Induced Peripheral Neuropathy Research Articles

Prevalence of Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients and Its Effects on Quality of Life: A Survey Study

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment, leading to nerve damage and impairing patients' quality of life.Objective: To evaluate the prevalence of CIPN among cancer patients and its effects on their quality of life.Methods: A cross-sectional study was conducted at Allied Hospital, Pinum Cancer Hospital, and Aziz Fatima Hospital in Faisalabad, Pakistan. The study included 54 cancer patients (20 males, 34 females) aged 13-71 years, undergoing chemotherapy for at least six months. Patients were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy 20-item scale (EORTC-QLQ-CIPN20) and the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS). Data were analyzed using SPSS version 25, with descriptive statistics and chi-square tests performed to evaluate associations.Results: CIPN was prevalent in 90.7% of patients, with mild (59.3%), moderate (27.8%), and severe (3.7%) neuropathy levels. Neuropathy was significantly correlated with reduced quality of life (p = 0.663).Conclusion: CIPN is highly prevalent among cancer patients and significantly affects their quality of life. Early detection and management are crucial to mitigate these effects.

Effect of Lycopene alone and along with Coenzyme-Q10 in Streptozotocin Induced Peripheral Neuropathy: Biochemical & Behavioural Study

Diabetic Neuropathy (DN) is major chronic consequences of the diabetes. DN is developed due to chronic hyperglycemia which is related with generation of oxidative stress (OS) and alteration in the neuronal function. This study was envisaged to find the desirable neuroprotective outcomes of natural antioxidants i.e., lycopene and coenzyme Q10 (CoQ10) as monotherapy or concomitant administration in rats subjected to DN induced by streptozotocin (STZ). Single subcutaneous dose of STZ (55 mg/kg) was used to induce DN in male wistar rats (200–250 g). Significant neuropathy was observed after four weeks of streptozotocin injection. Neuropathy was evaluated by behavioral parameters using mechanical allodynia, mechanical hyperalgesia, heat/thermal hyperalgesia and walking track analysis. Oxidative stress was determined by assessment of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and nitric oxide (NO) in homogenate of sciatic nerve. STZ significantly alters all the behavioral as well as biochemical parameters. Treatment with lycopene (5mg/kg/p.o.), CoQ10 (10mg/kg, p.o.) and their combination for four weeks significantly reduced blood glucose level. The behavioural and biochemical alteration was significantly improved with the combination of lycopene and CoQ10. The combination of both the antioxidants significantly reversed the streptozotocin induced neuropathy in rats compared to alone antioxidants as well as diabetic neuropathy group. It is concluded that neuroprotective effect of lycopene, CoQ10 alone and in combination might be due to their strong antioxidant property.

Role of Lumbar Sympathetic Block in Linezolid Induced Peripheral Neuropathy With Lower Limb Motor Dysfunction

Role of Lumbar Sympathetic Block in Linezolid Induced Peripheral Neuropathy With Lower Limb Motor Dysfunction

Development of a Treatment Pathway and Patient Education Tool for Chemotherapy Induced Peripheral Neuropathy

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of cancer therapy seen with platinum agents, taxanes, vinca alkaloids, and proteasome inhibitors that can have a profound and lasting impact on quality of life. Although recognized during treatment with dose reductions and pain management, there may be an opportunity for a more uniform approach to help reduce the severity and enhance recovery. Our interdisciplinary team developed a clinical pathway and educational tool for managing neuropathy in patients who received systemic antineoplastic therapy. The gynecologic oncology team developed the pathway that now will be used in the hematologic malignancy team, especially for our patients with lymphoid malignancies who also often experience CIPN. Methods: A multidisciplinary team of specialists, including physicians, advanced practice providers, nurses, and social workers from gynecologic oncology, medical oncology, physical medicine and rehabilitation (PM&R), and physical and occupational therapy (PT/OT), was convened. A literature review was performed to collate evidence-based practices for neuropathy management. The review informed the development of the clinical pathway and led to the creation of provider-facing and patient-facing materials. Dissemination and access to the pathway included uploading a schematic onto a shared health system clinical care platform (Dorsata). The tool provides clinical decision support to providers by standardizing the approach to triage, navigation, and multi-modality neuropathy treatment. The pathway structure is based on symptoms' severity and includes social needs. Implementation included clinical decision support built within the electronic medical records platform (EPIC) using smart phrases. These interventions facilitated PMR, PT/OT, Neurology & Palliative Care referrals. Simultaneously, patient-facing materials were also made accessible through EPIC. The content included the causes of neuropathy, interventions for management, and injury prevention. Armed with this knowledge, we aim to empower patients in understanding and taking control of their symptoms. Results: There have been 35 views since the pathway was published in April 2022. This pathway increased clinician recognition of neuropathy as a highly prevalent and burdensome side effect of antineoplastic therapy. The standardized pathway allowed the entire treatment team to facilitate care easily and without added time. Patients were highly interested in strategies to ameliorate neuropathy symptoms and learned that multi-modality treatment options are available. Feedback from the pilot process thus far has resulted in plans to: (1) utilize a nurse navigator and clinical nurses to assist in triaging patients through this clinical care pathway, (2) collect validated neuropathy assessments pre and post-multimodal intervention, (3) expand to all oncology services lines within the health system. Conclusion: We developed and piloted a clinical care pathway to manage neuropathy by leveraging expertise from a multidisciplinary team of oncology-centered providers. Preliminary results suggest it improved provider-based recognition, treatment for neuropathy, strong patient interest, and satisfaction for improved access to multi-modality neuropathy treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy of Wen-Luo-Tong on Peripheral Neuropathy Induced by Chemotherapy or Target Therapy: A Randomized, Double-Blinded, Placebo-Controlled Trial.

To evaluate the efficacy of Wen-Luo-Tong Granules (WLT) local administration in the treatment of patients with peripheral neuropathy (PN) induced by chemotherapy or target therapy. This study is a randomized, double-blinded, and placebo-controlled trial. Seventy-eight patients with PN induced by chemotherapy or target therapy were enrolled from China-Japan Friendship Hospital between July 2019 and January 2020. They were randomly assigned to WLT (39 cases) and control groups (39 cases) using a block randomization method. The WLT group received WLT (hand and foot bath) plus oral Mecobalamin for 1 week, while the control group received placebo plus oral Mecobalamin. The primary endpoint was PN grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE). The secondary endpoints included quantitative touch-detection threshold, neuropathy symptoms, Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (QLQ-CIPN20), and Quality of Life Questionnaire-Core30 (QLQ-C30). After treatment, the PN grade in the WLT group was significantly lower than that in the control group (1.00 ± 0.29 vs. 1.75 ± 0.68, P<0.01). The total effective rate in the WLT group was significantly higher than that in the control group (82.05% vs. 51.28%, P<0.01). Compared with the control group, the touch-detection thresholds at fingertips, neuropathy symptom score, QLQ-CIPN 20 (sensory scale, motor scale, autonomic scale, and sum score), and QLQ-C30 (physical functioning, role functioning, emotional functioning, and global health) in the WLT group significantly improved after treatment (P<0.01 or P<0.05). WLT local administration was significantly effective in the treatment of patients with PN induced by chemotherapy or target therapy. (Trial registration No. ChiCTR1900023862).

Docetaxel Chemotherapy Induced Peripheral Neuropathy in Breast cancer Patients and its Amelioration by Vitamin E

Background: Chemotherapy is used to treat different types of cancer. Its use is associated with neurotoxicity, the most common of them is peripheral neuropathy. Taxanes are recognized to cause peripheral neuropathy of which Docetaxel is studied. Aim: To evaluate the neurotoxicity of Docetaxel and assess the protective effect of vitamin E in breast cancer patients. Methods: In a prospective placebo controlled randomized study, 60 women with breast cancer were selected. Patients had surgery and planned for chemotherapy administration. Chemotherapy protocol used is TAC that includes Docetaxel, Doxorubicin and Cyclophosphamide given every 21 days. They are assessed for neuropathy clinically and by nerve conduction study at the baseline and after completion of chemotherapy. They are divided into 2 groups each composed of 30 patients. The 1st group is given Vitamin E and the second group is given placebo. Results: showed that the incidence of neuropathy is the same in both groups, but it was less severe in Vitamin E treated group compared to the placebo group. Conclusion: vitamin E ameliorates the severity of peripheral neuropathy and can be used for this purpose. Recommendation: We recommend large multicenter studies to be done and using other agents that possibly prevent or ameliorate Docetaxel induced neuropathy in the future.

Monosialotetrahexosylganglioside in the treatment of chronic oxaliplatin-induced peripheral neurotoxicity: TJMUCH-GI-001, a randomised controlled trial.

BackgroundChronic oxaliplatin-induced peripheral neurotoxicity (OIPN) is the most troublesome and dose-limiting side effect of oxaliplatin. There is no effective treatment for chronic OIPN. We conducted a randomised controlled trial to investigate the efficacy of monosialotetrahexosylganglioside (GM1) in treating chronic OIPN.MethodsIn this single-centre, double-blind, phase Ⅲ trial, gastrointestinal cancer patients with persistent chronic OIPN were randomised in 1:1 ratio to receive either GM1 or placebo at Tianjin Medical University Cancer Institute and Hospital, China. GM1 was dosed at 60 mg daily for every 3 weeks or 40 mg daily for every 2 weeks. Seven- and fourteen- day infusions were administered to concurrent oxaliplatin users and oxaliplatin discontinuation patients, respectively. The primary endpoint was the relief of neurotoxicity (≥30% improvement), measured by a newly developed patient reported outcome measure (MCIPN) based on prior questionnaires including the European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy Induced Peripheral Neuropathy Questionnaire twenty-item scale. Visual analogue score (VAS) was used as another instrument for patients to evaluate the total Chronic OIPN treatment effect. VAS responders (≥30% improvement), double responders (≥30% improvement in both MCIPN and VAS), and high responders (≥50% improvement in the MCIPN total score) were also calculated. The secondary endpoints were safety and quality of life. The additional endpoints are progression-free survival (PFS), disease-free survival (DFS), overall survival (OS), and tumour response. (Trial registration number: NCT02486198 at ClinicalTrials.gov).FindingsBetween May 2015 to December 2017, 145 patients were randomly assigned to receive either GM1 (n=73) and placebo (n=72). Majority of the patients in both arms (90% in GM1 and 83% in placebo) continued receiving oxaliplatin on the trial. More patients responded in the GM1 group than in the placebo group (MCIPN responders: 53% vs 14%, VAS responders: 49% vs 22%, double responders: 41% vs 7%, and high responders: 32% vs 13%, all P < ·01). Analyses were also performed in concurrent oxaliplatin users. The results were consistent with those of the whole group. No deleterious effects of GM1 on survival or tumour response were found. There were no ≥G3 GM1-related adverse events.InterpretationIn patients with chronic OIPN, the use of GM1 reduces the severity of chronic OIPN compared with placebo.FundingThis work was supported by clinical trial development fund of Tianjin Medical University Cancer Institute and Hospital (No.C1706).

Effect of Flavone Derivatives on Vincristine and Oxaliplatin Induced Peripheral Neuropathy in Mice

Introduction: Therapy with anticancer drugs like paclitaxel, platinum complexes and vincristine result in severe peripheral neuropathy. Very few treatment options are available to overcome this debilitating side effect. Flavone and its monohydroxy derivatives have been proved to possess anti-nociceptive and anti-inflammatory effects in animal models. Aim: To investigate flavone, 5-hydroxy flavone, 6-hydroxy flavone and 7-hydroxy flavone for their effect on neuropathy induced by vincristine and oxaliplatin in mice. Materials and Methods: In this experimental animal study, neuropathy was induced in mice by multiple doses of vincristine or a single dose of oxaliplatin. The manifestations of mechanical allodynia, cold allodynia and thermal hyperalgesia were measured by von Frey’s hair aesthesiometer, acetone spray test and hot water tail immersion test. The data was subjected to ANOVA followed by Dunnett’s test for multiple comparison and paired t-test at appropriate places. Results: Flavone and monohydroxy flavones significantly reduced the paw withdrawal response scores due to mechanical allodynia and cold allodynia resulting from vincristine or oxaliplatin administration (p&lt;0.05). The tail withdrawal latency due to thermal hyperalgesia was also significantly increased by different flavone derivatives (p&lt;0.05). However, 7-hydroxy flavone was ineffective in oxaliplatin-induced mechanical allodynia and vincristine induced thermal hyperalgesia. Analysis of the results indicated that the manifestations of neuropathy induced by vincristine or oxaliplatin were amenable to treatment with flavone derivatives in the following order; cold allodynia&gt;thermal hyperalgesia&gt;mechanical allodynia. Opioid mediated antinociceptive effect, interaction with cation channels and anti-inflammatory effect of the investigated flavones may be suggested as possible mechanisms for their beneficial effects in neuropathy due to chemotherapeutic agents. Conclusion: Various neuropathic manifestations induced by vincristine and oxaliplatin were effectively attenuated by flavone and monohydroxy flavones.

Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer

Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer

Effect of Exercise on Taxane Chemotherapy–Induced Peripheral Neuropathy in Women With Breast Cancer: A Randomized Controlled Trial

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse effect of taxanes. We sought to evaluate the effect of exercise on taxane CIPN in women with breast cancer. Patients and MethodsWomen (n = 27) were randomized to immediate exercise (IE, during taxane chemotherapy) or delayed exercise (DE, after chemotherapy). Supervised aerobic, resistance, and balance training was offered 3 days a week for 8-12 weeks. CIPN symptoms and quality of life were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and CIPN20 (scored from 0 to 100). The percentage of participants reporting moderate to severe sensory symptoms (‘3/4’ or ‘4/4’ for CIPN20 sensory items) was also evaluated, along with clinical sensory testing at the lower limb (vibration sense and pinprick). Taxane treatment adherence, including relative dose intensity, was extracted from patient medical records. Assessments occurred at: baseline (before taxane chemotherapy), pre-cycle 4 (before the final taxane cycle), the end of chemotherapy, and follow-up (10-15 weeks after chemotherapy). ResultsNo differences in the EORTC QLQ CIPN20 symptom scores were detected between groups at any time point. At pre-cycle 4, there was a significant difference between groups in patient-reported moderate to severe numbness in the toes or feet (IE: n = 1, 9%, DE: n = 7, 50%, P = .04) and impaired vibration sense in the feet (IE: n = 2, 18%, DE: n = 10, 83%, P < .01). Overall global health status/quality of life was higher in IE compared to DE at the end of chemotherapy (P = .05), yet both groups had worse CIPN20 sensory (Δ24.3 ± 4.6, P < .01) and motor symptom scores (Δ10.5 ± 1.9, P < .01) relative to baseline. By the end of chemotherapy, no differences between groups were found for moderate to severe numbness in the toes or feet (P = 1.0) or impaired vibration sense in the feet (P = .71). More IE participants received ≥ 85% relative dose intensity (IE: n = 12, 100%, DE: n = 10, 67%, P < .05). ConclusionExercise may attenuate CIPN over the course of taxane chemotherapy and possibly improve taxane adherence in women with breast cancer. These findings, as well as whether exercise can attenuate CIPN by the end of taxane chemotherapy, should be confirmed in larger trials.

Impact of Exogenous Neurotropic Factor Administration on Occurrence and Severity of Paclitaxel-Induce Neuropathy in Breast Cancer Patients. An open label Pilot Study.

Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a common toxicity with no proven agent beneficial for prevention. The potentiality of Nerve Growth Factor (NGF) as a protective agent for PIPN was suggested by several studies. Aim: This study aimed to test the impact of exogenously administered NGF on PIPN and to assess NGF levels in relation to PIPN severity. Methods: Forty patients were prospectively randomly allocated to paclitaxel alone (control group) or paclitaxel + exogenous NGF (test group). Neuropathy occurrence and severity was assessed before enrollment and after each cycle using the European Association for Treatment of Cancer Quality of Life Questionnaire for Chemotherapy Induced Peripheral Neuropathy (EORTC QLQ-CIPN20). Nerve Growth Factor level was assessed in both groups at baseline and at the end of the study. Nerve Growth Factor safety was assessed by laboratory investigations and the occurrence of adverse drug reactions. Results: There was significant increase in the EORTC QLQ-CIPN20 score in the control group (p < 0.001) and a stabilization in the score in the test group. Nerve Growth Factor levels significantly increased in the test group (p < 0.001) and declined in the control group. A highly significant negative correlation existed between NGF level and the EORTC QLQ-CIPN20 score (r=-0.781, p < 0.001). No significant difference was observed between the two groups in the occurrence of adverse drug reactions or other toxicities. Conclusion: Exogenous NGF may have a potential neuroprotective effect against PIPN in breast cancer patients. Higher endogenous NGF level is inversely correlated with the occurrence and severity of PIPN.

A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral Neuropathy.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in cancer patients. The aim of this review was to assess the effectiveness of herbal medicine in preventing and treating CIPN. Methods Randomised controlled trials were included in this review. Extracting and assessing the data independently, two authors searched 13 databases. Results Twenty-eight trials involving 2174 patients met the inclusion criteria. Although there were some exceptions, the methodological quality was typically low. Seventeen trials reported the incidence rate of CIPN assessed by various tools and 14 showed a significant difference regarding the decrease of the incidence rate between the two groups. For clinical improvement, 12 trials reported it using various tools and 10 showed a significant difference between two groups. Two cases of adverse events occurred in one trial; the other nine trials reported no adverse events. Conclusions We found that herbal medicines in combination with and/or without other therapies potentially have preventive or therapeutic effects on CIPN. However, conclusions cannot be drawn because of the generally low quality of the methodology, the clinical heterogeneity, and the small sample size for each single herbal medicine. Trials that are more rigorous and report sufficient methodological data are needed.

Home Intervention for Chemotherapy Induced Peripheral Neuropathy, Sensorimotor Program

Investigate the effects of a senorimotor rehabilitation intervention that can be performed at home for persons that have recied a taxane-based chemotherapy for early stage breast cancer.

Prevalence of vincristine induced-peripheral neuropathy among Sudanese cancer patients

: Background: Increasing clinical evidence suggests treatment of cancer with neurotoxic agents results in some degree of peripheral neuropathy. Objective: The main objective of the study was to evaluate vincristine induced peripheral neuropathy among Sudanese cancer patients. Methods: A descriptive cross-sectional study was carried out at Radiation and Isotopes Center, Khartoum State, Sudan. All patients suffering from cancer with an age of 18 to 65 years were reviewed. A self-developed data collection form was used to collect the demographic data; drug use history; medical diseases; and vincristine cycles. The World Health Organization criteria were used to grade the side-effects. Data was collected for a period of two months and were analyzed descriptively. Results: Out of 78 patients reviewed, majority were females (n=47, 60.3%). Most of the patients were in the age group of 18-30 (n=27, 34.6%) and 51-60 (n=27, 34.6%) years. Twenty six (33.3%) of the patients took analgesic and 15.3% (n=12) experienced hypertension. Most of the patients went through more than 6 cycles of therapy with vincristine (n=24, 30.9%). Our study showed that ‘altered bowel function (i.e constipation)’ was the most important neuropathic change, which occurred in 62 (79.5%) of the patients who received vincristine. The second common neuropathic change was the ‘lack of ability to go upstairs un-aided’, which occurred in 37 (47.4%) of patients receiving vincristine. Majority of the patients (n=37, 47.5%) showed mild paresthesia as graded by the ‘WHO grading scale’. Conclusion: More than three-fourth of the cancer patients experienced vincristine induced peripheral neuropathy. Healthcare professionals need some understanding regarding medical management that may decrease occurrence of neuropathy and a better planning and implementing special care for patients at risk.Key words: Cancer, Chemotherapy, Peripheral Neuropathy, Sudan, Vincristine.

A Case Report of Long-term Acupuncture Treatment in Bortezomib Induced Peripheral Neuropathy

We present a successful administration of acupuncture in alleviating persistant peripheral neuropathy due to bortezomib, a potent therapeutic agent of mutlple myeloma.

PP24 - Heat shock proteins in proteasome inhibitor related neuropathy

The proteasomal system seems to be a promising target in the cancer therapy due to the different levels and activities of its components in cancer and normal cells. Synthetic and naturally occurring proteasome inhibitors are used in research and also in clinical studies. Bortezomib (N-pyrazinecarbonyl-L-phenylalanine-L-leucine boronic acid) first-in-class proteasome inhibitor was approved by the FDA for the treatment of mantle cell lymphoma in 2006 and of multiple myeloma in 2008. Peripheral neuropathy is a common and often dose-limiting toxic side effect of bortezomib as many other active chemotherapeutic agents. Since bortezomib is the mostly used proteasome inhibitor in the clinic, several studies have been carried out to highlight the underlying mechanisms of Bortezomib Induced Peripheral Neuropathy (BINP) but current knowledge is still scarce and contradictory. Our first study was focused on identifying the possible proteins involved in the bortezomib induced neuropathy and also possible differences between bortezomib- and carfilzomib-treated cell proteomes because carfilzomib is believed to be less neurotoxic compared to bortezomib. In this direction, we treated neural stem cells with bortezomib and carfilzomib. Proteins were extracted from bortezomib and carfilzomib treated neural cells as well as from untreated cells using 1% β-octyl glucopyranoside lysis buffer. Extracts were tryptically digested on 3 kDa spin filters and the peptides were analyzed by nanoLC-MS/MS using a 7 T hybrid LTQ-FT mass spectrometer. Protein identification was carried out using MASCOT search engine with a confidence level of 95% and proteins were quantified using MaxQuant software. According to the results of the study, we showed significant changes for Heat Shock Proteins (HSPs) in different study groups besides many other proteins involved. Since HSPs have crucial roles in protein homeostasis, the possible involvement of these proteins in BINP has been discussed.

Acupuncture for Oxaliplatin Chemotherapy–Induced Peripheral Neuropathy in Colon Cancer: A Retrospective Case Series

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side-effect resulting from chemotherapy agents. CIPN is a significant concern for patients who have cancer, as CIPN has a negative impact on quality of life and can be a dose-limiting side-effect of chemotherapy, leading to decreased treatment efficacy. Currently, there are very few effective treatments for mitigating CIPN. However, several studies have shown that Traditional Chinese Medicine (TCM)–based acupuncture may be effective for preventing and/or treating CIPN. This article describes the current authors' experience in an integrative oncology setting, illustrating the use of TCM-based acupuncture for treating CIPN resulting from oxaliplatin chemotherapy regimens. Materials and Methods: This was a retrospective case series of 10 patients who were treated by physicians at the Southwestern Regional Medical Center (SRMC) of the Cancer Treatment Centers of America (CTCA) at. At this medical center, advanc...

Pain Following Hematopoietic Stem Cell Transplant: A Prospective Observational Study

Pain following hematopoietic stem cell transplantation (HSCT) is caused by several factors: chemotherapy, radiotherapy, infections, GVHD, and medications. Difficulties in defining and accurately diagnosing pain symptoms can lead to delays in starting effective analgesia and poorer quality of life. Pain syndromes following HSCT have not been well-studied and the actual prevalence is unknown. The goal of this study was to determine incidence, severity, and the time course of pain following HSCT. We designed a prospective, observational study which enrolled 100 patients undergoing HSCT (60% autologous, 40% allogeneic. 19 unrelated, 13 sibling, 8 double cord. Myeloma 44%, leukemia 29%, lymphomas 26%, and aplastic anemia 1%). Patients enrolling on the study completed 5 questionnaires before HSCT and 1, 2, 3, 6, 9, and 12 months after HSCT. The questionnaires were the Brief Pain Inventory (BPI), the EORTC Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy (EORTC-CIPN), the Muscle and Joint Measure (MJM), the MD Anderson Symptom Index – Graft-versus-Host Disease module (MDASI-cGVHD), and the Hospital Anxiety and Depression Scale (HADS). At the 9-month review, we found that there was a significant increase in pain reported after allogeneic HSCT compared to pre-HSCT. (71% increase at 3 months; p=0.01). This difference was independent of conditioning regimen, disease or GVHD. For autologous HSCT, there was an increase in reported neuropathic symptoms (47% increase at 3 months; p=0.02). We also found and increase in muscle cramping and spasms late after HSCT; both autologous and allogeneic (99% increase at 9 months; p=0.03). Muscle cramping interfered with sitting, standing and physical activity (21% at 6 months; p=0.04 and 136% at 9 months; p=0.04). The increase in muscle cramping symptoms was independent of conditioning regimen, disease or GVHD. Our current review of this study reveals that pain and muscle cramping is a significant symptom that develops after both allogeneic and autologous HSCT. This appears to be independent of conditioning regimen, disease or GVHD.

40. Point prevalence study of multiple myeloma induced-peripheral neuropathy

Peripheral neuropathy and neuropathic pain are common complications of multiple myeloma (MM) treatment. In this point prevalence study we aimed at assessing prevalence, clinical characteristics and predictive factors of peripheral neuropathy and neuropathic pain in patients with multiple myeloma. We collected 217 consecutive patients with multiple myeloma. All patients underwent clinical examination, DN4 questionnaire for neuropathic pain, the standard nerve conduction study. Patients with sensory disturbances but normal standard nerve conduction study underwent skin biopsy. Seventy-one percent of patients had a peripheral neuropathy. Sixty-four percent of patients had pain at the time of visit; 43% experienced neuropathic pain according to the DN4 questionnaire. Peripheral neuropathy was significantly associated with the duration of disease and treatment (the longer the disease and the higher the number of treatment during the disease the more frequent the neuropathy; P P

Development of Bortezomib Induced Peripheral Neuropathy (BiPN) In Multiple Myeloma: Incidence and Molecular Characterization In Newly Diagnosed Patients Treated with Bortezomib

AbstractAbstract 304 Background:Bortezomib, a proteasome inhibitor with activity in multiple myeloma (MM) achieves high response rates in newly diagnosed patients. Bortezomib induced peripheral neuropathy (BiPN) affects 15% (grade 3–4) to 40% (grade 1–4) of patients. BiPN frequently is the dose-limiting toxicity which requires dosing adjustments, and significantly influences the quality of life. The pathogenesis of BIPN and the background for the individual differences of susceptibility are largely unknown. Aim:This project was designed to obtain insight in the molecular characteristics underlying BiPN in MM patients. Methods:We investigated the susceptibility to BiPN in 369 patients who were included in a large prospective, randomized, phase III trial (HOVON65/GMMG-HD4) of bortezomib (PAD) versus conventional vincristine (VAD) based induction treatment. The study integrated inherited genetic background as well as the gene expression profile of the myeloma in patients who were closely monitored for BiPN. Genetic variation associated with BiPN was analyzed using a custom-built molecular inversion probe (MIP) based single nucleotide polymorphism (SNP) chip, designed by “Bank on a Cure” (BOAC), containing 3404 SNPs selected in “functional regions” within 983 genes that represent cellular functions and pathways. Gene expression profiles were analyzed in purified myeloma plasma cells (PCs) using Affymetrix 133 Plus 2.0 array and integrated with SNP profiles for an association analysis with BiPN. We used vincristine induced peripheral neuropathy (ViPN) in VAD-treated patients as a reference. Pathway analysis was performed using significant genes (FDR<.05) or significant SNPs (permuted P<.05). Results:Analysis of myeloma gene expression profiles and SNP data of patients with early onset BiPN (within one treatment cycle) showed an association of genes involved in apoptosis, in nervous system development and in response to oxidative stress. Among the top upregulated genes in myeloma PCs were two enzyme coding genes, RHOBTB2, involved in drug induced apoptosis and CPT1C, involved in mitochondrial dysfunction. Ingenuity pathway analyses revealed enrichment of genes involved in the canonical pathway AMPK signaling including CPT1C, CKM and PIK3CG. AMPK signaling stimulates signaling pathways that replenish cellular ATP supplies in response to low glucose, hypoxia, ischemia, or heat shock, which may be triggered in response of myeloma cells to bortezomib. Significant SNPs (permutated P<.01) in the same patients were located in apoptosis gene caspase 9, ALOX12, and IGF1R. Pathway analysis of these associated genes revealed enrichment of genes involved in cell death, DNA repair and nervous system development and function. The molecular profile of late onset BiPN (developing after 2–3 bortezomib cycles) was characterized by genes involved in nervous system development, inflammation and DNA repair. The highest association was found with SOD2 and MYO5A expression by myeloma PCs, involved in nervous system development and function, and SNPs in inflammatory genes MBL2 and PPARD and in DNA repair genes ERCC3, ERCC4, ATM, BRCA1, EXO1 and MRE11A. In contrast, early onset ViPN was characterized by cell cycle and proliferation genes, i.e. GAGE7, GAGE12I, GAGE2C, GAGE6 and GAGE4 expression in MMPC, and SNPs in BRCA1, ERBB2, and CCNA2, known to be involved in cell cycle and proliferation. In addition, SNPs in absorption, distribution, metabolism, and excretion (ADME) genes i.e. a group of 11 intronic SNPs in DPYD and 9 SNPs in the ABC transporter ABCC1 were associated with late onset ViPN. Conclusion.We identified molecular factors which are associated with BiPN in newly diagnosed multiple myeloma patients. First, apoptosis genes contribute to early BiPN, whereas genes involved in inflammatory pathways and DNA repair contribute to the development of late BiPN, indicating that distinct genetic factors are involved in the development of early and late onset BiPN. Second, myeloma-related factors and host genetic background interactively contribute to the development of BiPN. Comparison between BiPN and ViPN learned that genetic factors involved in the development of PN are involved in different molecular mechanisms. This investigation strongly suggests an interaction between myeloma-related factors and host genetic background in the development of bortezomib induced peripheral neuropathy. Disclosures:Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees; Ortho Biotec: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Ortho Biotec: Research Funding; Chugai Pharma: Research Funding; Amgen: Research Funding. Sonneveld:Ortho Biotech: Consultancy; Ortho Biotech: Research Funding; International Myeloma Foundation: Research Funding.