Melphalan Hydrochloride Research Articles

Cleaning Method Validation for Determination of Residues in Anti-Cancer Drug product for Injection by Using RP-HPLC Technique

Cleaning method validation is a part of good practices in pharmaceutical sector and need to seek the contamination present in production area. OBJECTIVE: An RP-HPLC method for the cleaning samples analysis for Anti-Cancer Drug product Melphalan Hydrochloride for Injection was develop and validated. The method was developed and validated for quantitation of Cleaning of residue left in the vessels of the production equipment’s. The analytical method used to determine the complete cleaning for Melphalan Hydrochloride for Injection by HPLC method. METHOD: The Cleaning validation was performed on Inertsil ODS,C18,(150mm×4.6mm,5μm) chromatographic column temperature at 40°C, and the detection wavelength was set at 260nm. Mobile Phase-A:10mL ammonium acetate, 88mL Purified water, 10mL acetic acid, 2mL Triethylamine, and Mobile Phase-B: 1mL Buffer, 10mL acetonitrile,190mL Purified water, and at a flow rate of 1.5 mL/min, and the injection volume was 10μL. RESULTS: The validation results of Melphalan Hydrochloride were linear over the concentration from 0.10 µg/mL to 0.75µg/mL (r = 1.00) and the recoveries from LOQ to 150% and precision ranged from 50% to 76% (RSD < 30%, n =9). CONCLUSION: This method has been validated successfully and all the results met the acceptance criteria. Hence method of Cleaning Validation is suitable for testing of residue sample of Melphalan Hydrochloride for Injection.

Improving timely melphalan administration completion for recipients of autologous stem cell transplant.

372 Background: Melphalan hydrochloride is a primary agent used in the conditioning regimen for autologous stem cell transplant indications including multiple myeloma and lymphoma. Brand Alkeran labelling indicates the drug concentration must not exceed 0.45 mg/mL and should be given over a minimum 15 minutes but infused in its entirety within 60 minutes from preparation. Caution is provided as data has shown a loss of potency by 1% every 10 minutes after melphalan dilution. Time and concentration constraints often require the dose being divided into two infusion bags with the option to Y-site. These limitations necessitated an optimized process to ensure melphalan completion within the 60-minute timeframe. Methods: Our institution began to formally audit melphalan administration data in November 2018 as part of a new program quality metric. A retrospective evaluation was performed which assessed the total time from melphalan dilution in a normal saline (NS) bag to melphalan infusion completion. The aim was to increase compliance within 60 minutes from 86.2% to 100%. We utilized the Plan-Do-Study-Act (PDSA) cycle method to address opportunities for improvement. PDSA 1 included staff education on the importance of timely administration; same-day audit forms were created to dissect any potential fallouts promptly. This form included documentation of the time from vial reconstitution to delivery to the pharmacist within the patient care unit. Secondary to re-evaluation of package insert verbiage and discussion with the manufacturer, we redefined the audit start time to be melphalan vial reconstitution instead of dilution in the infusion bag. PDSA 2 incorporated specific checkpoints for vial reconstitution (12 minutes) and bag delivery (20 minutes) and changed from concurrent to sequential bag administration. Results: A total 285 melphalan infusions were eligible for analysis (mean 1.91 bags per patient). Baseline data showed 86.2% of infusions completed within the 60-minute timeframe. Average time-to-completion was 50.2 minutes (N=73). PDSA 1 revealed 100% compliance of chemotherapy verification documentation and 97.9% infusion completion with an average time of 42.8 minutes (N=97). PDSA 2 resulted 99.1% compliance (one infusion fallout) and an average completion time of 41.2 minutes (N=115). Overall survival (OS) at 1-year for baseline, PDSA 1, and PDSA 2 groups was 94.7%, 95.9%, and 98.3% respectively ( p=0.66). Conclusions: The outcome measure average and mean time-to-completion improved from 86.2% to 99.1% and 50.2 to 41.2 minutes, respectively, secondary to process measure implementation despite the more stringent redefined vial dilution start time. A lone fallout of 62 minutes in PDSA 2 was triaged and determined to be due to unpredictable line complications. No significant differences in OS were observed. Ultimately, our process was optimized in terms of both compliance and efficiency.

Efficacy and safety of autologous hematopoietic stem cell transplantation pretreated with Melphalan hydrochloride for injection in the treatment of 125 cases of multiple myeloma

Efficacy and safety of autologous hematopoietic stem cell transplantation pretreated with Melphalan hydrochloride for injection in the treatment of 125 cases of multiple myeloma

A Phase IV, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) As a Myeloablative Conditioning Regimen in Chinese Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

A Phase IV, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) As a Myeloablative Conditioning Regimen in Chinese Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Intravitreal melphalan hydrochloride vs propylene glycol-free melphalan for retinoblastoma vitreous seeds: Efficacy, toxicity and stability in rabbits models and patients

The use of intravitreal chemotherapy has revolutionized the treatment of advanced intraocular retinoblastoma, as intravitreal melphalan has enabled difficult-to-treat vitreous tumor seeds to be controlled, leading to many more eyes being saved. However, melphalan hydrochloride (MH) degrades rapidly in solution, increasing logistical complexity with respect to time between medication preparation and administration for intravitreal administration under anesthesia for retinoblastoma. A new propylene glycol-free melphalan (PGFM) formulation has greater stability and could therefore improve access and adoption of intravitreal chemotherapy, allowing more children to retain their eye(s). We compared the efficacy and toxicity of both formulations, using our rabbit xenograft model and clinical patient experience. Three weekly 12.5 μg intravitreal injections of MH or PGFM (right eye), and saline (left eye), were administered to immunosuppressed rabbits harboring human WERI-Rb1 vitreous seed xenografts. Residual live cells were quantified directly, and viability determined by TUNEL staining. Vitreous seeds were reduced 91% by PGFM (p = 0.009), and 88% by MH (p = 0.004; PGFM vs. MH: p = 0.68). All residual cells were TUNEL-positive (non-viable). In separate experiments to assess toxicity, three weekly 12.5 μg injections of MH, PGFM, or saline were administered to non-tumor-bearing rabbits. Serial electroretinography, optical coherence tomography (OCT) and OCT-angiography were performed. PGFM and MH both caused equivalent reductions in electroretinography amplitudes, and loss of retinal microvasculature on OCT-angiography. The pattern of retinal degeneration observed on histopathology suggested that segmental retinal toxicity associated with all melphalan formulations was due to a vitreous concentration gradient-effect. Efficacy and toxicity were assessed for PGFM given immediately (within 1 h of reconstitution) vs. 4 h after reconstitution. Immediate- and delayed-administration of PGFM showed equivalent efficacy and toxicity. In addition, we evaluated efficacy and toxicity in patients (205 eyes) with retinoblastoma vitreous seeds, who were treated with a total of 833 intravitreal injections of either MH or PGFM as standard of care. Of these, we analyzed 118 MH and 131 PGFM monotherapy injections in whom serial ERG measurements were available to model retinal toxicity. Both MH and PGFM caused reductions in electroretinography amplitudes, but with no statistical difference between formulations. Comparing those patient eyes treated exclusively with PGFM versus those treated exclusively with MH, efficacy for tumor control and globe salvage was equivalent (PGFM vs. MH: 96.2% vs. 93.8%, p = 0.56), but PGFM-treated eyes received fewer injections than MH-treated eyes (average 3.2 ± 1.9 vs. 6.4 ± 2.1 injections, p < 0.0001). Taken together, these rabbit experiments and our clinical experience in retinoblastoma patients demonstrate that MH and PGFM have equivalent efficacy and toxicity. PGFM was more stable, with no decreased efficacy or increased toxicity even 4 h after reconstitution. We therefore now use PGFM over traditional MH for our patients for intravitreal treatment of retinoblastoma.

Safety and Efficacy of Propylene Glycol-Free Melphalan (Evomela) in Patients with AL Amyloidosis Undergoing Autologous Stem Cell Transplantation: Preliminary Results of a Phase II Study

INTRODUCTION: High dose melphalan and autologous stem cell transplantation (HDM/SCT) is effective for treatment of selected patients with light-chain (AL) amyloidosis with adequate functional status and preserved organ function. Despite rigorous patient selection, approximately 21% of AL amyloidosis patients receiving treatment with HDM/SCT develop acute renal injury and up to 22% develop cardiac arrhythmias in the peri-transplant period. Patients with AL amyloidosis are at greater risk of organ dysfunction in the peri-transplant period due to pre-existing amyloid deposition. This toxicity is potentially exacerbated by the co-solvent propylene glycol found in melphalan hydrochloride. Propylene glycol is reported to lead to metabolic acidosis, sepsis-like syndrome, renal dysfunction, and cardiac arrhythmias. Therefore a clinical trial investigating the use of propylene glycol-free melphalan during HDM/SCT was developed to evaluate the effect on organ toxicity in AL amyloidosis patients (NCT02994784). PROTOCOL: This Phase II clinical trial began enrollment in April 2018. Eligibility criteria included the following: histologic diagnosis of systemic AL amyloidosis, involvement of ≥1 vital organ, eGFR of ≥30 mL/min, DLCO ≥50%, LVEF ≥40%, ECOG &lt;3, NYHA status &lt;3, and no prior HDM/SCT. Subjects underwent autologous stem cell transplantation per institutional guidelines, receiving the conditioning regimen of 140 or 200 mg/m2 propylene glycol-free melphalan via IV infusion on Days -3 and -2. Stem cell infusion occurred on Day 0. Primary objectives included evaluation for renal dysfunction (defined as a ≥1 mg/dL increase in creatinine or a doubling of creatinine to ≥1.5 mg/dL for ≥2 days), cardiac dysfunction (defined as development of new arrhythmia), and autonomic dysfunction (defined as a drop in SBP ≥20 mmHg on orthostatic measurements). Secondary objectives included evaluation of time to engraftment, treatment related mortality, overall hematologic response at 6 months after SCT, organ response at 12 months after SCT, and number of hospitalizations. RESULTS : At the time of data cut-off (July 1, 2019) 17 patients had been enrolled. Median age was 59 years (range, 44-76) with 11 (65%) males. Median number of prior therapies was 0 (range, 0-2). Median number of organ systems involved was 1 (range, 0-3). 13 (76%) and 7 (41%) patients had renal and cardiac involvement, respectively. Median NT-proBNP level was 396 pg/mL (range, 63-6220), urine protein excretion was 3.14 g/24 h (range, 0-22.9), serum creatinine was 0.93 mg/L (range, 0.72-2.07), and median dFLC was 51 mg/L (range, 2-700). In the 7 patients with relapsed/refractory disease, median time from last therapy was 2 months. Subjects received either 140 mg/m2 (n = 2) or 200 mg/m2 (n = 15) of propylene glycol-free melphalan. There have been 0 deaths during the peri-transplant period or follow-up. Per the protocol defined criteria, 2 patients (11%) developed acute renal dysfunction, 3 subjects (18%) developed orthostatic hypotension, and 3 patients (18%) experienced a new cardiac arrhythmia (atrial fibrillation or ventricular tachycardia) while on study. Median time to neutrophil engraftment was 10 days. Median time to platelet engraftment was 17.5 days. Peri-transplant hospitalization occurred in 14 subjects (82%) and median hospitalization was 5 days. The most common non-hematologic adverse events included nausea/vomiting (82%), fatigue (82%), and diarrhea (88%). Of the 8 subjects who have completed their 6 month follow-up the hematologic response rates are as follows: 4 CRs (50%), 2 VGPRs (25%), 1 PR (13%) and 1 stable disease (13%). CONCLUSION: In this ongoing trial investigating the safety of propylene glycol-free melphalan in patients with AL amyloidosis the cardiac toxicities appear comparable to historical data with 18% of patients developing a cardiac arrhythmia and with potentially improved renal toxicity (11%), although additional data are required to confirm this finding. Time to engraftment is similar to published data for HDM/SCT and no peri-transplant mortality has been seen. Hematologic responses are also comparable to historical controls (50% CR and 25% VGPR). Additional data will be obtained with ongoing patient enrollment to determine if there are significant differences in the safety of propylene glycol-free melphalan in this population of patients with high risk of organ dysfunction during HDM/SCT. Disclosures Sarosiek: Acrotech: Research Funding. Sloan:Merck: Other: endpoint review commitee; Stemline: Consultancy; Abbvie: Other: Endpoint Review Committee. Sanchorawala:Proclara: Consultancy, Honoraria; Caelum: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Prothena: Research Funding; Celgene: Research Funding; Takeda: Research Funding. OffLabel Disclosure: propylene glycol-free melphalan is FDA approved for multiple myeloma, but not for AL amyloidosis (which has not FDA approved therapies)

Melphalan hydrochloride for the treatment of multiple myeloma

ABSTRACTIntroduction: Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation and overproduction of monoclonal paraprotein, hypercalcemia, renal failure, anemia, osteolytic bone lesions, and infections.Melphalan, a nitrogen mustard, is an alkylating agent synthesized in 1953, and it has been used in multiple myeloma therapy for fifty years. Although novel agents have been introduced in the past few decades improving prognosis of the disease, melphalan still maintains a crucial role in the treatment of MM acting both as cytotoxic agent through damage to DNA, and as immunostimulatory drug by inhibiting Interleukin-6, as well as interaction with dendritic cells, and immunogenic effects in tumor microenvironment.Areas covered: This review focuses on available data about melphalan pharmacology and its role in clinical practice.Expert opinion: Melphalan remains crucial in therapy of multiple myeloma because of its good manageability, safety profile, efficacy, and economic sustainability. These characteristics make it pivotal also for new regimens in combination with novel agents.

Solution stability of Captisol-stabilized melphalan (Evomela) versus Propylene glycol-based melphalan hydrochloride injection

Purpose: The objective of this study was to compare the stability of recently approved Captisol-stabilized propylene glycol-free melphalan injection (Evomela™) against currently marketed propylene glycol-based melphalan injection. The products were compared as reconstituted solutions in vials as well as admixture solutions prepared from normal saline in infusion bags.Methods: Evomela and propylene glycol-based melphalan injection were reconstituted in normal saline and organic custom diluent, respectively, according to their package insert instructions. The reconstituted solutions were diluted in normal saline to obtain drug admixture solutions at specific drug concentrations. Stability of the solutions was studied at room temperature by assay of melphalan and determination of melphalan-related impurities.Results: Results show that based on the increase in total impurities in propylene glycol-based melphalan injection at 0.45 mg/mL, Evomela admixture solutions are about 5, 9, 15 and 29 times more stable at concentrations of 0.45, 1.0, 2.0 and 5.0 mg/mL, respectively. Results confirmed that reconstituted Evomela solution can be stored in the vial for up to 1 h at RT or for up to 24 h at refrigerated temperature (2–8 °C) with no significant degradation. After storage in the vial, it remains stable for an additional 3–29 h after preparation of admixture solution in infusion bags at concentrations of 0.25–5.0 mg/mL, respectively. In addition, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan was bacteriostatic through 72 h storage at 2–8 °C.Conclusion: Formulation of melphalan with Captisol technology significantly improved stability compared to melphalan hydrochloride reconstituted with propylene-glycol based diluents.

Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma.

Demonstrating the usefulness and complications of multiagent intravitreal chemotherapy is necessary for successful treatment in patients with recalcitrant vitreous seeding of retinoblastoma. To determine the efficacy and complications of combined intravitreal chemotherapy (melphalan hydrochloride and topotecan hydrochloride) for viable vitreous seeding from retinoblastoma. This retrospective study was conducted in a hospital setting. Trans-pars plana intravitreal injection of melphalan hydrochloride (40 µg in 0.04 mL of diluent) combined with topotecan hydrochloride (8-20 µg in 0.04 mL of balanced salt solution) was performed in 9 eyes, followed by injection site cryotherapy. Complete regression of vitreous seeds of retinoblastoma. Nine eyes, initially classified as group D (n = 6) or E (n = 3) according to International Classification of Retinoblastoma categorization, received a standard 6 cycles of intravenous chemotherapy and/or intra-arterial chemotherapy and subsequently developed recurrent viable vitreous seeds. Intravitreal administration of melphalan combined with topotecan produced complete control of vitreous seeds in all 9 eyes following a mean of 1.9 injections (median, 2; range, 1-3 injections). In 3 cases (33%), tumor control was achieved with a single injection, whereas in 6 (67%) cases, 2 or 3 injections were necessary. Three patients (33%) subsequently underwent enucleation because of recurrent tumor and persistent anterior chamber lesions. During a mean 15.2 months of follow-up (median, 16; range, 7-25 months), there was no recurrence of new tumor or vitreous seeds in the remaining 6 eyes. Complications included temporary hypotonia of 2 weeks or less (2 [22%]), temporary epithelial defect (1 [11%]), and vitreous hemorrhage (1 [11%]). There was no case of episcleral or orbital retinoblastoma extension or remote retinoblastoma metastasis. There was no change in the a and b waves of bright-flash electroretinograms. Administration of combined intravitreal melphalan and topotecan in eyes not subsequently enucleated appears to be safe and effective for resistant or recurrent vitreous seeds from retinoblastoma. In 3 of the cases (33%), tumor control was achieved with a single injection.

A polyphosphoester conjugate of melphalan as antitumoral agent

The low molecular weight of many chemotherapeutics causes their untargeted distribution in the body and fast renal clearance, which leads to a loss of therapeutic activity and to unspecific toxic side effects. Therefore, there is a growing interest in conjugating anticancer drugs to water soluble polymers and thus, take advantage of the ‘enhanced permeability and retention’ (EPR) effect in tumors. In this study, water soluble polyphosphoesters were used as polymer carriers of melphalan hydrochloride (hydrochloride of p-bis(2-chloroethyl)amino-l-phenylalanine), which is a multifunctional alkylating agent. Melphalan was chemically immobilized by covalent bonding to poly(oxyethylene H-phosphonate) under Atherton-Todd reaction conditions. Novel polymer-melphalan complexes with ionic and hydrogen bonds were designed as controls, basing on two other biodegradable polyphosphoesters: poly(hydroxyoxyethylene phosphate) and poly(methyloxyethylene phosphate). The structure of the formed products was elucidated by 1H, 13C, 31P NMR and FT-IR spectroscopy. The cytotoxic effect of the melphalan formulations was evaluated on different tumor cell lines. The novel polymer formulations showed a concentration dependent antitumoral activity, comparable to the effect of unmodified melphalan. The polymer-melphalan conjugate was also evaluated in vivo in the human hepatocellular carcinoma HuH7 xenograft mouse model. It improved the therapeutic efficacy of pure melphalan without causing side effects.

Success of Intra-arterial Chemotherapy (Chemosurgery) for Retinoblastoma

To review results of orbital angiography performed during intra-arterial chemotherapy (chemosurgery) for treatment of retinoblastoma to assess the association of angiographic variability in orbitovascular anatomy with tumor response and outcomes. Medical records and 64 orbital angiograms were reviewed for 56 pediatric patients with retinoblastoma undergoing chemosurgery using a combination of melphalan hydrochloride, topotecan hydrochloride, or carboplatin. The major orbital arteries and capillary blush patterns were graded, and tumor response and recurrence were compared using the log-rank and Fisher exact tests. Statistically significant variables for tumor response were lacrimal artery prominence (P=.001), previous treatment (P=.003), and lacrimal blush (P=.004). The only statistically significant variable for vitreous seed response was ciliary body blush (P=.03). Statistically significant variables influencing time to recurrence and time to enucleation were choroidal blush absence (P=.01) and lacrimal artery presence (P=.03), respectively. The success of intra-arterial chemotherapy is dependent on delivery of drug to the target tumor within the eye via the ophthalmic artery. Because of the small volume of drug used (0.50-1.25 mL per treatment) and the selectivity of catheterization, variables affecting orbital blood flow greatly influence drug delivery and the success of chemosurgery.

What is happening with the supply of oncology drugs in Brazil and the world?

The continuity of the supply of drugs used in oncology and oncohematology, which are on the whole irreplaceable, has been the cause of major concern in recent years and, in particular during 2011. We have passed through, over the last few months, several 'crises' in the provision of remedies that mobilized and worried many in the medical and pharmaceutical professions in Brazil. The supply of many drugs was halted or at least unpredictable causing much anxiety throughout the oncohematological patient care system. These medications included: alkylating drugs (melphalan hydrochloride, cyclophosphamide and chlorambucil); derived from podophyllin (BCNU); enzymes (L-asparaginase); antimetabolite agents (hydroxyurea, e.g. cytarabine, 6-mercaptopurina); anthracycline antibiotic (daunorubicin and doxorubicin), vinca alkaloids (vinorelbine and vinblastine); bleomycin and procarbazine among others. Another important but little addressed aspect is related to the quality of available products as the vast majority of the 'old' drugs used in oncology are products considered 'similar medications', whose origin, bioequivalence, production process and comparative results are often unknown or nonexistent. In December 2011, in a publication of the American Society of Clinical Oncology,(1) Dr. Hagop M. Kantarjian, professor and director of the Leukemia Department at the M. D. Anderson Hospital in Houston, warned about a possible shortage in the United States of America of two key drugs used in the treatment of acute myeloid leukemia (AML), cytarabine and daunorubicin. The author recalled that Cytarabine-containing chemotherapy regimens cure 40% of patients with AML; without cytarabine, the cure is 0%. This is a specific problem in the modern history of the USA that will affect thousands of AML patients. However, for many years in Brazil, we have been faced with problems in the production, importation, marketing, quality control and supply of this group of drugs. We know that the number of cancer cases worldwide is increasing year by year (there are around 45 million new cases in the world at the moment). We also know that the world population is ageing and that companies in the Far East and Africa have started prescribing Western medicine to patients with neoplasms. The increasing utilization of similar and generic drugs in the Western world has reduced the prices of classical chemotherapeutic agents. This is certainly very good and important for access to cancer treatment except for two factors: i) possible reticence to innovate medications and to invest in research to discover new products and ii) the need for quality control by governments to guarantee the therapeutic action of medications and acceptable toxicity of alternative products. In relation to the theme of innovation, the pharmaceutical industry has reduced investment on new molecules due to the high cost of development and because of recent mergers between companies that has reduced competitiveness. Important newspapers both in Brazil and other countries had warned about this possibility. Probably the decade 2010-2020 will be 'poor' in terms of the discovery of new molecules which offer any great impact in oncology. Considering the current 'pipeline' of the pharmaceutical companies, I believe that we will have few advances of any great impact in the near future. Certainly we will advance, but within a less optimistic scenario to what we would like in spite of the extraordinary advancements in the field of biology. Data published by the National Institutes of Health (NIH)(2) suggest that, in the area of cancer, for every two million molecules synthesized or developed only 80 reach the stage of clinical trials and only eight are used in routine treatment. This makes the cost of developing one new drug more expensive; in the order of two billion dollars or more depending on the product and its indications. For this there is need to invest which, in general, the industries, governments and communities are unwilling to do. I believe that multilateral institutions such as the World Health Organization (WHO) and the regulatory agencies of different countries, including Brazil, should discuss this theme in depth. The recent increase in life expectancy was due to several factors. However, advances in medicine and, particularly, the advances in basic knowledge and clinical research in the fields of oncology and oncohematology are changing the way we can look to the future. I have always had the hope that the future of oncology would use less invasive and more 'intelligent' approaches, e.g. approaches based more on biological knowledge. However, these advances are slow disease-to-disease and depend on investment in the development of molecules or modern procedures and on much scientific support. We must work hard in order to fulfill our duty to medical science with humanity.

49-Year-Old Woman With Back Pain and Loss of Consciousness

49-year-old woman had a lO-month history of low­ back pain that had developed insidiously. Two months after the back pain was initially noted, it precipi­ tously worsened, and an evaluation by her local physician included a roentgenogram of the lumbar spine that showed a compression fracture of the L-2 vertebral body. Among the tests done in assessment, a serum IgG 1C level was increased at 3,910 mg/dL. A subsequent bone marrow biopsy specimen showed IgG 1C multiple myeloma. She was treated with melphalan hydrochloride and prednisone for 4 months (total melphalan dose, 172 mg). Her serum IgG decreased to 1,420 mg/dL. Three months later, the serum IgG level increased to 1,600 mg/dL. One month thereafter, she came to the Division of Hematology/ Oncology at Mayo Clinic Jacksonville for a second opinion on further treatment. On physical examination, the patient's weight was 70.9 kg and height was 157 cm. Her vital signs and findings on general physical and neurologic examinations were nor­ mal. Laboratory investigations showed abnormal serum IgG and total protein, and review of a slide of the previ­ ously obtained bone marrow biopsy specimen confirmed the diagnosis. Three 5-week cycles of chemotherapy were planned, with each cycle consisting of vincristine (0.5 mg/ day continuous intravenous infusion) and doxorubicin (10 mg/m- per day intravenously) on days 1 through 4 and dexamethasone (40 mg/day orally) on days 1 through 4, 9 through 12, and 17 through 20 of each 5-week treatment cycle. She returned home to begin treatment. One month after the aforementioned therapy was begun, while taking dexamethasone only, the patient suddenly felt sharp diffuse pain in her head and neck. The pain began while she was lying down and was associated with an ascending whiteout of her visual field bilaterally. The abnormal visual phenomenon lasted seconds and resolved

Amyloidosis with oral involvement. Case report

A patient with chronic renal failure was investigated after complaining of oral discomfort which was found to be due to macroglossia and generalized involvement of the oral soft tissues by amyloidosis. A search for multiple myeloma proved to be positive. She also had a previous history of Carpal-tunnel syndrome. Despite an initial good response to treatment with phenylalanine nitrogen mustard (melphalan hydrochloride), she finally succumbed to end-stage renal failure.