melphalan and Peripheral-Nervous-System-Diseases

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Denosumab; Diphosphonates; Humans; Imidazoles; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Prednisolone; Pyrazines; Randomized Controlled Trials as Topic; Thalidomide; Zoledronic Acid

Bortezomib (Btz) shows robust efficacy in patients with multiple myeloma (MM); however, some patients experience suboptimal responses and show specific toxicities. Therefore, we attempted to identify specific HLA alleles associated with Btz-related toxicities and response to treatment. Eighty-two transplant-ineligible patients with newly diagnosed MM enrolled in a phase II study (JCOG1105) comparing two less intensive melphalan, prednisolone, plus Btz (MPB) regimens were subjected to HLA typing. The frequency of each allele was compared between the groups, categorized based on toxicity grades and responses to MPB therapy. Among 82 patients, the numbers of patients with severe peripheral neuropathy (PN; grade 2 or higher), skin disorders (SD; grade 2 or higher), and pneumonitis were 16 (19.5%), 15 (18.3%), and 6 (7.3%), respectively. Complete response was achieved in 10 (12.2%) patients. Although no significant HLA allele was identified by multiple comparisons, several candidates were identified. HLA-B*40:06 was more prevalent in patients with severe PN than in those with less severe PN (odds ratio [OR] = 6.76). HLA-B*40:06 and HLA-DRB1*12:01 were more prevalent in patients with SD than in those with less severe SD (OR = 7.47 and OR = 5.55, respectively). HLA-DRB1*08:02 clustered in the group of patients with pneumonitis (OR = 11.34). Complete response was achieved in patients carrying HLA-DQB1*03:02, HLA-DQB1*05:01, and HLA-DRB1*01:01 class II alleles. HLA genotyping could help predict Btz-induced toxicity and treatment efficacy in patients with MM, although this needs further validation.

Topics: Aged; Antineoplastic Agents; Bortezomib; Female; Gene Frequency; Genotyping Techniques; HLA Antigens; Humans; Japan; Male; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Pneumonia; Prednisolone; Skin Diseases; Treatment Outcome

The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC0-3) in each patient. A total of 35 patients with complete data were analyzed and the overall response rate was 91.4%. Complete response (CR) was observed in 42.9% patients. The maximum plasma concentration (Cmax) was significant for the CR rate in two different models [full model: odds ratio (OR)=1.092; P=0.038, final model: OR=1.081; P=0.038]. In addition, Cmax was associated with a progression-free survival advantage. Overall, 48.6% of patients developed BIPN including peripheral sensory neuropathy and neuralgia. The VMP-treated patients had a higher risk compared with the VD-treated patients (OR=21.662; P=0.029). Cmax had a tendency to affect the occurrence of BIPN (≥grade 2) (OR=1.064; P=0.092). In real-world clinical practice using bortezomib for MM patients, Cmax among pharmacokinetic factors significantly affected the achievement of CR. The VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for more careful monitoring.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Nervous System Diseases; Prednisone

Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma.. We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance).. In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients.. Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Disease-Free Survival; Female; Follow-Up Studies; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Maintenance Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Neutropenia; Peripheral Nervous System Diseases; Prednisone; Pyrazines; Thalidomide; Thrombocytopenia; Treatment Outcome

Relapsed multiple myeloma has no standard treatment, and the role of autologous stem-cell transplantation (ASCT) has not been fully defined. We aimed to compare high-dose melphalan plus salvage ASCT with cyclophosphamide in patients with relapsed multiple myeloma who had previously undergone ASCT.. This multicentre, randomised, open-label, phase 3 study recruited patients aged at least 18 years with multiple myeloma who needed treatment for first progressive or relapsed disease at least 18 months after a previous ASCT from 51 centres across the UK. Before randomisation, eligible patients received bortezomib, doxorubicin, and dexamethasone (PAD) induction therapy and then underwent peripheral blood stem-cell mobilisation and harvesting if applicable. Eligible patients (with adequate stem-cell harvest) were randomly assigned (1:1), using an automated telephone randomisation line, to either high-dose melphalan 200 mg/m(2) plus salvage ASCT or oral cyclophosphamide (400mg/m(2) per week for 12 weeks). Randomisation was stratified by length of first remission or plateau and response to PAD re-induction therapy. The primary endpoint was time to disease progression, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00747877, and EudraCT, number 2006-005890-24.. Between April 16, 2008, and Nov 19, 2012, 297 patients were registered, of whom 293 received PAD re-induction therapy. Between Aug 26, 2008, and Nov 16, 2012, 174 patients with sufficient PBSCs were randomised to salvage ASCT (n=89) or cyclophosphamide (n=85). After a median follow-up of 31 months (IQR 19-42), median time to progression was significantly longer in the salvage ASCT than in the cyclophosphamide group (19 months [95% CI 16-25] vs 11 months [9-12]; hazard ratio 0·36 [95% CI 0·25-0·53]; p<0·0001). Frequently reported (in >10% of patients) grade 3-4 adverse events with PAD induction, salvage ASCT, and cyclophosphamide were: neutropenia (125 [43%] of 293 patients after PAD, and 63 [76%] of 83 patients in the salvage ASCT group vs 11 [13%] of 84 patients in the cyclophosphamide group), thrombocytopenia (150 [51%] after PAD, and 60 [72%] vs four [5%], respectively), and peripheral neuropathy (35 [12%] after PAD, and none vs none, respectively).. This study provides evidence for the improved efficacy of high-dose melphalan plus salvage ASCT when compared with cyclophosphamide in patients with relapsed multiple myeloma eligible for intensive therapy, which might help to guide clinical decisions regarding the management of such patients.. Cancer Research UK.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Consolidation Chemotherapy; Cyclophosphamide; Dexamethasone; Disease Progression; Doxorubicin; Female; Humans; Induction Chemotherapy; Intention to Treat Analysis; Male; Melphalan; Middle Aged; Multiple Myeloma; Neutropenia; Peripheral Nervous System Diseases; Proportional Hazards Models; Pyrazines; Recurrence; Retreatment; Salvage Therapy; Stem Cell Transplantation; Thrombocytopenia; Time Factors; Transplantation, Autologous

The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post-transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft-versus-host disease. The cumulative incidence of non-relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non-haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post-transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Boronic Acids; Bortezomib; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Cyclosporine; Drug Synergism; Female; Graft vs Host Disease; Hematologic Diseases; Humans; Immunosuppressive Agents; Maintenance Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Peripheral Nervous System Diseases; Protease Inhibitors; Pyrazines; Remission Induction; Reoperation; Salvage Therapy; T-Lymphocyte Subsets; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Vidarabine

This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone.. Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m(2), days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m(2), days 1-4, cycles 1-9; and prednisone 60 mg/m(2), days 1-4, cycles 1-9).. Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade ≥ 3 (<1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m(2). Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P=0.0065], grade ≥ 2 PN (HR 2.205, P=0.0032), and grade ≥ 3 PN (HR 2.438, P=0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN.. Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Multivariate Analysis; Peripheral Nervous System Diseases; Prednisone; Pyrazines; Risk Factors

In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Incidence; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Staging; Peripheral Nervous System Diseases; Prednisone; Pyrazines; Thalidomide; Treatment Outcome

Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome is a rare multisystem disorder. Overproduction of vascular endothelial growth factor (VEGF) by plasmocytoma could be responsible for the symptoms. The authors treated four patients with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Within 6 months, symptoms associated with rapid normalization of serum VEGF levels improved.

Topics: Adult; Aged; Down-Regulation; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Myeloablative Agonists; Peripheral Nervous System Diseases; Plasmacytoma; POEMS Syndrome; Transplantation, Autologous; Treatment Outcome; Vascular Endothelial Growth Factor A

Fifty patients with multiple myeloma >or=75 years of age received primary treatment with melphalan (M) 8 mg/m(2) on days 1-4, dexamethasone (D) 12 mg/m2 on days 1-4 and 17-20 and thalidomide (T) 300 mg at bedtime on days 1-4 and 17-20. This regimen was repeated every 5 weeks for three courses. Patients without evidence of disease progression received nine additional courses of MDT, but without DT on days 17-20, every 5 weeks. Sixty-two percent of patients achieved a partial response and 10% a complete response. The median time to response was 2 months. The median time to progression for all patients was 21.2 months. Deep venous thrombosis and peripheral neuropathy each occurred in 9% of patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Disease-Free Survival; Female; Humans; Male; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Remission Induction; Thalidomide; Venous Thrombosis

The appearance of peripheral neuropathy is the dose-limiting toxicity in many chemotherapy protocols, and glutamine has been proposed as a potentially neuroprotective agent in patients receiving paclitaxel.. In this non-randomised study, we assessed neurologic signs and symptoms, and changes in nerve-conduction studies in 46 consecutive patients given high-dose paclitaxel either with (n=17) or without (n=29) glutamine. Neurological assessments and electrodiagnostic studies were carried out at baseline and at least 2 weeks (median 32 days) after treatment.. Patients who received glutamine developed significantly less weakness (P = 0.02), less loss of vibratory sensation (P = 0.04) and less toe numbness (P = 0.004) than controls. The per cent change in the compound motor action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes after paclitaxel treatment was lower in the glutamine group, but this finding was not statistically significant in these small groups.. In this study, serial neurologic assessment of patient symptoms and signs seemed to be a better indicator of a possible glutamine effect than sensory- or motor-nerve-conduction studies. Prospective randomised trials are needed to clarify the effect of glutamine on paclitaxel and other types of chemotherapy-induced neuropathy.

Topics: Action Potentials; Administration, Oral; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Cyclophosphamide; Electrophysiology; Glutamine; Granulocyte Colony-Stimulating Factor; Humans; Melphalan; Neural Conduction; Neuroprotective Agents; Paclitaxel; Peripheral Nervous System Diseases; Stem Cell Transplantation; Thiotepa

Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side-effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side-effect.. Fifty-nine patients were treated with thalidomide alone or combined with oral melphalan. The median age was 69 yr. The initial dose of thalidomide was 100 mg/day increasing weekly by 100 mg increments until a maximum dose of 400 mg was attained. Melphalan was administered at a dose of 0.20 mg/kg/d for 4 d every 28 d.. Nearly one-fourth of patients discontinued thalidomide because of toxicity. Constipation (71%), somnolence (36%) and fatigue (20%) were the most common side-effects and they were not dose dependent. Peripheral neuropathy occurred in 39% of patients and a thalidomide median daily dose of more than 150 mg was significantly associated with higher frequency and actuarial risk of peripheral neuropathy without improving the response rate. Deep venous thrombosis was observed in 7% of patients and other side-effects were rare. In patients with advanced multiple myeloma we found that a thalidomide daily dose of 150 mg minimizes peripheral neuropathy without jeopardizing response and survival.

Topics: Aged; Aged, 80 and over; Constipation; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Fatigue; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Nervous System Diseases; Probability; Thalidomide; Venous Thrombosis

We evaluated the pharmacokinetics and pharmacodynamics of high-dose paclitaxel (HDP) monotherapy (825 mg/m2 continuous infusion over 24 h) with peripheral blood progenitor cell (PBPC) and G-CSF support in 17 women with metastatic breast cancer.. Pharmacokinetic and pharmacodynamic data were collected in 17 women entered in a phase II trial of sequential HDP, and high-dose melphalan and cyclophosphamide/thiotepa/carboplatin.. The maximal plasma concentration (Cmax), area under the plasma concentration time curve (AUC), apparent clearance (Clapp), duration of plasma concentration above 0.05 microM (t > 0.05 microM) for paclitaxel were (means SD): 9.11 +/- 7.45 microM, 145 +/- 88 microM x h, 8.06 +/- 2.90 l/h per m2 and 82.4 +/- 31.2 h, respectively. There was a significant correlation between the plasma paclitaxel concentration at 1 h (r2 = 0.87), 12 h (r2 = 0.85) and 23 h (r2 =0.92) and the AUC (P < 0.0001). Duration of neutropenia was brief (median 3 days, range 0-5 days) and neutrophil recovery occurred earlier (median 6 days, range 0-7 days) than could be attributed to infused PBPC. Median nadir count for platelets was 66 x 10(9)/l (range 13-160 x 10(9)/l). Pharmacodynamic analysis showed no correlation between pharmacokinetic parameters (Cmax, AUC, t > 0.05 microM) and time to neutropenic nadir, duration of neutropenia, platelet count nadir and grades of neuropathy or mucositis. In ten patients in whom detailed neurologic and nerve conduction studies were performed, linear regression analysis showed a significant correlation between pre- and post-HDP treatment total neuropathy scores (r2 = 0.46, P = 0.03).. HDP (825 mg/m2 continuous infusion over 24 h) did not appear to be myeloablative. The degree of neurotoxicity subsequent to HDP was associated with the degree of baseline neuropathy but was not predictable from pharmacokinetic parameters.

Topics: Adult; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Breast Neoplasms; Carboplatin; Cyclophosphamide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Middle Aged; Neutropenia; Paclitaxel; Peripheral Nervous System Diseases; Regression Analysis; Thiotepa; Time Factors

This study investigated the response rate and toxicity of blood cell transplantation as treatment for primary amyloidosis (AL). Twenty-three patients had stem cells collected between November 1995 and September 1998. Conditioning included melphalan and total body irradiation in 16 and melphalan alone in 4. Three patients did not undergo stem cell infusion because of poor performance status. Two died of progressive amyloid at 1 and 3 months. One patient is alive on hemodialysis. Fourteen males and six females (median age, 57 years) underwent transplantation. Renal, cardiac (by echocardiography), peripheral neuropathy or liver amyloidosis occurred in 14, 12, 3, and 1, respectively. Echocardiography demonstrated an interventricular septal thickness > or = 15 mm in six patients, five of whom died post transplantation. Three patients died of progressive amyloidosis at 7, 7, and 21 months. Thirteen patients are alive with a follow-up of 3 to 26 months. Twelve (60%) fulfilled the criteria of a hematologic or organ response. Severe gastrointestinal tract toxicity was seen in five (25%). We conclude that blood cell transplantation for amyloidosis had a much higher morbidity and mortality compared with transplantation for myeloma. The best results appear to occur in patients with nephrotic syndrome as the only manifestation of their disease.

Topics: Adult; Aged; Amyloidosis; Arrhythmias, Cardiac; Disease Progression; Female; Follow-Up Studies; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Liver; Male; Melphalan; Middle Aged; Myocardium; Nephrotic Syndrome; Peripheral Nervous System Diseases; Radiation Injuries; Renal Dialysis; Transplantation Conditioning; Treatment Outcome; Whole-Body Irradiation

The morbidity and lethality of AL amyloidosis is caused by the deposition of lg light chains as fibrillar amyloid protein in vital organs, disrupting their function, and not by the generally low burden of clonal plasma cells that produce the paraproteins. Survival of patients with AL amyloidosis is no more than 1 to 2 years from the time of diagnosis with current management approaches. Clearly, more effective therapies are needed for this rapidly lethal disease. Five patients were treated with dose-intensive melphalan and blood stem cell support and followed for a period of 1 year. Patients were diagnosed with AL amyloidosis by tissue biopsy and categorized by performance status and organ involvement. Their plasma cell dyscrasias were evaluated with immunofixation electrophoresis of serum and urine specimens, quantitative serum lgs, and immunohistochemical staining of bone marrow biopsy specimens. After treatment with dose-intensive intravenous melphalan followed by infusion of autologous growth-factor-mobilized blood stem cells, clinical evaluations and plasma cell studies were repeated at 3 and 12 months. Three men and 2 women aged 38 to 53 years were treated. Median performance status (SWOG) was 2 (1 to 3), and clinical presentations included nephrotic syndrome (n = 1), symptomatic cardiomyopathy (n = 1), gastrointestinal involvement with polyneuropathy (n = 2), and hepatomegaly (n = 1). With a median follow-up of 13 months (12 to 17 months), all five patients are well and have shown stable or improved performance status and clinical remission of organ-related dysfunction, including a 50% reduction in daily proteinuria with no change in creatinine, reversal of symptoms of cardiomyopathy and reductions of posterior wall and septal thickening, reversal of polyneuropathy and gastric atony, and resolution of hepatomegaly by computed tomographic scan. In 3 of the 5 patients (60%) at 12 months after treatment, plasma cell dyscrasias could not be detected. Dose-intensive chemotherapy with intravenous melphalan and growth-factor-mobilized blood stem cell support is feasible therapy for patients with AL amyloidosis, even when there is clinical evidence of cardiac involvement. At least some patients with AL amyloidosis achieve complete remission of their plasma cell dyscrasia, improvement in performance status, and clinical remission of organ-specific disease after this form of treatment.

Topics: Adult; Amyloidosis; Cardiomyopathies; Feasibility Studies; Female; Follow-Up Studies; Gastrointestinal Diseases; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hepatomegaly; Humans; Karnofsky Performance Status; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Neutropenia; Peripheral Nervous System Diseases; Prednisone; Remission Induction; Treatment Outcome

A study was undertaken adding the alkylating agent sensitizer etanidazole to intravenous melphalan and oral prednisone for patients with multiple myeloma. This study explored the toxicity profile of these agents when given together and assessed the ability to attain adequate serum levels of etanidazole to permit sensitization to occur.. Etanidazole was administered intravenously in two doses of 3 g/m2 and 5 g/m2 90 min apart immediately prior to the administration of intravenous melphalan and oral prednisone for three consecutive cycles (total dose 24 g/m2). Patients received three additional cycles without etanidazole, allowing a comparison of hematologic toxicity from melphalan with and without etanidazole.. Hematologic toxicity was moderate (Grade 3 or 4), but severity was similar during cycles with and without etanidazole. Only one patient developed a Grade 1 peripheral neuropathy questionably related to etanidazole. Most patients had etanidazole levels of > or = 70 ug/ml for 7 h, a level felt to be necessary for sensitization to occur.. Etanidazole, administered as described, results in adequate serum levels for potential alkylating agent sensitization, without significant toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Etanidazole; Humans; Infusions, Intravenous; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Prednisone

There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV.. We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT.. Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events.. This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.

Topics: Bortezomib; Cyclophosphamide; Dexamethasone; Humans; IgA Vasculitis; Immunoglobulin A; Lenalidomide; Melphalan; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Peripheral Nervous System Diseases; Plasma Cells; Prednisone; Retrospective Studies; Rituximab

Peripheral neuropathy is a common treatment-emergent side effect during the treatment of newly diagnosed multiple myeloma. Although bortezomib is most commonly implicated, real-world data suggest that lenalidomide and dexamethasone (VRd) and autologous stem cell transplantation (ASCT) may also contribute to neuropathy and health-related quality of life (HRQoL).. The Multiple Myeloma Research Foundation (MMRF) CoMMpass Registry was queried for all patients who received frontline VRd or bortezomib, cyclophosphamide and dexamethasone (VCd). Incidence of neuropathy and patient-reported HRQoL outcomes over the first 12 months after diagnosis were compared between patients receiving VRd or VCd with or without early ASCT before 6 months.. There were 368 and 191 patients treated with VRd and VCd, respectively. VRd with early ASCT was associated with worse grade 1 neuropathy compared to VRd without early ASCT, as well as compared to VCd with early ASCT. There were no differences in neuropathy between VRd and VCd without early ASCT, and no differences in grade ≥2 neuropathy. There were significant improvements in HRQoL between baseline and 12 months in both VRd and VCd cohorts, regardless of early ASCT. Development of neuropathy was not associated with decrements in progression-free survival or overall survival.. In this longitudinal database analysis, there were no differences in grade ≥2 neuropathy between VRd and VCd frontline induction, and overall HRQoL significantly improved across all cohorts. However, differences in grade 1 neuropathy between VRd and VCd induction suggest that lenalidomide and high-dose melphalan may augment the risk of neuropathy in newly diagnosed multiple myeloma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cyclophosphamide; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Melphalan; Multiple Myeloma; Patient Reported Outcome Measures; Peripheral Nervous System Diseases; Quality of Life; Transplantation, Autologous

Topics: Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Humans; Melphalan; Molecular Targeted Therapy; Multiple Myeloma; Peripheral Nervous System Diseases; Prednisone; Pyrazines; Thalidomide

Substantial efficacy has been demonstrated with bortezomib-melphalan-prednisone in phase III studies in transplant-ineligible myeloma patients using various twice-weekly and once-weekly bortezomib dosing schedules. In VISTA, the regimen comprised four 6-week twice-weekly cycles, plus five 6-week once-weekly cycles. In the GIMEMA MM-03-05 study, the bortezomib-melphalan-prednisone regimen was either per VISTA ('GIMEMA twice-weekly'), or comprised nine 5-week once-weekly cycles ('GIMEMA once-weekly'). In the GEM2005MAS65 study, the regimen comprised one 6-week twice-weekly cycle, plus five 5-week once-weekly cycles. We evaluated the cumulative bortezomib dose administered during bortezomib-melphalan-prednisone, as well as efficacy and tolerability, using patient-level study data. Over all bortezomib-melphalan-prednisone cycles (nine in VISTA/GIMEMA; six in GEM2005MAS65), the median cumulative bortezomib dose administered was 38.5, 42.1, 40.3, and 32.9 mg/m(2) in VISTA, GIMEMA twice-weekly, GIMEMA once-weekly, and GEM2005MAS65, respectively, and the respective proportions of planned bortezomib dose actually delivered were 57.0%, 62.3%, 86.1%, and 90.4%. Response rates following bortezomib-melphalan-prednisone were 74-87% and appeared generally similar between studies. Three-year survival rates were 67.9-75.7% across studies. Grade 3/4 peripheral neuropathy rates were 13% in VISTA and 14% in GIMEMA twice-weekly, but were lower at 2% in GIMEMA once-weekly and 7% in GEM2005MAS65. Discontinuations and bortezomib dose reductions due to peripheral neuropathy were reduced in GIMEMA once-weekly versus VISTA and GIMEMA twice-weekly. Exclusive or predominant use of once-weekly bortezomib dosing in GIMEMA once-weekly and GEM2005MAS65 resulted in high efficacy, comparable with that demonstrated in VISTA, and similar cumulative bortezomib dose with reduced toxicity. Trials are registered with ClinicalTrials.gov: VISTA (Identifier:00111319), GIMEMA MM-03-05 (Identifier:01063179), and GEM2005MAS65 (Identifier:00443235).

Topics: Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Disease Progression; Humans; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Prednisone; Pyrazines; Retrospective Studies; Treatment Outcome

We retrospectively investigated the efficacy and predictive factors for the treatment outcomes of bortezomib plus dexamethasone (BD) as second-line induction therapy prior to high-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) in multiple myeloma (MM) patients.. Sixty-six transplant eligible MM patients treated by the Kyoto Clinical Hematology Study Group between 2006 and 2011 were investigated. Conventional induction chemotherapy, including vincristine, doxorubicin and dexamethasone (VAD) and high-dose dexamethasone (HDD), was used as first-line induction therapy in all patients, seven (10.6%) of whom attained a very good partial response (VGPR). Of the 59 patients who did not attain VGPR with VAD or HDD, 33 were given BD as second-line induction therapy prior to HDT/ASCT.. Patients not treated with BD induction showed an overall response rate (ORR, i.e., better than partial response) of 85.3% after induction therapy, while the ORR of patients treated with BD induction improved from 42.4% after conventional induction therapy to 84.8% after BD. The overall survival (OS) and progression-free survival (PFS) of patients not treated with BD induction were not significantly influenced by the response to induction therapy. Among the patients treated with BD, failure in attaining VGPR prior to ASCT was associated with a significantly shorter PFS and it also tended to show a shorter OS, while the disease stage and achievement of a complete response after HDT/ASCT had no impact on OS or PFS.. The achievement of at least VGPR with second-line BD induction therapy is a prerequisite for attaining longer OS and PFS after HDT/ASCT.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Chromosome Aberrations; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Forecasting; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Peripheral Nervous System Diseases; Prednisone; Pyrazines; Remission Induction; Retrospective Studies; Transplantation, Autologous; Treatment Outcome; Vincristine

Renal impairment (RI) is a severe complication throughout the course of multiple myeloma (MM). Bortezomib has been shown to be highly active in MM patients with RI. We designed this retrospective analysis to investigate the safety and efficacy of bortezomib-based therapy in 117 MM patients with RI, 14 cases required dialysis. A total of 603 cycles of bortezomib were administered (median number, five cycles/patient). Ten patients required early discontinuation of bortezomib because of WHO grade IV toxicity. The rate of bortezomib discontinuation in cases with severe, moderate and mild RI was 11%, 5% and 0%, respectively (P = NS). Overall, 91 episodes of WHO grade III/IV toxicity were observed. At least a partial response was documented in 83/113 evaluable patients (73%), including complete response (19%) and near complete response (8%). The overall response rate was similar across RI subgroups. Reversal of RI was documented in 41% of patients after a median of 2.3 months (range 0.4-7.9). In three of 14 patients on dialysis, renal replacement therapy was discontinued after 1, 1 and 4 months. The 2-yr estimate of response duration and overall survival was 70% and 51%, respectively. In conclusion, bortezomib-based regimens are safe and effective and should be considered as appropriate treatment options for MM patients with any degree of RI.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cardiovascular Diseases; Clinical Trials as Topic; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Follow-Up Studies; Gastrointestinal Diseases; Glomerular Filtration Rate; Hematologic Diseases; Humans; Italy; Kidney Diseases; Male; Melphalan; Middle Aged; Multicenter Studies as Topic; Multiple Myeloma; Neoplasm Proteins; Peripheral Nervous System Diseases; Protease Inhibitors; Proteasome Inhibitors; Pyrazines; Retrospective Studies; Survival Analysis; Thalidomide

Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy.. We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation.. Light chain deposition disease should be recognized as an aetiology of sicca syndrome and peripheral neuropathy. Further studies should assess the prevalence of sicca syndrome in light chain deposition disease and better characterise the neurological manifestations.

Topics: Biopsy; Diagnosis, Differential; Electromyography; Female; Humans; Hypertrophy; Immunoglobulin kappa-Chains; Melphalan; Paraproteinemias; Peripheral Nervous System Diseases; Salivary Glands; Sialography; Sjogren's Syndrome; Stem Cell Transplantation; Tomography, X-Ray Computed; Transplantation, Autologous

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Dexamethasone; Female; Humans; Immunoglobulin A; Melphalan; Multiple Myeloma; Myeloma Proteins; Paresthesia; Peripheral Nervous System Diseases; Plasma Cells; Prednisone; Pyrazines; Remission Induction; Skin; Thalidomide; Xerophthalmia

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

Topics: Amyloidosis; Dexamethasone; Drug Therapy, Combination; Graft Rejection; Heart Failure; Heart Transplantation; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Male; Melphalan; Middle Aged; Nephrotic Syndrome; Paraproteinemias; Peripheral Nervous System Diseases; Secondary Prevention

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Blood Transfusion, Autologous; Bone and Bones; Castleman Disease; Charcot-Marie-Tooth Disease; Demyelinating Diseases; Diagnosis, Differential; DNA Mutational Analysis; Genetic Testing; Genotype; Humans; Inheritance Patterns; Male; Melphalan; Middle Aged; Myeloablative Agonists; Pedigree; Peripheral Nerves; Peripheral Nervous System Diseases; POEMS Syndrome; Treatment Outcome; Vascular Endothelial Growth Factor A

Sweet's syndrome is an uncommon acute skin disease, associated with a variety of medical problems. The drug-induced variant is even rarer. We describe two cases of this syndrome associated with the administration of the proteasome inhibitor bortezomib. The diagnostic criteria for drug-induced Sweet's syndrome as proposed by Walker and Cohen were fulfilled. Vasculitis and neutrophilic eccrine hidradenitis were excluded.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Drug Administration Schedule; Erectile Dysfunction; Humans; Immunosuppressive Agents; Male; Melphalan; Methylprednisolone; Multiple Myeloma; Pain; Peripheral Nervous System Diseases; Prednisolone; Protease Inhibitors; Pyrazines; Recurrence; Sleep Initiation and Maintenance Disorders; Sweet Syndrome; Testicular Diseases

A 12-year-old female, neutered German shepherd dog developed progressive hindlimb followed by forelimb ataxia leading to tetraplegia. Neurological examination suggested lower motor dysfunction. Biochemical evaluation revealed a monoclonal hypergammaglobulinaemia, hypoalbuminaemia and hypercalcaemia. Multiple lytic lesions were identified radiographically in numerous bones. A bone marrow aspirate confirmed the diagnosis of multiple myeloma, with large numbers of plasma cells seen in clusters. An electromyogram revealed positive sharp waves and fibrillation potentials in the skeletal muscles of the limbs, suggesting a polyneuropathy. The dog was treated with chemotherapy using melphalan and prednisolone. Both the hypergammaglobulinaemia and the polyneuropathy resolved and the dog had normal motor function four weeks after commencing treatment. Polyneuropathy may occur as a paraneoplastic syndrome secondary to myeloma, and in this case was reversible following treatment of the underlying disease.

Topics: Animals; Antineoplastic Agents; Dog Diseases; Dogs; Female; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Prednisolone

Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) is effective for advanced melanoma and sarcoma of the limbs. Ten patients undergoing HILP with TNFalpha were evaluated by neurological examinations, nerve conduction studies (NCS), sympathetic skin responses (SSR) and conventional and quantitative electromyography (EMG), performed before, 7 days and 6 weeks following HILP. Seven patients showed minimal clinical signs of peripheral nerve damage following HILP; in two the injury was evident electrophysiologically: 7 days following HILP five patients had paresthesias and/or hypoesthesia, one had a mild foot drop and one had autonomic disturbances in the affected limb. SSR was low in two patients in the affected limb, sensory nerve action potentials were not elicited in one, with normal motor NCS and EMG. At 6 weeks, four patients continued to have mild paresthesias and one had dysautonomia of the perfused limb. Sensory responses and SSR did not change, motor abnormalities were not found. These findings show that HILP with TNFalpha induces a mild, mainly sensory neuropathy in perfused limbs, not disturbing functionality and improving over time.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Arm; Autonomic Nervous System Diseases; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Electromyography; Female; Humans; Hyperthermia, Induced; Immunologic Factors; Leg; Male; Melanoma; Melphalan; Middle Aged; Neural Conduction; Paresthesia; Peripheral Nervous System Diseases; Prognosis; Reflex, Abnormal; Sarcoma, Kaposi; Soft Tissue Neoplasms; Tumor Necrosis Factor-alpha

We report eight patients with a solitary plasmacytoma of the spine associated with neurological complications. The patients included five men and three women with an average age at presentation of 59 years (range, 47 to 73 years). The tumour was confined to the thoracic spine in six cases, cervical spine in one and lumbar spine in one. Duration of symptoms ranged from 2.5 to 22 months. Treatment consisted of a combination of radiotherapy, melphalan and surgery. One patient progressed to multiple myeloma 7 years after surgery. Surgical treatment (anterior surgery in three cases and posterior surgery in five) produced neurological improvement in all patients. We stress the importance of an early diagnosis followed by appropriate treatment including surgery for this clinical entity and long-term follow-up to detect a disseminated disease.

Topics: Aged; Antineoplastic Agents, Alkylating; Cervical Vertebrae; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Laminectomy; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Multiple Myeloma; Neurologic Examination; Peripheral Nervous System Diseases; Plasmacytoma; Radiography; Radiotherapy; Spinal Neoplasms; Survival Rate; Thoracic Vertebrae; Treatment Outcome

The incidence of long-term (> or = 3 months) neuropathy in 350 melanoma patients treated with single normothermic or 'mild' hyperthermic perfusion with melphalan in the period 1978 to 1990 was studied. Long-term neuropathy was encountered in 14 patients; in 10/51 patients (20%) after perfusion at the axillary level and in 4/247 patients (2%) after perfusion at the iliac level. After brachial and femoro-popliteal perfusions no long-term neuropathy was observed. Neuropathy, mainly consisting of paresis/paralysis of the hand and/or fingers, anaesthesia, and/or paraesthesiae, improved over a mean period of 16 (3-43) months in eight patients, but three patients still had serious neuropathy one year after perfusion. In another six patients little improvement was seen and four died with permanent neuropathy. Acute regional toxicity after perfusion and the application of 'mild' hyperthermia did not seem to influence the incidence of long-term neuropathy. This complication is probably a result of the isolating Esmarch rubber bandage being applied too tightly during perfusion at a proximal level. At the axillary level, where the brachial plexus lacks the protection from enveloping tissues, nerve damage is especially prone to occur. We recommend applying this bandage no tighter than is necessary to maintain the isolation of the circuit. This implies meticulous surgical isolation of the vascular system and accurate monitoring of leakage.

Topics: Adolescent; Adult; Aged; Arm; Chemotherapy, Cancer, Regional Perfusion; Female; Fever; Humans; Leg; Male; Melanoma; Melphalan; Middle Aged; Paralysis; Paresis; Peripheral Nervous System Diseases; Retrospective Studies; Sensation Disorders; Skin Neoplasms; Time Factors

Topics: Bone Marrow; Drug Administration Schedule; Humans; Male; Melphalan; Middle Aged; Paraproteinemias; Peripheral Nervous System Diseases

Topics: Adult; Female; Humans; Melphalan; Multiple Myeloma; Peripheral Nervous System Diseases; Plasmapheresis; Prednisone

A patient with a severe polyneuropathy in association with osteosclerotic myeloma improved after melphalan and prednisone treatment. Aggressive treatment with chemotherapy is appropriate in this type of patient.

Topics: Drug Therapy, Combination; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neural Conduction; Osteosclerosis; Peripheral Nervous System Diseases; Prednisone

A patient with a severe remote-effect polyneuropathy and other paraneoplastic features of osteosclerotic myeloma improved dramatically with melphalan and prednisone treatment. Serial electrodiagnostic studies provided an objective means of following the response to therapy and documented the improvement. We believe this represents the first reported patient with multifocal osteosclerotic myeloma and a myelomatous polyneuropathy responding to melphalan and prednisone.

Topics: Adult; Drug Therapy, Combination; Electrodiagnosis; Female; Humans; Melphalan; Multiple Myeloma; Osteosclerosis; Peripheral Nervous System Diseases; Prednisone

Sixteen cases of osteosclerotic myeloma and peripheral neuropathy (SM-PN) were reviewed. The neuropathy resembled chronic inflammatory-demyelinating polyneuropathy with predominantly motor disability, high CSF protein levels, and low motor nerve conduction velocities. Twelve of the 16 patients had detectable levels of monoclonal serum proteins, all with lambda light chains, but results of other laboratory studies were usually normal. Most of the patients also had organomegaly, endocrine abnormalities, or both. Treatment of solitary lesions with tumoricidal irradiation usually improved the neuropathy and reversed the nonneurologic abnormalities; chemotherapy for multiple osteosclerotic lesions was less helpful.

Topics: Adult; Aged; Antibodies, Monoclonal; Bone Neoplasms; Female; Humans; Immunoglobulin kappa-Chains; Male; Melphalan; Middle Aged; Multiple Myeloma; Osteosclerosis; Peripheral Nervous System Diseases; Prednisone

Topics: Adult; Antineoplastic Agents; Bone Marrow; Burns; Creatine Kinase; Electroencephalography; Etoposide; Female; Humans; Hyperthermia, Induced; L-Lactate Dehydrogenase; Male; Melanoma; Melphalan; Middle Aged; Neoplasm Metastasis; Neoplasms; Peripheral Nervous System Diseases; Remission, Spontaneous; Tachycardia

Topics: Amyloidosis; Female; Humans; Melphalan; Middle Aged; Paraproteinemias; Peripheral Nervous System Diseases; Prednisone

Topics: Burns; Chemotherapy, Cancer, Regional Perfusion; Edema; Extremities; Fasciotomy; Humans; Melphalan; Muscular Diseases; Neoplasms; Paralysis; Peripheral Nervous System Diseases; Temperature

Topics: Aged; Blood Protein Electrophoresis; Follow-Up Studies; Hand; Humans; Immunoelectrophoresis; Leg; Male; Melphalan; Muscular Diseases; Neurologic Manifestations; Paresthesia; Peripheral Nervous System Diseases; Sensation; Waldenstrom Macroglobulinemia