scholarly journals Methotrexate-Loaded Biodegradable Polymeric Micelles for Lymphoma Therapy in Mouse Model

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4181-4181
Author(s):  
Mengyao Wang ◽  
Ying Qu ◽  
Zhiyong Qian ◽  
Ting Niu

Abstract Purpose: Methotrexate (MTX), a folate antimetabolite, competitively inhibits dihydrofolate reductase, the intracellular enzyme responsible for converting folic acid to folate cofactor, thus blocking the synthesis of thymine and purine, causing impairment of tumor growth and induction of cell death. High dose MTX (HD-MTX) is infused in doses of 3-5g/m2 and over a period of 6-24h to maintain the serum MTX at high levels, which shows benefit in the treatment of childhood leukemia and certain adult NHL, particularly the Burkitt type. However, the clinical implication of MTX is hampered for some reasons. On the one hand, the adverse effects of HD- MTX are severe, including bone marrow suppression, mucositis, hepatotoxicity, nephrotoxicity and neurological symptoms. On the other hand, leucovorin rescue, adequate hydration, urinary alkalization and monitoring of MTX concentration is required to avoid life-threating side effects of HD-MTX, which makes the administration rather complicated. In addition, the poor water solubility also impedes the application of MTX. To overcome these obstacles, a new drug delivery system is required to reduce the side effects of HD-MTX as well as to increase the solubility of the drug. So we designed a self-assembled micellar system to load MTX to overcome water solubility and to enhance therapeutic efficacy while reduce toxicity. Materials and Methods: Monomethyl poly (ethylene glycol)-poly (ε-caprolactone) (MPEG-PCL) our group previously synthesized was employed to load MTX through a one-step solid dispersion method. The preparation was done without any surfactants, organic solvents, or vigorous stirring. Results: MTX loaded micelles had a small particle size of 25.64±0.99nm and polydisperse index (PDI) of 0.176±0.05. Drug loading and encapsulation efficiency of MTX loaded micelle were 5.57±0.14% and 92.46±2.38%, respectively. Compared with free MTX, MTX loaded micelles demonstrated a much slower and sustained release behavior in vitro. MTT assay and cell apoptosis study suggested that MTX loaded micelles were more effective in inhibiting proliferation (IC50 value 137.8ug/ml vs 86.5ug/ml, p<0.05) and inducing apoptosis (p<0.01) on Raji lymphoma cells than MTX treatment, which was especially distinct in high dose groups (38.78% vs 22.17%). Cellular uptake study indicated that MPEG-PCL micelle had a 1.5 times higher uptake rate in Raji cells. As for in vivo studies, MTX loaded micelles were more competent to suppress tumor growth (p<0.01) and prolong survival time than MTX injection (p<0.05) in the subcutaneous Raji lymphoma mouse model. Notably, the high dose group of micelle formulation exhibited the strongest anti-tumor effect without additional toxicity. As for body weight, which represented systematic toxicity, no difference between control group and two kinds of MTX formulation group was observed (p >0.05). Furthermore, immunofluorescent and immunohistochemical studies showed that tumors of MPEG-PCL-MTX treated mice had more apoptotic cells (p<0.05) and fewer proliferative cells (p<0.01). Conclusions: In this work, MPEG-PCL-MTX micelle was fabricated with a thin-film hydration method to improve the water solubility of MTX and to meet the requirements of intravenous administration, which was stable, safe, effective, easy to produce and scale up, and showed potential clinical application. The enhanced therapeutic efficiency of MPEG-PCL-MTX micelle might be attributed to enhanced permeability and retention (EPR) effect, which increased drug accumulation in the tumor site. Besides, compared with MTX injection with highest concentration in our experiment, MPEG-PCL-MTX micelle with lowest concentration achieved similar or better therapeutic outcome, which indicated the amount of drug could be reduced to achieve the same therapeutic efficiency and alleviate adverse effects towards normal tissues and organs. Moreover, MPEG-PCL-MTX micelle of high dose (7mg/ml) achieved great therapeutic advantage without obvious toxicity, which makes micelle an effective and safe choice when HD-MTX is clinically employed. Disclosures No relevant conflicts of interest to declare.

2020 ◽  
Vol 20 ◽  
Author(s):  
Weihong Qu ◽  
Jianguo Zhao ◽  
Yaqing Wu ◽  
Ruian Xu ◽  
Shaowu Liu

Background:: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure although gene therapy may be a promising future alter-native. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgen-ic expression. Objective:: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Method:: The subcutaneous xenograft mode were induced by subcutaneous injection of 2×106 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single-stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9)by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 stain-ing to evaluate tumor angiogenesis. Results:: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion:: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and impli-cate rAAV9-Kal as a candidate for gene therapy of lung cancer.


2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Mina Mirnezami ◽  
Hoda Rahimi

Background. Acne vulgaris is an inflammatory disease of pilosebaceous units which may cause permanent dyspigmentation and/or scars if not treated. Isotretinoin is recommended in the treatment of recalcitrant or severe acne, but it is associated with common adverse effects that frequently result in patients incompliance and discontinuation of the drug. The present study was designed to assess the efficacy of oral omega-3 in decreasing the adverse effects of isotretinoin. Materials and Methods. In this randomized double-blind clinical trial, a total of 118 patients with moderate or severe acne were randomly divided into two (case and control) groups. The control group was treated with isotretinoin 0.5 mg/kg, and the case group was treated with the same dose of isotretinoin combined with oral omega-3 (1 g/day). The treatment was lasted for 16 weeks and mucocutaneous side effects of isotretinoin were recorded and compared between the two groups in weeks 4, 8, 12, and 16. Results. Cheilitis (at weeks 4, 8, and 12), xerosis, dryness of nose at all weeks, and dryness of eyes (at week 4) were less frequent in the group that received isotretinoin combined with oral omega-3 compared to the group that received isotretinoin alone. Conclusion. Administration of oral omega-3 in acne patients who are receiving isotretinoin decreases the mucocutaneous side effects of isotretinoin. This trial is registered with  IRCT201306238241N2.


2021 ◽  
Author(s):  
Emin Sengul ◽  
Volkan Gelen ◽  
Serkan Yildirim ◽  
Esra Senturk ◽  
Yusuf Dag ◽  
...  

Abstract Hepatotoxicity and nephrotoxicity are common side effects of 5-Fluorouracil (5-FU). The present study aimed to investigate the effects of Silymarin (SLY) on 5-FU induced hepatotoxicity and nephrotoxicity in mice. In our study, 10 mice in each group were randomly divided into four groups as the control group, 5-FU, SLY50+5-FU, and SLY100+5-FU group. SLY50+5-FU and SLY100+5-FU groups were administered at a dose of 50 and 100 mg/kg for seven days, respectively. 5-FU was administered at a dose of 400 mg/kg intraperitoneally on the fourth day. After the applications, the mice were decapitated under anesthesia. The liver and kidney functions which urea, creatinine, AST, ALT, and total bilirubin levels were analyzed in serum. In liver and renal tissues, MDA and GSH levels, SOD, CAT, and GR activity were determined. Also, histopathological and immunohistochemical changes were examined in liver and kidney sections. Urea, creatinine, ALT, AST, and total bilirubin levels increased 5-FU group according to control and prevented to this increases the especially high dose of SLY. 5-FU also causes histopathological and immunohistochemical changes such as degeneration, necrosis, hyperemia, DNA damage, and IL-6 increase in kidney and liver tissue. High doses of SLY prevented these changes caused by 5-FU. As a result of this study, it was determined that SLY has hepatoprotective and nephroprotective effects on 5-FU-induced liver and kidney damage in mice.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3327-3327 ◽  
Author(s):  
Charles W Shaffer ◽  
Naznin Haq ◽  
James B Bussel

Abstract Abstract 3327 Introduction: Adult immune thrombocytopenia (ITP) is an autoimmune disorder characterized by an isolated low platelet count. Options for initial therapy in children and adults include corticosteroids (CS), intravenous immunoglobulin (IVIG), and anti-D. Second-line treatments include splenectomy, rituximab, and the thrombopoietin receptor agonists (TPO-A) eltrombopag and romiplostim. Treatments are usually effective in raising platelet counts, but there are often associated toxicities. We designed and administered a patient survey to compare side effects reported with different ITP therapies to an off treatment control group. Methods: A literature search identified 56 distinct side effects reported by patients on medical therapy for ITP. A self-report questionnaire was designed that asked patients how frequently (never, occasionally, regularly, almost always, always) they had experienced each side effect during the last 30 days. If a respondent had experienced the side effect, he/she was also asked to indicate the level of distress associated with the symptom on a rating scale. Adult non-pregnant patients with ITP were eligible for the IRB-approved study if they were currently taking one of the following therapies, and had done so for at least 30 days: CS, rituximab plus pulse high dose dexamethasone [Dex-Ritux], eltrombopag, IVIG, romiplostim, or no therapy (control group). Clinical details were obtained from patient records. Side effects in the treatment groups were compared to the control sample using the Wilcoxon rank-sum test (alpha = .05). Results: Ninety-one eligible patients completed the survey. Eleven (12%) were on CS (9 patients on prednisone [median dose 20mg/day] and 2 on pulse high dose dexamethasone), 11 (12%) on Dex-Ritux, 21 (23%) on eltrombopag, 9 (10%) on IVIG, 22 (24%) on romiplostim, and 17 (19%) on no therapy. Sixty-two percent overall and 71% of control patients were female (n=56, n=12). One hundred percent of patients reported experiencing at least one side effect. The most commonly reported side effects were fatigue (n= 78; 86%), stress (n=70; 77%), anxiety (n=56; 62%), joint pain (n=55; 60%), and muscle pain (n=55; 60%). Most side effects reported by patients on treatment did not occur with significantly greater frequency or distress than in the control sample. Side effects that occurred with significantly greater frequency compared to the control sample were found in every treatment group except eltrombopag. Most of these symptoms were mild and not associated with greater distress compared to control patients who experienced the same side effect. The number of side effects occurring with greater frequency was 15 with romiplostim, 5 with Dex-Ritux, 3 with CS, and 2 with IVIG. Side effects that occurred with significantly greater distress compared to the control sample were found in every treatment group. Greater distress was not necessarily associated with greater frequency (see Table). Many unwanted effects, such as fatigue, insomnia, dyspepsia, and skin irritation, that have traditionally been associated with CS treatment did not occur with greater frequency or distress in that group; however, few patients were on long term or high dose CS therapy. Surprisingly, unlike published series, we found that romiplostim patients experienced fatigue with significantly greater frequency and more distress than the control group (see Figure). Conclusion: These results suggest that, while unwanted effects of ITP treatment in adults are common, the great majority are not associated with significant patient distress. Patients who participated in this study were being treated at a clinic where treatment guidelines for adult ITP favored TPO-As over CS. Thus our findings may not reflect general experience. Disclosures: Bussel: Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shinogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding; Portola: Consultancy.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A M Safan ◽  
M Samir ◽  
A M Saeed ◽  
A S I Farag

Abstract Background Bleeding is one of the most serious events that can occur intra-operative as well as post-operative in TURP, TURBT, PCNL and minimizing blood loss is of vital role in preventing or reducing morbidity and mortality following these procedures. Aim of the Work The aim of the present study was to to evaluate the efficacy of high dose tranexamic acid and etamsylate in reducing blood Loss during TURP, PCNL, TURBT and to determine if we can use them as a routine or not. Patient and Methods The study, was a prospective randomized control study, would be conducted on 70 patients admitted through the outpatient urology clinic in Ain shams University Hospitals and Nasser institute hospital. The 70 patients were divided into two main groups. Each one was 35 patients, each group is subdivided into 3 subgroups ((a)TURP,(b)PCNL AND (c)TURBT). Group 1 (all did not receive the combination of high dose tranexamic acid and ethamsylate) Group 2 (all received the combination of high dose tranexamic acid 2g per day and ethamsylate2.5g per day). Results We found that hemoglobin and hematocrit drop was significantly smaller in cases group and subgroups compared with the control group and subgroups, we also found that blood transfusion is reduced in control group and subgroups than in cases. Also procedure time was highly significant decreased in cases compared with controls. the high dose combination tranexamic acid 2g per day and ethamsylate2.5g per day was found to be safe without side effects especially thromboembolic side effects. Conclusion The study showed that High dose tranexamic acid and etamsylate is safe and effective in reducing blood loss during TURP,PCNL and TURBT. but we still cannot use them as a routine in all patients because our study is conducted on patients with selected criteria so further studies are needed.


2020 ◽  
Vol 19 (9) ◽  
pp. 1963-1968
Author(s):  
Kena Lu ◽  
Hanmei Lin

Purpose: To study the effect of berberine (BBR) on hyperandrogenemia (HA), ovulation dysfunction and inflammation in a mouse model of polycystic ovary syndrome (PCOS).Methods: Forty-five female Kunming mice were randomly divided into control group (9 mice), and mice injected with dehydroepiandrosterone (n = 36) for establishment of PCOS model. The PCOS mice were randomly divided into model group, low-dose BBR (0.25 g/kg), medium-dose BBR (0.5 g/kg) and highdose (1.0 g/kg) groups, with 9 mice in each group. Changes in ovarian morphology were monitored, and sex hormone levels i.e. testosterone (T) and luteinizing hormone (LH)), and inflammatory factors were determined.Results: The model group levels of T and LH were significantly higher than those of the blank control group (p < 0.05), but T and LH levels were significantly lower in middle- and high-dose BBR groups than in the model mice. There were marked increases in IL-6 and TNF-α levels in model mice, when compared to blank control mice, but reduced in the mice treated at the 3 doses of BBR, relative to model mice (p < 0.05). In contrast, the number of follicles was higher at each stage of development in mice for each BBR dose than in the model mice, with increase in corpus luteum.Conclusion: Berberine lowers the weight of PCOS mice, mitigates hyperandrogenemia and inflammatory state, and enhances recovery of ovulation. However, there is need for further studies on its clinic applicability. Keywords: Berberine, Polycystic ovary syndrome, Hyperandrogenemia, Ovulation dysfunction, Inflammatory


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5308-5308
Author(s):  
Theresa Deisher ◽  
Margaret Taylor ◽  
Arya Ashok ◽  
Peter Jarzyna ◽  
Yumna Zahid ◽  
...  

AVM0703 is a new treatment option for lymphoma patients that can eliminate or reduce the dose of standard chemotherapy in the overall treatment plan. Radiation and chemotherapy have dramatically improved survival for patients with cancer. However, the American Cancer Society has reported that chemotherapy and radiation increase the chances of secondary cancers. In fact, the report states that chemotherapy is known to be a higher risk factor than radiation in causing leukemia. The need to decrease chemotherapy administration in young adults and pediatric populations becomes even more essential considering the risk for secondary cancers. Therefore, there is an urgent need for new therapies that are as efficacious as chemotherapy and are without the harmful side effects. AVM0703 is a repurposed small molecule that has significantly extended survival in a mouse model with aggressive B cell lymphoma (A20 mouse model). In addition to being a standalone treatment, AVM0703 can also be administered as a preconditioning agent before CART cell infusion. Two FDA approved breakthrough therapies, Kymriah and Yescarta are not yet available for 33% of patients who are frail and elderly, as they are too weak to undergo the required chemotherapy preconditioning. AVM0703 can have the same preconditioning effect as chemotherapy without the toxic side effects of chemo while sparing red blood cells, stem cells and platelets. AVM0703 demonstrated a significant improvement of the effect of CART cells in a mouse model of melanoma (data not shown). Preconditioning with AVM0703 before CART administration will allow frail and elderly patients access to FDA approved cell therapy treatments. To demonstrate the efficacy of AVM0703 in a lymphoma model, A20 tumor cells were inoculated subcutaneously into the right flank in a cohort of BALB/c mice. When the tumors reached ~ 100mm3, the mice were randomized into two cohorts, control and AVM0703-treated. The control group were vehicle-treated while AVM0703-treated group were administered the active drug on day 7, 10, 17, 23, 24, 28 and 35. Tumor volumes and body weights were measured thrice weekly. Overall the treatment was very well tolerated with no treatment related deaths or toxicity observed. Dramatic body weight loss defined as greater than 20 % decrease from baseline is a frequent concern with chemo treatment, however, it was not observed in any AVM0703-treated mice. The median survival time for the control group was 16 days where as the AVM0703-treated group had a median survival time of 34 days. Therefore, this data suggests that AVM0703 treatment almost doubled the survival time of mice bearing A20 tumors (Figure 1), a fast growing B cell lymphoma model. Most interestingly, when the data was compared to the CHOP regimen, a combination of 4 therapies in the same A20 model, the efficacy results were better than 1 cycle CHOP without the extremely toxic effects observed with CHOP cycles (Figure 2). As mentioned previously AVM0703 is a repurposed molecule with decades of clinical information available on safety and toxicity, allowing a rapid clinical development program. AVM0703 is a novel high-volume formulation with a target dose that is 25 times what is used currently. It has a unique mechanism of action targeting only cancer cells, lymphocytes and monocytes while sparing platelets, RBCs and stem cells. Due to its unique profile, AVM0703 can replace chemotherapy and reduce the financial and physical toxicities associated with it. AVM0703 presents a new treatment option for lymphoma patients that is safe and effective. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14652-e14652
Author(s):  
Michael Molyneaux ◽  
John Xu ◽  
David M. Evans ◽  
Patrick Lu

e14652 Background: Cholangiocarcinoma (CCA) is a hepatobiliary cancer and although there have been advances recently there is a need for additional treatment methods for patients. Over expressions of TGF-β1 and COX-2 have been reported to play key roles in tumorigenesis of CCA. We studied the effect of STP705 on the growth of HuCCT-1 xenograft tumors in nude mice. STP705 is a TGF-β1/COX-2 specific siRNA combination product formulated in Histidine-Lysine co-Polymer nanoparticle delivery system. Methods: HuCCT-1 xenograft tumors were implanted subcutaneously into 24 BALB/c nude female mice (n = 8/group). Group 1 received vehicle control, group 2 (low-dose) received 8µg of STP705, and group 3 (high-dose) received 16µg of STP705. Intratumoral test article administration and tumor volume measurements were conducted twice a week for 3-weeks. Qualitative analysis was performed on H&E, Picrosirius red (PSR) and immunohistochemistry (IHC) stained sections of tumor tissues. Results: High- and low- dose groups of STP705 reported significantly lower mean tumor volume at day 21 (p = 0.005 & p = 0.036, respectively) as compared to control group. High-dose group reported significantly lower tumor volume at days 11 (p = 0.042), 15 (p = 0.003), and 18 (p = 0.007) as compared to the control group. IHC assessment demonstrated that STP705-treated animals had significantly lower (H-score ± SEM) TGF-β1, COX-2, HSP70, Bcl-xL and MMP-9 staining (52±9, 39±4, 178±8, 25±7 & 7±1, respectively) as compared to control animals (94±11, 66±8, 213±7, 59±8 & 11±2, respectively – with p < 0.05). Assessment of Caspase-3 and H&E (necrosis and inflammation) slides reported higher mean score for STP705-treated animals, while PSR staining reported lower fibroplasia for STP705-treated animals as compared to the control animals. Conclusions: The data suggests that STP705-treatment suppresses TGF-β1 and COX-2 expression resulting in inhibition of (i) tumor cell survival, (ii) fibrosis, (iii) promotes apoptosis, and (iv)decreased invasiveness of tumor cells. Overall, STP705 is an innovative siRNA-based treatment that results in significant suppression of tumor growth in a HuCCT-1 xenograft mouse tumor model.


2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Guo-Yan Qi ◽  
Peng Liu ◽  
Bu-Lang Gao

Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy.Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system.Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P<0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P<0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P<0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group.Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy.Erratum to “Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis”


2018 ◽  
Vol 25 (7) ◽  
pp. 1631-1637 ◽  
Author(s):  
Elaine Xiang ◽  
Jian Ni ◽  
Brett Glotzbecker ◽  
Jacob Laubach ◽  
Robert Soiffer ◽  
...  

Introduction For multiple myeloma patients who respond to primary therapy, autologous hematopoietic stem cell transplant (HSCT) is considered standard of care with high-dose melphalan for transplant candidates. There are now two different melphalan formulations available, including a propylene glycol containing (PG-MEL) product and a propylene glycol-free (PG-free MEL) product. Although considered bioequivalent, there remains limited literature directly evaluating the adverse events between the two agents. We seek to assess the tolerability and severity of side effects between the two formulations in a real-life practice setting. Methods A retrospective, descriptive analysis was conducted of multiple myeloma patients who received autologous stem cell conditioning with either melphalan formulation when dosed at 100 mg/m2/dose for two consecutive doses. The primary outcome was the assessment of tolerability and severity of side effects. Tolerability was split into four major categories including hematologic toxicity, gastrointestinal toxicity, renal toxicity, and highest recorded mucositis grade. Results There were a total of 78 patients who received a melphalan preparation during the study. The median time to myeloablation and neutrophil engraftment was five and seven days post-HSCT, respectively, for all patients. Patients who received PG-free MEL were less likely to develop mucositis, with 22 (56%) reported highest grade 0, defined by World Health Organization oral toxicity scale, compared to those who received PG-MEL (33%), p = 0.04. Conclusion There were minimal differences in tolerability or side effects observed between PG-free MEL and PG-MEL. These data may assist in better understanding the anticipated adverse effects of a high-dose melphalan conditioning therapy.


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