the first ASCT. These patients are best treated with active agents that they have not received before or have had good responses to in the past as well as clinical trials investigating novel therapies. Contrary to this literature knowledge, we did not give any maintenance treatment for our MM patients who were undergone ASCT.

For patients achieving complete or near-complete response with the first ASCT, it was suggested to reserve the cryopreserved stem cells for a second ASCT to be used at the time of relapse [6,7]. On the other hand, in our present study, we have performed ASCT to patients with stable or progressive disease, partial remission, and very good partial remission or CR.

In the literature, two randomized trials compared second ASCT vs treatment with chemotherapy alone in patients with late relapse after a first ASCT. After a median follow-up of 31 months, second ASCT resulted in a longer median time to progression (19 vs 11 months; hazard ratio 0.36) [8]. In another study, after a median follow-up of 37 months, PFS (median 21 vs 19 months) and OS (three-year OS, 72% each) were similar in the two treatment arms on intention-to-treat analysis [9]. In our present study, we did not find any benefit with double ASCT in MM patients in terms of PFS and OS or CR rates.

In another study, a single institution retrospectively analyzed 200 patients with MM who received a second ASCT after recurrence following initial therapy that included an ASCT (37% tandem) [10]. A partial or greater response was seen in 80% by Day 100. At a median follow-up of 57 months, the median PFS and OS times following the second ASCT were 15 and 42 months, respectively. Results were worse among cases that had an initial remission duration of <18 months and those who had less than a PR to re-induction therapy prior to ASCT.

The role of tandem ASCT as an upfront treatment in cases with MM and its advantage over single ASCT are a matter of debate [11,12]. The development of extramedullary plasmacytomas during proteasome inhibitor treatment is also associated with an unfavorable prognosis in MM [13], and tandem ASCT could be considered in such cases. Typically, in tandem autologous transplant, two autologous transplants are performed within a period of no more than 6 months. However, it was stated in the literature that if a second ASCT is contemplated, it is preferable to perform the procedure within 6–12 months of the first transplant [14]. In our study, the median time of second ASCT is approximately 3.6 years from the first ASCT indicating that our patients did not undergo tandem ASCT. In our study, the second ASCT was performed to patients who had elevations in serum or urine M-protein levels, elevation in bone marrow atypical plasma cells ratio, the occurrence of new lytic bone lesions or plasmacytoma, and any other evidence of clinical progression or relapse. Eventually, all of our patients had relapsed after the first ASCT. The relapse in our study represents the relapse of the disease detected by laboratory tests, imaging techniques, or bone marrow investigation.

Many studies have investigated the efficacy of ASCT in the relapse MM, and they have showed that ASCT for a second or even a third time is an efficient treatment choice for MM patients who had previously undergone ASCT procedure [15,16,17]. In a previous study, it was stated that one-year nonrelapse mortality of 2% and three-year OS of 46% were found in patients treated with a second ASCT. These data favor the second ASCT that is a safe and efficient treatment option for relapse MM [18]. Moreover, patients with a long relapse-free interval from previous ASCT (>36 months) had longer PFS (p: 0.045) and OS (p: 0.019) in comparison with patients with a shorter relapse-free interval (<36 months) [18]. In another study, second ASCT was found to be safe (TRM, 6%) and effective (CR rate: 44%; median PFS: 14 months) case that had been treated with maintenance agents after upfront ASCT [19]. In another study, 93% of the cases reached response after second ASCT, with 46% of them having a very good partial remission. The median PFS after second ASCT was 18 months, and no patients lost due to treatment [20]. The prospective studies are valuable for relapse MM patients investing the role of ASCT. In a study in which the patients were given a bortezomib-based re-induction after relapse MM, they were randomized to second ASCT or cyclophosphamide. Second ASCT prolonged the median PFS (19 vs 11 months; p < 0.001), but not OS (65 vs 56 months; p: 0.19), when compared to cyclophosphamide [21]. The comparison of the conventional treatment with second ASCT in relapse MM is another important question. In a study that compares second ASCT with conventional chemotherapy in cases that previously undergone ASCT, second ASCT prolonged the median OS (56 vs 25 months; p: 0.04) when compared to conventional chemotherapy [22]. All these data favor that the second ASCT is a safe and efficient treatment choice for the relapsed and refractory MM cases. On the other hand, the novel anti-myeloma drugs might change the need for a second transplant since these agents are much more effective than previous conventional myeloma therapies. The selected patients who had prolonged remission from first ASCT and adequate performance status might have the most beneficial group for second ASCT in the novel myeloma drug era.

The main limitations of our study are the relatively low number of patients and its retrospective design. On the other hand, our study included the analysis of previously treated patients between years 2003 and 2020; therefore, the treatment strategies for MM were changed during these 17 years. In the past years, novel MM treatment agents such as carfilzomib, ixazomib, daratumumab, lenalidomide, and other drugs were not available, and the treatment algorithm for MM was poorer and simpler than the present one.

5 Conclusion

To summarize, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates. There may be several reasons that lead to these results. First, the ISS stage of our double ASCT group was lower than that of single ASCT group. Second, the double ASCT patient group had a relatively low number of patients. The present study points out that the second ASCT treatment option in MM may not be effective as suggested, especially in the era of novel MM drugs, since our results come from the past data that novel drugs were not exist. The generalizability of the data presented here should be confirmed by future prospective studies. In conclusion, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates, and the novel anti-myeloma drugs might decrease the need for a second transplant.

tel: +90-312-3051543

  1. Author contributions: U. Y. M. and H. G. designed the study and wrote the manuscript; U. Y. M. and H. D. performed the analysis of the data; and Y. B., A. A. K., and E. A. participated in the care of included patients and collection of the data. All the authors reviewed and edited the final draft of the manuscript and approved its submission.

  2. Conflict of interest: The authors declare no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Received: 2020-07-24
Revised: 2020-10-31
Accepted: 2020-11-03
Published Online: 2021-01-27

© 2021 Umit Yavuz Malkan et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
  191. COVID-19, WHO guidelines, pedagogy, and respite
  192. Inflammatory factors in alveolar lavage fluid from severe COVID-19 pneumonia: PCT and IL-6 in epithelial lining fluid
  193. COVID-19: Lessons from Norway tragedy must be considered in vaccine rollout planning in least developed/developing countries
  194. What is the role of plasma cell in the lamina propria of terminal ileum in Good’s syndrome patient?
  195. Case Report
  196. Rivaroxaban triggered multifocal intratumoral hemorrhage of the cabozantinib-treated diffuse brain metastases: A case report and review of literature
  197. CTU findings of duplex kidney in kidney: A rare duplicated renal malformation
  198. Synchronous primary malignancy of colon cancer and mantle cell lymphoma: A case report
  199. Sonazoid-enhanced ultrasonography and pathologic characters of CD68 positive cell in primary hepatic perivascular epithelioid cell tumors: A case report and literature review
  200. Persistent SARS-CoV-2-positive over 4 months in a COVID-19 patient with CHB
  201. Pulmonary parenchymal involvement caused by Tropheryma whipplei
  202. Mediastinal mixed germ cell tumor: A case report and literature review
  203. Ovarian female adnexal tumor of probable Wolffian origin – Case report
  204. Rare paratesticular aggressive angiomyxoma mimicking an epididymal tumor in an 82-year-old man: Case report
  205. Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review
  206. Primary orbital ganglioneuroblastoma: A case report
  207. Primary aortic intimal sarcoma masquerading as intramural hematoma
  208. Sustained false-positive results for hepatitis A virus immunoglobulin M: A case report and literature review
  209. Peritoneal loose body presenting as a hepatic mass: A case report and review of the literature
  210. Chondroblastoma of mandibular condyle: Case report and literature review
  211. Trauma-induced complete pacemaker lead fracture 8 months prior to hospitalization: A case report
  212. Primary intradural extramedullary extraosseous Ewing’s sarcoma/peripheral primitive neuroectodermal tumor (PIEES/PNET) of the thoracolumbar spine: A case report and literature review
  213. Computer-assisted preoperative planning of reduction of and osteosynthesis of scapular fracture: A case report
  214. High quality of 58-month life in lung cancer patient with brain metastases sequentially treated with gefitinib and osimertinib
  215. Rapid response of locally advanced oral squamous cell carcinoma to apatinib: A case report
  216. Retrieval of intrarenal coiled and ruptured guidewire by retrograde intrarenal surgery: A case report and literature review
  217. Usage of intermingled skin allografts and autografts in a senior patient with major burn injury
  218. Retraction
  219. Retraction on “Dihydromyricetin attenuates inflammation through TLR4/NF-kappa B pathway”
  220. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part I
  221. An artificial immune system with bootstrap sampling for the diagnosis of recurrent endometrial cancers
  222. Breast cancer recurrence prediction with ensemble methods and cost-sensitive learning
https://doi.org/10.1515/med-2021-0216
Keywords for this article
second autologous stem cell transplantation; multiple myeloma
Creative Commons
BY 4.0

Articles in the same Issue

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  2. Identification of ZG16B as a prognostic biomarker in breast cancer
  3. Behçet’s disease with latent Mycobacterium tuberculosis infection
  4. Erratum
  5. Erratum to “Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome”
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  8. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  9. Additional baricitinib loading dose improves clinical outcome in COVID-19
  10. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats
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  18. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis
  19. LncRNA XIST regulates atherosclerosis progression in ox-LDL-induced HUVECs
  20. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates
  21. Rapid Communication
  22. COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution
  23. Case Report
  24. Rare squamous cell carcinoma of the kidney with concurrent xanthogranulomatous pyelonephritis: A case report and review of the literature
  25. An infertile female delivered a baby after removal of primary renal carcinoid tumor
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  27. Hypertension, BMI, and cardiovascular and cerebrovascular diseases
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  34. Research Articles
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  37. Comparison of single and double autologous stem cell transplantation in multiple myeloma patients
  38. The influence of smoking in minimally invasive spinal fusion surgery
  39. Impact of body mass index on left atrial dimension in HOCM patients
  40. Expression and clinical significance of CMTM1 in hepatocellular carcinoma
  41. miR-142-5p promotes cervical cancer progression by targeting LMX1A through Wnt/β-catenin pathway
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  43. Early MRI imaging and follow-up study in cerebral amyloid angiopathy
  44. Intestinal fatty acid-binding protein as a biomarker for the diagnosis of strangulated intestinal obstruction: A meta-analysis
  45. miR-128-3p inhibits apoptosis and inflammation in LPS-induced sepsis by targeting TGFBR2
  46. Dynamic perfusion CT – A promising tool to diagnose pancreatic ductal adenocarcinoma
  47. Biomechanical evaluation of self-cinching stitch techniques in rotator cuff repair: The single-loop and double-loop knot stitches
  48. Review Articles
  49. The ambiguous role of mannose-binding lectin (MBL) in human immunity
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  51. Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report
  52. Fertility problems in males carrying an inversion of chromosome 10
  53. Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature
  54. Metastatic renal Ewing’s sarcoma in adult woman: Case report and review of the literature
  55. Burkitt-like lymphoma with 11q aberration in a patient with AIDS and a patient without AIDS: Two cases reports and literature review
  56. Skull hemophilia pseudotumor: A case report
  57. Judicious use of low-dosage corticosteroids for non-severe COVID-19: A case report
  58. Adult-onset citrullinaemia type II with liver cirrhosis: A rare cause of hyperammonaemia
  59. Clinicopathologic features of Good’s syndrome: Two cases and literature review
  60. Fatal immune-related hepatitis with intrahepatic cholestasis and pneumonia associated with camrelizumab: A case report and literature review
  61. Research Articles
  62. Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study
  63. Significance of nucleic acid positive anal swab in COVID-19 patients
  64. circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p
  65. Ratios between circulating myeloid cells and lymphocytes are associated with mortality in severe COVID-19 patients
  66. Risk factors of left atrial appendage thrombus in patients with non-valvular atrial fibrillation
  67. Clinical features of hypertensive patients with COVID-19 compared with a normotensive group: Single-center experience in China
  68. Surgical myocardial revascularization outcomes in Kawasaki disease: systematic review and meta-analysis
  69. Decreased chromobox homologue 7 expression is associated with epithelial–mesenchymal transition and poor prognosis in cervical cancer
  70. FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer
  71. Platelet-rich fibrin: Basics of biological actions and protocol modifications
  72. Accurate diagnosis of prostate cancer using logistic regression
  73. miR-377 inhibition enhances the survival of trophoblast cells via upregulation of FNDC5 in gestational diabetes mellitus
  74. Prognostic significance of TRIM28 expression in patients with breast carcinoma
  75. Integrative bioinformatics analysis of KPNA2 in six major human cancers
  76. Exosomal-mediated transfer of OIP5-AS1 enhanced cell chemoresistance to trastuzumab in breast cancer via up-regulating HMGB3 by sponging miR-381-3p
  77. A four-lncRNA signature for predicting prognosis of recurrence patients with gastric cancer
  78. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression
  79. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway
  80. Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway
  81. COVID-19 severity in relation to sociodemographics and vitamin D use
  82. Clinical analysis of 11 cases of nocardiosis
  83. Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
  84. Four long noncoding RNAs act as biomarkers in lung adenocarcinoma
  85. Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens
  86. Relation between IL-8 level and obstructive sleep apnea syndrome
  87. circAGFG1 sponges miR-28-5p to promote non-small-cell lung cancer progression through modulating HIF-1α level
  88. Nomogram prediction model for renal anaemia in IgA nephropathy patients
  89. Effect of antibiotic use on the efficacy of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer: A meta-analysis
  90. NDRG2 inhibition facilitates angiogenesis of hepatocellular carcinoma
  91. A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1
  92. Clinical and prognostic features of MMP-2 and VEGF in AEG patients
  93. The value of miR-510 in the prognosis and development of colon cancer
  94. Functional implications of PABPC1 in the development of ovarian cancer
  95. Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy
  96. Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis
  97. Prediction of improvement after anterior cruciate ligament reconstruction
  98. Effluent Osteopontin levels reflect the peritoneal solute transport rate
  99. circ_0038467 promotes PM2.5-induced bronchial epithelial cell dysfunction
  100. Significance of miR-141 and miR-340 in cervical squamous cell carcinoma
  101. Association between hair cortisol concentration and metabolic syndrome
  102. Microvessel density as a prognostic indicator of prostate cancer: A systematic review and meta-analysis
  103. Characteristics of BCR–ABL gene variants in patients of chronic myeloid leukemia
  104. Knee alterations in rheumatoid arthritis: Comparison of US and MRI
  105. Long non-coding RNA TUG1 aggravates cerebral ischemia and reperfusion injury by sponging miR-493-3p/miR-410-3p
  106. lncRNA MALAT1 regulated ATAD2 to facilitate retinoblastoma progression via miR-655-3p
  107. Development and validation of a nomogram for predicting severity in patients with hemorrhagic fever with renal syndrome: A retrospective study
  108. Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events
  109. Laparoscopic versus open major liver resection for hepatocellular carcinoma: A case-matched analysis of short- and long-term outcomes
  110. Travelers’ vaccines and their adverse events in Nara, Japan
  111. Association between Tfh and PGA in children with Henoch–Schönlein purpura
  112. Can exchange transfusion be replaced by double-LED phototherapy?
  113. circ_0005962 functions as an oncogene to aggravate NSCLC progression
  114. Circular RNA VANGL1 knockdown suppressed viability, promoted apoptosis, and increased doxorubicin sensitivity through targeting miR-145-5p to regulate SOX4 in bladder cancer cells
  115. Serum intact fibroblast growth factor 23 in healthy paediatric population
  116. Algorithm of rational approach to reconstruction in Fournier’s disease
  117. A meta-analysis of exosome in the treatment of spinal cord injury
  118. Src-1 and SP2 promote the proliferation and epithelial–mesenchymal transition of nasopharyngeal carcinoma
  119. Dexmedetomidine may decrease the bupivacaine toxicity to heart
  120. Hypoxia stimulates the migration and invasion of osteosarcoma via up-regulating the NUSAP1 expression
  121. Long noncoding RNA XIST knockdown relieves the injury of microglia cells after spinal cord injury by sponging miR-219-5p
  122. External fixation via the anterior inferior iliac spine for proximal femoral fractures in young patients
  123. miR-128-3p reduced acute lung injury induced by sepsis via targeting PEL12
  124. HAGLR promotes neuron differentiation through the miR-130a-3p-MeCP2 axis
  125. Phosphoglycerate mutase 2 is elevated in serum of patients with heart failure and correlates with the disease severity and patient’s prognosis
  126. Cell population data in identifying active tuberculosis and community-acquired pneumonia
  127. Prognostic value of microRNA-4521 in non-small cell lung cancer and its regulatory effect on tumor progression
  128. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis
  129. 3D-printed porous scaffold promotes osteogenic differentiation of hADMSCs
  130. Association of gene polymorphisms with women urinary incontinence
  131. Influence of COVID-19 pandemic on stress levels of urologic patients
  132. miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer
  133. miR-519d downregulates LEP expression to inhibit preeclampsia development
  134. Comparison of single- and triple-port VATS for lung cancer: A meta-analysis
  135. Fluorescent light energy modulates healing in skin grafted mouse model
  136. Silencing CDK6-AS1 inhibits LPS-induced inflammatory damage in HK-2 cells
  137. Predictive effect of DCE-MRI and DWI in brain metastases from NSCLC
  138. Severe postoperative hyperbilirubinemia in congenital heart disease
  139. Baicalin improves podocyte injury in rats with diabetic nephropathy by inhibiting PI3K/Akt/mTOR signaling pathway
  140. Clinical factors predicting ureteral stent failure in patients with external ureteral compression
  141. Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway
  142. Triple-Endobutton and clavicular hook: A propensity score matching analysis
  143. Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis
  144. Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG
  145. miR-513b-5p inhibits the proliferation and promotes apoptosis of retinoblastoma cells by targeting TRIB1
  146. Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p
  147. The diagnostic and prognostic value of miR-92a in gastric cancer: A systematic review and meta-analysis
  148. Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study
  149. No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
  150. circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p
  151. Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions
  152. Educational program for orthopedic surgeons’ influences for osteoporosis
  153. Expression and function analysis of CRABP2 and FABP5, and their ratio in esophageal squamous cell carcinoma
  154. GJA1 promotes hepatocellular carcinoma progression by mediating TGF-β-induced activation and the epithelial–mesenchymal transition of hepatic stellate cells
  155. lncRNA-ZFAS1 promotes the progression of endometrial carcinoma by targeting miR-34b to regulate VEGFA expression
  156. Anticoagulation is the answer in treating noncritical COVID-19 patients
  157. Effect of late-onset hemorrhagic cystitis on PFS after haplo-PBSCT
  158. Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma
  159. VSTM1 regulates monocyte/macrophage function via the NF-κB signaling pathway
  160. Comparison of vaginal birth outcomes in midwifery-led versus physician-led setting: A propensity score-matched analysis
  161. Treatment of osteoporosis with teriparatide: The Slovenian experience
  162. New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB
  163. Superenhancer–transcription factor regulatory network in malignant tumors
  164. β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with type 2 diabetes: A cross-sectional study
  165. Clinical features of atypical tuberculosis mimicking bacterial pneumonia
  166. Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model
  167. Effect of electromagnetic field on abortion: A systematic review and meta-analysis
  168. miR-150-5p affects AS plaque with ASMC proliferation and migration by STAT1
  169. MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p
  170. Effects of remifentanil and propofol on distant organ lung injury in an ischemia–reperfusion model
  171. miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway
  172. Identification of LIG1 and LIG3 as prognostic biomarkers in breast cancer
  173. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy
  174. Dissecting role of founder mutation p.V727M in GNE in Indian HIBM cohort
  175. circATP2A2 promotes osteosarcoma progression by upregulating MYH9
  176. Prognostic role of oxytocin receptor in colon adenocarcinoma
  177. Review Articles
  178. The function of non-coding RNAs in idiopathic pulmonary fibrosis
  179. Efficacy and safety of therapeutic plasma exchange in stiff person syndrome
  180. Role of cesarean section in the development of neonatal gut microbiota: A systematic review
  181. Small cell lung cancer transformation during antitumor therapies: A systematic review
  182. Research progress of gut microbiota and frailty syndrome
  183. Recommendations for outpatient activity in COVID-19 pandemic
  184. Rapid Communication
  185. Disparity in clinical characteristics between 2019 novel coronavirus pneumonia and leptospirosis
  186. Use of microspheres in embolization for unruptured renal angiomyolipomas
  187. COVID-19 cases with delayed absorption of lung lesion
  188. A triple combination of treatments on moderate COVID-19
  189. Social networks and eating disorders during the Covid-19 pandemic
  190. Letter
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