Chemotherapy For Solid Tumors Research Articles

Assessment of Antibody Levels and Vaccine-induced Serologic Responses After Completion of Cancer Treatment in Pediatric Patients: A 6-year Experience in Turkey on HAV, HBV, VZV, and MMR Vaccinations

Objective: Childhood cancer treatment disrupts vaccination schedules and weakens or eliminates vaccine-induced immunity. In addition, post-treatment vaccine responses vary. This study aimed to assess post-treatment serum antibody levels and vaccine responses in children. Methods: Pediatric patients treated at Hacettepe University between years 2015 and 2020, achieved remission after chemotherapy for lymphoma and solid tumors were included. Post-treatment vaccination status, serum antibody levels for hepatitis A (HAV), hepatitis B (HBV), varicella-zoster (VZV), measles-mumps-rubella (MMR), and changes in vaccine responses were retrospectively analyzed. Results: The study included 533 patients. Post-treatment seronegativity rates were: measles (83.5%), HAV (64%), rubella (60.1%), HBV (48.5%), VZV (43.3%), and mumps (28%). Post-treatment antibody loss was observed for measles (47.1%), HAV (31.9%), HBV (31.4%), mumps (28.6%), VZV (21.7%), and rubella (11.4%). Seropositivity after 1 vaccine dose was seen with HAV (83.6%), rubella (82.9%), HBV (81.4%), VZV (63.5%), mumps (45.4%), and measles (33.3%). Seropositivity after 2 vaccine doses was achieved with HAV (98.8%), VZV (84.6%), rubella (80%), HBV (80%), measles (32.2%), and mumps (36.2%). Conclusion: Post-treatment serological vaccine responses in children were lower than anticipated despite multiple doses. Given the potential need for periodic serological assessments and booster vaccinations, long-term follow-ups are planned.

ESR Essentials: staging and restaging with FDG-PET/CT in oncology-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.

Metronomic chemotherapy for paediatric extracranial solid tumours: a systematic review and meta-analysis of randomised clinical trials

BackgroundMetronomic chemotherapy (‘less is more, regularly’) could be an alternative to the maximum tolerated dose (‘the more, the better’) in the chemotherapeutic cancer treatment of high-risk malignant solid extracranial tumours...

233 (PB221): Therapeutic targeting of NRF2 increases sensitivity to chemotherapy in various solid tumors

233 (PB221): Therapeutic targeting of NRF2 increases sensitivity to chemotherapy in various solid tumors

O14-3 Efficacy of platinum-based chemotherapy in BRCA-mut advanced solid tumors: analysis using the C-CAT database

O14-3 Efficacy of platinum-based chemotherapy in BRCA-mut advanced solid tumors: analysis using the C-CAT database

ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors.

In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial. The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel. ORIC-101 reversed chemoprotection induced by glucocorticoids in vitro and achieved tumor regressions when combined with paclitaxel in both taxane-naïve and -resistant xenograft models. In the phase 1 study, 21 patients were treated in dose escalation and 62 patients were treated in dose expansion. All patients in dose expansion had previously progressed on a taxane-based regimen. In dose escalation, five objective responses were observed. A preplanned futility analysis in dose expansion showed a 3.2% (95% confidence interval, 0.4-11.2) objective response rate with a median progression-free survival of 2 months (95% confidence interval, 1.8-2.8) across all four cohorts, leading to study termination. Pharmacodynamic analysis of tissue and plasma showed GR pathway downregulation in most patients in cycle 1. ORIC-101 with nab-paclitaxel showed limited clinical activity in taxane-resistant solid tumors. Despite clear inhibition of GR pathway signaling, the insufficient clinical signal underscores the challenges of targeting a single resistance pathway when multiple mechanisms of resistance may be in play. Glucocorticoid receptor (GR) upregulation is a mechanism of resistance to taxane chemotherapy in preclinical cancer models. ORIC-101 is a small molecule GR inhibitor. In this phase 1 study, ORIC-101 plus nab-paclitaxel did not show meaningful clinical benefit in patients who previously progressed on taxanes despite successful GR pathway downregulation.

Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody tislelizumab with or without chemotherapy in patients with advanced nasopharyngeal cancer and other malignant tumors: A phase Ib/II dose escalation/expansion study.

6033 Background: Dual inhibition of PD-1 and LAG-3 is expected to synergistically increase immune response against tumor growth while chemotherapy can enhance the efficacy of immunotherapy through various mechanisms. Here we report the safety and efficacy of LBL-007 (anti-LAG-3) in combination with tislelizumab (anti-PD1) with or without chemotherapy in advanced solid tumors (Phase Ⅰb) and previously untreated patients with advanced nasopharyngeal carcinoma (NPC) (Phase II). Methods: In phase Ⅰb, patients with relapsed and refractory advanced solid tumor received LBL-007 (300 or 600 mg) plus tislelizumab (200 mg) (both i.v. Q3W), and in phase Ⅱ, patients with previously untreated recurrent or metastatic NPC patients received LBL-007 (600 mg) plus tislelizumab (200 mg) in combination with GC chemotherapy [gemcitabine (1000 mg/m2) and cisplatin (80mg/m2)] (i.v. Q3W). The primary endpoints were tolerability, safety, and efficacy. Results: Updated data with more follow up including duration of response and progression free survival will be available to report at the meeting. As of January 10, 2024, 21 patients (4 NPC, 7 NSCLC, 7 melanoma and 3 others) and 42 NPC patients were enrolled in in phase Ⅰb and phase Ⅱ respectively. The median follow-up was 13.1 months. During the study, no Dose limiting Toxicity (DLT) was observed, and Recommended Phase 2 Dose (RP2D) was determined to be 600mg Q3W for both chemo and chemo free regimens. In phase II, all grades TRAEs occurred in 39 patients (92.9%), with grade ≥3 TRAE in 24/42 patients (57.1%). The most common TRAEs (≥20%) included white blood cell count decreased, neutrophil count decreased, anaemia, ALT increased, AST increased, platelet count decreased, nausea, hyponatraemia, hypochloraemia, blood creatinine increased, vomiting, and hypothyroidism. Treatment interruption due to TEAEs occurred in 31 (73.8%) patients. 13 patients (31%) experienced SAEs. 1 patient experienced Grade 5 AE due to exacerbation of cachexia unrelated to LBL-007/tislelizumab. The clinical efficacy is shown in the table. Conclusions: LBL-007/tislelizumab combination is well-tolerated in patients with advanced malignant tumors. LBL-007/tislelizumab/GC combination showed manageable, no new safety concerns and encouraging antitumor activity in previously untreated and advanced NPC patients. The encouraging efficacy and safety profile may support a pivotal study with LBL-007 in combination with tislelizumab and GC chemotherapy for NPC development in 1L setting. Clinical trial information: NCT05516914 . [Table: see text]

The tumor-associated fibrotic reactions in microenvironment aggravate glioma chemoresistance.

Malignant gliomas are one of the most common and lethal brain tumors with poor prognosis. Most patients with glioblastoma (GBM) die within 2 years of diagnosis, even after receiving standard treatments including surgery combined with concomitant radiotherapy and chemotherapy. Temozolomide (TMZ) is the first-line chemotherapeutic agent for gliomas, but the frequent acquisition of chemoresistance generally leads to its treatment failure. Thus, it's urgent to investigate the strategies for overcoming glioma chemoresistance. Currently, many studies have elucidated that cancer chemoresistance is not only associated with the high expression of drug-resistance genes in glioma cells but also can be induced by the alterations of the tumor microenvironment (TME). Numerous studies have explored the use of antifibrosis drugs to sensitize chemotherapy in solid tumors, and surprisingly, these preclinical and clinical attempts have exhibited promising efficacy in treating certain types of cancer. However, it remains unclear how tumor-associated fibrotic alterations in the glioma microenvironment (GME) mediate chemoresistance. Furthermore, the possible mechanisms behind this phenomenon are yet to be determined. In this review, we have summarized the molecular mechanisms by which tumor-associated fibrotic reactions drive glioma transformation from a chemosensitive to a chemoresistant state. Additionally, we have outlined antitumor drugs with antifibrosis functions, suggesting that antifibrosis strategies may be effective in overcoming glioma chemoresistance through TME normalization.

Anti-Emetics in Children Receiving Chemotherapy for Solid Tumors and Leukemia: Pharmacology and Optimization of Therapy for Nausea and Vomiting.

The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m2/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1-3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription.

Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-center Study.

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.

ECM1 and KRT6A are involved in tumor progression and chemoresistance in the effect of dexamethasone on pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Neoadjuvant chemotherapy is an effective PDAC treatment option, but chemotherapy causes unfavorable side effects. Glucocorticoids (e.g., dexamethasone [DEX]) are administered to reduce side effects of chemotherapy for solid tumors, including pancreatic cancer. Glucocorticoids have both beneficial and detrimental effects, however. We investigated the functional changes and gene-expression profile alterations induced by DEX in PDAC cells. PDAC cells were treated with DEX, and the cell proliferation, migration, invasion, and chemosensitivity to gemcitabine (GEM) were evaluated. The results demonstrated decreased cell proliferative capacity, increased cell migration and invasion, and decreased sensitivity to GEM. A comprehensive genetic analysis revealed marked increases in ECM1 and KRT6A in DEX-treated PDAC cells. We evaluated the effects of ECM1 and KRT6A expression by using PDAC cells transfected with those genes. Neither ECM1 nor KRT6A changed the cells' proliferation, but each enhanced cell migration and invasion. ECM1 decreased sensitivity to GEM. We also assessed the clinicopathological significance of the expressions of ECM1 and KRT6A in 130 cases of PDAC. An immunohistochemical analysis showed that KRT6A expression dominated the poorly differentiated areas. High expressions of these two proteins in PDAC were associated with a poorer prognosis. Our results thus demonstrated that DEX treatment changed PDAC cells' functions, resulting in decreased cell proliferation, increased cell migration and invasion, and decreased sensitivity to GEM. The molecular mechanisms of these changes involve ECM1 and KRT6A, whose expressions are induced by DEX.

Optimal control in reducing side effects during and after chemotherapy of solid tumors

In this paper, we discuss the effect of optimal chemotherapy doses on solid tumor during treatment and cancer recurrence after the end of treatment. First, an optimal control problem is designed. Then, by changing the control range, the objective function, and adding a control to the previous problem, three new optimal control problems are constructed. We pursue two critical ideas for the success of the drug delivery system to the patient: minimizing the normalized global population density of cancer cells during treatment and at the end of treatment and minimizing side effects during treatment. The optimal control problem is considered with two linear and quadratic objective functions. These models are solved by a well‐established numerical method with high accuracy and a low discretization cost. The numerical results have confirmed that reducing the total dose of the cytotoxic drugs during the treatment period leads to a rapid recurrence of cancer shortly after the end of the treatment period.

Treatment response assessment to chemotherapy with bevacizumab for colorectal liver metastasis by contrast-enhanced ultrasound.

Though contrast-enhanced ultrasound (CEUS) perfusion parameters have been approved to be potential indicators for response to chemotherapy in solid tumors, their ability in assessment of colorectal liver metastasis (CRLM) to chemotherapy with bevacizumab (Bev) has rarely been investigated. From March 2021 to May 2022, 115 consecutive CRLM patients with CEUS pre- and post-2 months' chemotherapy with Bev were prospectively enrolled. One target lesion per patient underwent CEUS quantitative analysis with SonoLiver software. Rise time, time-to-peak, mean transit time, maximal intensity (IMAX), and area under the time-intensity curve (AUC) were assessed with region of interest (ROI) selected on whole lesion, lesion periphery, and internal lesion, respectively. The reduction and ratio of post- to pre-treatment in parameters were investigated in development cohort (n=89) and validated in internal validation cohort (n=26) according to the chronological order. With modified Response Evaluation Criteria in Solid Tumor as reference, 48, 14 responders and 41, 12 non-responders were included in development and validation cohort, respectively. Significantly smaller values of IMAX and AUC on ROIwhole, ROIperipheral, and ROIinternal, were observed post-treatment in development cohort (all P<0.05). In predicting treatment response, the influence of ROI selection was observed when using ∆IMAX and ∆AUC, while no influence was observed using ratios. Areas under the receiver operating characteristic curve (AUROCs) for ∆IMAX and ∆AUC on ROIperipheral were 0.939 (0.867-0.979), 0.951 (0.883-0.985), and 0.917 (0.740-0.988), 0.923 (0.748-0.990) in development and validation cohort, respectively. For ratios of IMAX and AUC, AUROCs were 0.976 (0.919-0.997), 0.938 (0.865-0.978), and 0.899 (0.717-0.982), 0.982 (0.836-1.000) in development and validation cohort, respectively. IMAX and AUC showed significant reductions in responders, and different analyses ROIs influence the performance of ∆IMAX and ∆AUC in response assessment. Parameters derived from ROI peripheral exhibited the most promising results in predicting treatment response.

Organisms-on-a-chip

The progression of fibrosis is frequently related to a failed healing process, and it may affect many tissues and organs causing severe consequences including post-infarct heart insufficiency, post-injury limb paralysis, cirrhosis, nephropathy, retinopathy, failure of implanted devices and even resistance to chemotherapy in solid tumours. Experimental models, both in vitro and in vivo, are widely used for studies of basic pathophysiology, and for pre-clinical testing of pharmacological therapies counteracting fibrosis. However, conventional models are not able to realistically reproduce the revascularization aspect of the inflammatory reaction that leads to the generation of fibrotic tissue. In this talk, I will present the most advanced frontier in this sector, represented by the new concept of an “organism-on-a-chip”. This is a hybrid model, in which an organ-on-a-chip is implanted sub-cute in a living organism, such as a mouse or an embryonated avian egg, thus eliciting a foreign-body reaction with the formation of a fibrotic microenvironment. In an organism-on-a-chip, the fibrotic reaction can be guided using microscopic scaffolds incorporated in the implanted chip. The fibrotic microenvironment can then be imaged longitudinally, in high resolution, in single and multiphoton optical microscopy, with the added advantage of significantly reducing animal sacrifice. The optical measurements performed in the platform address parameters of the extra-cellular matrix (stiffness, collagen density, collagen orientation, coefficient of diffusion) and vascularity (number of blood vessels, length, blood velocity and vessel permeability).

Encapsulation of a small-molecule drug based on substituted 2-aminothiophenes in calcium carbonate carriers for therapy of melanoma.

Although small molecule drugs are widely used in chemotherapy, their low bioavailability, low-concentrated dose in the tumor zone, systemic toxicity, and chemoresistance can significantly limit the therapeutic outcome. These drawbacks can be overcome by two main strategies: (i) development of novel therapeutic molecules with more significant antitumor activity than currently available drugs and (ii) loading chemotherapeutic agents into drug delivery systems. In this study, we aimed to encapsulate a highly prospective small molecule drug based on substituted 2-aminothiophene (2-AT) into calcium carbonate (CaCO3) microparticles (MPs) for the treatment of melanoma tumors. In particular, we have optimized the encapsulation of 2-AT into MPs (2-AT@MPs), studied drug release efficiency, investigated cellular uptake, and evaluated in vivo biodistribution and tumor inhibition efficiency. In vitro results revealed that 2-AT@MPs were able to penetrate into tumor spheroids, leading to prolonged release of 2-AT. By performing intratumoral injection of 2-AT@MPs we observed significant melanoma suppressions in murine models: ∼0.084 cm3 for 2-AT@MPs at a dose of 0.4 g kg-1versus ∼1.370 cm3 for untreated mice. In addition, the 2-AT@MPs showed negligible in vivo toxicity towards major organs such as heart, lung, liver, kidney, and spleen. Thus, this work provided an efficient strategy for the improved chemotherapy of solid tumors by using an encapsulated form of small molecule drugs.

Core-Shell Microspheres Prepared Using Coaxial Electrostatic Spray for Local Chemotherapy of Solid Tumors.

Local chemotherapy is an alternative therapeutic strategy that involves direct delivery of drugs to the tumor site. This approach avoids adverse reactions caused by the systemic distribution of drugs and enhances the tumor-suppressing effect by concentrating the drugs at the tumor site. Drug-loaded microspheres are injectable sustained-release drug carriers that are highly suitable for local chemotherapy. However, a complex preparation process is one of the main technical difficulties limiting the development of microsphere formulations. In this study, core-shell structured microspheres loaded with paclitaxel (PTX; with a core-shell structure, calcium alginate outer layer, and a poly (lactic acid-co-glycolic acid) copolymer inner layer, denoted as PTX-CA/PLGA-MS) were prepared using coaxial electrostatic spray technology and evaluated in vitro and in vivo. PTX-CA/PLGA-MS exhibited a two-stage drug release profile and enhanced anti-tumor effect in animal tumor models. Importantly, the preparation method reported in this study is simple and reduces the amount of organic solvent(s) used substantially.

Targeted embolization and chemotherapy for solid tumors by microenvironment-responsive poly(amino acid)s

Transcatheter arterial embolization (TAE) has been used to treat advanced and unresectable tumors, whose treatment is complex and may involve other risks. Here, inspired by the acid and reductive microenvironment of the solid tumors, a new approach for noninvasive and targeted intravenous embolization and chemotherapy is developed. The method was based on a series of acid microenvironment-responsive polypeptides poly[(L-Glutamic acid -ran-L-Tyrosine) -b-L-Threonine-b-L-Cysteines]s, PGTTCs.) to construct the reduction-responsive chemoembolic agent by grafting modified paclitaxel (HS-PTX) to sulfhydryl side groups on PGTTCs for noncatheter targeted-embolization, which effectively improved the solubility of paclitaxel. HS-PTX could release in the presence of glutathione (GSH) due to disulfide bond disruption in vitro, and the results of tumor-bearing mice experiments showed that these polypeptides could effectively target to the tumor, embolize the tumor supply vessels rapidly and release paclitaxel in tumor sites. By comparing the therapeutic effect of embolization therapy only with that of embolization combined with chemotherapy, the chemoembolization agent showed excellent effect of embolization chemotherapy in subcutaneous tumor models, and cured tumor in mice within 20 days. Therefore, this polypeptide is expected to be a favorable candidate for effective catheterless inteavenous embolization combined with chemotherapy.

Molecular genetic markers of chemotherapy-induced cardiotoxicity in patients with oncohematological diseases (review)

Cardiotoxicity of anticancer therapy is a severe adverse cardiovascular event affecting the survival of cancer patients. Modern methods for diagnosing cardiotoxicity allow to identify already occurred myocardial transformations, accompanied by symptoms of heart failure and are not predict and detect early changes in the heart tissue during treatment. Recently, increasing attention is paid to the search for molecular genetic markers, a single identification of which before starting treatment will make possible to determining the risks of cardiotoxicity and change treatment taking into account individual genetic characteristics. At the same time, most research on the effect of allelic variants of genes on cardio-vascular complications relate to chemotherapy of solid tumors. The review considered possible prognostic genetic variants of cardiotoxicity induced by chemotherapy in patients with the hematopoietic and lymphatic malignancies.

160TiP Safety and antitumor activity of GEN1042 in combination with pembrolizumab ± chemotherapy in solid tumors: Phase IIb dose-expansion trial in progress

160TiP Safety and antitumor activity of GEN1042 in combination with pembrolizumab ± chemotherapy in solid tumors: Phase IIb dose-expansion trial in progress

Scalp Cooling to Prevent Hair Loss in Multiple Myeloma Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation

The best outcomes for multiple myeloma progression-free and overall survival include the use of high-dose melphalan and autologous peripheral blood stem cell transplantation. Melphalan is given at a dose of 140 - 200 mg/m2 as a single dose two days before or in divided daily doses immediately prior to the reinfusion of stem cells. Melphalan causes nearly complete hair loss in all patients at these doses, (CTCAE v5 Grade 2). Hair typically falls out after 10-15 days and doesn't begin to grow back for 10-12 weeks. This outcome is widely expected and leads some patients to avoid doing an otherwise life sustaining procedure. In those that do proceed with the transplant, the alopecia can be emotionally harmful. Cryotherapy is commonly used to reduce melphalan side effects in the GI tract. Melphalan typically will cause diarrhea, nausea, and mouth sores yet a randomized trial done in 2006 showed that swallowing ice chips for 6 hours starting 30 minutes before the melphalan is given can reduce these unpleasant and potentially dangerous side effects by 60% (Lilleby et. al. 2006). We at Cedars-Sinai routinely have patients do oral cryotherapy for 3.5 hours starting 30 minutes prior to each dose of melphalan. This has reduced patient side effects substantially in our experience and is considered our standard of care. Chemotherapy drugs, such as melphalan, typically injure bone marrow, intestinal lining and other cells with high metabolism and rapid cell division. Hair follicles also have these properties and is likely why many chemotherapeutics cause hair loss when used. Scalp cooling has been used to prevent hair loss in many patients undergoing chemotherapy for solid tumors. For some women with breast cancer, this hair loss was reported to be more traumatizing than losing a breast to mastectomy (Zhang et. al. 2022). The use of cold caps during chemotherapy exposure time has helped reduce hair loss, presumably by causing vasoconstriction and reducing distribution of the drug to the hair follicle. This intervention has been effective even when drugs which have longer durations of circulation have been given. While there is a theoretical risk that scalp cooling may impair the killing of malignant cells in the scalp by the chemotherapy, there is no evidence of a heightened risk in studies. The penetration of the cold should not reach the skull bone where myeloma cells may reside and is generally to a depth of only a few millimeters. The toxicity of scalp cooling is minimal. In a study of 27 participants using scalp cooling for solid tumors, 96% reported that the procedure was worth the time, effort, cost, and discomfort and would recommend usage to others undergoing the same chemotherapy treatment (Sitarz et. al. 2022). While scalp cooling has been used to prevent hair loss in patients undergoing chemotherapy for solid tumors, no reports were found for its usage for multiple myeloma or other hematologic malignancies. Since melphalan has a much shorter half-life, (70 minutes), than most other chemotherapy drugs used for solid tumors, it is anticipated that scalp cooling will be more efficacious when used with this drug. In fact, after 5 hours the concentration of melphalan should only be 5% of that present immediately after administration. A 57-year-old patient with multiple myeloma undergoing high-dose chemotherapy with melphalan 200 mg/m2 opted to use the commercially available Penguin Cold Cap to prevent losing her hair. The device was started 60 minutes before and continued for 5 hours after the melphalan infusion was started at Day -2 and Day -1 prior to her autologous stem cell transplant. The procedure was well tolerated, and the patient had no signs of any hair loss after the stem cell transplant. Based upon this experience, a study was initiated to further assess the efficacy of scalp cooling with the Penguin Cold Cap device in multiple myeloma patients receiving autologous stem cell transplants. An update with results of this study will be presented at the meeting. A positive outcome may improve the percentage of people willing to undergo this life-sustaining procedure and improve the quality of life of those who do it.